i 

# Solid Organ Transplantation and the Probability of Transmitting HIV, HBV, or HCV : A Systematic Review to Support an Evidence

- b ased Guideline

Evidence

- b ased Practice Center

ECRI Institute

Plymouth Meeting, Pennsylvania

April 14 , 2010ii 

# Acknowledgement

We wo uld like to recognize Jonathan R. Treadwell, Ph.D., Senior Research Analyst, and Meredith Noble, M.S., Senior Research Analyst, from the Evidence

- based Practice Center, ECRI Institute, Plymouth Meeting, PA, who authored this document.

We also would like to thank the following individuals who provided in

- depth review of the key evidence search questions, bibliography resulting from the literature review

, and th e evidence outlined in this document.

Blumberg, Emily, MD Professor of Medicine; Director, Transpl ant Infectious Diseases; University of Pennsylvania

Ison, Michael G, MD, MS 

### Associate Professor, Divisions of Infectious Diseases & Organ Transplantation; Director, Transplant & Immunocompromised Host Infectious Diseases Service; Northwestern University F einberg School of Medicine

Preiksaitis, Jutta K, MD Medical Director, Provincial Laboratory for Public Health; Walter Mackenzie Health Science Centreiii 

# Table of Contents

Introduction

................................ ................................ ................................ ................................ ...... 1

Methodology

................................ ................................ ................................ ................................ .... 5
Search Strategy

................................ ................................ ................................ ................................ ......... 5

Inclusion Criteria

................................ ................................ ................................ ................................ ....... 5
Quality Assessment

................................ ................................ ................................ ................................ . 12

GRADE Assessment

................................ ................................ ................................ ............................... 15
Statistical Analysis

................................ ................................ ................................ ................................ .. 16

Evidence Tables

................................ ................................ ................................ ................................ ...... 16



### Overview of the Evidence

................................ ................................ ................................ .............. 18

Evidence Reviews: I. Probability of t ransmission of HIV, HBV, or HCV through solid organ transplantation (SOT)

................................ ................................ ................................ .......... 20
Question 1. What are the prevalence and incidence rates of HIV, HBV, and HCV among potential solid organ donors?

................................ ................................ ................................ .................. 20 Potential Organ Donors

................................ ................................ ................................ ...................... 20

Pre

- 1991 Organ Donors Retrospectively Tested for HCV

................................ ................................ . 24

Potential Tissue Donors

................................ ................................ ................................ ...................... 26 General Population

................................ ................................ ................................ ............................. 28 GRADE Assessment of Epidemiology

................................ ................................ ............................... 29 Additional Evidence Tables for Question 1

................................ ................................ ........................ 33
Question 2. What are the rates of transmission to recipients from donors infected with HIV, HBV, or HCV? Do the rates vary by the organ transplanted or when the donor was infected?

............. 34 HBV Transmission from Liver Transplantation

................................ ................................ ................. 37

HBV Transmission from Kidney Transplantation

................................ ................................ .............. 42 HBV Transmission from Heart Transplantation

................................ ................................ ................. 45 HBV Transmission from Lung Transplant ation

................................ ................................ ................. 46 HCV Transmission from Liver Transplantation

................................ ................................ ................. 46 HCV Transmission from Kidney Transplantation

................................ ................................ .............. 48 HCV Transmission from Heart Transplantation

................................ ................................ ................. 50

GRADE Assessment of Transmission

................................ ................................ ................................ 52

Addit ional Evidence Tables for Question 2

................................ ................................ ........................ 59



### Evidence Reviews: II. Method ology to better estimate donor infection with HIV, HBV, or HCV

................................ ................................ ................................ ................................ ............... 96iv 

### Question 3. What behavioral risk factors are associated with an increased probability of infection with HIV, HBV, or HCV? What is the prevalence of these characteristics among potential solid organ donors?

................................ ................................ ................................ ................................ .......... 96



### And

................................ ................................ ................................ ................................ ................. 96
Question 4. What nonbehavioral risk factors are associated with an increased probability of infection with HIV, HBV, or HCV? What is the prevalence of these facto rs among potential solid organ donors?

................................ ................................ ................................ ................................ .......... 96 Studied Populations and Study Methods

................................ ................................ .......................... 100 Analysis Methods

................................ ................................ ................................ ............................. 126 Assessment of Risk of Bias (Quality of Study Design): Identification of Risk Factors

................... 127 Assessment of Risk of Bias (Quality of Study Design): Prevalen ce of Risk Factors

....................... 131

GRADE Assessment of Identification of Risk Factors

................................ ................................ ..... 132

GRADE Assessment of Prevalence of Risk Factors

................................ ................................ ......... 133
Question 3: Results

................................ ................................ ................................ ............................... 134 Exclusionary Behavioral Criteria from 1994 Guideline

................................ ................................ ... 134

Additional Potential Risk Factors Identified in the 2009 Literature Search

................................ ..... 140 Evidence Tables for Question 3

................................ ................................ ................................ ........ 147
Question 4: Results

................................ ................................ ................................ ............................... 204 Exclusionary Criteria from 1994 Guideline

................................ ................................ ...................... 204

Additional Potential Risk Factors Identified in the 20 09 Literature Search

................................ ..... 205 Evidence Tables for Question 4

................................ ................................ ................................ ........ 213
Question 5. What are the test characteristics of the screening metho ds available to detect HIV, HBV, and HCV in potential solid organ donors? Do test characteristics differ in particular populations and with donor clinical status (i.e., heart beating vs. non

- heart beating donors OR adult vs. pediatric donors)?

................................ ................................ ................................ ................... 295 Samples and Study Methods in Peer

- reviewed Publications

................................ ............................ 318 Analysis Methods

................................ ................................ ................................ ............................. 338

Assessment of Peer

- reviewed Studies

................................ ................................ .............................. 340

Results

................................ ................................ ................................ ................................ ............... 354



### Evidence Reviews: III. Donor interventions to decrease transmission of HIV, HBV,or HCV from infected donors

................................ ................................ ................................ .................... 399
Question 6. Which donor interventions reduce the probability of pathogen transmission from an organ donor infected with HIV, HBV, or HCV to a previ ously uninfected recipient?

......................... 399



### Evidence Reviews: IV. Potential risks and benefits of transplanting, or not transplanting, solid organs from donors positive for HIV, HBV, or HCV

................................ ......................... 403
Question 7. How do the clinical outcomes of recipients of organs from donors infected with HIV, HBV, or HCV compare to those who remain on the transplant list?

................................ .................... 403 Organs from Positive Donors Compared to Remaining on the Waitlist

................................ ........... 404 Organs from Positive Donors Compared to Organs from Negative Donors When the Recipients were Neg ative Before Transplant

................................ ................................ ................................ ..... 408v 

### Organs from Positive Donors Compared to Organs from Negative Donors When the Recipients were Positive Before Transplant

................................ ................................ ................................ ....... 410 Additional Evidence Tables for Question 7

................................ ................................ ...................... 421



### Evidence Reviews: V. Potential risks and benefits of transplanting, or not transplanting, solid organs from donors with ri sk factors for HIV, HBV, or HCV

................................ ........... 475
Question 8. How do the clinical outcomes of transplant recipients who receive organs from donors with behavioral or nonbehavioral risk factors compare to th ose who remain on the transplant list?

................................ ................................ ................................ ................................ ....... 475
Question 9. What is the impact of excluding potential solid organ donors with behavioral or nonbehavioral risk factors on the organ donor pool?

................................ ................................ ............ 488
Question 10. What is the impact of false positive tests on the organ donor pool?

................................ 489



### Gaps in the Current Literature

................................ ................................ ................................ ..... 490

References

................................ ................................ ................................ ................................ .... 491

Appendix A

................................ ................................ ................................ ................................ .. 503

Details of Literature Search

................................ ................................ ................................ .................. 503vi 

# Tables

Table 1. Questions for Systematic Review

................................ ................................ ............................. 1

Table 2. Original Question

- Specific Inclusion Criteria

................................ ................................ .......... 6

Table 3. Modified Question

- Specific Inclusion Criteria

................................ ................................ ......... 7

Table 4. Diagnostic Tests of Interest for Question 5

................................ ................................ ............. 10

Table 5. Quality Assessment Criteria

................................ ................................ ................................ .... 12

Table 6. Interpretation of GRADE Ratings

................................ ................................ ........................... 15

Table 7. Prevalence of Hepatitis and HIV among Potential Organ Donors

................................ .......... 22

Table 8. Prevalence of HCV among Pre

- 1991 Organ Donors

................................ .............................. 24

Table 9. Prevalence of Hepatitis and HIV Among Potential Tissue Donors

................................ ........ 27

Table 10. Methods of Studies Included on Incidence and Prevalence in the U.S. General Population

.. 28

Table 11. Incidence and Prevalence of HBV and HCV in the U.S. General Population

........................ 29

Table 12. GRADE Table for Question 1 (Epidemiology)

................................ ................................ ...... 30

Table 13. Question 1: Quality Assessment

................................ ................................ ............................. 33

Table 14. LIVER Transplantation: Ranges of HBV Results

................................ ................................ .. 38

Table 15. KIDNEY Transplantation: Ranges of HBV Results

................................ ............................... 42

Table 16. HEART Transplantation: Ranges of HBV Results

................................ ................................ . 45

Table 17. LUNG Transplantation: Ranges of HBV Results

................................ ................................ ... 46

Table 18. LIVER Transplantation: Ranges of HCV Results

................................ ................................ .. 46

Table 19. KIDNEY Transplantation: Ranges of HCV Results

................................ ............................... 48

Table 20. HEART Transplantation: Ranges of HCV Results

................................ ................................ . 50

Table 21. GRADE Table for Question 2 (Transmission)

................................ ................................ ........ 53

Table 22. Question 2: General Information about Included Studies

................................ ....................... 59

Table 23. Question 2: Details of Study Methods

................................ ................................ .................... 66

Table 24. Question 2: Pre

- transplant Patient Characteristics

................................ ................................ .. 78

Table 25. Question 2: Quality Assessment

................................ ................................ ............................. 85vii 

### Table 26. Question 2: Data Table of Results

................................ ................................ .......................... 87

Table 27. Included Studies, Questions 3 and 4

................................ ................................ ....................... 98

Table 28. Study Protocols for Questions 3 and 4

................................ ................................ .................. 102

Table 29. Participant Characteristics for KQ 4 and 5

................................ ................................ ........... 116

Table 30. Risk of Bias Assessment Items for Questions 3 and 4: Identification of Risk Factors

......... 127

Table 31. Quality Assessment for Questions 3 and 4: Iden tification of Risk Factors

.......................... 129

Table 32. Quality Assessment for Questions 3 and 4: Prevalence of Risk Factors

.............................. 131

Table 33. HBV Identification of Behavioral Risk Factors Data

................................ ........................... 147

Table 34. HCV Identification of Behavioral Risk Factors Data

................................ ........................... 159

Table 35. HI V Identification of Behavioral Risk Factors Data

................................ ............................. 180

Table 36. GRADE Table for Question 3 (Behavioral Risk Factors)

................................ ..................... 186

Table 37

. Prevalence of Behavioral Risk Factors

................................ ................................ ................. 198

Table 38. GRADE Table for Question 3: Prevalence of Behavioral Risk Factors

............................... 201

Tabl e 39. HBV Nonbehavioral Risk Factors

................................ ................................ ........................ 213

Table 40. HCV: Nonbehavioral Risk Factors

................................ ................................ ....................... 231

Table 41. HIV: Nonbehavioral Risk Factors

................................ ................................ ......................... 268

Table 42. GRADE Table for Question 4 (Nonbehavioral Risk Factors)

................................ .............. 276

Table 43. Prevalence of Nonbehavioral Risk Factors am ong Potential Organ Donors

........................ 293

Table 44. GRADE for Question 4: Prevalence of Nonbehavioral Risk Factors

................................ ... 294

Table 45. Included D ata Sets from Peer

- reviewed Publications

................................ ........................... 297

Table 46. Included Data Sets from Gray Literature

................................ ................................ .............. 314

Table 47. General Study and S ample Characteristics of Peer

- reviewed Studies

................................ .. 319

Table 48. Determining Diagnostic Performance

................................ ................................ ................... 339

Table 49. Study Design Items for Diagnostic Performance

................................ ................................ .. 342

Table 50. Quality Assessment of Question 5: Diagnostic Characteristics

................................ ............ 348

Table 51. Summary of Turnaround Times

................................ ................................ ............................ 355viii 

### Table 52. Summary of Window Periods and Related Data

................................ ................................ ... 356

Table 53. Summary of Sensitivity and Specificity D ata (Range of Reported Point Estimates)

........... 357

Table 54. Overview of Diagnostic Tests

................................ ................................ ............................... 358

Table 55. Diagnostic Characteristics

................................ ................................ ................................ ..... 377

Table 56. GRADE Table for Question 5: Diagnostic Performance (Sensitivity/Specificity)

............... 387

Table 57. Inactivation Methods in Zuc ker et al. (1994)

................................ ................................ ........ 400

Table 58. Inactivation Results in Zucker et al. (1994)

................................ ................................ .......... 401

Table 59. Question 6: Quality Assessment

................................ ................................ ........................... 401

Table 60. GRADE Table for Question 6 (Inactivation)

................................ ................................ ........ 402

Table 61. Baseline Characteristics in the Abbott et al. (2004) Study

................................ ................... 406

Table 62. Large Pre

- transplant Differences between Recipients of D+ and D

- Organs in Studies of Pre

transplant Positive Recipients

................................ ................................ ................................ ................... 411

Table 63. GRADE Table for Question 7 (Clinical Outcomes of Known Positive Organs vs. Waitlist or

Known Negative Organs)

................................ ................................ ................................ ......................... 417

Table 64. Question 7: General Information about Included Studi es

................................ ..................... 421

Table 65. Question 7: Details of Study Methods

................................ ................................ .................. 424

Table 66. Question 7: Pre

- transplant Patient Characteristics

................................ ................................ 428

Table 67. Question 7: Quality Assessment

................................ ................................ ........................... 448

Table 68. Question 7: Reported Data

................................ ................................ ................................ .... 449

Table 69. Assumptions in the Schweitzer et al. (2007) Model

................................ ............................. 4 78

Table 70. HIV Epidemiology Assumptions in the Schweitzer et al. (2007) Model

.............................. 480

Table 71. HCV Epidemiology Assumptions in the Schweitzer et al. (2007) Model

............................ 480

Table 72. Base Case Results of the Schweitzer et al. (2007) Model

................................ ..................... 481

Table 73. HIV and HCV Infection Results in Recipients of Kidneys from CDC

- IRD Donors

............ 482

Table 74. Waitlist Mortality Estimates by Freem an and Cohen (2009)

................................ ................ 484

Table 75. Questions 8/9: Quality Assessment

................................ ................................ ....................... 485

Table 76. GRADE Table for Question 8 (Clinical Outcomes of At

- risk Organs vs. Waitlist or Not

- at

risk Organs) 486ix 

### Table 77. Electronic Databases Searched

................................ ................................ ............................. 503x 

# Figures

Figure 1. Analytic Framework

................................ ................................ ................................ ................. 4

Figure 2. Study Attrition Diagram

................................ ................................ ................................ .......... 19

Figure 3. Question 2: Plot of Transplantation Dates

................................ ................................ .............. 36

Figure 4. LIVER Transplantation: HBV Positivity in Recipients After the Use of Anti

- HBc+ Donors 40

Figure 5. LIVER Transplan tation: HBV Positivity in Recipients After the Use of Organs from
Anti

- HBc+ HbsAg

- Donors

................................ ................................ ................................ ........................ 41

Figure 6. KIDNEY Transplantation: HBV Positivity in Recipients After the Use of Organs from
Anti

- HB c+ Donors or Anti

- HBc+ HbsAg

- Donors

................................ ................................ .................... 43

Figure 7. Other Results for HBV

................................ ................................ ................................ ............ 44

Figure 8. LIVER transplantation: HCV Positivity in Re cipients After the Use of Organs Donors
Positive for HCV

................................ ................................ ................................ ................................ ......... 47

Figure 9. KIDNEY Transplantation: HCV Positivity in Recipients After the Use of Organs from
Donors Positive For HCV

................................ ................................ ................................ ........................... 49

Figure 10. HEART Transplantation: HCV Positivity in Recipients After the Use of Organs from
Donors Positive for HCV

................................ ................................ ................................ ............................ 51

Figure 11. Adjusted Mo rtality Results of Transplanting Kidneys from DHCV+ Donors Compared to
the Waitlist 407

Figure 12. Clinical Outcomes of Negative Recipients: Positive vs. Negative Donors, any Pathogen, any Org an 409

Figure 13. Clinical Outcomes of Positive Recipients: Positive vs. Negative Donors, HBV, Kidney or
Liver 414

Figure 14. Cl inical Outcomes of Positive Recipients: Positive vs. Negative Donors, HCV, Kidney 415

Figure 15. Clinical Outcomes of Positive Recipients: Positive vs. Negative Donors, HCV, Liver

... 4161 

# Introduction

This systematic review addressed 10 Questions ( middle column of Table 1 ) pertaining to solid organ transplantation and three bloodborne pathogens (HI V, HBV, and HCV) . These que stions were carefully developed by the Centers for Disease Control and Prevention in consultation with the Center for
Evidence

- b ased Practice at the University of Pennsylvania and ECRI Institute. The se questions are not
intended to encompass all important issues related to infectious diseases and organ transplantation. Instead, they were specifically focused to support the development of an evidence

- based guideline.
The leftmost column of the table shows which section of the guideline pertains to the questi ons, and t he rightmost column provides explanatory comments.



### Table 1

. Questions for Systematic Review

Major topic area of the guideline Question for Systematic Review Comments

I. Probability of transmission of HIV, HBV, or HCV thro ugh solid organ transplantation (SOT) 1. What are the prevalence and incidence rates of HIV, HBV, and HCV among potential solid organ donors? This question addresses the extent of the possible problem. The focus is on the epidemiology rates for each of the three pathogens among people who are being considered for solid organ donation.

2. What are the rates of transmission to recipients from donors infected with HIV, HBV, or HCV ? Do the rates vary by the organ transplanted or when the donor was infected? A key concern is that a solid organ donor will transmit infection to a recipient. This question concerns the specific situation when the donor is positive for a pathogen but the recipient is not, and what percentage of such recipients become infected after transplantation.

II. Method ology to better estimate donor infect ion with HIV, HBV, or HCV 3

. What behavioral risk factors are associated with an increased probability of infection with HIV, HBV, or HCV ? What is the prevalence of these characteristics amon g potential solid organ donors? Some behaviors may be associated with infection of HIV, HBV or HCV, and the first half of the question attempts to identify these behaviors. This is accomplished by comparing the rate of infection among those who do engage in a behavior to the rate of infection among those who do not. The second half addresses the frequency of those behaviors among potential solid organ donors.

4

. What nonbehavioral factors are associated with an increased probability of infection with HIV , HBV, or HCV ? What is the prevalence of these factors among potential solid organ donors? This is similar to the previous question, except here the focus is on nonbehavioral factors. Our primary intent was to identify signs and symptoms of incident infec tions (i.e., recently acquired), but we also included data on signs and symptoms of chronic infection, medical comorbidities, socioeconomic information, and demographic factors.

5

. What are the test characteristics of the screening methods Numerous tests exist to detec t HIV, HBV and/or HCV in potential donors, and this question concerns the diagnostic2 Major topic area of the guideline Question for Systematic Review Comments

available to d etect HIV, HBV, and HCV in potential solid organ donors? Do test characteristics differ in particular populations and with donor clinical status (i.e., heart beating vs. non

heart beating donors OR adult vs. pediatric donors)? accuracy of those tests, as well as the length of the window period and the turnaround time. The window period is particularly important in this context, because an infect ed individual in the window period would not be detectable prior to donation of solid organs.

III. Donor interventions to decrease transmission of HIV, HBV, or HCV from infected donors 6. Which donor interventions reduce the probability of pathogen transmi ssion from an organ donor infected with HIV, HBV, or HCV to a previously uninfected recipient? Given an infected organ donor, it may be possible to inactivate the virus prior to transplantation into a recipient. This question seeks to identify effective

me thods for inactivation of viruses in solid organs donors.

IV. Potential risks and benefits of transplant ing, or not transplanting, solid organs from donors positive for HIV, HBV, or HCV 7

. How do the clinical outcomes of recipients of organs from donors i nfected with HIV, HBV, or HCV compare to those who remain on the transplant list? This question concerns whether a patient will live longer after 1) receiving a known infected organ or 2) remaining on the transplant list. Other clinical outcomes of interes t include graft survival and quality of life.

V. Potential risks and benefits of transplanting, or not transplanting, organs from donors with risk factors for HIV, HBV,

or HCV 8. How do the clinical outcomes of transplant recipients who receive organs f rom donors with behavioral or nonbehavioral risk factors compare to those who remain on the transplant list? This question is conceptually similar to question 7 . Here, however, the donor is not known to be infected, but the donor is at risk for infection b ased on a behavioral or clinical factor. As in question 7 , the comparison is between implanting or not implanting organs from such donors, with a fo cus on clinical outcomes (e.g., recipient survival).

9. What is the impact of excluding potential solid

or gan donors with behavioral or nonbehavioral risk factors on the organ donor pool? If at

- risk donors are excluded, one negative consequence is a reduction in the orga n donor pool. T his question attempts to quantify the size of the reduction.

10. What is t he impact of false positive tests on the organ donor pool? If donors testing positive are excluded from the donor pool, then f alse positives will result in an inappropriate reduction of the donor pool; this question attempts to quantify the size of the red uction.



### The questions are depicted in an analytic framework ( Figure 1 ) on the next page. The patient population of interest is candidates for solid organ transplantation. The availability of such organs can be in fluenced by numerous factors depicted in the lower half of the figure, notably the infection status of the donor, and3 

### donor behavioral and nonbehavioral risk factors. In this framework, e ach candidate either 1) receives an

organ or 2) remains on the waitli st. The clinical outcomes of interest include patient survival, graft survival, quality of life and recipient infection status

.

The rest of this document is divided into numerous sections, as follows:

**•** Methodology , where in we describe the methods used for c onducting the systematic review

**•** Overview of the evidence

, which paints a broad portrait of the included evidence

**•** Evidence for each question

, which is divided into 10 sections . All text and evidence tables for a given question are collated together with tha t question. Thus, there are no appendices of evidence
tables.

**•** Gaps in the current literature , which discussed the primary areas where further research is

necessary

**•** References , which provide s the full bibliography of included evidence

**•** Details of l iterature search, which provides the search strategies we employed4 

### Figure 1

. Analytic Framework

Potential solid organ donors Patient Population

Serological Test

Behavioral Risk Factor Non

- behavioral Risk Factor 

# 4 Outcomes

Donor Pool



# 9 Note : Circled numbers

, e

. g

. , denote questions addressed by the systematic review

. 

# 1 Inactivation Remain on Wait List

Receive Solid Organ Transplant



# 2 Candidates

for Solid

Organ Transplant Survival / Mortality

Recipient infection

status Intervention Organ Availability

Quality of Life

Exclusion Exclusion 

# 7

Exclusion Exclusion Graft Survival



# 3

1 False negative True positive False positive True negative 

### 10 

# 8

6

9 55 

# Methodology

**Search Strategy**

We searched six bibliographic databases including M EDLINE , EMBASE, and the Cochrane Library to identify clinical trials a nd other relevant publications. (All searched databases are
listed in Table 77 of Appendix A.) Separate date limits were used for some questions, although most spanned 1990 through 2009. Mechanisms used to retrieve additional relevant information included review of bibliographies/reference lists from peer reviewed and gray literature. (Gray literature consists of reports, studies, articles, and monographs produced by federal and local government agencies, p rivate organizations, educational facilities, consulting firms, and corporations. These documents do not appear in the pee r

- reviewed journal literature.) Alphabetical lists of the concepts searched and detailed search str ategies are provided in Appendix A 

### ( Details of Literature Search 

### ).



## I **nclusion C riteria** 

The following universal criteria were applied to all Questions for Systematic Review

**•** English language

**•** Peer

- reviewed, full

- length publication with origina l data

**•** Multiple publications of the same study were treated as a single study rather than as multiple
studies to avoid double

- counting patients.

**•** The study included at least one of the following bloodborne pathogens: HIV, HBV, and HCV.

**•** The determination of the presence or absence of HIV/HBV/HCV must have been based on laboratory test(s), rather than subjective estimates, physician interviews, or patient interviews.

Additional criteria were applied on a per

- question basis, as depicted in Table 2 on the next page

. For many questions, an insufficient number of studies was identified to support the development of the guideline. Consequently, in an effort to provide a sufficient amount of relevant information to support th e development of the guideline, committee members expanded the inclusion criteria in multiple iterations
over several months. The final question

- specific inclusion criteria are shown in Table 3

. The specific diagno stics tests of interest for Question 5 are listed in Table 4

.6 

### Table 2

. Original Question

- Specific Inclusion Criteria

Inclusion Criteria* Questions for Systematic Review

1 2 3 4 5 6 7 8 9 10

Pertinent data on at least five people          

Data collected in U

. S

. A

.      

Potential organ donors    

Rates not restricted to actual donors 

Not voluntary reporting 

Regardless of symptoms 

Data collected in year 2000 or later    

Donor seropositive pre

- transplant   

Recipient seronegative pre

- transplant  

Single type of organ, or separated data on different types of organs    

Waitlist co ntrol group  

Systematic review  

Addressed test sensitivity and specificity  

Experimental group with inactivation procedure 

Control group without an inactivation procedure 

Donor+ for behavioral or clinical factor pre

- transplant 

* For each Question for Systematic Review, five universal criteria were also applied (see text)

. A checkmark in a given column means that a study must have met

that criterion in order to be included for the number ed Question for Systematic Review.7 

### Table 3

. Modified Question

- Specific Inclusion Criteria

Inclusion Criteria * Questions for Systematic Review

1 2 3 4 5 6 7 8 9 10

Pertinent data on at least five people 

###         

Data co llected in U

. S

. A

. 

###    

Rates not restricted to actual donors 

### 

At least one of four populations: 1) Potential organ donors; 2) organ donors with samples taken prior to 1992 that were retrospectively tested for HCV; 3) potential tissue d onors; or 4) the general population (for this last population, we included only the most up

- to

- date epidemiological estimates) 

### 

Regardless of symptoms 

###  

Donor seropositive pre

- transplant 

###   

Recipient seronegative pre

- transp lant 

### 

Single type of organ, or separated data on different types of organs 

###   

Waitlist control OR Control is recipients of organs from uninfected donors 

### 

If pre

- transplant infected recipients and pre

- transplant uninfected r ecipients were included, the study must have reported separate outcome data on these two types of recipients

. 

### 

Reported patient survival, graft survival, or quality of life

. 

###  

At least one of four populations, enrolling individuals of any age: 1) Potential organ donors; 2) potential tissue donors; 3) potential blood donors; or 4) a sample representative of the general population (i.e., population unselected for any particular demographic, occupational, or behavioral characteristics, or health status other than HCV, HBV, or HIV infection status) 

###  

A study of a specific demographic or socioeconomic subpopulation was included for HBV, but excluded for HIV and HCV

. 

###  

A study of a specific subpopulation of patients who were all selected for having the same behavioral risk factor was excluded for all three pathogens

. 

###  8 Inclusion Criteria * Questions for Systematic Review

1 2 3 4 5 6 7 8 9 10

Article must have been published in 1990 or later if pertinent to HIV or HCV, or 1966 or later if pertinent to HBV

. 

###  

In order to ide ntify risk factors for the pathogen, study must have enrolled people with the risk factor as well as people without the risk factor; similarly, the study must have enrolled people positive for the pathogen as well as people negative for the pathogen

. 

###  

For identification of clinical signs and symptoms that may indicate infection, data may be from any country. For identification of co

- morbidities or demographic factors that may be associated with infection, data must be from U.S only. 

### 

Reported at least one of the diagnostic tests listed in Table 4

. 

### 

Reported at least one of the following:

• Sensitivity and specificity

• Positive and negative predictive values (clinical populations on ly)

• Positive and negative likelihood ratios (clinical populations only)

• Sufficient data to calculate the above

• Window period

• Turnaround time 

### 

Reported data on an individual test basis rather than multiple tests or algorithms

. 

### 

Inactivation procedure performed before transplant on organs obt ained from infected individuals. 

### 

Donor positive pre

- transplant for behavioral risk factor or signs/symptoms risk fa ctor or comorbidity risk factor. 

### 

Waitlist control O R Control is recipients of organs from donors without that risk factor

. 

### 

Reported the number of organs that would not be included in the organ pool if donors with behavioral or nonbehavioral risk factors identified in questions 3 and 4 were excl uded. 

### 

Reported the number of organs that would not be included in the organ pool if false positives were excluded

. 

### 9 * For each Question for Systematic Review, five universal criteria were also applied (see text) . A checkmark in a giv en column means that a study must have met

that criterion in order to be included for the numbered Question for Systematic Review.10 

### Table 4

. Diagnostic Tests of Interest for Question 5

Virus Test Name Manufacturer

Tests Currently i n Use by U

. S

. Organ Procurement Organizations

HIV Genetics System (GS) HIV

- 1/HIV

- 2 Plus 0 EIA Bio

- Rad Laboratories

HIVAB HIV

- 1/HIV

- 2 (rDNA) EIA Abbott Laboratories

HBV (HBsAg; the surface antigen) Abbott PRISM HbsAg Assay Abbott Laboratories

ADVIA Ce ntaur HbsAg Assay Siemens Healthcare Diagnostics

AxSYM HBsAg Abbott Laboratories

Genetic Systems (GS) HBsAg EIA 3.0 Bio

- Rad Laboratories

HBV (anti

- HBs; antibodies to the surface antigen) Ortho Antibody to HbsAg ELISA Test System 3 Ortho Clinical Diagn ostics

HBV (anti

- HBc;
antibodies to the core antigen) Abbott PRISM HBcore Abbott Laboratories

ADVIA Centaur HBc Total Assay Siemens Healthcare Diagnostics

AxSYM Core 2.0 Abbott Laboratories

CORZYME Abbott Laboratories

Ortho HBc ELISA Test System Ortho Clinical Diagnostics

HCV Abbott HCV EIA 2.0 Abbott Laboratories

ADVIA Centaur Anti

- HCV Siemens Healthcare Diagnostics

AxSYM Anti

- HCV Abbott Laboratories

Ortho HCV Version 3.0 ELISA Test System Ortho Clinical Diagnostics

HIV NAT COBAS AmpliSc reen HIV

- 1 Test v. 1.5 Roche Diagnostics

HCV NAT COBAS AmpliScreen HCV Test v. 2.0 Roche Diagnostics

HBV NAT COBAS AmpliScreen HBV Test Roche Diagnostics

HCV and HIV

- 1 NAT ProCleix HIV

- 1/HCV Assay Gen

- Probe Incorporated

Fourth Generation Tests

HIV ARC HITECT HIV Combo Abbott Laboratories

AxSYM HIV Ag/Ab Combo Abbott Laboratories

COBAS Core HIV Combo Roche Diagnostics

Coulter HIV

- 1 p24 Antigen Assay Coulter Corporation

Enzygnost HIV Integral II Siemens Healthcare Diagnostics

Genscreen Plus HIV Ag/Ab Combo Bio

- Rad Laboratories

Genscreen HIV Ultra Ag

- Ab Assay Bio

- Rad Laboratories

Murex HIV Ag/Ab Combo Abbott Laboratories

Modular HIV Combo Roche Diagnostics

VIDAS DUO ULTRA bioMerieux Clinical Diagnostics

VIDAS DUO QUICK bioMerieux Clinica l Diagnostics

Vironostika HIV Uni

- Form II Ag/Ab bioMerieux Clinical Diagnostics11 Virus Test Name Manufacturer

HCV INNOTEST HCV Ab IV Innogenetics NV

Monolisa HCV Ag/Ab Ultra Bio

- Rad Laboratories

Murex 4.0 Abbott Laboratories

EIA or ELISA

– Enzyme

- linked immunosorbent assay NAT

– Nucleic acid test12 

## Quality Assessment

In order to assess the quality of the data for each Question for Systematic Review, we applied the criteria
listed in Table 5 . Due to substantial differences among the questio ns, we generally used different criteria for each question. These criteria were determined after examining existing ins truments for quality assessment and selecting the most appropriate items.



### Table 5

. Quality Assessment C riteria

Qu estion Quality C riteria

1. What are the prevalence and incidence rates
of HIV, HBV, and HCV among potential solid organ donors? 1a. Was the population potential solid organ donors?

1b. For other populations , was the p opulation unselected (i.e., not bas ed on demog raphic or behavioral characteristics)? ( studies of potential solid organ donors were scored as Yes, because they enrolled the population of interest) )

1c. Was infection status determined accurately? ( i.e., accuracy of diagnostic test method used to determine i nfection status)

2. What are the rates of transmission to recipients from donors infected with HIV, HBV, or HCV ? Do the rates vary by the organ transplanted or when the donor was infected? 2a. Was the stu dy planned prospectively (i.e., before any data were co llected)

2b. Were all cons ecutive patients enrolled (or a random sample of eligible patients)?

2c. Were laboratory tests performed on recipients regularly in order to monitor antigens/antibodies? (greater frequency means greater accuracy at estimating the rate)

2d. D id all patients receive the same prophylaxis strategy (or none received any prophylaxis)? (a mix of prophylaxis strategies means a less interpretable rate)13 Qu estion Quality C riteria

3

. What behavioral risk factors are associated with an increased probability of infection with HIV, HBV, or HCV ? What is the prevalence of these characteristics among potential solid organ donors? 3a. Was the population potential solid organ donors?

3b. For other populations, w as the population unselected (i.e., not based on demographic or behavioral character istics)? Were infected and uninfected participants similar on other risk factors?

3c. Were infected and uninfected participants similar on other risk factors?

3d. If not, were statistical adjustments performed to control for other risk factors?

3e. Was risk factor dat a collected in a valid manner ( e.g., confidential or anonymous collection of sensitive risk factor data, collection of personal information from the person directly instead of someone else)

3f. Was infection status determined accurately? ( i.e., accuracy of dia gnostic test method used to determine infection status)

4

. What nonbehavioral factors are associated with an increased probability of infection with HIV, HBV, or HCV ? What is the prevalence of these factors among potential solid organ
donors? Same as Que stion 3

5

. What are the test characteristics of the screening methods available to detect HIV, HBV, and HCV in potential solid organ
donors? Do test characteristics differ in particular populations and with donor clinical status (i.e., heart beating vs. n on

- heart beating donors OR adult vs. pediatric donors)? 5a. For measures of diagnostic performance other than window period detection and turnaround time, were the sample sets representative of real

- world use in terms of infection prevalence, infection genotyp es, and proportion of samples in window period?

5b. For measures of diagnostic performance other than window period detection and turnaround time, was a reference standard with excellent
accuracy used? If not, was a reference standard with very good accuracy used?

5c. Were all consecutive patients enrolled (or a random sample of eligible patients)?

5d. Were readers of the diagnostic test of interest blinded to the results of the reference standard?

5e. Were readers of the reference standard blinded to the results of the diagnostic test of interest?

5f. Was the funding for this study derived from a source that would not benefit financially from either data favorable to the test or data unfavorable to the test?14 Qu estion Quality C riteria

6

. Which donor interventions reduce the probability of pathogen tr ansmission from an organ donor infected with HIV, HBV, or HCV to a previously uninfected recipient? 6a. Were the patients randomly assigned to treatments?

6b. Was the stu dy planned prospectively (i.e., before any data were collected)

6c. Were all consecutive patients enrolled (or a random sample of eligible patients)?

6d. Were the two groups comparable at baseline? (age, sex, comorbidities, indication for transplant, previous duration on waitlist)

6e. If not, were statistical adjustments performed to control for baseline diffe rences?

6f. Were the two groups treated concurrently?
6g. Did at least 85% of the study enrollees provide data?

6h. Was the between

- group difference in study completion rates less than 15%?

7

. How do the clinical outcomes of recipients of organs from donors infected with HIV, HBV, or
HCV compare to those who remain on the transplant list? Same as Question 6

8. How do the clinical outcomes of transplant recipients who receive organs from donors
with behavioral or nonbehavioral risk factors compare to those who remain on the transplant list? Same as Question 6

9. What is the impact of excluding potential solid organ donors with behavioral or
nonbehavioral risk factors on the organ donor pool? Same as Question 6

10. What is the impact of false positive tests on
the or gan donor pool? Same as Question 615 

## GRADE Assessment

We used the GRADE evidence rating methodology, which has been developed for treatment comparisons (Questions 6 , 7 and 8) 1 

### and diagnostics (Question 5 ). 2 

### The GRADE system determines the quality of the evidence for a single outcome of a single comparison based on n ine factors

. “Quality” here encompasses not only quality in terms how well the study was designed, but also eight additional factors including inconsistency, indirectness, and imprecision of the evidence base (evidence base being all studies
included for t hat outcome). The first factor (study design) sets the starting GRADE, in which randomized studies start at High, observational studies start at Low, and all other study designs start at Very Low.
The next four factors can only be used to downgrade from th is starting level (study quality limitations, inconsistency, indirectness, imprecision). The other four factors are grouped under “ Other
considerations ” , and they are reporting bias (which can only be used to downgrade), large magnitude of effect, all plau sible confounders would have reduced the effect, and dose

- response association (these latter three factors can only be used to upgrade, if applicable). Ultimately, the GRADE system yields a n overall rating for each outcome , which ranges from “very low” to “high”. The interpretation of these ratings is summarized in Table 6

. 3 

### The details of the application of the GRADE system for each question
are described in those section s

.



### Table 6

. Interpretation of GRADE Ratings

Quality Rating Interpretation

High Further research is very unlikely to change our confidence in the estimate of effect

Moderate Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estima te

Low Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate

Very Low Any estimate of effect is very uncertain

Note : These interpretations are from Box 2 of Guyatt e t al. (2008). 3



### GRADE me thodology has not been developed for the questions on epidemiology (Question 1), transmission (Question 2), risk factors (Question s 3 and 4 ), and the impact of exclusions on the donor pool (Questions 9 and 10). For these, we created GRADE methodology as fo llows. For Questions 1 and 2, no randomized trials are necessary to address the questions, therefore the starting evidence grade was High, and we applied the other components of the GRADE system as appropriate. For Questions 3 and 4

, we used a starting evi dence grade of Low because risk factor studies are by nature observational. Portions of Questions 3 and 4 involve the prevalence of risk factors; these were graded similarly as Question 1 (epidemiology). For Questions 9 and 10, it was not necessary to deve lop new GRADE methodo lo gy, because for Question 9 there was only one study and it had already been graded in Question 8, and for Question 10 there were no included studies.16 

## Statistical Analysis

To compute the 95% confidence interval around a single percent age, we used the Wilson score method

. 4,5



### For comparing pre

- transplant characteristics, we computed the size of the between

- group difference using Hedges ’ g for continuous da ta and the difference in percentages for dichotomous data. We defined a large difference at baseline as a Hedges ’ g of 0.4 or more for continuous data, or a difference in percentage of 15 percentage points or more for dichotomous data. Where appropriate, w e combined the results of multiple studies using DerSimonian and Laird random

- effects meta

- analysis 6 

### using specialized software (Comprehensive Meta

- Anal ysis, Biostat Inc., Englewood, New Jersey)

. We measured heterogeneity using
the I 2 

### statistic. 7 

### For risk factors, we computed the odds ratio and/or relative risk (and 95% confidence intervals) using standard methods with a 0.5 continuity correction applied to studies with a 0% rate in either group. For diagnostics, we computed sensitivity and spe cificity (and 95% confidence intervals) using MetaDisc 1.4

. Additional statistical methods are described for each question in the text for that question.



## Evidence T **ables**

For each question, we constructed evidence tables displaying numerous details about ea ch study.
These varied by question, and included:

**•** Question 1 (epidemiology): Years of data collection, donor population, data sources, relevant viruses, diagnostic methods, whether diagnoses were confirmed, quality assessment criteria, and relevant data

**•** Qu estion 2 (transmission): Country, specific transplantation centers, which organ(s), number of transplantation centers, study funding source, the use of pre

- transplant prophylaxis, the frequency of
post

- transplant testing for infection, duration of follow

- u p, timing of post

- transplant infections, diagnostic methods, p re

- transplant patient characteristics

, quality assessment criteria, which antigen/antibody was used for defining donor positivity, which antigen/antibody was used for defining recipient positivi ty after transplant, and the relevant data.

**•** Question 3 (behavioral risk factors): Virus(es), data source(s), country, selection methods, how risk factor data were collected, relevant blood tests used, study funding source, years of data collection, partici pant characteristics, specific risk factor(s) under investigation, specific population(s) included,
how enrollees were selected, which confounders were adjusted for (if applicable), quality assessment criteria, reported statistical test results, and the re levant data

**•** Question 4 ( nonbehavioral risk factors): Generally the same as in Question 3

**•** Question 5 (diagnostics): the index test and its category, data source(s), country, whether the infection status of samples was known before the study was conducted, w hether the sample was unselected, the reference standard, other tests performed, test manuf acturer, FDA approval date (if applicable), test format, whether specimens can be obtained from living donors or deceased donors or both, whether tests are applied t o serum of plasma or both, quality assessment criteria, GRADE tables, reported data on diagnostic performance, window period, and turnaround time

**•** Question 6 (inactivation): all steps in the inactivation procedure, when the viral load was measured, quality assessment criteria, GRADE tables

, the total viral burden before and after inactivation, the percentage of viral copies that had been removed17 

### • Question 7 (clinical outcomes of known positive organs vs. waitlist or known negative organs): Country, specific transplantation centers, which organ(s), number of transplantation centers, study funding source, p re

- transplant patient characteristics , which antigen/antibody was used for defining donor positivity, diagnostic methods, quality assessment criteria, GRADE tables, whether “survival” meant graft survival or patient survival, duration of follow

- up for each data point, any adjustments for confounding, reported statistical test results, and the relevant data

**•** Question 8 (clinical outcomes of at

- risk organs vs. wa itlist or not

- at

- risk organs): for models, key assumptions about donors/recipients/death rates/costs/QALYS, assumed incidence and prevalence in specific subpopulations, quality assessment criteria, GRADE tables, and relevant data

**•** Question 9 ( impact of excl uding donors with risk factors on the donor pool ): Same as in Question 8

**•** Question 10 ( impact of false positives on the donor pool ): Same as in Question 818 

# Overview of the Evidence

A graphical depiction of the process of article identification appears in Figure 2

. The three most common
reasons for exclusion were: Not an empirical study (review, letter, commentary, etc.), d id not address any

q uestions for s ystematic r eview, and d ata on participants outside the U.S., an d did not meet inclusion criteria for any of the qu estions that included non

- U

. S. data

. Of the 167 included articles, the largest evidence bases were for Question 2 on transmission ( 60 articles) and Qu estion 5 on diagnostic tests ( 45 articles). The counts for other questions are shown in the figure.

For Question 5 (diagnostics), 99 items from the gray literature were reviewed for potentially useful data. These included literature from manufacturers’ Web sites (40), the internet (6), the Food and Drug
Admini stration (FDA) (23), agencies in the United Kingdom (14), agencies from Australia (13), and items from the World Health Organization (3). We included data on window period or turnaround time
from 26 of the 99 items.19 

### Figure 2

. Study A ttrition D iagram

3

, 532 articles identified

167 articles met inclusion criteria Articles reviewed 3

, 366 articles excluded : 1008

- Not an empirical study ( review

, letter

, commentary
, etc .)

667

- Did not address any questions for systematic review
494

- Data on participants outside the U

. S

. , and did not meet inclusion criteria for any of the questions that included non

- U

. S

. data
299

- Not a diagnostic test of interest
233

- Special population
113

- Did not report any outcomes of interest
84

- Used inactivation

, but the target was not solid organs
80

- Fewer than five people enrolled

71

- Study of a pathogen or condition other
than HIV / HBV / HCV
316

- Other

NOTE : The counts add to more than 166 because some articles were included for multiple questions

. 

### Question 1 ( epidemiology ): 22 articles Question 2 ( transmission rate ): 60 articles Question 3 ( behavioral risk factors ): 22 articles Question 4 ( nonbehavioral risk factors ): 29 articles Question 5 ( diagnostic tests ): 45 articles Question 6 ( inactivation ): 2 articles Question 7 ( clinical outcomes of organs from infected donors vs

. waitlist or uninfected donors ): 25 articles Question 8 ( clinical outcomes of organs from at

- risk donors vs

. waitlist or not

- at

- risk donors ): 2 articles Question 9 ( impact on pool of exclusion of those with risk factors ): 1 article Question 10 ( impact on pool of exclusion of false positives ): 0 articles20 

# Evidence **Reviews: I. Probability**  **of transmission of HIV, HBV, or** 

**HCV through solid organ transplantation (SOT)** 

**Question 1.**  **What are the prevalence and incidence rates of HIV, HBV,** 
**and HCV among potential solid organ donors?** 

This questi on involves the frequency of HIV, HBV, and HCV among individuals whose organ(s) are being considered for donation. These rates may differ from rates in the general population or from the rates in individuals who actually did donate organ(s). W e consider ed both the prevalence (the percentage of potential organ donors at a given time who test positive for the pathogen) as well as incidence (the percentage of potential organ donors who newly acquire the pathogen in a one

- year period).

Due to the small amount of evidence on potential solid organ donors, we expanded the scope to include other possibly relevant populations. Thus, the evidence for this question is described in separate sections:

1 ) Potential solid organ donors ( three studies)

2) A ctual solid organ donors who had donated prior to 1991 and their lab samples were retrospectively tested for HCV (four studies)

. Hepatitis C virus (HCV) was discovered in April of 1989, and serological screening for it was not widely performed until 1991. Therefore, anothe r possible source of epidemiological data is studies of stored blood or plasma samples from actual organ donors before 1991

. Because of the early donation date, the samples had not been screened for HCV prior to donation.

3) Potential tissue donors (two st udies). This population may be a reasonable approximation of potential solid organ donors.

4) The general population (six studies)

. T his population may also approximate potential solid organ
donors

.



### P **otential O**  **rgan D**  **onors**

Three studies reported prevalence estimates of HIV, HCV, and/or HBV among potential organ donors.
The definition of “ potential organ donor ” involved liver donor referrals in two studies (relatives wishing to donate to children, 8,9 

### and deceased donors in the other stud ies

. 10,11 

### Testing methods and diagnostic criteria were not consistently reported and may have varied among the studies. Diffe rences in donor populations and methods used to diagnose and report infection probably contributed to the range in reported prevalence. It is not clear that the antibody tests were confirmed by a more specific method such
as Western blot

, recombinant immun oblot assay (RIBA), or nucleic acid

- amplification test s (NAT) in

most of these studies; lack of confirmation may have contributed to overestimation of prevalence due to
anti body reaction false

- positives. Lack of confirmation could also lead to an underesti mation of prevalence if less sensitive antibody are used and if recent infections are missed. One study 10 

### tested for HBV DNA among those whose serological tests was equivocal or positive for antibodies for the core antigen ( anti

- HBc ) or the surface antigen ( HBsAg )

.

In t he study that reported it, the prevalence of HCV was 3.6% among potential living donor relatives. 8 

### The prevalence of active hepatitis, type unspecified, among deceased potential donors rejected from21 

### donation was reporte d as 5.3 % (95% CI : 2.2 % to 12.2 %) in a study of potential deceased donors. 11 

### The remaining study reported the prevalence of unspecified hepatitis at 18.2 % (95% CI : 7.0 % to 39.6 %) among potential living donor relat ives excluded at the second stage of evaluation

. 9



### HIV prevalence was also reported by two of those studies. A study of living adult potential donors did not detect any cases of HIV out of the 45 individuals screened 9,9 

### , and the study on potential deceased donors reported the prevalence of HIV or syphilis (data for HIV alone not reported) at 2 .1 % (95% CI : 0. 5 % to
8.1 %). 11



### The quality assessment items are listed in Table 13

. Meta

- analysis was not performed because there were no instances where at least two studies reported the prevalence of the same virus. These data and additional information regarding the studies they were extracted from are shown in Table 7 , below.22 

### Table 7

. Prevalence of Hepatitis and HIV among Potential Organ D onors

Citation Year Year of Data C ollection Donor Population Data Collection Virus Diagnostic M ethod Confirmed? Prevalence

Hepatitis

Hidalgo et al. 8 2001 1990 to 1999 Living adult parents Retrospective chart review HCV Not reported Not reported 3.6% (95% CI: 1% to 12.3%) ¶ (2/55)

Domen et al. 10 2000 10/94 to 10/98 Potential organ donors Retrospective chart review HBV Unspecified serology HBV

- DNA was also test ed in 16 of 22, and it was positive in 1/16. 4.9% * (95% CI: 3.3% to 7.4%) ¶ (22/446)

Renz et al. 9 1995 5/1992 to 5/1994 Living adult relatives Retrospective review Hepatitis (both B and C were screened for) Unspecified serology Not reported 18.2 % (95% CI: 7.0 % to 39.6 %) (4/ 22 ) ¶

Richards 11 1993 9/19 89 to 8/1991 De ceased donors ; potential cardiac donors Retrospective data review Active viral hepatitis (Authors did not report how many of the 430 potential donors had been tested for hepatitis. ) Not reported Not reported Of the 94 potential donors exclud ed from donation for medical reasons, 5 .3 %; 95% CI : 2 .2 % to 12 .2 %) ¶ were excluded due to active hepatitis

.

HIV

Renz et al. 9 1995 5/1992 to 5/1994 Living adult relatives Retrospective review HIV Unspecified serology Not reported (no positives) 0% (95% CI: 0% to 100 %) (0/ 22 ) ** ¶23 Citation Year Year of Data C ollection Donor Population Data Collection Virus Diagnostic M ethod Confirmed? Prevalence

Richards 11 1993 9/1989 t o 8/1991 P otential deceased cardiac donors Retrospective data review HIV or syphilis (not reported separately)

. Authors did not report how many of the 430 potential donors had been tested for HIV. Not reported Not reported Of the 94 potential donors exclud ed from donation for medical

reasons, 2 .1 %; 95% CI : 0. 5 % to 8.1 %) ¶

were excluded due to HIV or syphilis

.

* Domen et al. 10 included those with equivocal tests as well as those with positive tests, but did not report the corresponding counts. 95% confidence interval (CI) calculated by ECRI Institute. ¶ ** The denominator of 22 is the number of candidates who underwent phase 2 of evaluation for donation, out of 75 total considered for evaluation.24 

### Pre

**- 1991 O**  **rgan D**  **onors R**  **etrospectively T**  **ested for HCV**

We included four such studi es, the methods and results are shown in Table 8

. All four studies met two of the three quality criteria (not selecting patients on the basis of behavioral or demographic factors, and using a standardized diag nostic test for determining infection status). Two studies only included deceased donors, and the other two did not report whether donors were living. The studies found a wide range of prevalence from

2.4 % to 6.8%. Because the studies ’ methods were suffici ently similar, we combined the results in a random

- effects meta

- analysis, and this revealed substantial heterogeneity (I 2 

### = 85%); the combined estimate of HCV prevalence was 4.0 % (95% CI: 2.2% to 7.3%).

These rates may be influenced by geography as well a s the specific anti

- HCV tests used by investigators. Shah et al. (1993) 12 

### collected data from those who had received transplants in Pittsburgh, and they used a second generation ELISA assay (no further specifics reporte d). Vincenti et al. (1993) 13 

### assessed organ donors from California and tested samples for anti

- HCV using an ELISA but did not report the generation , and also tested
for HCV RNA . Pereira et al. (1992) 14 

### assessed organ donors from New England using a second generation ELISA assay (the HCV Elisa 2.0 Test System from Ortho Diagnostics) that "detects antibody to four recombinant HCV antig ens (5

- 1

- 1, c100, c33, and c22) " , the RIBA HCV Test system from Chiron, and test for H CV RNA using PCR. 14 

### Roth et al. (1992) 15 

### assessed organ donors from Miami "using a commercial ELISA (Ortho Diagnostic Systems) " (unreported generation), "a seco nd generation RIBA" (Chiron Corporation)" , and test for HCV RNA via PCR

. 15



### Table 8

. Prevalence of HCV among Pre

- 1991 Organ D onors

Citation Dates of Organ D onation Donor Population Data Collection Diagnostic M ethod Confirmed? Prevalence

Shah et al. (1993) 12,16 Mar

- 86 to Mar

- 90 Liver donors (unreported whether living or deceased ) Retrospective testing of lab samples Anti

- HCV by ELISA2 Not reported 5.8% ( 95% CI: 4.1% to 8.2%) (30/516) ¶

Vincenti et al. ( 1993) 13 Jan

- 86 to Dec

- 88 Deceased kidney donors Retrospective testing of lab samples Anti

- HCV by ELISA ( unreported version) Yes, all four positives were confirmed as HCV RNA+ 2.8% ( 95% CI: 1.1% to 7.0%) (4/143) ¶

Pereira et al. (1992) 14,17

- 19 198 5 to 199 2 Deceased organ donors Retrospective testing of lab samples Anti

- HCV by ELISA1 and ELISA2 Of those positive by ELISA1, 47% were positive for HCV

RNA. 2.4 % ( 95% CI: 1.9% t o 3.0 %) ( 73 / 3078 ) a ¶

Roth et al. (1992) 15,20 Jan

- 79 to Feb

- 91 Deceased organ donors Retrospective testing of lab samples ELISA (unreported version) and RIBA Half of the RIBA+ donors were HCV RNA+ 6.8% ( 95% CI: 4.9% to 9.4%) ( 33/ 484) ¶25 Citation Dates of Organ D onation Donor Population Data Collection Diagnostic M ethod Confirmed? Prevalence

Combined prevalence (random

- effects meta

- analysis; I 2 = 85%) 4. 2 % (2.2% to 7. 7 %)

¶ 95% confidence interval (CI) calculated by ECRI Institute.

a The prevalence in the Pereira et al. study was based on the largest publication, which included 3078 tested donors

. 17 The number in the table is the study ’ s

estima ted prevalence of positivity for HCV RNA, based on the two findings that 5.1% of the 3078 donors were ELISA1 positive , and 47% of those were HCV RNA positive (i.e., 47% of 5.1% is 2.4%)26 

### P **otential T**  **issue D**  **onors**

We included one retrospective stud y on this population. Zou et al. assessed the frequency of HBV, HCV, and/or HIV among tissue donors and estimated both incidence and prevalence

. 21 

### Four of the 5 tissue centers in Zou et al. reported confirmed positive results whereas one center reported screening results only

. Z ou et al. estimated confirmed positive results for the fourth center using data from the other sites

.

Table 9 shows the pertinent data. The prevalence of confirmed HIV was 0.093% (95% CI 0.036% to 0.150%) of dono rs

. . The prevalence of confirmed HBV was 0.229% (95% CI 0.139% to 0.319%) among
donors in Zou et al. Zou et al. also used the tissue donor data as well as blood donor data to estimate the incidence of early viral infection undetected during the serologic w indow period. Their estimated incidence rates per 100,000 person years were 30.11 for anti

- HIV, 18.325 for HbsAg, and 12.380 for anti

HCV.27 

### Table 9

. Prevalence of Hepatitis and HIV A mong Potential Tissue D onors

Citation Year Year of Data C ollection Donor Population Data Collection Virus Diagnostic M ethod Confirmed? Prevalence*

Hepatitis

Zou et al. 21 2004 2000 through 2002 Tissue donors,

no other information provided Prevalence data retrospectively collected from tissue bank databases of 5 tissue banks; Incidence estimated HBV HbsAg Yes 0.229% ( 95% CI: 0.139% to 0.319%) ¶

HCV Anti

- HCV Yes 1.091% ( 95% CI: 0.896% to 1.286%) ¶

HIV

Zou et al. 21 2004 2000 through 2002 Tissue donors,

no other information provided Prevalence data retrospectively collected from tissue bank databases of
5 tissue banks; Incidence estimated HIV Anti

- HIV Yes 0.093% (95% CI: 0.036% to 0.150%) ¶

* Denominator represents all potential donors who were tested for HIV, HBV and HCV

. ¶ 95% confidence interval (CI) calculated by ECRI Institut e.28 

### G **eneral P**  **opulation**

The six included general population studies are listed in Table 10

. All six studies met two of the three quality criteria (not selecting patients on the basis of behavioral or demographic fa ctors, and using a standardized diagnostic test for determining infection status).

For HIV in the general population , the CDC has estimated that the annual U.S. incidence in 2006 was 56,300 22,23 

### and th e prevalence was 1,106,400. 24 

### The U.S. population was approximately 299 ,000,000 in that year, 25 

### thus the incidence was approximately 0.019% (1 in 5

, 308 ) and the pre valence was approximately 0.37 % (1 in 270 ).

For HBV and HCV in the general population

, Table 11 provide s the most recently available estimates

. The U.S. population was approximately 302,000,000 in 2007, 25 

### , which means the incidence rates for
HBV and HCV were 0.014% (1 in 7,023) and 0.0056% (1 in 17,765) , respectively. These data are based on estimates from multiple sources including the National Health and Nutrition Examination Survey (NHANES), the National Notifiab le Diseases Surveillance Sys tem (NNDSS)

, the Emerging Infection Program , and the American Community Survey

.



### Table 10

. Methods of S tudies Included on Incid ence and Prevalence in the U.S. General P opulation

Citation Year of Data C ollection Data Collection Virus ( es) Diagnostic M ethod * Confirmed?

Hepatitis

Daniels et al. (2009) 26,27 2007 NNDSS HBV, HCV Vario us; specifics not reported Yes

Weinbaum et al. (2008) 28 2006 NHANES, ACS HBV Not reported NR

McQuillan et al. (1999) 29 1988

- 1994 NHANES HBV N ot reported NR

Armstrong et al. (2006) 30 1999

- 2002 NHANES HCV 3 rd generatio n ELISA Yes, using RIBA or HCV

- RNA test

HIV

Prejean et al. (200 9 ) 22,23 2006 A new national case reporting system HIV STARHS NR

Centers for Disease Control (2008) 24 2006 A new national case reporting system HIV STARHS NR

* A CS

– American Community Survey

ELISA

– En zyme

- linked immunosorbent assay NHANES

– National Health and Nut rition Examination Survey NNDSS

– National Notifiable Disease Surveillance System STARHS

– Serological testing algorithm for recent HIV seroconversion29 

### Table 11

. Incidence and P revalence of HBV and HCV in the U.S. General P opulation

HBV HCV

Incidence 4 3 ,000 ( in 2007 ) 26,27 17 ,000 ( in 2007 ) 26,27

N umber of acute clinical cases a 13,00 0 (in 200 7 ) 26,27 2

, 8 00 (in 200 7 ) 26 ,27

N umber of people with chronic infection b Betwee n 0.8 million and 1.4 million ( in 2006 ) 28 Between 2.7 million and 3.9 million ( in 1999

- 2002) 30

Percent age of people ever infected c Between 4.3 % and 5.6% ( in 1988

- 1994) 29 Between 1.3 and 1.9% ( in 1999

- 2002) 30

a For hepatitis B, the incidence estimates and the estimated number of acute clinical cases are “ derived from catalytic

modeling of seroprevalence data from the Third National Health and Nutrition Examination Survey (NHANES III) applied to cases reported to the National Notifiable Diseas es Surveillance System (NNDSS)

. ” 27 For h epatitis C in 2007, these estimates were based on data from the Emerging Infection Progra m. 27 The number of acute clinical cases is different from incidence, beca use most new infection s are asymptomatic (and thus not diagnosed or reported).

. b For hepatitis B, the number of people with chronic infection was based on the 2006 American Community Survey

and a U .S. Department of Justice study of prison and jail inmates

. 28 For h epatitis C, the number s were based on NHANES data from 1999

- 2002

. 30

c For hepatitis B, the percentage of people ever infected was based on NHANES data from 1988

- 1994. 29

For h epatitis C, the numbers were based o n NHANES data from 1999

- 2002. 30



### GRADE Assessment of Epidemiology

The GRADE t able for this question appears in Table 12

. We graded the evidence as Low for all three pathogens. This was due to two concerns: varying estimates of epidemiological statistics, and the use of populations other tha n potential organ donors. The variation in estimates between the different studies was not simply due to their enrollment of different populations. For example, even within the four studies of pre

- 1991 actual organ donors who were retrospectively tested fo r HCV, prevalence estimates ranged widely (by a factor of more than three: from 1 in 15 to 1 in 55 )

.30 

### Table 12

. GRADE Table for Question 1 (E pidemiology)Pathogen

Outcome Quantity and Type of Evidence FindingsStarting Grade Decre ase GRADE Increase GRADE

GRADE of
Evidence for
Outcome Overall
GRADE of
Evidence
BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounderswouldreduce the effect

HIV Incidence 1 study of potent ial tissue donors 21 1 study of the U.S. general population 22,23 In the study of potential tissue donors , incidence of 30.11 per 100,000 person

- years In the general population study

, incidence of 56,300 in 2006 , whic h corresponds to 18.8 per 100,000 person years High 0

- 1

- 1 0 0 0 0 0 Low

Prevalence 2 studies of potential organ donors 9,11

1 stud y of potential tissue donors 21 1 study of the U.S. general population 24 In the studies of tested pot ential or gan donors, prevalence of HIV was 0/

22 (0% ) , and prevalence of HIV or syphilis was and 2/

94 ( 2.1 % or 1 in 48 ).

In the stud y of potential tissue donors, prevalence was 1 0/ 10

, 910 (0.093% or
1 in 1

, 090)

. In the general population study, prevalence was 1,106,400 in 2006 (0.37%, or
1 in 270) High 0

- 1

- 1 0 0 0 0 0 Low Low31Pathogen

Outcome Quantity and Type of Evidence FindingsStarting Grade Decre ase GRADE Increase GRADE

GRADE of
Evidence for
Outcome Overall
GRADE of
Evidence
BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounderswouldreduce the effect

HBV Incidence 1 study of potential tissue donors 21 1 study of the U.S. general population 26,27 In the study of potential tissue donors , incidence of 18.325 per 100,000 person

- years In the general population study

, 43,000 incidence in 2007 , which corresponds to 14.4 per 100,000 person

- years High 0 0

- 1 0 0 0 0 0 Moderate

Prevalence 1 study of HBV in potential organ donors 10

2 studies of hepatitis (including HBV and HCV) in tested potential organ donors 9,11

1 stud y of potential tissue donors 21 1 study of the U.S. general population 28 In the study of HBV in potential organ donors , prevalence was 22/446 (4.9%, or 1 in 20).

In the two studies of hepatitis in potential organ donors

, prevalence of 5 / 94 ( 5.3 %, or 1 in 19 ) and4/22 ( 18.2%, or 1 in 6)

. T he stud y of potential tissue donors reported a prevalence of 25/10901 (0.229%, or 1 in
436 ).

. In the general population study , prevalen ce of chronic infection was 1.1 million in 200 6 (0.36% or 1 in 274) High 0

- 1

- 1 0 0 0 0 0 Low Low32Pathogen

Outcome Quantity and Type of Evidence FindingsStarting Grade Decre ase GRADE Increase GRADE

GRADE of
Evidence for
Outcome Overall
GRADE of
Evidence
BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounderswouldreduce the effect

HCV Incidence 1 study of potential tissue donors 21 1 study of the U.S. general population 26,27 In the study of potential tissue donors , incidence of 12.38 per 100,000 person

- years In the general population study

, 17,000 incidence in 2007 , which corresponds to 5.7 per 100,000 person

- years High 0

- 1

- 1 0 0 0 0 0 Low

Prevalence 1 study of HCV in potential organ donors 8

1 stud y of “ hepatitis ” in potential organ donors 9
4 studies of p revalence
among p re

- 1991 organ d

onors 12

- 18,20 1 study of potential tissue donors 21 1 study of the U.S. general population 30 In the study of HCV in potential organ donors , prevalence was 2

/55 (3.6%, or 1 in 28).

In the study of HBV and HCV in potential organ donors, prevalence was 5/430 (1.2%,

o

r 1 in 86)
In the studies of p re

- 1991 organ d onors , combined estimate of prevalence of 4.0% or 1 in 25. In the study of potential tissue donors, pr evalence of 119/10915 (1.091%, or 1 in 92).
In the general population study , prevalence of chronic infection was 3.3 million in 1999

- 2002 (1.1 % or 1 in 86) High 0

- 1

- 1 0 0 0 0 0 Low Low33 

### Additional Evidence Tables for Question 1

Table 13

. Question 1: Quality A ssessment

Study 1a 1b 1c

Potential Solid Organ D onors
Hidalgo et al. (2001) 8  

Domen et al. (2000) 10   

Renz et al. (1995) 9  

Richards (1993) 11  

Actual Solid Organ Donors P re - 1991 Retrospectively T ested for HCV

Shah et al. (1993) 12,16  

Vincenti et al. (1993) 13  

Pereira et al. (1992) 14,17

- 19  

Roth et al. (1992) 15,20  

Potential Tissue D onors

Zou et a l. (2004) 21  

General P opulation

Daniels et al. (2009) 26,27  

Weinbaum et al. (2008) 28  

Mc Quillan et al. (1999) 29  

Armstrong et al. (2006) 30  

Prejean et al. (200 9 ) 22,23  

Centers for Disease Control (2008) 24  

A checkmark (  ) means that the study met the quality criterion for this Question; the lack of a checkmark means that the study either did n o t meet the criterion, or i t was unclear whether the study met the criterion. The criteria specific to this Question were:

1a. Was the population potential solid organ donors?

1b. For other populations , was the population unselected (i.e., not based on demographic or behavioral characteris tics)? ( S tudies of potential solid organ donors were scored as Yes, because they enrolled the population of interest

. )

1c. Was infection status determined accurately? ( i.e., accuracy of diagnostic test method used to determine infection status)34 

## Question **2. Wha t are the rates of transmission**  **to recipients from donors**  **infected with HIV, HBV, or HCV ? Do the rates vary by the organ**  **transplanted or when the donor was infected?**

For this question, the rate of transmission is the chance that an infected organ donor tra nsmits the infection to a previously uninfected recipient. The observed rate of transmission likely depends on numerous factors, including the bloodborne pathogen (HIV, HBV, or HCV), the organ transplanted, the specific antigens or antibodies for which the donor was positive, whether HBV prophy l axis was used, and
the type of serologic testing used for detection . Thus, as we tabulated information from the large evidence base for this question, we carefully delineated those facets that could potentially influ ence the results

.
Sixty articles met the inclusion criteria. These contained some duplication of patients, and after careful perusal, the evidence comprise d 44 unique studies ( a single “ study ” can involve multiple publications
from the same center on the s ame kinds of patients who were enrolled in overlapping timeframes ). All
studies addressed either HBV or HCV , and we extracted data on those recipients who were negative before transplant and who had received organs from donors who had tested positive

. The lack of evidence

on HIV is probably a result of federal regulations that prohibit transplantation of organs from individuals
known to be HIV

- positive

.
The evidence for this question is considered in seven separate sections, according to different pathogen s and organs:

- 16 studies of HBV transmission from liver transplantation

- 9 studies of HBV transmission from kidney transplantation

- 6 studies of HBV transmission from heart transplantation

- 1 study of HBV transmission from lung transplantation

- 2 studies of HC V transmission from liver transplantation

- 10 studies of HC V transmission from kidney transplantation

- 4 studies of HC V transmission from heart transplantation

Reported results on transmission can vary greatly based on numerous factors

. Obviously, the specif ic pathogen and the specific organ are critical factors. Also

, the type of serological testing will matter, specifically 1) For which antigen/antibody was the donor positive? and 2) For which antigen/antibody was the recipient tested? One study might inclu de organ donors who were anti

- HBc+ and HBsAg

- , and report the rate of HBsAg positivity among recipients. Another study might include the same types of donors, but report the rate of positive HBV DNA in serum among recipients. These studies are detecting

in fection in different ways , therefore it would not make sense to consider their results together

. Still o ther important factors include the use of prophylaxis (e.g., lamivudine), specific diagnostic tests used, the frequency and timing of these tests , and t he length of follow

- up after transplantation. In our presentation of the evidence, we provide information about these factors to aid interpretation of results

.

General characteristics of the 44 included studies are listed in Table 22 and Table 23

. Twenty

- six studies were conducted in the U.S., with the remaining 17 studies conducted in Spain (four studies), Japan (three35 

### studies)

, Italy (three studies) , France (two studies)

, Latvia, Belgium, Germany, Taiwan, Canada, and the U.K. (one study each). Thirty

- five studies were conducted at only a single center. Data were collected retrospectively in 35 studies, prospectively in seven studies, and not reported in the other two studie s. Consecutive enrollment was performed in 26 studies. The pre

- transplant patient characteristics are listed

in Table 24

, quality assessments appear in Table 25 , and the re ported results are listed in Table 26

.
A plot of the transplantation dates appears in Figure 3 below

. The start dates of organ transplantations ranged from January 1979 to April 2001 , with the median at June 1994 . The end dates ranged from
December 1988 to June 2004 , with the median at July 1999

. The median length of the transplantation period (the period of time when data were collected) was 4. 4 years, with a range from 1.7 to 15.7

. Only 13 studies reported information about study funding. These generally involved national funding sources, not corporations with conflicts of interest. The mean or median length of follow

- up was reported by 26 studies, and it ranged from five m onths to 5.25 years, with a median of two years.36 

### Figure 3

. Question 2: Plot of Transplantation Dates

1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005



### Studies investigating rate of HBV transmission Veroux (2005) Hartwig (2005) Tenderich (2005) Fabrega (2003) Miedouge (2003) Loss (2003) Suehiro (2005) Pinney (2005) Holt (2002) Nery (2003) Roque

- Afonso (2002) De Feo (2005) Yu (2001) Donataccio (2006) Dodson (1999) Castells (2002) Blanes (2002) Preito (2001) Fong (2002) Ko (2001) Madayag (1997) Montalti (2004) Uemoto (1998) Satterthwaite (1997) Dickson (1997) Kadian (1994) Wachs (1995)

Rozental (2002) Abbott (2004) Marelli (2002) Gudmundsson (2003) Haji (2004) File (2003) Everhart (1999) Tesi (1994) Mendez (1993) Tokumoto (1996) Pereira (1992) Preiksaitis (1997) Shah (1993) Wreghitt (1994) Vincenti (1993) Roth (1992) Range of dates of transplantation



### Studies investigating rate of HCV transmission37 

### Thus, the “ typical ” study for Question 2 was a single

- center U.S. study of unknown funding source that collected data retrosp ectively on consecutive patients who received an organ transplant in a four

- year period in the mid

- late 1990 ’ s, and were followed for an average of two years.

Pre

- transplant characteristics of donors and recipients are listed in Table 24 . M ost studies (30 of 44

, or 68 %) did not report any characteristics specifically for those donor

- recipient pairs in which the donor was positive and the recipient was negative before transplant. For the 13 studies that did report th ese characteristics , the following characteristics were reported by three or more studies :

**•** The mean donor age ranged from 39 to 43 (in the three studies reporting donor age)

**•** The mean recipient age ranged from 33 to 57 ( nine studies)

**•** The percentage of males among donors ranged from 42% to 74% (three studies)

**•** The percentage of males among recipients ranged from 33% to 90% ( ten studies )

**•** The percentage or recipients who were UNOS Status 1 ranged from 56% to 100% (three studies ; these were studies of HCV transmi ssion after heart transplantation )

Regarding quality assessment ( Table 25 )

, 37 of 44 studies (84%) were retrospective

, and 26 of 44 studies ( 59 % ) enrolled patients consecutive ly

. Twelve of 44 studies ( 27 %) used som e form of prophylaxis (e.g., HBIg, lamivudine) for all recipients, six used it for some but not all recipients, two used it for no recipients, and the other 23 studies did not report whether prophylaxis had been used. The frequency of
post

- transplant serol ogy testing was reported by 21 studies, and the methods varied widely:

**•** Seven studies performed relatively intensive monitoring for hepatitis (e.g., “ a t weeks 1, 2, 3, 4, then monthly for one year, then every three months. ” ) 31



### • Four studies performed re latively moderate monitoring (e.g., “ At months 1, 3, and 6, then yearly ” ) 32



### • Six studies used only sporadic monitoring. (e.g., “ When possi ble, samples were obtained at

4 months, one year, and two years after transplant ” ) 33



### • Three studies reported regular monitoring without stating a frequency (e.g., each patient was

“ tested on one or more occasions during routine clinical visits ” ) 34



### • One study reported the use of liver biopsy “ when clinically indicated ” 35



### The next seven sub sections describe the study results for this question.



### HBV T **ransmission from**  **Liver T ransplantation** 

Studies measured virus transmission in 14 different ways for the transmission of HBV from liver transplantation ( Table 14 ). As shown in the next to rightmost column, the range of rates was very wide.

The results are shown graphically in Figure 4 and Figure 5

. One p ossible explanation for the differences among studies is the use of prophylaxis , which may result in negative recipient test ing despite potential
transmission . Studies that used HBV prophylaxis for all patients are depicted with ope n circles; s tudies
that used HBV prophylaxis for some but not all patients are depicted with gray circles; s tudies that used HBV prophylaxis for no patients are depicted with black circles; studies that did not report whether38 

### patients received prophylaxis are depicted with X ’ s. T he graphs suggest that rates were lower when prophylaxis was used.



### Table 14

. LIVER T ransplantation: Ranges of HBV Results

Donor was: Recipient was tested for post

- transplant positivity of: # of S tudies Range of Results Studies

Anti

- HBc+ HBsAg 5 0% to 94% Roque

- Afonso et al. (2002) 36

, Yu et al. (2001) 35

, Dodson et al. (1999) 37

, Uemoto et al. (1998) 38

- 41

, Kadian et al. (1994) 42

Anti

- HBc+ HBeAg 2 40% to 94% Uemoto et al. (1998) 38

- 41

, Kadian et al. (1994) 42

Anti

- HBc+ anti

- HBs 2 0% to 44% Roque

- Afonso et al. (2002) 36

, Yu et al. (2001) 35

Anti

- HBc+ anti

- HBc 2 0% to 78% Roque

- Afonso et al. (2002) 36

, Yu et al. (200 1) 35

Anti

- HBc+ serum HBV

- DNA 2 4 0% to 94% Uemoto et al. (1998) 38

- 41

, Kadian et al. (1994) 42

Anti

- HBc+ “ Developed de novo infection ” 1 6% Montalti (2004) 43

Anti

- HBc+ and HBsAg

HBsAg 9 0% to 78% De Feo et al. (2005) 44,45

, Holt et al. (2002) 46

, Donataccio et al. (2006) 47

, Suehiro et al. (2005) 48

, Fabrega et al. (2003) 49

, Nery et al. (2003) 50

, Preito et al. (2001) 32

, Dickson et al. (1997) 33

, Wachs et al. (1995) 51

Anti

- HBc+ and HBsAg

HBeAg 2 13% to 67% Nery et a l. (2003) 50

, Preito et al. (2001) 32

Anti

- HBc+ and HBsAg

anti

- HBs 2 0% to 5% Castells et al. (2002) 52

, Wachs et al. (1995) 51

Anti

- HBc+ and HBsAg

a nti

- HBc 3 0% to 37% Holt et al. (2002) 46

, Donatac cio et al. (2006) 47

, Castells et al. (2002) 52

Anti

- HBc+ and HBsAg

liver HBV

- DNA 2 0% to 13% Holt et al. (2002) 46

, Nery et al. (2003) 50

Anti

- HBc+ and HBsAg

serum HBV

- DNA 7 0% to 71% Holt et al. (2002) 46

, Suehiro et al. (2005) 48 , Fabrega et al. (2003) 49 , Loss et al. (2003) 31,53

, Nery et al. (2003) 50

, Castells et al. (2002) 52

, Preito et al. (2001) 3239 Donor was: Recipient was tested for post

- transplant positivity of: # of S tudies Range of Results Studies

Anti

- HBc+ and HBsAg

lymphocytes HBV

- DNA 1 0% Fabrega et al. (2003) 4940 

### Figure 4

. LIVER T ransplantation: HBV Positivity in Recipients After the Use of Anti

- HBc+ D onors

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 

### Transmission rate DONOR

was : RECIPIENT was post

- transplant

positive for:

HBsAg

serum HBV anti

- HBc anti

- HBs

HBeAg

"Developed de
novo infection" LIVER TRANSPLANT

anti

- HBc+

Note : This figure displays the reported rates of positivivity among pre

- transplant negativ e recipients after receiving organs from positive donors. . The title of the figure indicates the relevant pathogen(s) and organ(s). These data also appear in Table 26

. The definitions of donor positivity appear on the left side of the figure, and the definitions of recipient post

- transplant positivity appear on the right side of the figure. White circles indicate
studies where all recipients received prophylaxis; gray circles indicate studies where some but not all recipients received prophylaxis; black circles indicate studies where none of the recipients received prophylaxis; an X indicates studies that di d not report whether prophylaxis was used.41 

### Figure 5

. LIVER T ransplantation: HBV Positi vity in Recipients After the Use of Organs from Anti

- HBc+ HbsAg

- D onors

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 

### Transmission rate HBsAg

serum HBV DNA

anti

- HBc anti

- HBs HBeAg

lymphocytes HBV DNA liver HBV DNA LIVER TRANSPLANT

anti

- HBc+

HBsAg

DONOR

was : RECIPIENT was post

- transplant

positive for:

Note : This figure displays the reported rates of positivivity among pre

- transplant negative recipients after receiving organs from positive donors

. The title of the figure indicates the relevant pathogen(s) and organ(s). These data also appear in Table 26

. The definitions of donor positivity appear on the left side of the figure, and the definitions of recipient post

- transplant positivity appe ar on the right side of the figure. White circles indicate
studies where all recipients received prophylaxis; gray circles indicate studies where some but not all recipients received prophylaxis; black circles indicate studies where none of the recipients received prophylaxis; an X indicates studies that did not report whether prophylaxis was used.42 

### HBV T **ransmission from**  **Kidney T ransplantation** 

Studies measured virus transmission in 13 different ways for the transmission of HBV from kidney transplantation ( Table 15 ). These rates were very low. The reported results are shown graphically in Figure 6 and the top section of Figure 7

.



### Table 15

. KIDNEY Transplantation: Ranges of HBV Results

Donor was: Recipient was tested for post

- transplant positivity of: # of S tudies Range of Results Studies

anti

- HBc+ HBsAg 1 0% Kadian et al. (1994) 42

anti

- HBc+ HBeAg 1 0% Kadian et al. (1994) 42

anti

- HBc+ anti

- HBs 1 0% Kadian et al. (1994) 42

anti

- HBc+ anti

- HBc 1 0% Kadian et al. (1994) 42

anti

- HBc+ serum HBV

- DNA 1 0% Kadian et al. (1994) 42

HBsAg

- , anti

- HBc+ HBsAg 6 0% De Feo et al. (2005) 44,45

, Veroux et al. (2005) 54

, Fong et al. (2002) 55

, Madayag et al. (1997) 56

, Satterthwaite et al. (1997) 57

, Wachs et al. (1995) 51

HBsAg

- , anti

- HBc+ anti

- HBs 4 0% to 11% Akalin et al. (2005) 58

, Madayag et al. (1997) 56

, Satterthwaite et al. (1997) 57

, Wachs e t al. (1995) 51

HBsAg

- , anti

- HBc+ anti

- HBc 7 0% to 13% De Feo et al. (2005) 44,45

, Akalin et al. (2005) 58

, Veroux et al. (2005) 54

, Fong et al. (2002) 55

, Madayag et al. (1997) 56

, Satterthwaite et al. (1997) 57

, Wachs et al. ( 1995) 51

HBsAg

- , anti

- HBc+ anti

- HBs and anti

- HBc 1 0% Satterthwaite et al. (1997) 57

HBsAg

- , anti

- HBc+ “ HBV viremia ” 1 0% Akalin et al. (2005) 58

HBsAg

- , anti

- HBc+,

serum HBV

- D NA

HBsAg 1 0% Miedouge et al. (2003) 59

HBsAg

- , anti

- HBc+,

serum HBV

- DNA

anti

- HBc 1 0% Miedouge et al. (2003) 59

HBsAg

- , anti

- HBc+,

se rum HBV

- DNA

serum HBV

- DNA 1 0% Miedouge et al. (2003) 5943 

### Figure 6

. KIDNEY T ransplantation: HBV Positivity in Recipients After the Use of Organs from Anti

- HBc+ Donors or A nti

- HB c+ HbsAg

- D onors

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 

### Transmission rate HBsAg

serum HBV DNA anti

- HBc anti

- HBs HBeAg

anti

- HBc+

anti

- HBc+

HBsAg

HBsAg

anti

- HBs

anti

- HBc KIDNEY TRANSPLANT DONOR

was : RECIPIENT was post

- transplant

positive for:

Note : This figure displays the reported rates of positivivity among pre

- transplant negative recipients after receiving organs fr om positive donors . The title of the figure indicates the relevant pathogen(s) and organ(s). These data also appear in Table 26 . The definitions of donor positivity appear on the left side of the figure, and the
de finitions of recipient post

- transplant positivity appear on the right side of the figure. White circles indicate
studies where all recipients received prophylaxis; gray circles indicate studies where some but not all recipients received prophylaxis; black circles indicate studies where none of the recipients received prophylaxis; an X indicates studies that did not report whether prophylaxis was used.44 

### Figure 7

. O ther Results for HBV

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 

### Transmission rate HBsAg

serum HBV DNA

anti

- HBc anti

- HBs or anti

- HBc KIDNEY TRANSPLANT

anti

- HBc+

HBsAg

anti

- HBc+

HBsAg

serum HBV

- "HBV viremia"

LUNG TRANSPLANT HEART TRANSPLANT

anti

- HBc+ HBsAg

anti

- HBs

anti

- HBc

anti

- HBc+, HBsAg

anti

- HBs+

anti

- HBc+

HBsAg

serum HBV

HBsAg

serum HBV DNA

lymphocyte HBV DNA

anti

- HBc+

HBsAg

HBsAg

anti

- HBc DONOR

was : RECIPIENT was post

- transplant

positive for:

anti

- HBc+, HBsAg

HBsAg

Note : This figure displays the reported rates of positivivity among pre

- transplant negative recipients after receiving organs from positive donors . The title of the figure indicates the relevant pathogen(s) and organ(s). These data also appear in Table 26

. The d efinitions of donor positivity appear on the left side of the figure, and the definitions of recipient post

- transplant positivity appear on the right side of the figure. White circles indicate
studies where all recipients received prophylaxis; gray circles indicate studies where some but not all recipients received prophylaxis; black circles indicate studies where none of the recipients received prophylaxis; an X indicates studies that did not report whether prophylaxis was used.45 

### HBV T **ransmission from**  **Heart T**  **ransplantation**

Studies measured virus transmission in nine different ways for the transmission of HBV from heart transplantation ( Table 16 ). The reported results are shown graphically in the middle section of Figure 7
above

.



### Table 16

. H EART T ransplantati on: Ranges of HBV Results

Donor was: Recipient was tested for post

- transplant positivity of: # of S tudies Range of Results Studies

anti

- HBc+ HBsAg 1 0% to 4% Pinney et al. (2005) 60

, Kadian et al. (1994) 42

anti

- HBc+ anti

- HBs 3 8% to 48% Pinney et al. (2005) 60

, Ten derich et al. (2005) 61

, Kadian et al. (1994) 42

anti

- HBc+ anti

- HBc 2 18% to 65% Tende rich et al. (2005) 61

, Kadian et al. (1994) 42

HBsAg

- , anti

- HBc+ HBsAg 1 0% De Feo et al. (2005) 44,45

HBsAg

- , anti

- HBc+, anti

- HBs+ HBsAg 1 0% Ko et al. (2001) 62,63

HBsAg

- , anti

- HBc+,

serum HBV

- DNA

HBsAg 1 0% Blanes et al. (2002) 64

HBsAg

- , anti

- HBc+,

serum HBV

- DNA

anti

- HBc 1 0% Blanes et al. (2002) 64

HBsAg

- , anti

- HBc+,

serum HBV

- DNA

serum HBV

- DNA 1 0% Blanes et al. (2002) 64

HBsAg

- , anti

- HBc+,

serum HBV

- DNA

lymphocyte HBV

- DNA 1 20% Blanes et al. (2002) 6446 

### HBV T **ransmission from**  **L ung**  **T ransplantation** 

Studies measured virus transmission in two different ways for the transmission of HBV from lung transplantation ( Table 17 ). Both rates were 0%. The reported results are shown graphically in the lower
section of Figure 7 ( above )

.



### Table 17

. LUNG Transplantation: Ranges of HBV Results

D onor was: Recipient was tested for post

- transplant positivity of: # of S tudies Range of Results Studies

HBsAg

- , anti

- HBc+ HBsAg 1 0% Hartwig et al. (2005) 65

HBsAg

- , anti

- HBc+ anti

- HBc 1 0% Hartwig et al. (2005) 65



### HCV T **ransmission from**  **Liver T ransplantation** 

Studies measured virus transmission in three different ways for the transmission of HCV from liver transplantation ( Table 18 ). The reported results are shown graphically in Figure 8

.



### Table 18

. LIVER T ransplantati on: Ranges of HCV Results

Donor was: Recipient was tested for post

- transplant positivity of: # of S tudies Range of Results Studies

anti

- HCV+ anti

- HCV 1 24% Shah et al. (1993) 12,16

anti

- HCV+,

serum HCV

- RNA+ anti

- HCV 1 67% Everhart et al. (1999) 66

anti

- HCV+,

serum HCV

- RNA+ HCV

- RNA 1 100% Everhart et al. (1999) 6647 

### Figure 8

. LIVER transplantation: HCV Positivity in Recipients After the Use of Organs Donors Positive for HCV

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 

### Transmission rate LIVER TRANSPLANT

anti

- HCV+

anti

- HCV+,
serum HCV+ anti

- HCV

HCV

- RNA DONOR

was : RECIPIENT was post

- transplant

positive for:

anti

- HCV

anti

- HCV+,
serum HCV+

Note : This figure displays the reported rates of positivivity among pre

- transplant negative recipients after receiving organs from positive donors . The title of the figure indicates the relevant pathogen(s) and organ(s). These dat a also appear in Table 26

. The definitions of donor positivity appear on the left side of the figure, and the definitions of recipient post

- transplant positivity appear on the right side of the figure. Prophylaxis was not generally applicable to the HCV studies, therefore all studies are represented by X ’ s

.48 

### HCV T **ransmission from**  **Kidney T ransplantation** 

Studies measured virus transmission in eight different ways for the transmission of HCV from kidney transplantation ( Table 19 ). The reported results are shown graphically in Figure 9 below.



### Table 19

. KIDNEY Transplantation: Ranges of HCV Results

Donor was: Recipien t was tested for post

- transplant positivity of: # of S tudies Range of Results Studies

anti

- HCV+ anti

- HCV 8 6% to 91% Abbott et al. (2004) 67,68

, Rozental et al. (2002) 69

, Tokumoto et al. (1996) 70

, Tokumoto et al. (1996) 70

, Wreghitt et al. (1994) 71

, Mendez et al. (1993) 72,73

, Pereira et al. (1992) 14,17

- 19

, Roth et al. (1992) 15,20

anti

- HCV+ HCV

- RNA 2 50% to 100% Tokumoto et al. (1996) 70

, Wreghitt et al. (1994) 71

anti

- HCV+,

serum HCV

- RNA+ anti

- HCV 2 0% to 19% Tesi et al. (1994) 74,75

, Vincenti et al. (1993) 13

anti

- HCV+,

serum HCV

- RNA+ anti

- HCV or indeterminate 1 35% Tesi et al. (1994) 74,75

anti

- HCV+,

serum HCV

- RNA+ HCV

- RNA 2 0% to 57% Tesi et al. (19 94) 74,75

, Vincenti et al. (1993) 13

anti

- HCV+,

serum HCV

- RNA+ RIA 1 0% Vincenti et al. (1993) 13

anti HCV+ and RIBA+ anti

- HCV 1 62% Preiksaitis et al. (1997) 76

anti HCV+ and RIBA+ HCV

- RNA 1 67% Preiksaitis et al. (1997) 7649 

### Figure 9

. KIDNEY Transplantation: HCV Positivity in Rec ipients After the Use of Organs from Donors Positive For HCV

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 

### Transmission rate anti

- HCV

HCV

- RNA

Radio

- immuno

- assay KIDNEY TRANSPLANT

anti

- HCV+

anti

- HCV+,
serum HCV+ anti

- HCV

anti

- HCV OR indeterminate

HCV

- RNA DONOR

was : RECIPIENT was post

- transplant

positive for:

anti

- HCV+,

RIBA+ anti

- HCV

HCV

- RNA

Note : This figure displays the reported rates of positivivity among pre

- transplant negative recipients after receiving organs from positive donors . The title of the figure indicates the relevan t pathogen(s) and organ(s). These data also appear in Table 26

. The definitions of donor positivity appear on the left side of the figure, and the definitions of recipient post

- transplant positivity appear on the r ight side of the figure. Prophylaxis was not generally applicable to the HCV studies, therefore all studies are represented by X ’ s

.50 

### HCV T **ransmission from**  **Heart T**  **ransplantation**

Studies measured virus transmission in six different ways for the transmission of HCV from heart transplantation ( Table 20 ). The reported results are shown graphically in Figure 10

.



### Table 20

. HEART Transplantation: Ranges of HCV Results

Donor was: Recipient was tested for post

- transplant positivity of: # of
S tudies Range of
Results Studies

anti

- HCV+ “ detectable ” anti

- HCV 3 11% to 24% Haji et al. (2004) 77

- 79

, Gudmundsson et al. (2003) 80

, Marelli et al. (2002) 81

anti

- HCV+ HCV

- RNA 3 12% to 75% Haji et al. (2004) 77

- 79

, Gudmundsson et al. (2003) 80

, Marelli et al. (2002) 81

anti

- H CV+ liver HCV 1 29% Gudmundsson et al. (2003) 80

anti

- HCV+ “ Any HCV infection ” 1 43% Gudmundsson et al. (2003 ) 80

anti

- HCV+,

serum HCV

- RNA+ anti

- HCV 1 44% File et al. (2003) 34

anti

- HCV+,

serum HCV

- RNA+ HCV

- RNA 1 100 % File et al. (2003) 3451 

### Figure 10

. HEART Transplantation: HCV Positivity in Recipients After the Use of Organs f rom Donors Positive for HCV

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1


### Transmission rate HEART TRANSPLANT

anti

- HCV+

anti

- HCV+,
serum HCV+ "detectable" anti

- HCV

anti

- HCV

HCV

- RNA

liver HCV

"Any HCV infection"

anti

- HCV

HCV

- RNA DONOR

was : RECIPIENT was post

- transplant

positive for:

Note : This figure displays the reported rates of positivivity among pre

- transplant neg ative recipients after receiving organs from positive donors . The title of the figure indicates the relevant pathogen(s) and organ(s). These data also appear in Table 26 . The definitions of donor positivity appear on the left side of the figure, and the definitions of recipient post

- transplant positivity appear on the right side of the figure. Prophylaxis was not generally applicable to the HCV studies, therefore all studies are represented by X ’ s.52 

### GRADE Assessment **of Transmission** 

The GRADE table for this question appears in 

### Table 21 ; the seven categories of evidence were graded separately. There are numerous permutations of antigens/antibodies, and the committee decided that of these, the most critical HBV results were when the donor was positive for anti

- HBc and may or may not have been HBsAg+ (e.g.

, studies w h ere donor HBsAg status was not reported). The only ex c ep tion to this was when the recipient was being tested for anti

- HBs, whic h wa s not considered critical. For HCV, we
considered it a critical result whenever the donor was positive for HCV RNA. To acknowledge the s e priorities , we shaded the rows summarizing and grading the corresponding evidence. The unshaded rows represent less cri tical results

. For the seven categories of evidence, the primary reasons for the Low or Very Low grades involve study quality and consistency. Results were often widely different, even within the specific antigens and antibodies being tested.53 

### Table 21

. GRADE Table for Question 2 (Transmission )

Definitions of Donor P ositivity Recipient tested for: Quantity and Type of Evidence Range of ResultsStarting Grade Decrease GRADE Increase GRADE

GRADE of Evidence for Outcome Overall GRADE of Evidence BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders wouldreduce the effect

HBV and Liver T ransplantation

Anti

- HBc+ HBsAg 5 OBS 35

- 42 0% to 94% High

- 1

- 1 0 0 0 0 0 0 Low

Low Anti

- HBc+ HBeAg 2 OBS 38

- 42 40% to 94% High

- 2

- 1 0 0 0 0 0 0 Very Low

Anti

- HBc+ anti

- HBc 2 OBS 35,36 0 % to 78% High

- 1

- 1 0 0 0 0 0 0 Low

Anti

- HBc+ serum HBV

DNA 2 OBS 38

- 42 4 0% to 94% H igh

- 1

- 1 0 0 0 0 0 0 Low

Anti

- HBc+ “Developed de novo infection” 1 OBS 43 6% High

- 2

- 1 0 0 0 0 0 0 Very Low

Anti

- HBc+ anti

- HBs 2 OBS 35,36 0% to 44% High

- 1

- 1 0 0 0 0 0 0 Low

Anti

- HBc+ and HBsAg

HBsAg 9 OBS

32,33,44

- 51 0% to 78% High

- 2

- 1 0 0 0 0 0 0 Very L ow

Anti

- HBc+ and HBsAg

HBeAg 2 OBS 32,50 13% to 67% High

- 2

- 1 0 0 0 0 0 0 Very Low

Anti

- HBc+ and HBsAg

anti

- HBs 2 OBS 51,52 0% to 5% High

- 1 0 0 0 0 0 0 0 Moderate

Anti

- HBc+ and HBsAg

anti

- HBc 3 OBS 46,47,52 0% to 37% High

- 1

- 1 0 0 0 0 0 0 Low54 Definitions of Donor P ositivity Recipient tested for: Quantity and Type of Evidence Range of ResultsStarting Grade Decrease GRADE Increase GRADE

GRADE of Evidence for Outcome Overall GRADE of Evidence BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders wouldreduce the effect

Anti

- HBc+ and HBsAg

liver HBV

DNA 2 OBS 46,50 0% to 13% High

- 2

- 1 0 0 0 0 0 0 Very Low

Anti

- HBc+ and HBsAg

serum HBV

DNA 6 OBS

32,46,48

- 50,52,53 0% to 71% High

- 1

- 1 0 0 0 0 0 0 Low

Anti

- HBc+ and HBsAg

lymphocytes HBV

- DNA 1 OBS 49 0% High 0

- 1 0 0 0 0 0 0 Moderate

HBV and Kidney T ransplantation

anti

- HBc+ HBsAg 1OBS 42 0% High

- 2 0 0 0 0 0 0 0 Low

Low anti

- HBc+ HBeAg 1 OBS 42 0% High

- 2

- 1 0 0 0 0 0 0 Very Low

anti

- HBc+ anti

- HBc 1OBS 42 0% High

- 2 0 0 0 0 0 0 0 Low

anti

- HBc+ serum HBV

DNA 1 OBS 42 0% High

- 2

- 1 0 0 0 0 0 0 Very Low

anti

- HBc+ anti

- HBs 1 OBS 42 0% High

- 2

- 1 0 0 0 0 0 0 Very Low

HBsAg

- , anti

- HBc+ HBsAg 6 OBS

44,45,51,54

- 57 0% High

- 1 0 0 0 0 0 0 0 Moderate

HBsAg

- , anti

- HBc+ anti

- HBs 4 OBS 51,56

- 58 0% to 11% High

- 1 0 0 0 0 0 0 0 Moderate

HBsAg

- , anti

- HBc+ anti

- HBc 7 OBS

44,45,51,54

- 58 0% to 13% High

- 1 0 0 0 0 0 0 0 Moderate55 Definitions of Donor P ositivity Recipient tested for: Quantity and Type of Evidence Range of ResultsStarting Grade Decrease GRADE Increase GRADE

GRADE of Evidence for Outcome Overall GRADE of Evidence BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders wouldreduce the effect

HBsAg

- , anti

- HBc+ anti

- HBs and anti

- HBc 1 O BS 57 0% High

- 1

- 1 0 0 0 0 0 0 Low

HBsAg

- , anti

- HBc+ “HBV viremia” 1 OBS 58 0% High

- 2

- 1 0 0 0 0 0 0 Very Low

HBsAg

- , anti

- HBc+, serum HBV

DNA

HBsAg 1 OBS 59 0% High

- 2

- 1 0 0 0 0 0 0 Very Low

HBsAg

- , anti

- HBc+, serum HBV

DNA

anti

- HBc 1 OBS 59 0% High

- 2

- 1 0 0 0 0 0 0 Very Low

HBsAg

- , anti

- HBc+, serum HBV

DNA

serum HBV

DNA 1 OBS 59 0% High

- 2

- 1 0 0 0 0 0 0 Very Low

HBV and Heart T ransplantation

anti

- HBc+ HBsAg 2 OBS 42 ,60 0% to 4% High

- 2 0 0 0 0 0 0 0 Low

Very Low anti

- HBc+ anti

- HBc 2 OBS 42,61 18% to 65% High

- 2

- 1 0 0 0 0 0 0 Very Low

anti

- HBc+ anti

- HBs 3 OBS 42,60,61 8% to 48% High

- 1

- 1 0 0 0 0 0 0 Low

HBsAg

- , anti

- HBc+ HBsAg 1 OBS 44,45 0% High

- 2

- 1 0 0 0 0 0 0 Very Low56 Definitions of Donor P ositivity Recipient tested for: Quantity and Type of Evidence Range of ResultsStarting Grade Decrease GRADE Increase GRADE

GRADE of Evidence for Outcome Overall GRADE of Evidence BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders wouldreduce the effect

HBsAg

- , anti

- HBc+, anti

- HBs+ HBsAg 1 OBS 62,63 0% High

- 1

- 1 0 0 0 0 0 0 Low

HBsAg

- , anti

- HBc+,

serum HBV

DNA

HBsAg 1 OBS 64 0% High

- 2

- 1 0 0 0 0 0 0 Very Low

HBsAg

- , anti

- HBc+,

serum HBV

DN A

anti

- HBc 1 OBS 64 0% High

- 2

- 1 0 0 0 0 0 0 Very Low

HBsAg

- , anti

- HBc+,

serum HBV

DNA

serum HBV

DNA 1 OBS 64 0% High

- 2

- 1 0 0 0 0 0 0 Very Low

HBsAg

- , anti

- HBc+,

serum HBV

DNA

lymphocyte HBV

- DNA 1 OBS 64 20% High

- 2

- 1 0 0 0 0 0 0 Very Low

HBV and Lung T ransplantation

H BsAg

- , anti

- HBc+ HBsAg 1 OBS 65 0% High

- 1

- 1 0 0 0 0 0 0 Low

L ow HBsAg

- , anti

- HBc+ anti

- HBc 1 OBS 65 0% High

- 1

- 1 0 0 0 0 0 0 Low5 7 Definitions of Donor P ositivity Recipient tested for: Quantity and Type of Evidence Range of ResultsStarting Grade Decrease GRADE Increase GRADE

GRADE of Evidence for Outcome Overall GRADE of Evidence BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders wouldreduce the effect

HCV and Liver T ransplantation

anti

- HCV+ anti

- HCV 1 OBS 12,16 24% High

- 2

- 1 0 0 0 0 0 0 Very Low

Low anti

- HCV+, serum HCV

RNA+ anti

- HCV 1 OBS 66 67% High

- 1

- 1 0 0 0 0 0 0 Low

anti

- HCV+, serum HCV

RNA+ HCV

- RNA 1 OBS 66 100% High

- 1

- 1 0 0 0 0 0 0 Low

HCV and Kidney T ransplantation

anti

- HCV+ anti

- HCV 8 OBS 14,15,17

-

20,67

- 70,70

- 73 6% to 91% High

- 2

- 1 0 0 0 0 0 0 Very Low

Very Low anti

- HCV+ HCV

- RNA 2 OBS 70,71 50% to 100% High

- 1

- 1 0 0 0 0 0 0 Low

anti

- HCV+, serum HCV

RNA+ anti

- HCV 2 OBS 13,75 0% to 19% High

- 2

- 1 0 0 0 0 0 0 Very Low

anti

- HCV+, serum HCV

RNA+ anti

- HCV or indeterminate 1 OBS 74,75 35% High

- 2

- 1 0 0 0 0 0 0 Very Low

anti

- HCV+, serum HCV

RNA+ HCV

- R NA 2 OBS 13,74,75 0% to 57% High

- 2

- 1 0 0 0 0 0 0 Very Low58 Definitions of Donor P ositivity Recipient tested for: Quantity and Type of Evidence Range of ResultsStarting Grade Decrease GRADE Increase GRADE

GRADE of Evidence for Outcome Overall GRADE of Evidence BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders wouldreduce the effect

anti

- HCV+, serum HCV

RNA+ RIA 1 OBS 13 0% High

- 2

- 1 0 0 0 0 0 0 Very Low

anti

- HCV+ RIBA+ anti

- HCV 1 OBS 76 62% High

- 2

- 1 0 0 0 0 0 0 Very Low

anti

- HCV+ RIBA+ HCV

- RNA 1 OBS 76 67% High

- 2

- 1 0 0 0 0 0 0 Very Low

HCV and Heart T ransplantation

anti

- HCV+ anti

- HCV 3 OBS 77

- 81 11% to 24% High

- 2 0 0 0 0 0 0 0 Low

Very Low anti

- HCV+ HCV

- RNA 3 OBS 77

- 81 12% to 75% High

- 2

- 1 0 0 0 0 0 0 Very Low

anti

- HCV+ liver HCV 1 OBS 80 29% High

- 2

- 1 0 0 0 0 0 0 Very Low

anti

- HCV+ “Any HCV infection” 1 OBS 80 43% High

- 2

- 1 0 0 0 0 0 0 Very Low

anti

- HCV+, serum HCV

RNA+ anti

- HCV 1 OBS 34 44% High

- 2

- 1 0 0 0 0 0 0 Very Low

anti

- HCV+, serum HCV

RNA+ HCV

- RNA 1 OBS 34 100% High

- 2

- 1 0 0 0 0 0 0 Very Low

Note : T he shaded rows denote evidence on rates whe re the donor was positive for anti

- HBc but it was not reported whether the dono r was positive for HBsAg; these were considered “ critical ” outcomes. The only expectation to this was when the recipient was being tested for anti

- HBs, which was not considered critical

. For HCV, we considered the result critical whenever the donor was positive for HCV RNA (thus the row was shaded).59 

### Additional Evidence Tables for Question 2

Table 22

. Question 2: General Information about I ncluded S tudies

Study Country Center (s) or P rogramKidneyLiverHeartLungCentersTransplantationdates

Funding

Studies of HBV Transmission

De Feo et al. (2005) 44,45 Italy North Italy Transplant program    39 Jan

- 97 to Dec

- 99 Supported in part by a grant from the Italian Institute of Health

Kadian et al. (1994) 42 USA Mount Sinai Medical Center (NY)    1 Sep

- 90 to Jun

- 92 Not reported (NR )

Akalin et al. (2005) 58 USA Mt. Sina i School of Medicine, New York, NY  1 NR NR

Veroux et al. (2005) 54 Italy University Hos p ital of Catania  1 Jan

- 01 to Jun

- 04 NR

Miedoug e et al. (2003) 59 France Toulouse University Hospital  1 Jan

- 99 to Nov

- 01 NR

Fong et al. (2002) 55 USA UNOS Scientific Renal Transplant Registry  >1 1994 to 1999 NR

Madayag et al. (1997) 56 USA Uni versity of Maryland, Baltimore, MD  1 Jan

- 92 to Jul

- 96 NR

Satterthwaite et al. (1997) 57 USA St. Vincent Medical Center, Los Angeles, CA  1 1990 to 1995 NR60 Study Country Center (s) or P rogramKidneyLiverHeartLungCentersTransplantationdates

Funding

Wachs et al. (1995) 51 USA University of California (San Francisco, CA)  1 Jun

- 85 to Dec

- 93 NR

Donataccio et al. (2006) 47 Belgium Universite catholique de Lo uvain  1 Feb

- 92 to Mar

- 04 One author was the recipient of a grant from Associzaone Italiana Trapiantati di Fegato (AITF), First Department of General Surgery, Verona University, Verona Italy

Suehiro et al. (2005) 48 Japan Gunm a University Hospital or Kyushu University Hospital  2 Oct

- 96 to Mar

- 03 S upported in part by a Grant

- in

- Aid for Scientific Research and the 21st Century COE Program from the Ministry of Education, Culture, Sports Science and Technology, Japan

Montalti et al. (2004) 43 Italy University of Bolo gna  1 Apr

- 86 to Jan

- 02 NR

Fabrega et al. (2003) 49 Spain University Hospital Marques de Valdecilla  1 Nov

- 99 to Mar

- 02 Fundacion Marques del Valdecilla

Loss et al. (2003) 31,53 USA Ochsner Clinic Foundation, New Orleans, LA  1 Jan

- 99 to Aug

- 01 NR61 Study Country Center (s) or P rogramKidneyLiverHeartLungCentersTransplantationdates

Funding

Nery et al. (2003) 50 USA Jackson Memorial Hospital Medical Center, Miami, FL  1 Mar

- 96 to Mar

- 02 NR

Castells et al. (2002) 52 Spain Hospital General Vall d ’ Hebron  1 Jun

- 94 to Jun

- 00 NR

Holt et al. (2002) 46 USA Loyola University Medical Center, Chicago, IL  1 Feb

- 98 to Mar

- 01 NR

Roque

- Afonso et al. (2002) 36 France Ho s pital Paul Brousse  1 Jan

- 97 to Sep

- 00 NR

Preito et al. (2001) 32 Spain University Hospital la Fe  1 Mar

- 95 to Dec

- 98 NR

Yu et al. (2001) 35 USA C edars

- Sinai Medical Center, Los Angeles, CA  1 Mar

- 96 to Mar

- 00 NR

Dodson et al. (1999) 37 USA Thomas E. Starzl Transpl antation Institute, Pittsburgh, PA  1 Aug

- 96 to Jun

- 98 NR

Uemoto et al. (1998) 38

- 41 Japan Kyoto University  1 Jun

- 90 to Jun

- 95 Scien tific Research Fund of the Ministry of Education in Japan62 Study Country Center (s) or P rogramKidneyLiverHeartLungCentersTransplantationdates

Funding

Dickson et al. (1997) 33 USA University of Virginia Hospital (Charlottesville, VA), May o Clinic (Rochester, MN), University of Nebraska (Omaha, NE), an d University of California (San Francisco, CA)  4 Aug

- 89 to Jun

- 94 NR

Pinney et al. (2005) 60 USA Columbia P resbyterian Medical Center, New York, NY  1 Jan

- 97 to Dec

- 02 NR

Tenderich et al. (2005) 61 Germany Herz und Diabeteszentrum NRW  1 Feb

- 99 to May

- 04 NR

Blanes et al. (2002) 64 Spain University Hospital la Fe  1 Jan

- 95 to Jun

- 99 NR

Ko et al. (2001 ) 62,63 Taiwan National Taiwan University Hospital  1 Jan

- 92 to Aug

- 99 NR

Hartwig et al. (2005) 65 USA Duke University Medical Center, Durham, NC  1 Apr

- 01 to Aug

- 03 “ The authors have no conflict of interest with regard to this work ”63 Study Country Center (s) or P rogramKidneyLiverHeartLungCentersTransplantationdates

Funding

Studies of HCV T ransmission

Abbott et al. (2004) 67,68 USA United States Renal Data System (USRDS)  >1 Jan

- 96 to Jul

- 00 Supported in part by a grant NIDDK. One author had received an award from the American Kidney Fund.

Rozental et al. (2002) 69 Latvia P. Stradin Clinical University Hospital  1 1997 to Jul

- 01 NR

Preiksaitis et al. (1997) 76 Canada University of Alberta Hospitals, Alberta  1 1984 to Apr

- 92 NR

Tokumoto et al. (1996) 70 Japan Nigata University  1 Nov

- 89 to Nov

- 92 NR

Tesi et al. (1994) 74,75 USA Ohio State Univers ity, Columbus, OH  1 Sep

- 90 to Jan

- 93 a NR

Wreghitt et al. (1994) 71 UK Cambridge or Papworth  2 1984 to 1991 Bloomsbury and Islington Health Authority

Mendez et al. (1993) 72,73 USA St. Vincent Medical Center, Los Angele s, CA  1 Jul

- 90 to Jun

- 92 NR

Vincenti et al. (1993) 13 USA University of California (San Francisco, CA)  1 Jan

- 86 to Dec

- 88 NR64 Study Country Center (s) or P rogramKidneyLiverHeartLungCentersTransplantationdates

Funding

Pereira et al . (1992) 14,17

- 19 USA New England Organ Bank (MA)  14 1986 to 1990 International Society of Nephrology, New England Organ Bank, Nephrology Clinical Research Fellowship T raining Program. One author was a stockholder in Ortho Diagnostic Systems, and three authors were stockholders in Chiron Corporation.

Roth et al. (1992) 15,20 USA Jackson Memorial Hospital Medical Center, Miami, FL  >1 Jan

- 79 to Feb

- 91 Miami Veterans Affairs Hospital Research Support and NIH DK grant

Everhart et al. (1999) 66 USA Mayo Clinic (Rochester, MN), University of Nebraska (Omaha, NE), an d University of California (San Francisco, CA)  3 Apr

- 90 to Jun

- 94 Support from NIH NO1

- DK grants

Shah et al. (1993) 12,16 USA Presbyterian University Hospital, Pittsburgh, PA  1 Mar

- 86 to Mar

- 90 Supported in part by grants from NIDDK

Haji et al. (2004) 77

- 79 USA Cleveland Clinic, Cleveland, OH  1 Jul

- 93 to Dec

- 98 NR65 Study Country Center (s) or P rogramKidneyLiverHeartLungCentersTransplantationdates

Funding

File et al. (2003) 34 USA Ochsner Clinic Foundation, New Orleans, LA  1 1991 to 1999 NR

Gudmundsson et al. (2003) 80 USA Advanced Heart Failure/Heart Transplant Program, Maywood, IL  1 Jan

- 95 to Jul

- 97 Robert D. Van Kampen Research Fund

Marel li et al. (2002) 81 USA University of California (Los Angeles, CA)  1 Jul

- 94 to Dec

- 99 NR

a January 1993 is an approximate estimate of the latest transplant date ( based on the publication date of the p rimary publication of March 1994), so that the study

could be included in the plot of transplant dates.

NR

– Not reported

.66 

### Table 23

. Question 2: Details of Study M ethods

StudyProspectiveConsecutive

Prophylaxis Frequency of Post

transplant Serological T esting Duration of P ost

transplant F ollow

- up If any **de novo** infec tions occurred, how lon g after surgery did they occur? Diagnostic T ests

Studies of HBV T ransmission

De Fe o et al. (2005) 44,45 No No NR NR NR NR Microparticle Enzyme Im munoassay for HBV, and ImxCORE and ImxAVSAB

Kadian et al. (1994) 42 No No NR NR Range : 12

- 33 months Liver : R ange : 8

- 16 months;
Kidney :

no pos itives after transplant;

Heart : N R NR

Akalin et al. (2005) 58 NR NR Lamivudine NR Median : 36 months (R ange : 6

- 60) NA Tests NR; PCR for HBV

- DNA

Veroux et al. (2005) 54 No Yes HBIg NR Mean : 17 months (R ange : 6

- 48) NR NR

Miedouge et al. (2003) 59 No Yes NR NR M ean : 11 mon ths (R ange : 6

- 29) NA Abbott Diagnostics and AxSYM for HBV, and Amplicor for HBV

- DNA67 StudyProspectiveConsecutive

Prophylaxis Frequency of Post

transplant Serological T esting Duration of P ost

transplant F ollow

- up If any **de novo** infec tions occurred, how lon g after surgery did they occur? Diagnostic T ests

Fong et al. (2002) 55 No Yes NR “ The majority of centers do not perform routine HBsAg or anti

- HBc testing ” NR NR NR

Madayag et al. (1997) 56 No Yes NR Performed

“ regularly ” after transplant;

no frequ ency reported Range : 6

- 36 months Range : 3

- 12 months Abbott Diagnostics for HBV

Satterthwaite et al. (1997) 57 No Yes No HBIg, NR others NR NR NR NR

Wachs et al. (1995) 51 No No NR NR NR NR NR

Donataccio et al. (2006) 47 No Yes Of 11 patients, 4 had none, 6 had HBIg, and one had both HBIg and lamivudine At weeks 1, 2, 3, 4, then at months 2 , 3, 6 and 12, a nd then yearly. Liver biopsy
at days 0, 7, and also 6 mo. And 12 mo. Infect ions occurred at a median of 27 months (R ange : 12

- 60) after transplant NR AxSYM or Abbott Diagnostics for HBV68 StudyProspectiveConsecutive

Prophylaxis Frequency of Post

transplant Serological T esting Duration of P ost

transplant F ollow

- up If any **de novo** infec tions occurred, how lon g after surgery did they occur? Diagnostic T ests

Suehiro et al. (2005) 48 NR No HBIg and lamivudine At weeks 1, 2, 3, 4, then monthly for
one year, then e very three months. M ean : 38.5 months (R ange : 25

- 86) NA Abbott Diagnostics for HBV , and Amplicor PCR for HBV

- DNA

Montalti et al. (2004) 43 No Yes NR for the 18 negative recipients; of 44 total recipients, 11 received no
p r ophylaxis, 13 received HbIg, 19 received both HbiG and lamivudine, and 1 received lamivudine only NR NR NR NR

Fabrega et al. (2003) 49 Yes Yes HBIg At weeks 1, 2, 4, and 13;
every 13 weeks thereafter 23 months (R a nge : 9

- 36) NA EIA or Sorin Miomedical for HBV69 StudyProspectiveConsecutive

Prophylaxis Frequency of Post

transplant Serological T esting Duration of P ost

transplant F ollow

- up If any **de novo** infec tions occurred, how lon g after surgery did they occur? Diagnostic T ests

Loss et al. (2003) 31,53 Yes Yes Recombivax HB, HBIg, and la mivudine At weeks 1, 2, 3, 4, then monthly for
one year, then every three months. 5 months (R ange : 1

- 12) NA Qiagen for HBV

, PCR for HBsAg

Nery et al. (2003) 50 No No Of 8 patients, 1 had non e, 6 had lamivudine only, and 1 had both HBIg and lamivudine Every 1

- 6 months or
at discret ion of physician minimum 4 months NR Abbott Diagnostics for HBV , and Qiagen for HBV

- DNA, also in

- house PCR

Castells et al. (2002) 52 Ye s No Engerix HB, and lamivudine after transplant if infection detected At months 1, 3, and 6, then yearly At least 6 months Median : 24 months (R ange : 6

- 48) HBV using Abbott AxSYM; HBeAg and anti

- Hbe using Diasorin; HBV

- DNA using PCR

Holt et al. (2002) 46 No Yes “ Vaccination ”

, HBIg and lamivudine “ All pat ients have been followed closely in the follow

- up period ”

. Liver biopsies at 6 mo., 1 year, and 2 years. 29 months (R ange : 6

- 29) NA PCR on liver biopsy for HBV70 StudyProspectiveConsecutive

Prophylaxis Frequency of Post

transplant Serological T esting Duration of P ost

transplant F ollow

- up If any **de novo** infec tions occurred, how lon g after surgery did they occur? Diagnostic T ests

Roque

- Afonso et al. (2002) 36 No Yes Of 9 patients, 4 had none, and 5 had HBIg At least once every fou r months sometimes more often Median : 24 (R ange : 6

- 45) At months 8, 9, 11, 15, and 17 anti

- HBs using Dade Behring; anti

- HBc using Merux Biotech; HBeAg using BioMerieux ; HBV

- DNA using Quantiplex

Preito et al. (2001) 32 No No Some had lamivudine, but did not report how many At months 1 , 3, and 6, then yearly or when clinically indicated Mean : 24, SD : 14 Median time: 12 months (R ange : 3

- 24) HBsAg using Abbott product; antiHBs and anti

- HBc and anti

- Hbe using Diasiron; HBV

- DNA using PCR via Diogene

Yu et al. (2001) 35 No Yes Lamivudine Did not report frequency of serological test monitoring; only analyzed the most
recent serological test result; liver biopsy only when clinically indicated Mean : 17 months (R ange : 2

- 40) NA HBV

- DNA with Qiogen and nested PCR

Dodson et al. (1999) 37 Yes Yes Of 8 patients, 1 had HBIg only, and the other 7 had both HBIg and lamivudine Daily for 7 days, then monthly for 6 months, then every six months Median : 15 months (R ange : 7

- 20) At 6 months NR71 StudyProspectiveConsecutive

Prophylaxis Frequency of Post

transplant Serological T esting Duration of P ost

transplant F ollow

- up If any **de novo** infec tions occurred, how lon g after surgery did they occur? Diagnostic T ests

Uemoto et al. (1998) 38

- 41 No Yes None NR NR The 15 new infecti ons were found at a mean of

one year (R ange : 5

- 26 months) Dinabot for HBV

, and nested PCR for HBV

- DNA

Dickson et al. (1997) 33 No No NR When possi ble, samples were obtained at 4 months,

one year, and two years after transplant Mean : 19 months (R ange : 4

- 60) Median : 12 months (R ange : 2

- 37) HBV using Abbott product; HBV

- DAN by PCR via National Genetics Institute

Pinney et al. (2005) 60 No Yes Some h ad lamivudine, but did not report how many Every year after transplant NR T he one infection

occu rred at 10 months after transplant NR72 StudyProspectiveConsecutive

Prophylaxis Frequency of Post

transplant Serological T esting Duration of P ost

transplant F ollow

- up If any **de novo** infec tions occurred, how lon g after surgery did they occur? Diagnostic T ests

Tenderich et al. (2005) 61 No Yes NR Within four months bef ore transplant, and between six hours and one year after transplant; did not report a standard monitoring frequency NR HBV was

“ already detectable in several blood samples with in 6

- 10 hours after heart transplant ” ; others detecte d at 5 weeks and 4 months after transplant HBV using Abbott AxSYM; also analyzed two samples of Flebogamma

Blanes et al. (2002) 64 No No NR NR Mean : 37.7 NR HBcAg using AxSYM; anti

- HBc and anti

- HBs using Diasori n; HBV

- DNA by nested PCR

Ko et al. (2001) 62,63 No No HBIg At least once
every four weeks, sometimes more often 32 months (R ange : 6

- 98) NA Well

- cozyme or Chatillon for HBV

, and Qiagen for HBV

- DNA

Hartwig et a l. (2005) 65 No Yes Recombivax HB NR Median : 21.5 months NA NR73 StudyProspectiveConsecutive

Prophylaxis Frequency of Post

transplant Serological T esting Duration of P ost

transplant F ollow

- up If any **de novo** infec tions occurred, how lon g after surgery did they occur? Diagnostic T ests

Studies of HCV T ransmission

Abbott et al. (2004) 6 7,68 No Yes NR NR Range : 6

- 36 months NR ELISA2 or ELISA3

Rozental et al. (2002) 69 No Yes NR NR 18 months (did not report whether th is

was a mean or median) NR HCV using MEIA74 StudyProspectiveConsecutive

Prophylaxis Frequency of Post

transplant Serological T esting Duration of P ost

transplant F ollow

- up If any **de novo** infec tions occurred, how lon g after surgery did they occur? Diagnostic T ests

Preiksaitis et al. (1997) 76 No Yes NR One year after transplant, and/or the time of latest followup Overall median followup of kidney recipients was 54 months (range 9

- 154). Positive anti

HCV tests occurred in 8 kidney recipients at an average of 22 months af ter transplant (median 6.5 months, range 2 to 60.5). Positive HCV RNA tests occurred in 7 kidney recipients at an average of 5.9 years after transplant (median 5.3
years , range 2 to 60.5). Anti

- HCV using Ortho HCV 3.0 ELISA, RIBA using Chiron RIBA HCV 3.0 strip immunoblot assay, and HCV RNA by PCR using the Amplicor HCV virus
test.

Tokumoto et al. (1996) 70 Yes Yes Interferon Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24 Mean : 40 months (R ange : 30

- 65) NR RIBA1; HCV

- RNA using PCR

Tesi et al. (1994) 74,75 Yes No NR NR Mean : 20 months (R ange : 2

- 38 ) NR ELISA1, ELISA 2, Matrix (Abbott) and PCR75 StudyProspectiveConsecutive

Prophylaxis Frequency of Post

transplant Serological T esting Duration of P ost

transplant F ollow

- up If any **de novo** infec tions occurred, how lon g after surgery did they occur? Diagnostic T ests

Wreghitt et al. (1994) 71 No No NR Only the latest serological test results were analyzed Mean : 41 (R ange : 12

- 72) Two at
7 months and 9 months after transplantation; timing of other de novo infections were not reported N R

Mendez et al. (1993) 72,73 No Yes NR NR Range : 12

- 23 months At 4 and 11 months after transplant ELISA2

Vincenti et al. (1993) 13 No Yes NR NR Range : 36

- 40 months NA HCV using Chiron

- Orth; if reactive, then tested for HCV

- RNA

Pereira et al. (1992) 14,17

- 19 No No NR Only the most

rec ent serological test was analyzed Median : 29 months (R ange : 12

- 39) NR ELISA2 and RIBA2; HCV

- RNA using PCR

Roth et al. (1992) 15,20 No No NR NR Median : 55 months (R ange : 3

- 73) At 10 weeks after transplant ELISA1, and if reactive, RIBA2

Everhart et al. (1999) 66 Yes No NR At 4 months,
one year, two years and at study end (which was 2

- 5 years after transplant) NR NR ELISA2, and if that was reactive, then RIBA2; HCV

- RNA using Amplicor76 StudyProspectiveConsecutive

Prophylaxis Frequency of Post

transplant Serological T esting Duration of P ost

transplant F ollow

- up If any **de novo** infec tions occurred, how lon g after surgery did they occur? Diagnostic T ests

Shah et al. (1993) 12,16 No No NR At six months, one year, and two years NR Mean : 21 months (plus or minus 16; did not report whether the plus or minus meant SD, or S E, or CI, or IQR, or SIQR, or range) ELISA2

Haji et al. (2004) 77

- 79 No No NR NR Mean : 50 months (SD : 23) NR ELISA2; HCV

- RNA using PCR

File et al. (2003) 34 No Yes NR Each patient

was “ tested on

one or more occasions during routine clinical visits ” ; nothing else reported abou t monitoring frequency NR NR ELISA2; HCV

- RNA using PCR (Amplicor)

Gudmundsson et al. (2003) 80 No Yes NR NR M ean : 63 months (R ange : 28

- 86) At 19, 39, and 55 months after transplant ELISA2; HCV

- RNA using PCR (Roche)77 StudyProspectiveConsecutive

Prophylaxis Frequency of Post

transplant Serological T esting Duration of P ost

transplant F ollow

- up If any **de novo** infec tions occurred, how lon g after surgery did they occur? Diagnostic T ests

Marelli et al. (2002) 81 No Yes NR NR Median : 22 months (R ange : 7

- 112) NR ELISA2; HCV

- RNA using PCR (Amplicor)

NA

– Not applicable NR

– Not reported78 

### Table 24

. Question 2: Pre

- transplant Patient C haracteristics

Study Patient Characteristics P re - transplant Mean (SD) or % (N/N) Comments

Studies of HBV T ransmission

De Feo et al. (2005) 44,45

, Kadian et al. (1994) 42

, Akalin et al. (2005) 58

, Veroux et al. (2005) 54

, Miedouge et al. (2003) 59

, Madayag et al. (1997) 56

, Wachs et al. (1995) 51

, Donataccio et al. (2006) 47

, Montalti et al. (2004) 43

, Fabrega et al. (2003) 49

, Loss et al. (2003) 31,53

, Nery et al. (2003) 50

, Castells et al. (2002) 52

, Preito et al. (2001) 32

, Dodson et al. (1999) 37

, Uemoto et al. (1998) 38

- 41

, Dickson et al. (1997) 33

, Pinney et al. (2005) 60

, Blanes et al. (2002) 64

, Ko et al. (2001) 62,63

, Hartwig et al. (2005) 65 These studies did not report pre

- transplant characteristics for pre

- transplant negative patients who received organs from positi ve patients

Fong et al. (2002) 55 Cold ischemia time ( hours ) 22.1 ( SD : 8.5 )

Donor % Africa n

- American 17% ( 130/763)

Donor % death due to stroke 51% ( 389/763)

Donor % HCV+ 11% ( 84/763)

Donor % male 42% ( 320/763)

Donor mean age 40.5 ( SD: 16)

Num. of HLA mismatches 3.7 ( SD: 1.6)79 Study Patient Characteristics P re - transplant Mean (SD) or % (N/N) Comments

Recipient % African

- American 34% ( 259/763)

Recipient % Asian

- American 5% ( 38/763)

Recipient % being retransplanted 12% ( 92/763)

Recipient % HCV+ 11% ( 84/763)

Recipient % male 63% ( 481/763)

Recipient mean age 47.8 ( SD: 13.1)

Recipient duration of dialysis (months) 38.1 ( SD: 34.6 )

Recipient Peak Panel Reactive Antibody 13.2 ( SD: 24.3)

Satterthwaite et al. (1997) 57 “ Aver mean age match ” (not defined) 1.6 ( SD: NR)

% with Cold ischemia time >36 hours 41% ( 11/27)

Recipient % age <12 7% ( 2/27)

Recipient % being retransplanted 11% ( 3/27)

Recipient % African

- American 15% ( 4/27)

Recipient % Caucasian

- American 44% ( 12/27)

Recipient % Hispanic

- American 30% ( 8/27)

Recipient % Other race 4% ( 1/27)

Recipient % male 63% ( 17/27)

Re cipient % with diabetes 15% ( 4/27)

Recipient panel reactive antibody <40 0% ( 0/27)

Suehiro et al. (2005) 48 Donor % male 53% ( 8/15)

Donor mean age 43.3 ( SD: 10.2)

Recipient % male 33% ( 5/15)

Recipient mean age 35.3 ( SD: 14.4)80 Study Patient Characteristics P re - transplant Mean (SD) or % (N/N) Comments

Holt et al. (2002) 46 Recipient % indication for transplant was active hepatitis, IgA deficiency 13% ( 1/8)

Recipient % indication for transplant was acute Budd

- Chiari syndrome 13% ( 1/8)

Recipient % indication for transplant was alcoholic cirrhosis 13% ( 1/8)

Recipient % indication for transplant was chronic active HCV 13% ( 1/8)

Recipient % indicatio n for transplant was fulminant liver failure 13% ( 1/8)

Recipient % indication for transplant was liver failure secondary to amyloidosis 13% ( 1/8)

Recipient % indication for transplant was primary biliary cirrhosis 13% ( 1/8)

Recipient % indicati on for transplant was primary biliary cirrhosis and scleroderma 13% ( 1/8)

Recipient % male 50% ( 4/8)

Recipient mean age 48.9 ( SD: 13.5)

Roque

- Afonso et al. (2002) 36 Recipient % blood type A+ 56% ( 5/9)

Recipient % blood type B+ 11% ( 1/9)

Recipi ent % blood type O+ 33% ( 3/9)

Recipient % indication for transplant was alcoholic cirrhosis 44% ( 4/9)

Recipient % indication for transplant was Budd

- Chiari syndrome 11% ( 1/9)

Recipient % indication for transplant was HCV+ alcoholic cirrhosis 11 % ( 1/9)81 Study Patient Characteristics P re - transplant Mean (SD) or % (N/N) Comments

Recipient % indication for transplant was primary biliary cirrhosis 11% ( 1/9)

Recipient % indication for transplant was symptomatic amyloidosis 22% ( 2/9)

Yu et al. (2001) 35 Recipient % indication for transplant was HCC (NR what this meant) 60% ( 3/5)

Recipient % indication for transplant was HCV cirrhosis 100% ( 5/5)

Tenderich et al. (2005) 61 Recipient % indication for transplant was coronary heart disease 43% ( 10/23)

Recipient % indication for transplant was dilated cardiomyopathy 48% ( 11/23)

Recipient % male 83% ( 19/23)

Recipien t % other indication for transplant 9% ( 2/23)

Recipient mean age 53.5 ( “ +/

- 5.4 ” ; NR what this meant)

Serum creatinine 1.25 ( “ +/

- 0.49 ” ; NR what this meant)

Recipient height (cm) 171 ( “ +/

- 21 ” ; NR what this meant)

Recipient left ventricular ejection fraction (%) 29.6 ( “ +/

- 12.9 ” ; NR what this meant)

Recipient serum creatinine 72.4 ( “ +/

- 20.6 ” ; NR what this meant)82 Study Patient Characteristics P re - transplant Mean (SD) or % (N/N) Comments

Studies of HCV transmission

Abbott et al. (2004) 67,68

, Rozental et al. (2002) 69

, Preiksaitis et al. (1997) 76

, Tesi et al. (1994) 74,75

, Wreghitt et al. (1994) 71

, Vincenti et al. (1993) 13

, Pereira et al. (1992) 14,17

- 19

, Everhart et al. (1999) 66

, Shah et al. (1993) 12,16 These studies did not report pre

- transplant characteristics for pre

- transplant negative patients who received organs f rom positive patients

Tokumoto et al. (1996) 70 Recipient HLA AB mismatch 1.3 ( SD: 0.8)

Recipient HLA DR mismatch 0.7 ( SD: 0.8)

Recipient % male 50% ( 3/6)

Recipient % received organs from deceased donors 50% ( 3/6)

Recipient mean age 36.7 ( SD: 13.3)

Mendez et al. (1993) 72,73 Donor % CMV+ 85% ( 28/33)

Recipient % CMV+ 76% ( 25/33)

Recipient % etiology diabetes 27% ( 9/33)

Recipient % etiology hypertension 18% ( 6/3 3)

Recipient % male 45% ( 15/33)

Recipient mean age 33 ( SD: 11)

Recipient pre

- transplant dialysis tie (months) 25 ( SD: 6)

Recipient prior number of blood transfusions 9 ( SD: 4)83 Study Patient Characteristics P re - transplant Mean (SD) or % (N/N) Comments

Roth et al. (1992) 15,20 Donor % chronic active hepatitis 45% ( 5/11) 3 of the 14 donors ’ pre

- tr ansplant CMV status was not reported

Donor % chronic persistent hepatitis 9% ( 1/11) 3 of the 14 donors ’ pre

- transplant CMV status was not reported

Donor % CMV+ 50% ( 7/14)

Donor % normal liver histology 45% ( 5/11) 3 of the 14 donors ’ pre

- transplant CMV status was not reported

Recipient % CMV+ 69% ( 9/13) 1 of the 14 recipients ’ pre

- transplant CMV status was not reported

Haji et al. (2004) 77

- 79 % “ Cause ” was dilated cardiomyo pathy 32% ( 11/34)

% “ Cause ” was ischemic cardiomyopathy 62% ( 21/34)

% “ Cause ” was something else 5% ( 2/34)

Donor % male 74% ( 25/34)

Donor mean age 39 ( SD: 9)

Recipient % male 76% ( 26/34)

Recipient mean age 57 ( SD: 10)

Recipient mean age biopsy score 1.31 ( SD: 0.65)

Recipient episodes of acute rejection before this transplant 1.7 ( SD: 1.5)

File et al. (2003) 34 Recipient % history of alcohol abuse 10% ( 1/10)

Recipient % ischemic cardiomyopathy 100% ( 10/10)

Recipien t % male 90% ( 9/10)

Recipient % UNOS status I 100% ( 10/10)

Recipient mean age 52 ( SD: 7.1) SD calculated by ECRI Institute based on Table 1 of the article84 Study Patient Characteristics P re - transplant Mean (SD) or % (N/N) Comments

Gudmundsson et al. (2003) 80 Recipient % anti

- HBs+ 13% ( 1/8)

Recipient % indication for transplant was idiopathic dilation 25% ( 2/8)

Recipient % indication for transplant was ischemia 50% ( 4/8)

Recipient % indication for transplant was restrictive cardiomyopathy 13% ( 1/8)

Recipient % indication for transplant was valvular 13% ( 1/8)

Recipient % male 88% ( 7/8)

Recipient % UNOS status I 88% ( 7/8)

Recipient % with HCV+ serology 0% ( 0/8)

Recipient % with other positive HBV serology 0% ( 0/8)

Recipient mean age 55 ( SD: NR)

Marelli et al. (2002) 81 Recipient % UNOS status 1 56% ( 10/18)

SD

– S tandard deviation85 

### Table 25

. Question 2: Quality A ssessment

Study 2a 2b 2c 2d

Studies of HBV T ransmission

De Feo et al. (2005) 44,45

Kadian et al. (1994) 42

Akalin et al. (2005) 58 

Veroux et al. (2005) 54  

Miedouge et al. (2003) 59 

Fong et al. (2002) 55 

Madayag et al. (1997) 56  

Satterthwaite et al. (1997) 57  

Wachs et al. (1995) 51

Donataccio et al. (2006) 47  

Suehiro et al. (2005) 48  

Montalti et al. (2004) 43 

Fabrega et al. (2003) 49    

Loss et al. (2003) 31,53    

Nery et al. (2003) 50 

Castells et al. (2002) 52   

Holt et al. (2002) 46   

Roque

- Afonso et al. (2002) 36  

Preito et al. (2001) 32 

Yu et al. (2001) 35  

Dodson et al. (1999) 37    

Uemoto et al. (1998) 38

- 41  

D ickson et al. (1997) 33 

Pinney et al. (2005) 60  

Tenderich et al. (2005) 61  

Blanes et al. (2002) 64

Ko et al. (2001) 62,63  

Hartwig et al. (2005) 65  86 Study 2a 2b 2c 2d

Studies of HC V T ransmission

Abbott et al. (2004) 67,68 

Rozental et al. (2002) 69 

Preiksaitis et al. (1997) 76 

To kumoto et al. (1996) 70    

Tesi et al. (1994) 74,75 

Wreghitt et al. (1994) 71

Mendez et al. (1993) 72,73 

Vincenti et al. (1993) 13 

Pereira et al. (1992) 14,17

- 19

Roth et al. (1992) 15,20

Everhart et al. (1999) 66  

Shah et al. (1993) 12,16 

Haji et al. (2004) 77

- 79

File et al. (2003) 34 

Gudmundsson et al. (2003) 80 

Marelli et al. (2002) 81 

A checkmark (  ) means that the study met the quality criterion for this Question; the lack of a checkmark means that the study either did not meet the criterion, or it was unclear whether the study met the criterion. The criteria specific to this Question were:

2a. Was the study planned pr ospectively (i.e., before any data were collected) ?

2b. Were all consecutive patients enrolled (or a random sample of eligible patients)?

2c. Were laboratory tests performed on recipients regularly in order to monitor antigens/antibodies? (G reater frequency means greater accuracy at estimating the rate

. )

2d. Did all patients receive the same prophylaxis strategy (or no ne received any prophylaxis)? (A mix of prophylaxis strategies means a less interpretable rate

. )87 

### Table 26

. Question 2: Data Tabl e of Results

Study Specific Test Results in these D onors The rate applies to recipient positivity for what specific antigen/antibody? Percentage of recipients who tested positive (95% CI) ¶ (Number of Recipients Positive Post

- transplant/ Number of Recipien ts Negative P re - transplant)

HBV Transmission from LIVER T ransplantation
Roque

- Afonso et al. (2002) 36 anti

- HBc+ HBsAg 56% (95% CI: 27% to 81%) (5/9)
Yu et al. (2001) 35 anti

- HBc+ HBsAg 0% (95% CI: 0% to 43%) (0/5)
Dodson et al. (1999) 37 anti

- HBc+ HBsAg 13% (95% CI: 2% to 47%) (1/8)
Uemoto et al. (1998) 38

- 41 anti

- HBc+ HBsAg 94% (95% CI: 72% to 99%) (15/16)
Kadian et al. (1994) 42 anti

- HBc+ HBsAg 40% (95% CI: 17% to 69%) (4/10)
Uemoto et al. (1998) 38

- 41 anti

- HBc+ HBeAg 94% (95% CI: 72% to 99%) (15/16)

Kadian e t al. (1994) 42 anti

- HBc+ HBeAg 40% (95% CI: 17% to 69%) (4/10)
Roqu e

- Afonso et al. (2002) 36 anti

- HBc+ anti

- HBs 44% (95% CI: 19% to 73%) (4/9)
Yu et al. (2001) 35 anti

- HBc+ anti

- HBs 0% (95% CI: 0% to 43%) (0/5)
Roque

- Afonso et al. (2002) 36 anti

- HBc+ anti

- HBc 78% (95% CI: 45% to 94%) (7/9)
Yu et al. (2001) 35 anti

- HBc+ anti

- HBc 0% (95% CI: 0% to 43%) (0/5)
Uemoto et al. (1998) 38

- 41 anti

- HBc+ seru m HBV

- DNA 94% (95% CI: 72% to 99%) (15/16)88 Study Specific Test Results in these D onors The rate applies to recipient positivity for what specific antigen/antibody? Percentage of recipients who tested positive (95% CI) ¶ (Number of Recipients Positive Post

- transplant/ Number of Recipien ts Negative P re - transplant)

Kadian et al. (1994) 42 a nti

- HBc+ serum HBV

- DNA 40% (95% CI: 17% to 69%) (4/10)
Montalti (2004) 43 anti

- HBc+ “ Developed de novo infection ” 6% (95% CI: 1% to 26%) (1/18)
De Feo et al. (2005) 44,45 HBsAg

- , anti

- HBc+ HBsAg 43% (95% CI: 21% to 67%) (6/14)
Holt et al. (2002) 46 HBsAg

- , anti

- HBc+ HBsAg 0% (95% CI: 0% to 32%) (0/8)
Donataccio et al. (2006) 47 HBsAg

- , anti

- HBc+ HBsAg 64% (95% CI: 35% to 85%) (7/11)
Suehiro et al. (2005) 48 HBsAg

- , anti

- HBc+ HBsAg 0% (95% CI: 0% to 20%) (0/15)
Fabrega et al. (2003) 49 HBsAg

- , anti

- HBc+ HBsAg 0% (95% CI: 0% to 39%) (0/6)
Nery et al. (2003) 50 HBsAg

- , anti

- HBc+ HBsAg 13% (95% CI: 2% to 47%) (1/8)
Preito et al. (2001) 32 HBsAg

- , anti

- HBc+ HBsAg 71% (95% CI: 50% to 86%) (15/21)
Dickson et al. (1997) 33 HBsAg

- , anti

- HBc+ HBsAg 78% (95% CI: 58% to 90%) (18/23)
Wachs et al. (1995) 51 HBsAg

- , anti

- HBc IgM+ HBsAg 60% (95% CI: 23% to 88%) (3/5)
Nery et al. (2003) 50 HBsAg

- , anti

- HBc+ HBeAg 13% (9 5% CI: 2% to 47%) (1/8)
Preito et al. (2001) 32 HBsAg

- , anti

- HBc+ HBeAg 67% (95% CI: 45% to 83%) (14/21)89 Study Specific Test Results in these D onors The rate applies to recipient positivity for what specific antigen/antibody? Percentage of recipients who tested positive (95% CI) ¶ (Number of Recipients Positive Post

- transplant/ Number of Recipien ts Negative P re - transplant)

Castells et al. (2002) 52 HBsAg

- , anti

- HB c+ anti

- HBs 5% (95% CI: 1% to 25%) (1/19)
Wachs et al. (1995) 51 HBsAg

- , anti

- HBc IgM+ anti

- HBs 0% (95% CI: 0% to 43%) (0/5)
Holt et al. (2002) 46 HBsAg

- , anti

- HBc+ anti

- HBc 0% (95% CI: 0% to 32%) (0/8)
Donataccio et al. (2006) 47 HBsAg

- , anti

- HBc IgM+ anti

- HBc 20% (95% CI: 4% to 62%) (1/5)
Castells et al. (2002) 52 HBsAg

- , anti

- HBc+ anti

- HBc 37% (95% CI: 19% to 59%) (7/19)
Holt et al. (2002) 46 HBsAg

- , anti

- HBc+ liver HBV

- DNA 0% (95% CI: 0% to 32%) (0/8)
Nery et al. (2003) 50 HBsAg

- , anti

- HBc+ liver HBV

- DNA 13% (95% CI: 2% to 47%) (1/8)
Holt et al. (2002) 46 HBsAg

- , anti

- HBc+ serum HBV

- DNA 0% (95% CI: 0% to 32%) (0/8)
Suehiro et al. (2005) 48 HBsAg

- , anti

- HBc+ serum HBV

- DNA 0% (95% CI: 0% to 20%) (0/15)
Fabrega et a l. (2003) 49 HBsAg

- , anti

- HBc+ serum HBV

- DNA 0% (95% CI: 0% to 39%) (0/6)
Loss et al. (2003) 31,53 HBsAg

- , anti

- HBc+ serum HBV

- DNA 0% (95% CI: 0% to 43%) (0/5)
Nery et al. (2003) 50 HBsAg

- , anti

- HBc+ serum HBV

- DNA 13% (95% CI: 2% to 47%) (1/8)
Castells et al. (2002) 52 HBsAg

- , anti

- HBc+ serum HBV

- DNA 0% (95% CI: 0% to 17%) (0/19)90 Study Specific Test Results in these D onors The rate applies to recipient positivity for what specific antigen/antibody? Percentage of recipients who tested positive (95% CI) ¶ (Number of Recipients Positive Post

- transplant/ Number of Recipien ts Negative P re - transplant)

Preito et al. (2001) 32 HBsAg

- , anti

- HBc+ serum HBV

- DNA 71% (95% CI: 50% to 86%) (15/21)
Fabrega et al. (2003) 49 HBsAg

- , anti

- HBc+ lymphocytes HBV

DNA 0% (95% CI: 0% to 39%) (0/6)

HBV Transmission from KIDNEY T ransplantation
Kadian et al. (1994) 42 anti

- HBc+ HBsAg 0% (95% CI: 0% to 22%) (0/14)
Kadian et al. (1994) 42 anti

- HBc+ HBeAg 0% (95% CI: 0% to 22%) (0/14)
Kadian et al. (1994) 42 anti

- HBc+ anti

- HBs 0% (95% CI: 0% to 22%) (0/14)
Kadian et al. (1994) 42 anti

- HBc+ anti

- HBc 0% (95% CI: 0% to 22%) (0/14)
Kadian et al. (1994) 42 anti

- HBc+ serum HBV

- DNA 0% (95% CI: 0% to 22%) (0/14)
De Feo et al. (2005) 44,45 HBsAg

- , anti

- HBc+ HBsAg 0% (95% CI: 0% to 6%) (0/62)
Veroux et al. (2005) 54 HBsAg

- , anti

- HBc+ HBsAg 0% (95% CI: 0% to 32%) (0/8)
Fong et al. (2002) 55 HBsAg

- , anti

- HBc+ HBsAg 0% (95% CI: 0% to 1%) (2/763)

Mad ayag et al. (1997) 56 HBsAg

- , anti

- HBc+ HBsAg 0% (95% CI: 0% to 26%) (0/11)
Satterthwaite et al. (1997) 57 HBsAg

- , anti

- HBc+ HBsAg 0% (95% CI: 0% to 12%) (0/27)

Wa chs et al. (1995) 51 HBsAg

- , anti

- HBc IgM+ HBsAg 0% (95% CI: 0% to 10%) (0/34)91 Study Specific Test Results in these D onors The rate applies to recipient positivity for what specific antigen/antibody? Percentage of recipients who tested positive (95% CI) ¶ (Number of Recipients Positive Post

- transplant/ Number of Recipien ts Negative P re - transplant)

Akalin et al. (2005) 58 HBsAg

- , anti

- HBc+ anti

- HBs 0% (95% CI: 0% to 23%) (0/13)
Madayag et al. (1997) 56 HBsAg

- , anti

- HBc+ anti

- HBs 55% (95% CI: 28% to 79%) (6/11)
Satterthwaite et al. (1997) 57 HBsAg

- , anti

- HBc+ anti

- HBs 11% (95% CI: 4% to 28%) (3/27)
Wachs et al. (1995) 51 HBsAg

- , anti

- HBc IgM+ anti

- HBs 0% (95% CI: 0% to 10%) (0/34)
Veroux et al. (2005) 54 HBsAg

- , anti

- HBc+ anti

- HBc 0% (95% CI: 0% to 32%) (0/8)
Akalin et al. (2005) 58 HBsA g

- , anti

- HBc+ anti

- HBc 0% (95% CI: 0% to 23%) (0/13)
Veroux et al. (2005) 54 HBsAg

- , anti

- HBc+ anti

- HBc 13% (95% CI: 2% to 47%) (1/8)
Fong et al. (2002) 55 HBsAg

- , anti

- HBc+ anti

- HBc 2% (95% CI: 1% to 4%) (17/763)
Madayag et al. (1997) 56 H BsAg

- , anti

- HBc+ anti

- HBc 9% (95% CI: 2% to 38%) (1/11)
Satterthwaite et al. (1997) 57 HBsAg

- , anti

- HBc+ anti

- HBc 7% (95% CI: 2% to 23%) (2/27)
Wachs et al. (1995) 51 HBsAg

- , anti

- HBc IgM+ anti

- HBc 0% (95% C I: 0% to 10%) (0/34)
Satterthwaite et al. (1997) 57 HBsAg

- , anti

- HBc+ anti

- HBs and anti

- HBc 0% (95% CI: 0% to 12%) (0/27)
Akalin et al. (2005) 58 HBsAg

- , anti

- HBc+ “HBV viremia” 0% (95% CI: 0% to 23% ) (0/13)92 Study Specific Test Results in these D onors The rate applies to recipient positivity for what specific antigen/antibody? Percentage of recipients who tested positive (95% CI) ¶ (Number of Recipients Positive Post

- transplant/ Number of Recipien ts Negative P re - transplant)

Miedouge et al. (2003) 59 HBsAg

- , anti

- HBc+,

serum HBV

- DNA

HBsAg 0% (95% CI: 0% to 39%) (0/6)
Miedouge et al. (2003) 59 HBsAg

- , anti

- HBc+,

serum HBV

- DNA

anti

- HBc 0% (95% CI: 0% to 39%) (0/6)
Miedouge et al. (2003) 59 HB sAg

- , anti

- HBc+,

serum HBV

- DNA

serum HBV

- DNA 0% (95% CI: 0% to 39%) (0/6)

HBV T ransmission f rom HEART T ransplantation
Pinney et al. (2005) 60 anti

- HBc+ HBsAg 4% (95% CI: 1% to 19%) (1/26)
Kadian et al. (1994) 42 anti

- HB c+ HBsAg 0% (95% CI: 0% to 26%) (0/11)
Pinney et al. (2005) 60 anti

- HBc+ anti

- HBs 8% (95% CI: 2% to 24%) (2/26)
Tenderich et al. (2005) 61 anti

- HBc+ anti

- HBs 48% (95% CI: 29% to 67%) (11/23)
Kadian et al. (1994) 42 anti

- HBc+ anti

- HBs 18% (95% CI: 5% to 48%) (2/11)
Tenderich et al. (2005) 61 anti

- HBc+ anti

- HBc 65% (95% CI: 45% to 81%) (15/23)
Kadian et al. (1994) 42 anti

- HBc+ anti

- HBc 18% (95% CI: 5% to 48%) (2/11)
De Feo et al. (2005) 44,45 HBsAg

- , anti

HBc+ HBsAg 0% (95% CI: 0% to 18%) (0/18)
Ko et al. (2001) 62,63 HBsAg

- , anti

- HBc+, anti

- HBs+ HBsAg 0% (95% CI: 0% to 28%) (0/10)

Blanes et al. (2002) 64 HBsAg

- , anti

- HBc+,

serum HBV

- DNA

HBsAg 0% (95% CI: 0% to 43%) (0/5)93 Study Specific Test Results in these D onors The rate applies to recipient positivity for what specific antigen/antibody? Percentage of recipients who tested positive (95% CI) ¶ (Number of Recipients Positive Post

- transplant/ Number of Recipien ts Negative P re - transplant)

Blanes et al. (2002) 64 HBsAg

- , anti

- HBc+,

serum HBV

- DNA

anti

- HBc 0% (95% CI: 0% to 43%) (0/5)
Blanes et al. (2002) 64 HBsAg

- , anti

- HBc+,

serum HBV

- DNA

serum HBV

- DNA 0% (95% CI: 0% to 43%) (0/ 5)
Blanes et al. (2002) 64 HBsAg

- , anti

- HBc+,

serum HBV

- DNA

lymphocyte HBV

DNA 20% (95% CI: 4% to 62%) (1/5)

HBV Transmission from LUNG T ransplantation
Hartwig et al. (2005) 65 HBsAg

- , anti

- HBc+ HBsAg 0% (95% CI: 0% to 13%) (0/26)
Hartwig et al. (2005) 65 HBsAg

- , anti

- HBc+ anti

- HBc 0% (95% CI: 0% to 13%) (0/26)

HCV Transmission from KIDNEY T ransplantation
Abbott et al. (2004) 67,68 anti

- HCV+ anti

- HCV 9% (95% CI: 6% to 14%) (17/187)
Rozental et al. (2002) 69 anti

- HCV+ anti

- HCV 25% (95% CI: 7% to 59%) (2/8)
Tokumoto et al. (1996) 70 anti

- HCV+ anti

- HCV

- 1 33% (95% CI: 10% to 70%) (2/6)
Tokumoto et al. (1996) 70 anti

- HCV+ anti

- HCV

- 2 60% (95% CI: 23% to 88%) (3/5)
Wreghitt et al. (1994) 71 anti

- HCV+ anti

- HCV 25% (95% CI: 7% to 59%) (2/8)
Mendez et al. (1993) 72,73 anti

- HCV+ anti

- HCV 6% (95% CI: 2% to 20%) (2/33)
Pereira et al. (199 2) 14,17

- 19 anti

- HCV+ anti

- HCV 91% (95% CI: 62% to 98%) (10/11)
Roth et al. (1992) 15,20 anti

- HCV+ anti

- HCV 7% (95% CI: 1% to 31%) (1/14)94 Study Specific Test Results in these D onors The rate applies to recipient positivity for what specific antigen/antibody? Percentage of recipients who tested positive (95% CI) ¶ (Number of Recipients Positive Post

- transplant/ Number of Recipien ts Negative P re - transplant)

Tokumoto et al. (1996) 70 anti

- HCV+ HCV

- RNA 50% (95% CI: 19% to 81%) (3/6)
Wreghitt et al. (1994) 71 anti

- HCV+ HCV

- RNA 100% (95% CI: 65% to 100%) (7/7)
Tesi et al. (1994) 74,75 anti

- HCV+,

serum HCV

- RNA+ anti

- HCV 19% (95% CI: 10% to 33%) (8/43)
Vincenti et al. (1993) 13 anti

- HCV+,

serum HCV

- RNA+ anti

- HCV 0% (95% CI: 0% to 39%) (0/6)
Tesi et al. (1994) 74,75 anti

- HCV+,

serum HCV

- RNA+ anti

- HCV or indeterminate 35% (95% CI: 22% to 50%) (15/43)
Tesi et al. (1994) 74,75 anti

- HCV+,

serum HCV

- RNA+ HCV

- RNA 57% (95% CI: 41% to 71%) (21/37)

Vin centi et al. (1993) 13 an ti

- HCV+,

serum HCV

- RNA+ HCV

- RNA 0% (95% CI: 0% to 39%) (0/6)
Vincenti et al. (1993) 13 anti

- HCV+,

serum HCV

- RNA+ RIA 0% (95% CI: 0% to 39%) (0/6)
Preiksaitis et al. (1997) 76 anti HCV+ and RIBA+ anti

- HCV 62% (95%CI 36% to 82%) (8/13)
Preiksaitis et al. (1997) 76 anti HCV+ and RIBA+ HCV

- RNA 67% (95% CI: 35% to 88%) (6/9)

HCV Transmission from LIVER T ransplantation
Shah et al. (1993) 12,16 anti

- HCV+ anti

- HCV 24% (95% CI: 11% to 43%) (6/25)
Everhart et al. (1999) 66 anti

- H CV+,

serum HCV

- RNA+ anti

- HCV 67% (95% CI: 30% to 90%) (4/6)
Everhart et al. (1999) 66 anti

- HCV+,

serum HCV

- RNA+ HCV

- RNA 100% (95% CI: 61% to 100%) (6/6)

HCV Transmission from HEART T ransplantation95 Study Specific Test Results in these D onors The rate applies to recipient positivity for what specific antigen/antibody? Percentage of recipients who tested positive (95% CI) ¶ (Number of Recipients Positive Post

- transplant/ Number of Recipien ts Negative P re - transplant)

Haji et al. (2004) 77

- 79 anti

- HCV+ “detectable” anti

HCV 11% (95% CI: 4% to 27%) (3/28)
Gudmundsson et al. (2003) 80 anti

- HCV+ anti

- HCV 14% (95% CI: 3% to 51%) (1/7)
Marelli et al. (2002) 81 anti

- H CV+ anti

- HCV 24% (95% CI: 10% to 47%) (4/17)
Haji et al. (2004) 77

- 79 anti

- HCV+ HCV

- RNA 75% (95% CI: 57% to 87%) (21/28)
Gudmundsson et al. (2003) 80 anti

- HCV+ HCV

- RNA 43% (95% CI: 16% to 75%) (3/7)
Marelli et al. (2002) 81 anti

- HCV+ HCV

- RNA 12% (95% CI: 3% to 34%) (2/17)
Gudmundsson et al. (2003) 80 anti

- HCV+ liver HCV 29% (95% CI: 8% to 64%) (2/7)
Gudmundsson et al. (2003) 80 anti

- HCV+ “Any HCV infection” 43% (95% CI: 16% to 75%) (3/7)
File et al. (2003) 34 anti

- HCV+,

serum HCV

- RNA+ anti

- HCV 44% (95% CI: 19% to 73%) (4/9)
File et al. (2003) 34 anti

- HCV+,

serum HCV

- RNA+ HCV

- RNA 100% (95% CI: 72% to 100%) (10/10)

¶ The 95% confidence inte rval (CI) around each rate was calculated by ECRI Institute.96 

# Evidence Reviews: **I I. Methodology**  **to better estimate**  **donor**
**infection with HIV, HBV, or HCV** 

**Question 3** 

**. What behavioral**  **risk factors are associated with an**  **increased probability of infection with**  **HIV, HBV, or HCV ? What is the**  **prevalence of these characteristics among potential solid organ donors?**

And



## Question **4 . What**  **nonbehavi o**  **ral risk factors are associated with an**  **increased probability of infection with HIV, HBV, or HCV**  **? What is the prevalence of**  **these factors**  **among potential solid organ donors?**

As most of the included studies address both Questions 3 and 4 , information regarding study populations and protocols, study risk of bias, and our methods of analysis are reported together for both questio ns in this section. Findings regarding behavioral risk factors are reported in Question 3: Results , and findings regarding nonbehavioral risk factors (e.g., signs and symptoms suggestive of infection, co

- morbidity, socioeconomic factors, demographic factors) are reported in Question 4: Results

.

The CDC document Guidelines for Preventing Transmission of Human Immunodeficiency Virus Through Transplantation of Human Tissue and Organs (1994)

, 100 

### listed seven “ Behavior/History Exclusionary Criteria

. ” According to the guideline, any potential donor with any of these characteristics should not donate organs regardless of HIV test results:

1. “ Men who have had sex with another man in the preceding 5 years. ”

2. “ Persons who report nonmedical intravenous, intramuscular, or subcutaneous injection of drugs in the preceding 5 years. ”

3. “ Persons with hemophilia or related clotting disorders who have received human

- derived clotting factor concentrates. ”

4. “ Men and women who have engaged in sex in exchange for mo ney or drugs in the preceding 5 years. ”

5. “ Persons who have had sex in the preceding 12 months with any person described in items 1

- 4 above or with a person known or suspected to have HI V infection. ”

6. “ Persons who have been exposed in the preceding 12 months to known or suspected HIV

- infected blood through percutaneous inoculation or through contact with an open wound, nonintact skin, or mucous membrane. ”

7. “ Inmates of correctional systems. (This exclusion is to address issues such as difficulties with informed consent and increased prevalen ce of HIV in this population.) ”

The 1994 guideline also excludes children with certain risk factors from donating, regardless of HIV test
result status. T he guideline states:97 

### 1. “ Children meeting any of the exclusionary criteria listed above for adults should not be accepted
as donors.

2. Children born to mothers with HIV infection or mothers who meet the behavioral or laboratory exclusionary criteria for adult d onors (regardless of their HIV status) should not be accepted as donors unless HIV infection can be definitely excluded in the child as follows:

Children >18 months of age who are born to mothers with or at risk for HIV infection,
who have not been breast fed within the last 12 months, and whose HIV antibody tests, physical examination, and review of medical records do not indicate evidence of HIV infection can be accepted as donors.

3. Children **≤** 18 months of age who are born to mothers with or at risk for HIV infection or who have been breast fed within the past 12 months should not be accepted as donors regardless of
their HIV test results. ”

The purpose of Questions 3 and 4 is to search and sum marize evidence regarding potential risk factors for the transmission of HIV, and also HBV and HCV. Behavioral factors are presented in Question 3 , and
nonbehavi o r al factors are presented in Question 4

. Nonbehavioral factors include signs and symptoms

sugg estive of acute or chronic infection, co

- morbidity, socioeconomic factors, and demographic factors.

To be included in these questions, studies had to meet inclusion criteria, as discussed in the Introduction

. Although data restricted to potential solid org an donors were initially sought to identify risk factors , the paucity of evidence motivated the inclusion of data from three additional populations: potential tissue donors, blood donors, and the general population. Because there was still little data on t he identification
of risk factors for HBV infectio n, for HBV only the criteria were expanded to include demographic and socioeconomic subpopulations. Such subpopulation studies may have limited enrollment to people with a particular eth n ic heritage or occu pation. Risk factors identified in these populations may not be generalizable to other populations, including potential solid organ donors. In addition, they cannot be used to determine whether the characteristic all participants were selected for is a ris k factor, unless there is a control or comparison group in the study.

Inclusion criter i a for prevalence and incidence of identified risk factors were stricter. We did not include prevalence estimates from populations with pre

- screened blood donors (which would underestimate prevalence), special demographic or socioeconomic subpopulations (which could overestimate or underestimate prevalence, depending on the population), or populations that over

- selected for infected
individuals in case

- control study desig ns (which would overestimate prevalence). We also did not extract demographic prevalence (e.g., race or sex) or infection incidence or prevalence data (e.g., proportion co

infected) because there are other, more accurate, sources of this type of informatio n available than the studies included for this question provide (such as in Question 1). Some data on the prevalence of risk
factors appeared to overlap between Armstrong et al. 30 

### and McQuillan et al. 101 

### , as both used NH ANES IV (1992 to 2002) data. In these instances we used the prevalence data from Armstrong et al. because the data set they used was larger. No studies that assessed risk factors associated with incident in fection were
identified.

Thirty studies comprise the evidence base for Questions 3 and 4 , with 22 addressing Question 3 and
29 addressing Question 4 . Of the 29 studies that associated behavioral and/or nonbehavioral risk factors98 

### with infection, 12 addresse d HBV, 12 addressed HCV, and 6 addressed HIV (one study addressed both HBV and HCV). Twenty one studies reported identification of behavioral factors (such as drug use or sexual activities) and are included in Question 3 . Only eigh t studies reported the pr evalence of identified behavioral risk factors in potential donors or the general population, including one study that did not provide data for the identification of risk factors. 8 

### (One additional study reported informa tion on prevalence of risk factors from the National Health and Nutrition Examination Surveys (NHANES)

- III (1988

- 1994) 29 

### but this information was super seded by NHANES

- IV (1992

- 2002) data from other
studies. 30,101 

### Twenty

- nine studies reported on the identification of nonbehavioral risk factors . Of those, only f our reported prevalence of identified factors. Al though we sought information on signs and symptoms that may be associated with infection, extremely little information on this was identified

. Included studies and the Questions they address are listed below in Tabl e 27

.



### Table 27

. Included Studies, Questions 3 and 4

Citation Year Virus(es) Question 3 Question 4

Identification Prevalence Identification Prevalence

Potential and Actual Organ Donors

Gasink et al. 102 2006 HCV   

Hidalgo et al. 8 2001 Not Applicable * 

Potential Tissue Donors

Sanchez et al. 103 2006 HBV   

Blood Donors

Orton et al. 104 2004 HCV  

Murphy et al. 105 2000 HCV  

Conry

- Cantilena et al. 106 1996 HCV  

Murp hy et al. 107 1996 HCV 

General Populati on

McGinn et al. 108 2008 HCV 

McQuillan et al. 29 1999 HBV  

Mehta et al. 109 2008 HIV    

Nguyen et al. 110 2008 HIV    

Zetola et al. 111 2008 HIV 

Armstrong et al. 30 2006 HCV    

McQuillan et al. 101 2006 HIV  

Hand and Vasquez 112 2005 HCV  

Nguyen et al. 113 2005 H CV  

Fischer et al. 114 2000 HCV  99 Citation Year Virus(es) Question 3 Question 4

Identification Prevalence Identification Prevalence

Alpert et al. 115 1996 HIV  

Kaur et al. 116 1996 HBV, HCV    

Alter et al. 117 1989 HBV  

Children an d Adolescents

Luban et al. 118 2007 HCV 

D ’ Angelo et al. 119 1991 HIV 

Demographic and Socioeconomic Subpopulation (HBV Only)

Lee et al. 120 2008 HBV 

Tabibian et al. 121 2008 HBV  

Hann et al. 122 2 007 HBV 

Lin et al. 123 2007 HBV 

Hwang et al. 124 2006 HBV  

Butterfield et al. 125 2004 HBV  

Butterfield et al. 126 1990 HBV  

Turner et al. 127 1989 HBV  

* Hidalgo et al. assessed the prevalence of a general risk factor only (unspecified substance abuse), and did not attempt associate the factor

with any particular infec tion.100 

### Studied Populations and Study Methods
This section provides a brief description of the enrollees and methods in the included studies. The studies are organized by population type (as divided in Table 27 ). Add itional information regarding study protocols, including setting and location of study, method of data collection, relevant blood test used to determine infection status, funding source, and year(s) of data collection, are shown in Table 28 . Details regarding participant characteristics, including methods of participant selection and selection criteria, demographic descriptors (e.g., percent male, race, age), are shown in Tab le 29

.

Data on potential or actual solid organ donors were very limited. Two retrospective studies, each with few factors reported, were identified. Only one of those studies focused on potential solid organ donors, Hidalgo et al. 8 

### This study provides reasons for donor ineligibility among a cohort of 5 5 potential living who were able to provide data regarding their health status. A second study, Gasink et al. 102



### , statistically assessed the association between donor characteristics and HCV infection to indentify risk factors for

HC V in a cohort of 10,915 actual heart donors, in cludin g 261 with HCV, using data from the Scientific Registry of Transplant Recipients (SRTR). Prevalence of some factors was also reported.

Potential Tissue Donors
One study on risk factors for HCV among potential cornea donors, Sanchez et al., was also i ncluded. 103 

### Eighty three potential donors with positive serological result(s) and 56 randomly selected controls were
included. In this study, infection status was retrospectively tested for association with behavioral and clinical factors in a questionnaire completed by next of kin. This study is unique in that the identification of risk factors relied upon next

- of

- kin interviews rather than medical record review or self

- report.

Actual Blood Donors
Also included were four studies that examined risk factors for HCV among actual blood donors, Conry

Cantilena et al., 106 

### Murphy et al. (2000), 105 

### Murphy et al. (1996), 107 

### and Orton et al. 104 

### We included these studies with the intent of examining facto rs other than those that potential donors are screened for ( e.g., other than men having sex with men or injection drug use). However, in all four studies, some
donors who were followed

- up with questionnaires or interviews admitted to exclusionary behaviors

. Therefore, it was possible to investigate these factors for association with HCV. However, because potential donors who were not deceptive about these factors were screened out and not permitted to donate, we did not consider the prevalence of these fact ors among actual donors because the prevalence would be underestimated. We did not identify any studies on potential ( i.e., pre

- screened) blood donors, or potential donors who were eliminated from the donor pool as a result of the sc reening process.

The fo ur studies used different approaches to identifying risk factors. Co nry

- Cantilena et al. and Murphy et al. (2000) were case

- control studies that enrolled samples of infected and uninfected donors and compared the factors among them. 105,106 

### Conry

- Cantilena et al. enrolled 248 individuals with HCV and 131 without. Murphy et al. (2000) enrolled 758 infecte d individuals and 1

, 039 uninfected individuals. Both of these studies identified participants by retrospective assessment of their HCV status and prospectively collected data on risk factors using questionnaires. Orton et al. recalled blood donors who
init ially tested anti

- HCV positive for further testing and collection of risk factor data and prospectively

re

- tested them using nucleic acid tests, and administered in

- person qu estionnaires. Of those who completed follow

- up at the time of donation, t he factor s of 65 participants who were confirmed as positive by nucleic acid tests were compared to the factors among the 225 participants who were101 

### ultimately deemed uninfected (initial false

- positives)

. Murphy et al. (1996) was a much larger (n = 862,398) study th at examined consecutive blood donors and retrospectively evaluated infection status and demographic information collected at this time of donation. 107



### General Population
Thirteen additional studies enrolled participants representative of a general population. By “ general population, ” we mean a popu lation unselected for any particular demographic, occupational, or behavioral characteristics, or health status other than HCV, HBV, or HIV infection status. These studies recruited participants from various settings including emergency departments, 111,115 

### prim ary care clinics, 108 

### medical centers, 109,112,113,117 

### health plan enrollees, 114 

### using advertisements to the public, 116 

### or NHANES data. 29,30,101,110 

### (When extracting data we were careful to ensure that duplicate NHANES d ata were not included. Where data from probably overlapping pools of participants were reported, we used
the statistic from the study with the larger sample size. We only collected prevalence information from the most recent NHANES data.)

The general desi gn of these studies was to collect blood samples to test for infection and administer questionnaires or interviews regarding potential risk factors. Most of thes e studies were prospective.
The studies were generally large, with only four enrolling under 1, 000 participants

. Five of these studies addressed HIV, five addressed HCV, and o ne addressed both HCV and HBV.

Children
Two included studies specifically assessed children. Luban et al. performed a record review of 2,758
children who had received a blood t ransfusion and targeted factors for HCV. 118 

### D ’ Angelo et al. reviewed records of 3,520 adolescents with leftov er serum from other tests and considered factors for HIV
infection. 119



### Demographic and Socioeconomic Subpopulations
A total of eight subpopulation studies that evaluated risk factors and HBV were included. Populations assessed in these studies include mentally ill veterans in inpatient Veterans Administr ation (VA) Hospital psychiatric care, 121,125 

### women registered for o bstetric care at a military hospital, 126 

### college students, 124


### embalmers, 127 

### Asian Americans, 123 

### and Korean

- American church

- goers. 120,122 

### Most of the Asian
Americans and Korean American church

- goers were foreign

- born. All of these studies were prospective. On the whole, these studies were smaller than the general population studies: Half enrolled fewer than 1,000 people, with the smallest study enrolling 108 individual s. 127102 

### Table 28

. Study Protocols for Questions 3 and 4

Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

Potential and Actual Organ Donors

Gasink et al. 102 2006   Hepatitis C Virus (HCV) Hospitals

– heart transplant donors Na tion wide All actual heart donations during time period Scientific Registry of Transplant Recipients (SRTR) record review, including blood test results Patients considered positive if medical chart marked

“ recipient anti

HCV, ” or

“ recipient RIBA [recombinan t immunoblot assay)

, ” or

“ recipient RNA ” positive No (for outcomes of interest) Retrospective Academic division of cardio

vascular unit. No disclosures reported. 1994 to 2003

Hidalgo et al. 8 2001  Not Applicable (pre va lence of risk factors only) Relatives of children with end

stage renal disease Brooklyn, NY Potential related donors of all children <21 with end stage renal disease (ESRD) and surviving transplant between 1990 and 1999 Retrospective chart review and in

terview Not reported (and not relevant because only included for prevalence of risk factors) Not applicable Retrospective Not reported. Authors affiliated with and data collected from academic hospital. 1990 to 1999103 Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

Potential Tissue Donors

Sanchez et al. 103 2006   All Potential corneal donors Dallas, TX All potential donor

corneas with positive serological results for infecti ous disease Retrospective review of next

- of

kin questionnaire HIV 1/2, HIV p24 antigen ( Ag

),
HIV DNA, HIV nucleic acid test ( NAT ) , HbsAg, HB Core, HCV, HCV

- NAT No Retrospective Not reported. Authors affiliated with university medical
centers. 2002 to 2004

Blood Donors

Conry

- Cantilena et al. 106 1996   HCV Actual volunteer blood donors Greater Chesa peak e and Potomac

area Blood donors to American Red Cross with positive EIA results, including those with false positiv es as determined by RIBA Medical history taken by physician, private drug use questionnaire Enzyme linked immunosorbent assay (EIA) 1.0 Ortho Diagnostics, EIA 2.0 Ortho diagnostics, RIBA 2.0 Chiron Yes Prospective questionnaire of donors identified retro

s

pectively by initial positive EIA result Not reported. Most authors affiliated with National Institutes of Health. 1991 to 1994104 Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

Murphy et al. 105 2000   HCV Actual blood donors Baltimore/ Wash ington, Southeast Michigan, Oklahoma City, San Francisco, Los Angeles Cases were all HCV positive donors during time period, Controls by HCV negativity and matche d to controls Mailed
anonymous questionnaire Not reported, but tested through U

. S

. blood donation centers so should be valid Yes Prospective questionnaire of donors identified retro

spectively by initial positive EIA result National Heart Lung and Blood In

stitute 1994 to 1995

Murphy et al. 107 1996  HCV Actual blood donors Baltimore, Washington DC, Detroit, Oklahoma City, San Francisco, Los Angeles All donations in a time period Demographic informat ion collected at donation time Second

generation HCV EIA with RIBA HCV 2.0 E IA (Abbott) or Matrix (U nlicensed) for confirmation Yes Retro spective National Heart, Lung, and Blood Inst itute 1992 though 1993

Orton et al. 104 2004   HCV Actual blood donors Apparent ly nation wide Blood donors to American Red Cross Quest ionnaire administered in person by donation counselor or physician ProCleix HIV

- 1 and HCV assay (Chiron Corporation) with confirmation with RT

- PCR (reverse

transcriptase polymerase chain reaction) (NCI) Yes Prospective questionnaire of donors identified re tro

spectively by initial EIA negative and NAT reactive result Not reported, but appears to be American Red Cross, Centers for Disease Control and Prevention 1999 to 2003105 Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

General Population

Alpert et al. 115 1996   Human Immuno

deficiency Virus (HIV) Inner

- city

emer

gency depart

ment Bro nx, NY Consecu

tive adult noncritical medical patients In

- person interview by physician EIA (Genetic systems) with Western blot confirmation (Cambridge

Biotech) Yes Prospective In part by Centers for Disease Control (CDC) and National Institute of Allergy and Infectious Diseases 1993 to 1994

Alter et al. 117 1989   HBV Cases reported to health depart

ment, controls from general population Alabama, Wash ington State Cases

se lected by reporting to

coun ty health department and had

no known cause of hepatitis, Controls selected by randomly dialing other county residents Interviews by

nurses HBV core antigen test Yes Prospective Not reported, appears to have been publically funde d 1985 to 1986106 Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

Armstrong et al. 30 2006   HCV General population Nation

- wi

de Participants in National Health and Nutrition Examina

tions Surveys (NHANES) IV National Center for Health Statistics (NHANES) IV survey with sensitive items on computer Ortho HCV ELISA v. 3.0 (Ortho

- Clinical Diagnostics); Repeatedly reactive samples
te

sted with Chiron RIBA HCV Strip Immunoblot Assay v. 3.0 ( Chiron Corp). RIBA positive or indeterminate tested for RNA with COBAS Amplicor HCV Monitor Test v. 2.0 (Roche Molecular Diagnostics) Yes Prospective National Centers for Disease Control (CDC) 1999 t o 2002

Fischer et al. 114 2000   HCV HMO enrollees Twin Cities metro area of Minnesota Health plan patients identified as being at elevated or normal risk though database (plus health

care workers) Anonym ous risk profile questionnaire Polymerase chain reaction (PCR) Yes Prospecti ve Contract with Integrated Thera

peutic Group of Schering

Plough 1996 to 1997107 Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

Hand and Vasquez 112 2005   H CV General population Patients at university medical
center Patients who had HCV test and positive (case) or negative (control) results Interview in person in hosp ital setting or by telephone if not available in person Abbott HCV EIA 2.0 Yes Prospective in

terview based
upon retrospective review of lab results State of Texas Tobacco Settlement Endow

ment for Texas Tech University Health Sciences Center 2000 to 2002

Kaur et al. 116 199 6   Hepatitis B Virus (HBV), HCV General population Nation wide, primarily urban Volunteers responding
to advertise

ment Risk profile questionnaire. Details not reported. HbsAg and anti

- HBC (Abbott Diagnostics) and HCV EIA 2.0 (Abbott Laboratories) confir med by MATRIX HCV dot

- blot immunoassay (Abbott Laboratories) Yes Prospective Schering Pharma

ceuticals, Abbott Labora

tories, American Liver Foundation 1992

McGinn et al. 108 2008  HCV Adult primary care clinic Inner city New York, NY Random selection Survey by in
person interview and medical record review HCV EIA 2.0 Recombinant c100

- 3, H C31, and HC

- 34, (Abbott Laboratories) No (only univariate used) Prospective No disclosures reported 2002 to 2003108 Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

McQuillan et al. 101 2006   HIV General population Nation wide Participants in National Health and Nutrition Examinatio ns Surveys (NHANES) versions 1988 to 1994 and 1999 to 2002 Confidential
surveys ELISA (Genetic Systems, or Organon

T eknika Corporation) and confirmed by Western blot (Biotech/DuPont) or HIV

- 1/HIV

- 2 peptide EIA (Genetic Systems) confirmed by Western blot (Calypte Biomedical Corporation) or urinalysis (Calypte HIV01 Peptide EIA confirmed by Western blot (Calpype Biomedica l) No (ECRI Institute calculated univariate analyses) Prospective Federal 1999 to 2002 for risk factors109 Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

McQuillan et al. 29 1999   HBV General popula tion Nation wide Participants in National Health and Nutrition Examina

tions Surveys (NHANES) Confidential
surveys NHANES II Antibody to HBV surface antigen or core antigen and HBV surface antigen by EIA (AUSAB, CORZYME, AUSZYME, Abbott)

NHANES III HBC

cor e antibodies radio

immunoassay (CORAB) and confirmation by surface antigen and surface antigen antibody (AUSRIA and AUSAB, Abbott) Yes Prospective Not specifically stated. All authors employed by National Center for Infectious Diseases, Centers for Disease Control (CDC) 1976 through 1994110 Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

Mehta et al. 109 2008   HIV Hospital urgent

care center, inpatient floors, outpatient primary

care, non

clinical drop

- in center,

emer

gency depart

ment Boston, MA Consecu

tive (all) or self

selected for HIV test, depending on setting where sample was drawn from Personal interview in medical center OraQuick Rapid HIV

- 1 Antibody Test (Orasure Technologies) with confirmation by both ELISA and We stern blot No Retrospective Public health department and CDC 2002 to 2004

Nguyen et al. 110 2008   HIV General population New York City Random selection from NYC households In

- perso n interview plus computer

assisted survey for sensitive information Unnamed HIV

- 1/HIV

- 2 EIA with Western blot confirmation, Remnants tested for HIV

- 1 RNA by PCR. No Prospective CDC 2004

Nguyen et al. 113 2005   HCV General internal medicine clinic (controls)

a nd hepa

tology clinic (cases)
at urban medical university Phila delphia, PA Not reported Anonymous written questionnaire HCV antibody (Home Access Health Corp, Hoffman Associates) Yes Prospective In part by Schering

Plough;

no financial disclosure Not
repo rted111 Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

Zetola et al. 111 2008  HIV Patients in general hospital

emer

gency depart

ment San Francisco, CA Emergency department patients who had blood drawn and
were not known to be HIV+ Re cord review of demographic and medical records All screened by EIA (Genetic Systems HIV

1/HIV

- 2 plus O EIA, Bio

- Rad Laboratories); positives confirmed with immunofluoresce nt assay (IFA) (Fluorognost
HIV

- 1 IFA, Sanochemia Pharmazeutika AG), and discordant

r esults resolved with RNA transcription mediated amplification test (TMA Aptima
HIV

- 1 RNA Quantitative Assay, Gen

Probe Inc.) Yes Retrospective Division of Research Resources of National Institutes of Health (NIH), California HIV Research Program Grant, San Fran

cisco Depart ment of Health 2007112 Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

Children and Adolescents

Luban et al. 118 2007  HCV Tertiary

care

u rban university childrens ’ hospital and

commun

ity controls Washing ton, D.C. Record identificatio n of children who had blood transfusion Record review Abbott anti

- HCV EIA with confirmation by Chiron RIBA

- 2 and COBAS AmpliCore HCV PCR test No Retrospective NIH Transfusi

ons administer ed between 1982 and 1992

D ’ Angelo et al. 119 1991  HIV Children ’ s National Medical Center Washing ton, D.C. Leftover serum from other tests Record review Abbott EIA, DuPont Western Blot and another EIA for confirmation No Retrospective Not reported, authors either affiliated with a university hospital or federal health
agency 1987 to 1989113 Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

Demographic and Socioeconomic Subpopulations (HBV only)

Butterfield et al. 125 2004   HBV Veterans Adminis

tra tion (VA) psych

iatric inpatient unit Durham, NC Consecu

tive admissions Standardized in

person risk interview Abbott Corzyme test for HBV core antibody Yes Prospective VA research grants 1998 to 2000

Butterfield et al. 126 1990   HBV Women registered for obstetric
care at military hospital El Paso, TX Consecu

tive enrollment Questionnaire at initial physician consultation AUSRIA II

- 125 radio

immunoassay kit, Abbott No Prospective Not reported 1987 and 19

88

Hann et al. 122 2007  HBV Korean

American church

goers North eastern U.S. Recruited from church Questionnaire completed by family (no highly sensitive or personal information) HbsAg, anti

- HBs, H beAg, anti

- HBe tests by Abbott No Prospective Not reported 1988 to 1990

Hwang et al. 124 2006   HBV College students Houston, TX Recruited from large classes of required

courses and public areas of universities Anonymous self

administered questionnaire Abbott anti

- HBc, anti

- HBs, and HbsAg Yes Prospective CDC 19 99114 Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

Lee et al. 120 2008  HBV Korean

American church

goers Colorado Recruited from church Collection of demographic data and vaccinatio n history HBsAg, anti

HBs, brand unspecified but run on Advia Centaur XP immunoassay system No Prospective University school of nursing research grant, Shil

- IL Overseas Korean Health Founda

tion, Equality Fund from Colorado Trust 2004 to 2007

Lin et al. 123 2007  HBV Recruited Through advertise
ments and screened
at

commun

ity

- based
events San Francisco bay

area None reported other than Asian

American and signed informed
consent Questionnaire about demographic information and vaccination history HBsAg, plus in

some cases, HBs, brands unspecified Yes Prospective Not explicitly reported, possibly Asian Liver Center at Stanford University 2001 through 2006

Tabibian et al. 121 2008   HBV Veterans acutely and voluntarily hospital

ized in psych

iatric ward West Los Angeles Consecu

tive

a dmissions Interview using standardized questionnaire, VA risk assessment tool HbsAg, HBsAb, HbcAg, brands unspecified Yes Prospective Not reported 2002 to 2003115 Citation YearQuestion3Question4

V irus(es) Setting(s) Selected From Location Selection Methods Method of Risk Factor Data Collection Relevant Blood Test Used Clearly States Adjusted / Controlled Statistics Reported Prospective or Retro spective Funding Year(s) Data Collected

Turner et al. 127 1989   HBV Embalm

ers in an urban

area Boston and Worcester MA metro

politan areas Not reported Oral questionnaire HBV surface antigen and antibody and core tests using Abbott brand
tests. Con firmation by Western blot Yes Prospective Biomedical research grant from National Institutes of health and National Institute for Occupation al Health and Safety 1986 to 1987116 

### Table 29

. Participant Characteristics for KQ 4 and 5

Cit ation Year KQ4 KQ5 Virus(es) Participant Selection Selection Criteria Number of Participants Percent Male Race (a s reported in study) Age

Potential and Actual Organ Donors

Gasink et al. 102 2006   Hepatitis C Virus (HCV) Actual heart donors registered in Scientific Registry of Transplant Recipients All heart donors of transplant recipients at least 18 years wh o received their transplant between 4/1/1994 and 7/31/2003 18,618 initially considered eligible, 10,915 met inclusion criteria, 261 with HCV+ donor 69% White: 86%;

Black: 12%;

Other: 2% Median: 29 years

Hidalgo et al. 8 2001  Not applicable (prev alence of risk factors only) Potential living donor parents of child transplant candidates Potential related donors of all children <21 years with end

stage renal disease and surviving transplant between 1990 and 1999 55 poten tial donors screened 36% Race of potential donors not reported. Their children transplant candidates were:

Black: 60%
Hispanic: 30%

Caucasian: 7%

Asian: 3% Mean : 38.8 years

Potential Tissue Donors

Sanchez et al. 103 2006   All All donor corneas with positive serological results for infectious disease plus negative controls Consecutive tissues with positive serological results in time period 83 donors with positive serological results plus 56 randomly selected seronegative controls 62% White: 75%;

Black: 17%;

Other: 4% Mean : 54 years117 Cit ation Year KQ4 KQ5 Virus(es) Participant Selection Selection Criteria Number of Participants Percent Male Race (a s reported in study) Age

Blood D onors
Conry

- Cantilena et al. 106 1996   HCV Bl ood donors with positive enzyme linked immunosorbent assay (EIA) enrolled consecutively until target enrollment attained Consecutive volunteer whole blood donors who donated between 1991 and 1994 and had positive EIA 4,585 donors screened positive, 481 of them enrolled. 248 enrolled as positive and 131 as negative (and 102 indetermin

ate) 57% Black: 12.7% Mean: 40 years

Murphy et al. 105 2000   HCV All HCV positive and during time period and matched HCV negative blood donors By serostatus;

cases and controls matched by age, sex, race/ethnicity, first time vs. repeat donor status 2,316 HCV+ invited, 758 participated. 2,316 HCV

invited, 1039 participated 54% White non

Hispanic: 73%,

Black non

Hispanic: 10%,
Hispanic: 8%,

Asian: 2%,

Other: 2% Most aged 30 to 49 years

Murphy et al. 107 1996  HCV All blood donors Consecutive blood donors 862,398 53% White: 81%,

Black: 7%,
Hispanic: 6%,

Asian: 3%,

O ther: 1%, Missing: 2% Majority between 20 and 49 years,
Range: 11 to 93 years118 Cit ation Year KQ4 KQ5 Virus(es) Participant Selection Selection Criteria Number of Participants Percent Male Race (a s reported in study) Age

Orton et al. 104 2004   HCV Blood donors anti

- HCV

- but unconfirmed nucleic acid test (NAT) reactive results Blood donors anti

HCV

- but

un

confirmed reactive NAT results who donated blood in time period and completed questionnaire 810 potential participants, of whom 116 confirmed positive. 65 cases and 225 controls completed study. 54% 88% White non

Hispanic, rest

“ other ” Mean : 39 years

Gen eral Population

Alpert et al. 115 1 996   Human Immunodefi ciency Virus (HIV) Consecutive noncritical adults in emergency department Consecutive 1,744 patients, with 988 having blood drawn and 875 with adequate amount for testing and no known HIV Not reported (NR) NR NR119 Cit ation Year KQ4 KQ5 Virus(es) Participant Selection Selection Criteria Number of Participants Percent Male Race (a s reported in study) Age

Alter et al. 117 1989   HBV Cases reported to county health department, controls selected randomly Cases had acute HBV infection and none of the fo llowing factors within last six mon ths: blo od transfusion, IV drug use, male homosexual activity, health care employment requiring frequent contact with blood, hemodialysis, sexual or household contact with HBV carrier. Controls were HBV

- uni nfected and were matched by
age within 5 years,

sex, race, area code, and telephone exchange. 76 cases, 152 controls Not reported Not reported Not reported

Armstrong et al. 30 2006   HCV Nationally representative sample of civilians and non

institutionalized population Selected to be representative of general population 21,509 eligible, 17,548 interviewed, and 15,079 gave sufficient bl ood sample and were included 48% Non

- Hispanic White: 40%;

Non

- Hispanic Black: 23%;

Mexican

American: 29% NR120 Cit ation Year KQ4 KQ5 Virus(es) Participant Selection Selection Criteria Number of Participants Percent Male Race (a s reported in study) Age

Fischer et al. 114 2000   HCV Health plan patients identified as being at elevated or normal risk though database, (or health care workers, not included in this analysis). Based upon diagnostic codes suggestive of Hepatitis C, plus controls without any liver

- related diagnoses 8

, 800 identified in database. 1

, 380 total completed study, including 454 at higher risk and 926 controls. 34% NR NR, 26% less than 50 years

Hand and Vasquez 112 2005   HCV Clinic or hospital patients selected by HCV test result For cases, positive HCV test, for controls, negative HCV test. Patients were tested due to suspected liver disease, planned hemodialysis, or hepatitis risk factors People who participated in interview could be included. 627 70% Hispanic: 87%,

Non

- Hispanic : 13% Mean age : 45.5, Range: 14 to 99

Kaur et al. 116 1996   Hepatitis B Virus (HBV), HCV Volunteers responding to advertisement None reported 8581 42% White: 77%,

African American: 14%,

Asian: 3%,

Other: 6% Mean: 45 (Standard error [SE] 15)
years121 Cit ation Year KQ4 KQ5 Virus(es) Participant Selection Selection Criteria Number of Participants Percent Male Race (a s reported in study) Age

McGinn et al. 108 2008  HCV A stochastically

ran domized sample of all patients attended primary care were invited to participate Age 18 or older, English or Spanish language proficient 1,485 invited, 1,000 enrolled 27% Latino: 54%;

Black: 32%;

White: 10%;

Other: 4% Mean: 50.1 (SD : 14.7)
years

McQuilla n et al. 101 2006   HIV “ Stratified multi

staged probability cluster design that selected a

s

ample representative of the U.S. civilian

non

institutionalized population. ” Participants aged 18 to 59 who were anonymously tested for HIV antibody NHANES III: 15,141 participants total, 13,022 agreed to interview, 11,203 agreed t o exam and had sufficient

serum

NHANES 99

-

’ 02 : 6,458 invited, 5,926 agreed to exam and had HIV test NR NR NR

McQuillan et al. 29 1999   HBV Stratified, multistage, probabilit y cluster design of U.S. households Random selection Analysis of risk factors

“ generally restricted ” to NHANES III, which enrolled 40,000 people NR NR NR122 Cit ation Year KQ4 KQ5 Virus(es) Participant Selection Selection Criteria Number of Participants Percent Male Race (a s reported in study) Age

Mehta et al. 109 200 8   HIV Consecutive patients in hospital system were approached for participation All patients who consented 17,594 pretest counseling sessions and 16,750 HIV tests, 229 new HIV diagnoses 59% Black: 39%;

White: 23%;
Hispanic: 19%;

Haitian: 8% Median age : 36 years

Nguyen et al. 110 2008   HIV Random selection or representative households of adults aged
at least 20 years Not institutionalized or homeless 4,026 randomly selected, 3,38 8 screened, 3,047 eligible, 1,999 completed interview and at least one component of physical exam, and 1,626 provided blood 46.2% White: 30%

Black: 21%

Asian: 13%
Hispanic: 36% Mean age NR; 57.3% at least 40 years old

Nguyen et al. 113 2005   HCV Patients with known HCV under care at hepatology clinic (cases) and asymptomatic patients with unknown status in general medical clinic (controls) Aged 18 to 60 years
English proficient 429 total,

225 HCV positive;

204 HCV negative 42% White: 63%;

African

- American: 27%;

Asian: 4%;

Latino: 3%;

Other: 3% NR; wide range of decades of birth123 Cit ation Year KQ4 KQ5 Virus(es) Participant Selection Selection Criteria Number of Participants Percent Male Race (a s reported in study) Age

Zetola et al. 111 2008  HIV All patients seeking
emergency medical attention who had blood drawn and were not kn own to be infected with HIV Consecutive patients 1,820 had blood drawn, 1,674 were of unknown or negative HIV status and met inclusion criteria 62.3% White: 27.4%,

Black: 28.4%,

Latino: 22.6%,

Other: 17.6%,

Unknown: 4% Mean : NR,

24.9% 18

- 30 years,

29.1% 3

1

- 45 years,

44.1% >45 years

Children and Adolescents

Luban et al. 118 2007  HCV Children who had blood or blood product transfusions Under 15 years at time of transfusion, no perinatal transmission, and

no malignancy, hemophilia, rheumatologic disease, HIV, or
organ or marrow transplantation or dialysis 5,473 identified as potentially eligible,

4,726 locatab le,

2,758 tested 59% African

- American: 38%,

Asian: 1.5%,

Caucasian: 48.3%,
Hispanic: 3.4%,

Other/unknown: 8.8% NR, age at time of transfusion less than

one year on average

D ’ Angelo et al. 119 1991  HIV Children attending ambulatory care hospital services with leftover

serum Appears to be all children with leftover

serum 3,520 33% NR Mean NR, all patients 20 years and
younger124 Cit ation Year KQ4 KQ5 Virus(es) Participant Selection Selection Criteria Number of Participants Percent Male Race (a s reported in study) Age

Demographic and Socioeconomic S ubpopulations (HBV only)

Butterfield et al. 125 2004   HBV Inpatien ts in Veterans Administration (VA) psychiatric unit Consecutively admitted veterans with severe mental illness who were either African American or Caucasian and had blood test results 399 consecutive recruits, 376 included 90% Caucasian: 41%,

African

- Ameri can: 59% NR

Butterfield et al. 126 1990   HBV Consecutive women seeking prenatal care All patients included 1,466 0% NR NR

Hann et al. 122 2007  HBV Korean

- American church

- goers None reported besides participant selection method 6,130 48% Korean

- American: 100% NR

Hwang et al. 124 2006   HBV College students For HBV risk assessment, U.S. or Canada born and

no evidence of immunization 7,960, of whom 4,328 were U.S. or Canada born and had no evidence of imm unization 39.2% Non

- Hispanic white: 41.5%,

non

- Hispanic black: 26.1%,
Hispanic: 22.2%,

Asian: 6.8%,

Other :3.5% Median age: 21 years

Lee et al. 120 2008  HBV Korean

Americans attending church Adult, literate Korean

Americans (18 to 70 years old) willing to sign informed
consent 609 46% Korean

- American: 100%, 98% of adults born in Korea Mean age: 49 years

Lin et al. 123 2007  HBV Asian Americans Adults (at least 18 years old) willing to sign informed
consent 3,279 tested. 3,163 included 39.7% Asian Americans: 100%, 93.4% born in Asia Median age: 52.9 years125 Cit ation Year KQ4 KQ5 Virus(es) Participant Selection Selection Criteria Number of Participants Percent Male Race (a s reported in study) Age

Tabibian et al. 121 2008   HBV Voluntarily admitted veteran psychiatric inpatients Consecutive volunta ry admissions with consent 234 admissions, with 129 participants 98% Caucasian: 50.3%,

African

- American: 33.3%,
Hispanic: 9.3%, Other, including Asian and Native American: 7% Mean age: 48.9 years (SD : 8.9 years)

Turner et al. 127 1989   HBV Have embalmed more than 20 bodies Not reported 108 NR NR NR126 

### Analysis Methods

We extracted all data on the identification of ri sk factors from the included literature, including factors that were investigated but not found to be associated with infection. For Question 3 these data are presented in Table 33 (HBV), Table 34 (HCV), and Table 35 (HIV). For Question 4 these data are shown

in Table 39 (HBV), Table 40 (HCV), and Table 41 (HIV) . We grouped the extracted data by category as
listed in the 1994 CDC document Guidelines for Preventing Transmission of Human Immunodeficiency Virus Through Transplantation of Human Tissue and Organs 100



### , and qualitatively summarized the evidence for each of the risk factors listed in the guideline by describing which studies identified associations for which infection in which population type. Following that, in the same manner we
summarized the evidence for additional risk factors not listed in the 1994 guideline. Information on behavioral risk factors is presented first (Question 3 ), followed by information on nonbehavioral factors (Question 4 ).

We performed the analysis qualitatively (i.e., u sing narrative descriptive analysis) because the methodologic and reporting differences among the studies made combining them in quantitative analysis (i.e., meta

- analysis) inappropriate. These fundamental between

- study differences fell into four main

cate gories:

1. Population: We included data from organ, tissue and blood donors, as well as from general populations drawn from various settings, and, for HBV, various special subpopulations

2. Outcomes: Potential risk factors were often reported in different ways. For instance, studies used
different numbers to define “ multiple ” sex partners or gathered data regarding different time spans (i.e., lifetime drug use, drug use within past 6 months).

3. Comparators: Some studies used different bases of comparison. For insta nce, in assessing whether MSM is a risk factor, one study compared the prevalence of infection in MSM to heterosexual men, and another compared it to the prevalence of infection among men who have
never had sex.

4. Analysis type: Although use of various metri cs can be dealt with in secondary quantitative analysis, most of these studies differed with respect to whether univariate or multivariate analyses were used. Some reported one but not the other. Data reporting methods did not provide sufficient
informatio n to make standardization possible. Not having information on both clouds the independence of the relationship between the factor of interest and the infection in question, especially since data from various populations were considered. For more informatio n on this, please see the following text.

We considered data calculated in two main ways, through univariate analyses and multivariate analysis. Univariate analyses look at the association between the factor of interest and infection. These may be the only type of analysis performed in a study, or it may be the first step in identifying which potentially important factors should be included in the multivariate model

. Multivariate models look at the
association between the factor of interest and infection wh ile taking into consideration additional confounding factors

. This is the type of analysis required to determine if the risk factor is an independent
risk factor

. This is important because many of the behavioral risk factors are found together in
individua ls. For instance, among individuals who have been incarcerated, is exposure during incarceration itself or the illicit activity that led to incarceration (e.g., sex work, drug use) that is the true risk factor?127 

### Demographic and socioeconomic factors are not risk factors in and of themselves but proxies for other
risk factors. On the other hand, dependent factors identified by univariate analyses may be useful for identifying at

- risk potential donors. To provide as much information as possible about these fac tors, we
extracted information on both univariate and multivariate analyses where both were provided. Where ECRI Institute calculated effect sizes and p

- values, unadjusted univariate analyses were performed by necessity because that is what the reported da ta permits.



### Assessment of Risk of Bias ( **Quality of Study Design )**  **: Identification of Risk Factors**

To assess the risk of bias of the included studies, we asked the questions listed in Table 30 . (Itemized quality ass essment for each study for both questions is provided in Table 31 .) Following Table 30

we provide a discussion of each o f the quality domains assessed.



### Table 30

. Risk of Bias Assessment Items for Questions 3 and 4 : Identification of Risk Factors

Domain Question Item Question

Comparability of uninfected and infected participants Identification (I)

- A Were infected and uninfected participants similar on other risk factors?

I

- B If not, were statistical adjustments performed to control for other risk factors?

Validity of risk factor data collection I

- C Was risk factor data collected in a valid manner (e.g., confidential or anonymous collection of sensit ive risk factor data, collection of personal information from the person directly instead of someone else)?

Validity of method used to determine infection status I

- D Was infection status determined accurately? (i.e., accuracy of diagnostic test method use d to determine infection status)



### Comparability of Uninfected and Infect ed Participants (Quality Items I

- A and I

- B )
Regarding item A, none of the studies were uninfected and infected groups of participants similar on all risk factors besides the one being investigated at the time (most studies investigated multiple factors). That is, infected and uninfected participants differed in many ways. Therefore, none of the studies can be considered to satisfy these item s . However, many of the studies did perform s tatistical adjustments to control for confounding factors. Whether controlled or adjusted analyses were performed for each study is reported in the table of study protocols ( Table 28 ), in the data extraction tables , and in the text of the
results section.

Although not all studies met items A or B, all of these studies drew all of their participants from a single pool, either selecting them from the pool based upon their infection status or including all participants in the pool and subdivi ding them by infection status.128 

### Validity of Risk Factor Data Collection (Quality Item I

- C )

Much of the data collected for Question 3 , regarding behavioral risk factors, is very private and highly sensitive. Much of these data also pe rtain to illicit activity. Therefore, to promote reliable reporting of risk factor data, confidentiality and anonymity are preferable

. Although not all studies went to great pains to ensure privacy (e.g., anonymous questionnaires, interview given through c omputer interface only), all of the included studies for Question 4 offered confidentiality, at the very least within the context of medical

care

. In addition, because behavioral risk factors are nearly always personal matters, the most reliable
informatio n will come from the individual about him or herself.

Although objective record and database reviews are generally regarded as being more reliable than patient interview, most types of information of interest, especially behavioral risk factors, are unlik ely to be catalogued in such records. The applicability of these interview and questionnaire self

- report data to potential solid organ donors is unclear, since most solid organ donors are deceased.

Data on deceased actual o rgan donors in Gasink et al. wer e collected from a registry and record review, but most of the items inquired about were not highly sensitive, and this is unlikely to compromise the integrity of their findings. However, sensitive data for Sanchez et al. was collected from next of kin of deceased potential tissue donors

. Findings from Sanchez et al. suggest that next

- of

- kin may be unaware of (or unwilling to report) important factors including high

- risk sexual activities, or history of sexually transmitted infection (STI). Although the dat a in Sanchez et al. were not verified against objective records, it is unlikely that the prevalence of these items was actually zero, as the next

- of

- kin reported

. The next

- of

- kin data in Sanchez et al. may be inaccurate. This was the only study tha t did no t satisfy quality item c

.
Although not all studies that only addressed Question 4 appear to have explicitly offered confidentiality, most of these studies investigated factors that are less sensitive ( e.g., country of birth, race, age) and so it
is unlikel y that the validity of the findings will be affected, and this should not be considered a threat to the validity of Question 4

.
Validity of Infection Stat us Determination (Quality Item I

- D )
In accord with the general inclusion criteria for this review, the infection status of all participants had to be determined using objective laboratory testing methods. The validity of infection status determination therefore is based upon the accuracy of diagnostic test used (see Table 28 for which test(s) were used in each study; nearly all studies reported it). Most studies confirmed antibody or antigen tests with more specific methods such as Western blot, nucleic acid tests, or immunoblots. These studies should have
fewer fal se positives than studies that did not confirm positives. On the whole, the validity of infection status determination is good. Studies nearly universally used reputable commercially

- available diagnostic tests. No studies relied upon rapid or oral tests or home brew (i.e., noncommercial, unregulated) tests alone. Only one study, Nguyen et al., used a test with potentially compromised accuracy. In this study, participants were given a kit to take home and test themselves with. Although the test may be accura te with appropriate use, because the test was not administered under supervision and were not verified with
follow

- up testing, it is not possible to be as confident in the results.

Itemized quality assessment for each of the studies is shown in Table 31 , below.129 

### Table 31

. Quality Assessment for Questions 3 and 4 : Identification of Risk Factors

Study Year Question 3 Question 4

I

- A I

- B I

- C I

- D I

- A I

- B I

- C I

- D

Potential and Actual Organ Donor s

Gasink et al. 102 2006   

Hidalgo et al. 8 2001   Not appl icable

Potential Tissue Donors

Sanchez et al. 103 2006  

Blood Donors

Conry

- Cantilena et al. 106 1996      

Murphy et al. 105 2000      

Murphy et al. 107 2000 Not applicable   

Orton et al. 104 2004      

General Population

Alpert et al. 115 1996      

Alter et al. 117 1989      

Armstrong et al. 30 2006      

Fischer et al. 114 2000      

Hand and Vasquez 112 2005      

Kaur et al. 116 1996      

McGinn et al. 108 2008 Not applicable  

McQuillan et al. 101 2006    

McQuillan et al. 29 1999      

Mehta et al. 109 2008    

Nguyen et al. 110 2008    

Nguyen et al. 113 2005    

Zetola et al. 111 2008 Not applicable   

Children and Adolescents

Luban et al. 118 2007 Not applicable  

D ’ Angelo et al. 119 1991 Not applicable  130 Study Year Question 3 Question 4

I

- A I

- B I

- C I

- D I

- A I

- B I

- C I

- D

Demographic and Socioeconomic Subpopulations (HBV only)

Butterfield et al. 125 2004      

Butterfield et al. 126 1990    

Hann et al. 122 2007 Not applicable  

Hwang et al. 124 2006      

Lee et al. 120 2008 Not applicable  

Lin et al. 123 2007 Not applicable   

Tabibian et al. 121 2008      

Turner et al. 127 1989      

A checkmark (  ) means that the study met the quality criterion for this Question; the lack of a checkmark means that the study either did not meet the criterion, or it was unclear whether the study met the criterion. The criteri a specific to this Question were:

3/4 I

- A. Was the population potential solid organ donors?

3/4 I

- B. For other populations , was the population unselected (i.e., not based on demographic or behavioral characteristics)? Were infected and uninfected participa nts similar on other risk factors?

3/4 I

- C. If not, were statistical adjustments performed to control for other risk factors?

3/4 I

- D. Was risk factor data collected in a valid manner ( e.g., confidential or anonymous collection of sensitive risk factor dat a, collection of personal information from the person directly instead of someone else)

3/4 I

- E. Was infection status determined accurately? ( i.e., accuracy of diagnostic test method used to determine infection status)131 

### Assessment of Risk of Bias (Quality o **f Study Design): Prevalen c**  **e of Risk Factors**
To assess the risk of bias of the included studies, we used the same quality assessment instrument as was used in Question 1. One modification was made for the third item. Rather than ask about the accuracy of de termining infection status, we ask about the accuracy of determining the prevalence of the risk factor

. Specifically , highly personal information should be reported by the person in question. Ideally, medical history (e.g., history of STD) would be collect ed using objective data, but we considered subject self

report acceptable as well. Studies meeting 2 or 3 criteria were not penalized for quality in the GRADE system. Studies meeting only 0 or 1 criterion were penalized one level.



### Table 32

. Quality Assessment for Questions 3 and 4 : Prevalence of Risk Factors

Study Year Question 3 Question 4

P*

- A P

- B P

- C P

- A P

- B P

- C

Potential Organ Donors

Hidalgo et al. 8 2001    Not applicable

Actual Organ Donors

Gasink et al. 102 2006

- -  Not applicable

General Population

Armstrong et al. 30 2006

-  

-  

Kaur et al. 116 1996

-  

-  

McQuillan et al. 101 2006

-   Not Applicable

Mehta et al. 109 2008

-  

-  

Nguyen et al. 110 2008

-  

-  

*P: Prevalence A checkmark (  ) means that the s tudy met the quality criterion for this Question; the lack of a checkmark means that the study either did not meet the criterion, or it was unclear whether the study met the criterion. The criteria specific to this Question were:

3/4 P

- A. Was the populatio n potential solid organ donors?

3/4 P

- B

. For other populations, was the population unselected (i.e., not based on demographic or behavioral characteristics)? (studies of potential solid organ donors were scored as Yes, because they enrolled the population of interest)

3/4 P

- C. Was risk factor prevalence determined accurately? (i.e., were personal factors reported by subject themselves?)132 

### GRADE Assessment of Identification of Risk Factors
To assess the strength of the evidence regarding the identification of risk factors, we applied a GRADE system modified for this purpose. We assigned GRADE ratings for evidence bases comprised of at least two studies addressing a certain factor, divided by virus. The steps used to assign a rating are described in
this section . The GRADE table for Question 4 is Table 36 , and the table for Question 5 is Table 42 , which appear following the results secti ons.

Because all of these studies are observ ational, they were all assigned a starting grade of “ Low, ” per convention. The following factors could be used to decrease this grade: Overall quality, consistency, directness, and precision . Large magnitude of effect could be used to increase one grade. C riteria for these are provided in the following text. If a direct relationship between infection and the factor was suggested (e.g., higher number of sex partners associated with higher odds of infection), the GRADE was increased by one. Explanation of all plausible confounders could also increase the GRADE. These steps are described in the following subsections. We did not assess publication bias.

Overall Risk of Bias
Overall quality was determined in two steps. First, each study was assessed for risk of b ias , as shown in
Table 31 . Then, the overall risk of bias of the evidence base was determined using the median number of quality items. Evidence bases with a median of 3 or 4 criteria were considered “ moderate, ” th ose with a
median of 2 criteria were considered “ low, ” and those with only 1 criterion were considered “ very low. ”
Evidence bases with a “ very low ” quality rating were decreased by one grade.

Consistency
Consistency was determined based upon how well the q ualitative findings of the studies agreed with each other. If studies were consistent with the exception of a special population study or a very low

- quality study; or if all studies (two or more) had large magnitudes of effect (OR>5) with the exception of one study, the evidence base was still considered consistent because these studies are least reliable. Other inconsistency that was easily explained for a single reason (with no other possible explanation) would not be downgraded. Evidence bases with only one study were downgraded due to lack of demonstrated consistency, because scientific replication is an important component of evidence

.

Directness
Only one study 8 

### examined potential organ donors, and this was a very sm all study of living relative donors, who comprise the minority of potential donors. One study on actual heart donors that did not
exclude donors with HCV was included. 102 

### Although a large number of donors were examined in this study, it is not possible to determine how highly selected they were ( i.e., how many potential donors were
excluded a nd for what reasons) because the s e data are not reported.

Most of the remaining studies studied potential tissue donors, actual blood donors, or members of the general population. These studies were not downgraded due to indirectness

, despite the fact that they
did not enroll potential organ donors. This is because the identification of a risk factor in these populations may be generalizable to potential organ donors. By contrast, studies of demographic and socioeconomic subpopulations are probably not very representative of po tential organ donors. Some of the populations have high prevalence of multiple high

- risk behaviors and a relatively high prevalence of133 

### HBV (e.g., psychiatric inpatient veterans with co

- morbid substance abuse problems), while others had few high

- risk behavi ors and a relatively low prevalence of HBV (e.g., women receiving prenatal care). We therefore downgraded evidence bases that predominately had this type of study ( i.e.

, - 1 ).

Precision
We considered all evidence bases with three or more studies to be preci se (and therefore did not downgrade for imprecision). When there were only two studies, we considered the factor precise if one of
two criteria were met. We considered the evidence base precise if both effects were statistically significant. If this criter ion was not met, we evaluated the evidence base for precision by combining the two studies’ data in a summary effect size and evaluating the confidence interval s around the point estimate. We considered the evidence base precise if the confidence intervals were sufficiently narrow,
defined as a maximum difference of 0.4 between the estimated log odds ratio and the upper bound of its
95% confidence interval . For example , if the summary effect size was 1.1 with a 95% CI from 0.8 6 to 1. 4

, this was deemed suffi ciently precise (because ln(1. 4 )

- ln(1.1) is less than 0.4), whereas if the summary effect size was 1.1 with a 95% CI from 0.6 to 2.0, this was considered im precise (because ln(2)

- ln(1.1) is greater than 0.4 , and the evidence is consistent with important ef fects in either direction ) . When there was only a single study, we considered the evidence base precise if either the effect was statistically significant, or if the confidence interval around the effect size was sufficiently narrow (defined in the

same wa y as with two studies ).

Large Magnitude of Effect

We up graded the rating for any evidence base in which the studies consistently showed a large magnitude
of effect. We defined this as any statistically significant odds ratio with a point estimate of 2.0 o r higher. We did not require that the confidence interval s around the effect size point estimate be fully above 2.0

.

Dose

- Response Association

Evidence of a dose

- response association is suggested if increasing levels of the factor corresponded to
increasin g risk of infection. Although studies could have measured such outcomes using continuous reporting (e.g., total number of lifetime sex partners), in this evidence base studies measured a risk factor on a categorical basis. For example, Nguyen et al. ( 2005 ) 113 

### ex amined the risk factor of number of lifetime sex partners by placing each respondent into one of five categories: 0, 1, 2

- 9, 10

- 49, or 50+

. If the risk of infection increased along with the number of sex partners, we considered this a dose

response associa tion. We upgraded some evidence bases +1 whe re the dose

- response association was clear multiple studies

. Significant Association Found Despite Confounders
If the studies in an evidence base found a factor to have a statistically significant relationship wi th infection despite the fact that the evidence base was clearly biased against finding such a relationship

,

we upgraded +1 GRADE Assessment of Prevalence of Risk Factors



### GRADE Assessment of Prevalence of Risk Factors
To assess the prevalence of behavioral and nonbehavioral risk factors, we used the system described in Question 1.134 

## Question **3 : Results** 
The results on identification of risk factors are presented in this section. Information pertinent to the exclusionary factors listed in the 1994 guideline is presented first, and then information regarding additional factors is presented. Text was prepared for all factors that were reported by at least two studies. All of the data used to produce this section is provided in Table 33 (HBV), Table 

### 34 (HCV), Table 35 (HIV), and Table 37 (prevalence of factors), which follow the text.



### Exclusionary **Behavioral C riteria from 1994 Guideline** 
The following sections present all data identified as relevant to the exclusion criteria from the 1994 guideline. Specifically, we did not restrict the information provided to original timeframes (e.g., engaged
in a particular behavior “ within 5 preceding years

, ” “ currently ” incarcerated.). We also included additional very relevant information in these sections, such as sex partners not identified in the original guideline.

Men Who Have Sex with Men
The 1994 guideline excludes from donating “ Men who have had sex with another man in the preceding

5 years. ” We identified zero studies that inquired whether men engaged in sex with other men (MSM) in this particular time frame. However, several studies addressed lifetime hi story of having sex with other

men

. Briefly, two studies found associations with HBV, two did not find associations with HCV, and two
studies found an association with HIV.

HBV : In a sample of men aged 17 to 59 years drawn from the general population, McQu illan et al. compared the prevalence of HBV among men who reported having sex with other men to those who did not and found a significantly increased prevalence of HBV among MSM. 29 

### Hwang et al. compared HBV infection rates among MSM compared to men who have never had sex in a population of college students and found that the rate of HBV was higher among MSM in both univariate and multivariate analyses. 124



### HCV : Murphy et al. (2000) compared HCV prevalence between homosexual or bisexual men to men who had never had sex among blood donors and did not find an increased prevalence when th e comparison was controlled for intravenous drug use (IDU). However, the unadjusted risk was elevated. 105 

### Hand and Vasquez compared the rates of HCV among MSM and non

- MSM among adults tested for HCV because of clinical suspicion and did not find a significant difference in a univariate analysis. 112



### HIV : McQuillan et al. reported the prevalence of HIV among MSM to non

- MSM in a sample drawn from the general population (using NHANES data), and the unadjusted rate shows MSM have a significantly higher prevalence of HIV. 101 

### Using New York City (NYC) HANES dat a from a later year, Nguyen et al. 110 

### also found a significantly higher rate of HIV among MSM in a univariate analysis.

GRADE Summary : The evidence associating MSM with HBV and HIV was moderate. For both the evidence bases consistently found an association, and the magnitude of the effect was large. However, t he strength of evidence associating MSM with HCV infection in blood donor and general populations
studies was very low due to inc onsistent findings. N either pertinent study found MSM to be an independent risk factor for HCV (although MSM may be an important proxy factor; the evidence is insufficient to tell).135 

### Prevalence : Reported prevalence of MSM in the included studies were 3.7% 101 

### and 9.3%. 110



### GRADE Summary of Prevalence: The evidence for the prevalence data was rated as low due to indirectness and inconsistency.

Injection Drug Users
The 1994 guideline excludes from donating “ Persons who report nonmedical intravenous, intramuscular,
or subcutaneous i njection of drugs in the preceding 5 years. ” We identified zero studies that investigated the risk of injection drug use (IDU) within this time frame. Most identified studies associated lifetime
IDU with infection , and one considered the association with I DU greater or less than 6 months before the
blood draw . Some studies reported IDU, and others reported intravenous drug use (IVU). In general, studies did not report both or distinguish between the two. Briefly, IDU/IVU was associated with HBV by
three stu dies but not in a fourth (the fourth study being a smaller study of a special obstetric population), HCV in seven studies, and HIV in two of three studies.

HBV : Kaur et al. associated IDU with HBV in a multivariate analysis of volunteers from the general

p opulation. 116 

### Tabibian et al. 12 1 

### and Butterfield et al. (2004) 125 

### identified an increased risk of HBV among IVU veterans in inpatient psychiatric hospitals, and Hwang et al. identified an increased risk of HBV among IDU college students. 124 

### Butterfield et al. (1990) 126 

### did not find an elevated risk in an obstetric population. However, it app ears that this is probably due to the low prevalence of HBV and IDU in this population. Only one individual in the population reported IDU, and she was HBV negative. Rather than contradict the association between IDU and HBV, the study was probably underpo wered to detect an association given the low prevalence of both in this special low

- risk subpopulation.

HCV : Among blood donors, Orton et al. 104 

### and Murphy et al. 105 

### detected an association between IDU and HCV, and Conry

- Cantilena et al. 106 

### detected an association between IVU an d HCV. Orton et al., use within the last six months only was associated with infection. 104 

### Among people in a study group drawn
from the general population, an increased prevalence of HCV was associated with IDU in Armst rong et al., 30 

### Fischer et al., 114 

### and Hand and Vasquez, 112 

### and with IVU in Kaur et al. 116



### HIV : McQuillan et al. 101 

### studied IDU and the national general population, and Nguyen et al. 110 

### assessed ever having used a needle for drugs, and in univariate analyses both found an increased rate of HIV.
Mehta et al. 109 

### did not find an assoc iation between IDU and HIV among hospital patients; the reason for
this is unclear.

Two studies specifically investigated the association between infection and injection steroid use, and neither found any association. Hwang et al. did not detect an increas ed risk of HBV among college students who injected steroids, 124 

### and Orton et al. did not find an increased risk of HCV among blood
donors. 104 

### Howe ver, the Orton study did find a trend toward higher infection rate among blood donors who had injected steroids longer than six months ago (P = 0.07), and a larger study might detect an
association.

GRADE Summary : The strength of the evidence associating IDU with HCV was “moderate” due to the consistently large effect sizes found in all studies that associated this factor (with the exception of one small study on steroid use only that did not find an association with infection). For HBV, the evidence
was “ low.” All but one special population study found an association, but not all of the studies found a136 

### large magnitude of effect (not including the findings of one study that injection steroid use was not associated with HBV). For HIV, the evidence was “ low .”

Prevalence : Prevalence of injection drug use reported in the general population studies were 1.4%, 110


### 1.7%, 30 

### 3.5%, 116 

### and 7.9%. 109 

### Of the IDUs in one of those studies, 63.2% reported that they did not use a needle exchange program. 109



### GRADE Summary of Prevalence: The prevale nce data for injection drug abuse was rated as low due to inconsistency and indirectness.

Related Factors: In addition, reporting living with an IDU was associated with HCV among blood donors, even when IDU was controlled for, 105 

### as was living with an IDU in the last six months. 104



### Alter et al. grouped household and s exual contact with an IDU during the last six months and found it was associated with recent HBV infection in a univariate, but not multivariate, analysis. 117 

### Among the gen eral population, both being at a social gathering with injection drugs and witnessing the use of injection drugs
were associated with HCV. 113 

### See the section High Risk Sex Partners for information on infection risk among people who have sex with IDUs.

We also id entified information on other types of substance abuse. For information, under Risk Factors Identified in the Literature as of 2009 see “ Non

- injection substance use and abuse. ”

Sex Work
The 1994 guideline excludes from donating “ Men and women who have enga ged in sex in exchange for money or drugs in the preceding 5 years. ” We did not find any literature that studied the association between this factor and the given time frame, but we did find literature that studied lifetime sex work and
infection risk. Bri efly, sex work was not associated with HBV in three studies (one was the next

- of

- kin tissue donor interview study, the other two enrolled special subpopulations of psychiatric inpatient veterans) or with HIV in one study (the next

- of

- kin interview study) b ut was associated with HCV in
three studies.

HBV : In their study of tissues donors, Sanchez et al. did not find any association between sex work and infection with HBV upon univariate analysis. However, their data came from next

- of

- kin interviews, and

none of the relatives of infected potential donors reported sex work. 103 

### Among psychiatric inpatient veterans, Tabibian et al. 121 

### did not detect an association between “ sex bartering ” in a multivariate analysis. In that population rate s of sex bartering were high among both HBV negative (30%) and HBV positive (37%) participants. Unprotected sex for drugs was not associated with HBV infection upon multivariate analysis in the other study that enrolled psychiatric inpatient veterans, Butt erfield et al. (2004). 125



### HCV : Sanchez et al. did not find any association between sex work and infection with HBV among tissue donors, with sex work as reported by next of kin. 103 

### Sex work was associated with HCV among blood donors in Murphy et al. in a multivariate analysis 105 

### and in general populations studies by Hand and Vasquez 112 

### and Nguyen et al. in univariate analyses. 113 

### (In Hand and Vasquez, all women who reported sex work also reported IDU.)137 

### HIV : In the study of tissues donors, Sanchez et al. did not fin d any association between sex work and
infection with HIV. 103



### GRADE Summary: The evidence relating sex work and HBV and HIV i nfection was rated as very low

. For HBV this was due to indirectness; the data were from primarily special populations. For HIV, this was due to having only one study of very low quality

. In the HBV and HIV studies, no relationship was detected. For HCV, t he evidence was rated as low. Three studies found associations

. A fourth study
did not, but we did not downgrade the evidence due to inconsistency because it was of very poor quality.

Prevalence : One study reported the prevalence of exchanging sex for drug s or money among patients in
an urban medical care center at 2.3%

. 109



### GRADE Summary of Prevalence: The prevalence of sex work was rated as low due to indirectness and
lack of proof of consistency.

High

- Risk Sex Partners
The 1994 guideline excludes from donating “ Persons who have had sex in the preceding 12 months with any person described in items 1

– 4 above [refers to MSM, IDU, sex workers, and people with clotting
disorder s, who are covered in Question 4 ] or with a person known or suspected to have HIV infection. ” We did not identify any literature on infection risk in people with high

- risk sex partners during this time frame, but we did identify literature on infection risk a ssociated with having high

- risk sex partners at some point in life. As the scope of this evidence report encompasses HBV and HCV in addition to HIV, we have also included data on infection risk among people having sex with a person with known or suspected hepatitis. Briefly, having a high

- risk or infected sex partner was associated with HBV in six of seven studies (the seventh being a special subpopulation study of psychiatric inpatient veterans), with HCV in ten studies, and with HIV in one study.

Sex wit h IDU

HBV : Sex with an IDU was associated with HBV in general population groups (including when use of IDU was controlled for) by Kaur et al. 116 

### and in univariate analyses among col lege students by Hwang et al., 124 

### but not among psychiatric inpatient veterans in Tabibian et al. 121 

### Sex or household contact with an
IDU was associated with HBV infection in Alter et al. 117 

### upon univaria te investigation, but not when use
of IDU was controlled for.

HCV : Sex with an IDU or IVU was found to be associated with HCV in blood donors by Murphy et al. (2000) 105 

### in univariate analysis and Orton et al., 104 

### in multivariate analysis, and in the general population by Nguyen et al. 113 

### in univariate analysis and Kaur et al. 116 

### in multivariate analysis. In Orton et al. the time frame was limited to the six months prior to donation.

GRADE Summary: The evidence associating HBV infection with having a sex partner who uses injection drugs was rated as very low due to inconsistent findings. For HCV, the evidence was moderate due to the consistent findings of association with large magnitude of effect.

Prevalence : In one study, 5% of respondents r eported h aving sex with an IDU. 116138 

### GRADE Summary of Prevalence : The evidence of prevalence of having a n IDU sex partner was low due to indirectness and lack of proof of consistency.

Sex wit h a Sex Worker

HBV : Sex with a sex worker was not associated with HBV among psychiatric inpatient veterans in a univariate analysis in Tabibian et al. 121



### HCV : Sex with a sex worker was associated with HCV among blood donors in a multivariate analysis in Murphy et al. 105 

### and in univariate analyses of general population studies by Ngyuen et al. 113 

### and Hand and Vasquez. 112 

### However, in Hand and Vasquez the relationship was no longer significant in the multivariate analysis.

GRADE Summary: A single special population study did not associate HBV with sex with a sex worker,
bu t this evidence is rated as “ve ry low” due to indirectness and lack of proof of consistency of evidence. Three studies associated having sex with a sex worker with HCV in univariate analyses . This evidence
was rated as “ very low

. ”

Prevalence : In one study , 7.4% of respondents indicated they had had sex with a sex worker. 109



### GRADE Summary of Prevalence : The estimate of prevalence of having sex with a sex worker was graded
as l ow due to indirectness and lack of proof of consistency.

Sex with People Known to Have Infection

HBV : Sex with a partner with hepatitis was found to be a risk factor for HBV in college students in Hwang et al., 124 

### but not in an obstetric population in Butterfield et al. (1990). 126 

### Both of these analyses
were univariate.

HCV : Among blood donors, sex with someone with hepatitis at any poin t in life in Murphy et al. (2000) 105 

### in a multivariate analysis, or during the last six months in Or ton et al. 104 

### in a univariate analysis, was
associated with HCV.

HIV : H aving sex with someone known to have HIV was associated with having HIV by Mehta et al. in a group of patients from a general population using univa riate analysis. 109



### GRADE Summary : The evidence associating HBV and having a sex partner with a known infection was rated as very low due to low quality, inconsistency, and in directness. The evidence associating the factor with HIV was also rated as low, for ha ving no proof of consistency but a large effect size magnitude . For HCV the evidence was rated as low for consistently identifying sex with people known to have infection
as a risk factor for HCV.

Prevalence : On study stated that 3.6% of participants reported having sex with someone known to be
infected with HIV. 109



### GRADE Summary of Prevalen ce : The estimate of prevalence of having sex with someone known to be

HIV

- positive was graded as low due to indirectness and lack of proof of consistency.

Other High

- Risk Sex Partners139 

### Some miscellaneous types of high

- risk sex partners pertinent to high

- ris k sex partners not mentioned in the original guideline were also reported. Sexual promiscuity (defined as history of STD, sex with a sex worker, or at least five sex partners per year) was associated with HCV infection in blood donors in Conry

- Cantilena et al. 106 

### Alter et al. did not associate HBV infection with sex with a blood transfusion recipient, with a health care worker, or a person with a foreign birth in an endemic area. 117 

### Sex with a transfusion recipient was associated with HCV in blood donors in Murphy et al. 105 

### We report these other high

- risk sex partners here because they are germane to the larger issue of having high

- risk sex partners. However, we did not grade this evidence because these factors w ere reported by one study only.

Inmates
The 1994 guideline excludes from donating “ Inmates of correctional systems. (This exclusion is to address issues such as difficulties with informed consent and increased prevalence of HIV in this population.) ” No studies that examined the association between present incarceration and infection were identified. However, the searches did identify studies that examined the association between recent or lifetime history of incarceration. In brief, a history of incarceration was associated with HBV in three of four studies, with HCV in four of five studies, and was not associated with HIV in one study. The study that did not detect an association of incarceration and HBV, HCV, or HIV infection was Sanchez et al., the tissue donor study based upo n information provided by next of kin.

HBV : A history of incarceration as reported by next

- of

- kin was not associated with HBV in potential
tissue donors in Sanchez et al. 103 

### In general population studies , imprisonment within the last six months was associated with recent HBV infection in a univariate analysis, but not a multivariate analysis in Alter
et al. 117 

### Incarceration was also associated with HBV upon univariate analysis among psychiatric inpatient
veterans in Tabibian et al. 121 

### and among college students incarcerated for at least 24 hours in Hwang et
al. 124



### HCV : A history of incarceration as reported by next

- of

- kin was not associated with HCV infection in potential tissue donors in Sanchez et al. 1 03 

### Incarceration was associated with HCV in three studies of blood donors, Orton et al., 104 

### Murphy et al. (2000), 105 

### , and Conry

- Cantilena et al. 106 

### Two of those studies also tested whether incarceration was an independent risk factor; in both of those studies incarceration

was associated with IDU. Murphy et al. (2000) found that incarceration for more than three days was an independent risk factor (although, compared with the unadjusted odds, odds were not as large once IDU was controlled for in the multivariate model), 105 

### while Conry

- Cantilena et al. found that, once adjusted for IDU, it was not. 106 

### In addition, having been arrested was associated with HCV infection in a general population sample by Nguyen et al. 113



### HIV : A history of incarceration as reported by next

- of

- kin was not associated with HIV infection in potential tissue donors in Sa nchez et al. 103



### GRADE Summary: Aside from one very low

- quality study, a history of incarceration was consistently
associated with HCV, and rated as low in strength overall . The association with HBV was inconsistent due to conflicting findings, and the association with HIV is unclear because only one very low

- quality study addressed this outcome. Th e ratings for HBV and HIV were therefore both very low.

Risk Factors in Children140 

### We identified no literature on any behavioral risk factors in children, or on the risk of infection from mothers who engage in those risk behaviors

. While vertical transmission is generally recognized as a mode of hepatitis or HIV transmission, this body of literature lacks the evidence to assess the 1994 criteria as risk factors. This may be because of the relative infrequency of this mode of transmission, and
because of the lack of data on children. For in stance, although they used NHANES data from the general nationwide population, Armstrong et al. reported identifying only three people under the age of 20 years that were infected with HCV, which precluded the investigation of risk factors in children and adolescents in their study. 30 

### In the literature base analyzed in this report , only one individual, a 17

- year

- old first

- time
blood donor with HCV RNA but not anti

- HCV, had perinatal exposure as a possible mode of
transmission. 104 

### Her mother had an HCV infection during her pregnancy, and no other likely causes exposure were identified.



### Additional Potential Risk Factors Identified in the 2009 Literature Search
In addition to the factors identified in the 1994 guideline, we extracted data on all other reported
behavioral risk factors identified in t he literature and describe the findings regarding factors reported by

at least two studies.

Other Sex Practices
Multiple Partners
Having multiple partners, including heterosexual partners, was associated with increased risk of infection across different po pulations. In brief , various measures of having multiple partners were associated with HBV in five studies, with HCV in six studies, and w ith HIV in one of three studies.

HBV : HBV infection was associated with sex with multiple partners in general populati ons in Kaur et al. 116 

### in multivariate analysis. In multivariate analyses, multiple partners within the last six months was associated with recent HBV infection in a general populati on in Alter et al. 117 

### and among psychiatric inpatient veterans in Butterfield et at. (2004). 125 

### In a sample of people representative of the general population

, compared to individuals with zero or one lifetime sex partners, having at least two lifetime sex partners was associated with HBV in McQuillan et al. in a multivariate analysis, and the odds of infection increased with greater numbers of partners. 29 

### Among college students in the study by Hwang et al., both having at least 50 lifetime hetero sexual partners and having at least 5 heterosexual partners in the preceding
four months were associated with HBV infection in univariate analyses. 124



### HCV : HCV infection in women bloo d donors was associated with having at least 11 male sexual partners (compared to having zero sexual partners) in Murphy et al. (2000) 105 

### in multivariate analysis. Having the same number of lifetime female partners among men was not associated with HCV in the same study

. Having two or more sexual partners, whether same sex or not, in the last six months was associated with
an increased rate of HCV infection overall in Orton et al. 104 

### in a univariate analysis. In general population univariate analyses, HCV was also associated with having “ frequent ” sex partners in Fisch er et al., 114



### “ multiple ” s ex partners in Kaur et al., 116 

### and at least 20 sexual partners in Armstrong et al. 30 

### Greater numbers of sex partners was also associated with HCV infection in Nguyen et al. 113 

### Hand and Vasquez noted the strong association between greater numbers of sex partners a nd IDU in their study. Of the 18.5% of their patients who reported having at least 10 sex partners in their sample, 84% also reported

IDU. 112141 

### HIV : In the general population, having multiple sex partners in the past year was not associated with HIV in Nguyen et al., 110 

### nor was having at least 10 lifetime sex partners in Mehta et al. 109 

### , but having 50 or more lifetime sex partners was associated with HIV in McQuillan et al. 101 

### All of these analyses were
univariate.

GRADE Summary: Studies used different thresholds to define “multiple sex partners,” (ranging from as few as 2 to as many as 50 or more) so identifying the minimum number of partners associated with an increased risk of infection is not possible based upon this evidence base. However, using their various definition, HBV and HCV studies did (with th e exception of heterosexual men in one HCV study) consistently associate infection with having multiple sex partners. For HBV and HCV, the strength of this association was moderate due to a positive “dose” response association. For HIV there was also a dos e

response relationship in two studies (one study found a relationship with having at least 50 partners, the other did not find a relationship with having at least 10 partners). The third study did not find a relationship with having “multiple” sex partner s in the past year. The evidence was rated as low for having a dose

- response relationship but inconsistent findings.

Prevalence : In a national general population, 29% of survey respondents indicated having had at least 10
sex partners, 30 

### and 3.5% reported having at least 50 sex partners. 101 

### Among New Yorkers, 6.6% reported at least 50 sex partners. 110 

### 22% of New Yorkers reported having sex with multiple partners during the previous year, 110 

### and 26% of volunteers from an urban area reported sex with multiple partners. 116



### GRADE Summary of Prevalence: Prevalence estimates of having “multiple” sex partners (number undefined) and having at least 2 sex partners (but not more than 49 in one study) were both rated as moderate due to indirectness. The prevalence of having at least 50 partners was rated as low due to indirectness and lack of consistency.

Same

- Sex Partners, Not Restricted to Men
Three studies investigated having same sex partners but did not restrict the analysis to MSM. Two associated this factor with HCV, and the other associated it with HIV.

HCV : Having same

- sex partners among women was associated with an increased risk of HCV among women blood donors in Murphy et al. (2000) 105 

### in multivariate analysis. For women who had had only

one same

- sex partner, this risk was no longer significant when adjusted for IDU, but it remained significant if there were two or more same

- sex partners. Among outpatients, Nguyen did not find any association between having sex with a person of the same sex and HCV infection. 113



### HIV : Mehta et al. detected a univariate association be tween having a same

- sex partner and HIV, including both men and women in the sample. 109



### GRADE Summary : The evidence for HCV was rated as very low due to inconsistency and imp recision. The evidence for HIV was rated as low because the single study had large magnitude of effect but could provide no proof of consistency for the evidence base.

Prevalence : One study asked both men and women if they had same

- sex sex partners, and 8. 2% reported that they did. 109142 

### GRADE Summary of Prevalence : This evidence was rated as low due to indirectness and lack of proof of consistency.

Age at First Sexual Intercour se Younger age at the time of first sexual experience was also associated with infection among adults in univariate analyses. One study associated it with HBV, two associated it with HCV, and one associated it
with HIV.

HBV : Age of 18 years or younger was not associated with HBV in McQuillan et al. (1990) in a multivariate analysis. 29 

### Age at first intercourse of 15 years or younger was associated with HB V infection among college students in Hwang et al. in a univariate analysis. 124



### HCV : In the general population, age of 17 years or younger was associated with HCV in Armstrong et al. in a univariate analysis. The study stratified age at first intercourse by age younger than 11, age 12

- 15, and age 16

- 17 years. The groups of people who were younger at the time of their first sexual intercourse had the highest risk of HCV. 30



### HIV : Age of 18 years or younger was associated with HIV in McQuillan et al. (2006) in a univariate analysis. The size of this effect was large. 101



### GRADE Summary : For HBV, one study associated HBV with age at first intercourse 15 or younger, and another did not find a relationship with age at first intercourse 18 or younger. This evidence was rated as low because, although the findings were not necessarily consistent, they do suggest a ‘dose

- dependent’ relationship between younger age at first intercourse and increased risk of HBV. For HCV, one study found that younger age was associated with infection in a dose

- dependent relationship, and the evidence rating for it was ‘low.’ For HIV, age younger than 18 was associated with increased risk of infection, and the evidence for this was rated as ‘low’ for having a large magnitude of effect despite no proof of consistency.

Prevalence : The proportion of adults who reported having sex at age 1 8 or younger were 58% 30 

### and
59% 101 

### in two studies.

GRADE Summary of Prevalence : This estimate was rated as moderate due to lack of directness to potential organ donors.

A dditional Various Associations
We report additional reported associations between sexual practices and infection below because they are relevant to this overall section. However, we did not assign Grade ratings because these factors were reported by so few studies.

**•** Unprotected sex was associated with HCV infection in a general population by Fischer et al. 114



### , although not using condoms consistently was not associated with HIV infection in a general population by Mehta et al. 109 

### or Nguyen et al. 110



### • Anal

- insertive sex that occurred at least six weeks ago was associated with HIV infection among men in a general population, and anal

- rec eptive sex at least six weeks ago among women and men in a general population in Mehta et al. 109143 

### • Having vaginal sex was associated with a reduced risk in HIV compared with pe ople who did not have vaginal sex (but may have been having anal sex) in the general population study by Mehta et al. 109



### Non

- injection Substance
Other Illicit Drugs

Of the st udies that inquired about the association between non

- injection illicit drug use (mostly inhaled drugs, predominantly intranasal cocaine), two of five found an association with HBV and seven of eight
found an association with HCV. Two of the studies that d id not find an association with HBV both enrolled a special subpopulation (psychiatric inpatient veterans). The other study that did not find an association
with either HBV or HCV was the next

- of

- kin interview study of tissue donors, Sanchez et al. 103



### HBV : Illicit drug use was not associated with HBV in the tissue donor study by Sanchez et al. 103 

### Ever having used cocaine was associated with HBV in the general population by McQuillan et al. 29 

### in a multivariate analysis. HBV infection was associated with intranasal drug use among the college students in Hwang et al. 124 

### However, in Tabibian et al. 121 

### and Butterfield et al. 125 

### , who enrolled psychiatric inpatient veterans, HBV infection was not associated with inhaled or ‘ snorted ’ drugs.

HCV : Any illicit drug use was not associated with HCV in the tissue donor study by Sanchez et al. 103 

### Intranasal drugs were associated with HCV infection in blood donors in Orton et al., 104 

### Conry

- Cantilena
et al. 106 

### and Murphy et al. 105 

### , including when adjusted for IDU or oth er facto rs in two of those studies (the third study did not perform adjusted analyses

. 104 

### In a general population, use of snorting or inhaling nonprescription drugs, 113 

### inhaling cocaine, 114 

### using intranasal cocaine, 112 

### and use of non

- injection drugs other than marijuana 30 

### were all associated with increased prevalence of HCV. Two of the studies investigated whether this factor was independently associated with HCV, and Armstrong et al . found it was using NHANES data 30 

### while Hand and Vasquez found it was not b ased upon a smaller set of data on adults tested for HCV because of clinical suspicion. 112 

### However, Hand and V asquez note that cocaine use in the absence of IDU or tattoos was unusual in their sample. Although 39% of patients admitted to intranasal cocaine, only 2% of whom did not have tattoos or IDU used cocaine.

Being at a social gathering with cocaine was asso ciated with HCV in Nguyen et al. 113 

### Having friends who

use “ street drugs ” was associated with an increased risk of HCV among bl ood donors Orton et al. 104



### HIV : HIV was associated with ever using cocaine or street drugs in a un ivariate analysis by McQuillan et al. (2006) 101 

### and in a multivariate analysis by Alpert et al

. 115 

### among members of the general p opulation.

GRADE Summary: The evidence associating non

- injection illicit drug use and HBV was inconsistent and graded as “very low” due to this inconsistency . Aside from one very low

- quality study, studies consistently associated non

- injection drug use wit h HCV. The evidence associating HCV with non

injection drugs was rated as low . Two studies associated HIV with non

- injection drug use, and this
evidence was rated also rated as low

.

Prevalence : Among potential living organ donors in one smaller study, 5.5% reported having ongoing drug abuse problems. 8 

### In the general population, 17% reported lifetime use of drugs other than marijuana, 30 

### 18% reported ever having used street drugs, 110 

### and 21% reported using street drugs/cocaine

. 101144 

### GRADE Summary of Prevalence: The estimate of ongoing drug use prevalence in living potent ial organ donors was rated as low due to imprecision and lack of proof of consistency. The estimates of drug use in the general population were rated as moderate due to indirectness.

Alcohol

The association between alcohol intake and infection was less con sistent.

HBV : Alcohol use, as reported by next

- of

- kin, was not associated with HBV infection among potential tissue donors in a univariate analysis in Sanchez et al. 103 

### HBV was not associated with alcohol use disorder among psychiatric inpatient veterans in Butterfield et al. in a multivariate analysis (2004)

. 125



### HCV : HCV was associated with “ heavy ” alcohol use in heart donors in Gasink et al. 102 

### , and with ha ving at least two units of alcohol per day among adults tested for HCV because of clinical suspicion in Hand and Vasquez. 112 

### However, HCV was not associated with alcohol use among tissue donors in Sanchez et al., 103 

### having at least 5 al coholic drinks weekly in patients in Nguyen et al. 113 

### or alcoholism in HMO
enrollees in Fischer et al. 114 

### All of these analyses were univariate.

HIV : HIV was associated with having an alcohol and/or (unspecified) drug problem among HMO
enrollees in Fischer et al. 114 

### (as identified in a claims database), but not w ith alcohol use among potential
tissue donors in Sanchez et al. 103 

### Both of these analyses were univariate.

GRADE Summary: Alco hol use was not associated with HBV and was inconsistently associated with
HCV and HIV. These evidence bases were all rated as “ver y low” due to inconsistency and/or imprecision

.

Prevalence : In a database study of actual organ donors, 20% reportedly drank heavily. 102



### GRADE Summary of Prevalence: The estimate of heavy alcohol abuse was rated as low due to low stud y quality and lack of proof of consistency. The directness to potential donors is also unclear.

Tobacco

HBV: No association was found between cigarette smoking and HBV among tissue donors in the study by
Sanchez et al. 103



### HCV : A history of tobacco use was associated with HCV in heart donors in Gasink et al., 102 

### and cigarette smoking was associated with HCV (but not HBV or HIV) in tissue donors in Sanchez et al. 103 

### Both of these associations were made using univariate analyses.

HIV: The same tissue donor study that did not find an association between cigarette smoking and HBV or
HCV also did not find one betwe en cigarette smoking and HIV. 103



### GRADE Summary : One organ donor study associated tobacco with HCV, but the tissue donor study did not; the strength of the evidence base as very low. For HBV and HIV the evidence was rated as very low because only one study that did not find a relationship was identified.

Prevalence : Among actual heart donors

, 36% had a history of tobacco use. 102145 

### GRADE Summary of Prevalence: The estimate of tobacco use was rated as low due to low study quality
and lack o f proof of consistency. The directness to potential donors is also unclear.

Tattoos and Piercing
Tattoos and piercings were not associated with HBV in any of five studies or with HIV in one study, but tattoos were associated with HCV in six studies and pie rcings were associated with HCV in three of six
studies. We report on tattoos and piercing because the tissue donor study, Sanchez et al. 103 

### reported on them together.

HBV : Tattoos, piercing, and acupuncture (as collectively analyzed as one outcome and reported by next

of

- kin) were not associated with HBV in tissue donors in Sanchez et al. 103



### Tattoos were not associated with HBV infection among psychiatric inpatient veterans in Tabibian et al., 121 

### women receiving prenatal care in Butterfield et al. (1990), 126 

### or among college students in Hwang et al., 124


### unless the college students were tattooed with reused non

- autoclaved needles. Having a tattoo in the last six months was not associated with acute HBV infection by Alter et al. 117



### Piercings were not associated with HBV among psychiatric inpatient veterans in Tabibian et al. 121 

### , and body piercings (other than ears) were not associated with HBV among college students in Hwang et al. 124



### P iercings within the last six months were not associated with acute HBV in the general population either
in Alter et al. 117



### HCV : Tattoos, piercing, and acupuncture (as colle ctively analyzed as one outcome and reported by next

of

- kin) were not associated with HCV in potential tissue donors in Sanchez et al. 103



### Tattoos were associated with HCV in three univariate analyses of blood donors, Orton et al., 104 

### Conry

Cantilena et al., 106 

### and Murphy et al. (2000) 105 

### Orton et al. focused on having had a tattoo within the last six months and the appearance of acute H C V. Two of thes e studies also performed multivariate analyses. Conry

- Cantilena found that tattoos were not significantly associated with infection once other factors are
controlled for. 106 

### Murphy et al. found that, although the odd s of infection were reduced once IDU was controlled for, tattoos were an independent predictor of HCV. 105 

### Three general populations studies, Nguyen et al., 113 

### Fischer et al., 114 

### and Hand and Vasquez et al., 112 

### also detected significant associ ations between tattoos and HCV. Only Hand and Vasquez investigated further and found that tattoos were an independent predictor. In that study, adults were enrolled based upon clinical suspicion of hepatitis. Most patients enrolled in the Hand and Vasquez study reported that their tattoos had been applied by friends, fellow gang members, or fellow inmates (as opposed to professional tattooists working from commercial parlors).

Among blood donors, HCV was not associated with body piercing in the last 6 month s by Orton et al., 104


### but was associated with ear piercing among men in Conry

- Cantilena et al., 106 

### and with pierced ears or body parts in Murphy et al. (2000). 105 

### Fischer et al. 114 

### and Hand and Vasquez 112 

### considered the association between body piercing and HCV in general population patients and did not find an
association. Nguyen et al. 113 

### and Hand and Vasquez 112 

### investigated ear piercing in adult patients, and while Nguyen et al. detected an association Hand and Vasquez did not.146 

### HIV : Tattoos, piercing, and acupuncture (as c ollectively analyzed as one outcome and reported by next

of

- kin) were not associated with HIV in potential tissue donors in Sanchez et al. 103



### GRADE Summary: Tattoos and piercings were consistently not assocated with HBV. The rating of this
evidence is low . Aside from one very low

- quality study, tattoos were consistently associated with HCV, and piercings were inconsistently assoc iated with HCV. The rating of this evidence is also low. Only one very low study considered piercing and tattoos and HIV, and did not find an associati on. This evidence was rated as very low due to low quality , lack of proof of consistency, and imprecision

.

International Travel
Several studies inquired whether participants had traveled outside the U.S. but none detected an association with infection. Among potential tissue donors in Sanchez et al., international travel was not associated with HBV, HCV, or H IV. 103 

### International travel within the last six months was not associated with acute HBV in a general population by Alter et a l. 117 

### Among blood donors, traveling outside the U.S. during the last six months was not found to be significantly associated w ith HCV in Orton et al., 104 

### and having ever lived outside the U.S. was not found to be significantly associated with HCV in Murphy et
al. 105



### GRADE Summary : International travel was not associated with any of the viruses. For HBV and HIV the evidence was rated as very low due to imprecision and, for HIV, low quality. For HCV the evidence was
rated as low.147 

### Evide **nce Tables for Question 3** 

Table 33

. HBV Identification of Behavioral Risk Factors DataCategory

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Potential Tissue DonorsSex Work Prostitution, history of Sanchez et al. 103 2006 Not
repor

te

d (NR) 47 NR 56 NR Not significant (NS)† Proportion in HBV+ vs. HBV

No Potential tissue donors,

as reported by next of kinIncarceration Incarceration, history of Sanchez et al. 103 2006 NR 47 NR 56 NR NS † Proportion in HBV+ vs. HBV

No Potential tissue donors,

as reported by next of kinNon-IDU Drugs Illicit drug use (any) Sanchez et al. 103 2006 NR 47 NR 56 NR NS † Proportion in HBV+ vs. HBV

No Potential tissue donors,

as reported by next of kin

Alcoho l use Sanchez et al. 103 2006 NR 47 NR 56 NR NS † Proportion in HBV+ vs. HBV

No Potential tissue donors,

as reported by next o f kin

Smoking history Sanchez et al. 103 2006 NR 47 NR 56 NR NS † Proportion in HBV+ vs. HBV

No Potential tissue donors,

as reported by next of kinTattoos/Piercing Tattoos, body piercing, or acupuncture Sanchez et al. 103 2006 NR 47 NR 56 NR NS † P roportion in HBV+ vs. HBV

No Potential tissue donors,

as reported by next of kin148Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

PopulationOther Foreign travel Sanchez et al. 103 2006 NR 47 NR 56 NR NS † Proportion in HBV+ vs. HBV

No Potential tissue donors,

as reported by next of kin

General PopulationMSM Men who have had sex with men McQuillan et al. 29 1999 6.5 % 323 1.2 % 5

, 058 5.7 (3.4 to 9.5)†¶ <0.001† Proportion in HBV+ vs. HBV

Yes General population aged 17 to 59 yearsIDU Intravenous drug use Kaur et al. 116 1996 62.6 % 6,121 17.2 % 1,417 8.11 (5.47 to 12.03)‡ SS Proportion in HBV+ vs. HBV

Yes Volunteers from general populationHigh-risk Sex Partner Sex with intravenous drug user Kaur et al. 116 1996 44.7 % 1

, 189 16.7 % 5

, 373 2.57 (1.78 to 3.17)‡ SS Proportion in HBV+ vs. HBV

Yes Volunteers from general population

Household/ sexual contact with someone wi th history of IV drug use, last 6 months Alter et al. 117 1989 9 % 76 0.7 % 152 NR <0.01†;

NS‡ Proportion in HBV+ vs. HBV

Yes (uni

variate only) General population adults with no obvious cause of acute HBV and matched controls

Sexual contact with blood transfusion recipient Alter et al. 117 1989 3 % 76 5 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controls149Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Sexual contact with
person employed in health care Alter et al. 117 1989 0 % 76 5 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obv ious cause of acute HBV and matched controls

Sexual contact with person of foreign birth in area with high endemic HBV
rate Alter et al. 117 1989 3 % 76 0 % 152 NR NS† Propo rtion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controlsIncarceration Imprisonment last 6 months Alter et al. 117 1989 7 % 76 0 % 152 NR <0.01†;

NS‡ Proportion in HBV+ vs. HBV

Yes (uni

variate only) General population adults with no obvious cause of acute HBV and matched controlsOther Sex Practices Sex with multiple partners Kaur et al. 116 1996 22.6 % 1

, 402 17.9 % 5

, 923 1.33 (1.08 to 1.64)‡ NR Proportion in HBV+ vs. HBV

Yes Volunteers from general population

Multiple (>1) sexual partners, last 6 months Alter et al. 117 1989 26 % 76 7 % 152 6.0‡ (confidence intervals not reported) <0.01 Proportion in HBV+ vs. HBV

Yes General population adults with no obvious cause of acute HBV and matched controls150Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Lifetime sex
p

artner s 2 to 9 McQuillan et al. 29 1999 47 % 505 50 % 10

, 613 2.1 (1.4 to 3.2)‡ SS Prevalence HBV+ vs. HBV

- vs. 0 to 1 Yes General population aged 17 to 59 years

Lifetime sex partners 10 to 49 McQuillan et al. 29 1999 26 % 505 20 % 10

, 613 2.9 (1.9 to 4.3)‡ SS Prevalence HBV+ vs. HBV

- vs. 0 to 1 Yes General popul ation aged 17 to 59 years

Lifetime sex partners 50+ McQuillan et al. 29 1999 4 % 505 11 % 10

, 613 6.5 (3.5 to 12.2)‡ SS Prevalence HBV+ vs. HBV

- vs. 0 to 1 Yes General population aged 17 to 59 years

Age at first intercourse <18 McQuillan et al. 29 1999 69% 496 60% 9,978 1.2 (0.9 to 1.6) NS Prevalence H BV+ vs. HBV

- vs. >18 years No General population aged 17 to 59 yearsNon-Injection Drugs Ever used cocaine McQuillan et al. 29 1999 22 % 541 11 % 10

, 773 1.8 (1.2 to 2.7)‡ SS Proportion in HBV+ vs. HBV

Yes General population aged 17 to 59 yearsTattoo Tattoo, last six months Alter et al. 117 1989 1 % 76 1 % 152 NR NS† Proport ion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controls151Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

PopulationPiercing Ear piercing, last six months Alter et al. 117 1989 3 % 76 3 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controlsTravel International travel, last six months Alter et al. 117 1989 1 % 76 <1 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controlsOther Raw shellfish, ingesting, last six months Alter et al. 117 1989 15 % 76 8 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controls

Raw shellfish, shucking, last six months Alter et al. 117 1989 4 % 76 3 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controls

Sharing a

razor or toothbrush with someo ne in household Alter et al. 117 1989 22 % 76 27 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controls152Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Demographic and Socioeconomic SubpopulationMSM Men who have sex with

men Hwang et al. 124 2006 6 % 245 3 % 3

, 824 Relative risk (RR):
2.06 (1.17 to 3.61)†

OR: 3.54 (1.31 to 9.59)‡ p <0 .05 for both Prevalence HBV+ vs. HBV

- vs. never had

sex Yes College studentsIDU Intravenous drug use Tabibian et al. 121 2008 62.5 % 40 27 % 89 4.51 (2.04 to 9.96) †¶ <0.0 01 Prevalence in HBV+ vs

. HCV

Yes Psychiatric inpatient
veterans

Intravenous drug use Butterfield et al. 125 2004 NR 80 NR 276 4.54 (2.28 to 9.04)‡ <0.001 Prevalence HBV+ vs. HBV

Yes Psychiatric inpatient
veterans

Intravenous drug use Butterfield et al. 126 1990 0 % 12 0.2 % 1

, 454 16.59 (0.81 to 338.24)†¶ 0.07¶ Prevale nce HBV+ vs. HBV

No Obstetric population

Injected illegal drugs Hwang et al. 124 2006 6 % 266 2 % 3

, 968 RR : 3.02 (1.91 to 4.77)† <0.05 Prevalence HBV+ vs. HBV

Yes College students

Injected steroids Hwang et al. 124 2006 1 % 268 1 % 4

, 013 RR : 0.98 (0.32 to 2.94)† NS Prevalence HBV+ vs. HBV

No College studentsSexWork Sex bartering Tabibian et al. 121 2008 30 % 40 37 % 89 NR NS† Prevalence in HBV+ vs. HBV

No Psychiatric inpatient
veterans153Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Unprotected sex for drug s Butterfield et al. 125 2004 NR 80 NR 276 1.25 (0.60 to 2.61)‡ NS Prevalence HBV+ vs. HBV

No Psychiatric inpatient
veteransHigh-Risk SexPartners Sex with intravenous drug user Tabibian et al. 121 2008 17.5 % 40 11 % 89 NR NS† Prevalence in HBV+ vs. HBV

No Psychiatric inpatient
vet erans

Sex with injection drug

user Hwang et al. 124 2006 8 % 267 4 % 4

, 006 RR : 2.05 (1.36 to 3.09)† <0.05 Prevalence HBV+ vs. HBV

Yes College students

Sex with prostitute Tabibian e t al. 121 2008 32.5 % 40 18 % 89 NR NS† Prevalence in HBV+ vs. HBV

No Psychiatric inpatient
veterans

Sex ual partner with hepatitis Hwang et al. 124 2006 4 % 268 2 % 4

, 010 RR : 2.28 (1.30 to 3.99)† p <0.05 Prevalence HBV+ vs. HBV

Yes College students

Sexual contact with partner with hepat itis Butterfield et al. 126 1990 0 % 12 0.1 % 1

, 454 0.36 (0.02 to 6.09)†¶ 0.48¶ Prevalence HBV+ vs. HBV

No Obstetric populationIncarceration Previous Incarceration Tabibian et al. 121 2008 85.0 % 40 67 % 89 NR <0.05† Prevalence in HBV+ vs. HBV

Yes Psychiatric inpatient
veterans

Incarcerated >24 hours Hwang et al. 124 2006 13 % 268 8 % 4

, 026 RR : 1.71 (1.22 to 2.41)† <0.05 Prevalence HBV+ vs. HBV

Yes College students154Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

PopulationOther Sex Practices Li fetime heterosexual partners >0 ≤50 Hwang et al. 124 2006 67 % 243 74 % 3

, 824 RR 0.89 (0.65 to 1.24)† NS Prevalence HBV+ vs. HBV

- vs.

no hetero

sexual partners No College students

Lifetime heterosexual partners ≥50 Hwang et al. 124 2006 4 % 243 1 % 3

, 824 RR 3.08 (1.60 to 5.93)† <0.05 Prevalence HBV+ vs. HBV

- vs.

no hetero

sexual partners Yes College students

Het erosexual partners last 4 months ≥5 Hwang et al. 124 2006 3 % 240 1 % 3

, 790 RR : 2.02 (1.00 to 4.10)†;

OR : 2.61 (0.91 to 7.47)‡ NS†,

<0.05‡ Prevalence HBV+ vs. HBV

- vs. <5 Yes College stu dents

Multiple sex partners last 6 months Butterfield et al. 125 2004 NR 80 NR 276 2.01 (1.06 to 3.78‡ <0.05 Prevalence HBV+ vs. HBV

Yes Psychiatric inpatient
veterans

Age at first intercours e ≤15 years Hwang et al. 124 2006 20 % 249 13 % 3

, 810 RR : 1.52 (1.01 to 2.27)† <0.05 Prevalence HBV+ vs. HBV

- vs. never had

sex Yes College students155Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Age at first intercourse ≥15 years Hwang et al. 124 2006 65 % 249 70 % 3

, 810 RR : 0.97 (0.69 to 1.36)† NS Prevalence HBV+ vs. HBV

- vs. never had

sex No College studentsNon-Injection Substance Intranasal drug use Tabibian et al. 121 2008 80 % 40 66 % 89 NR NS† Prevalence in HBV+ vs. HBV

No Psychiatric inpatient
veterans

Intranasal drug use Hwang et al. 124 2006 19 % 262 14 % 3

, 921 RR : 1.39 (1.03 to 1.86)† <0.05 Prevalence HBV+ vs. HBV

Yes College students

Sniffed/

sno rted drugs Butterfield et al. 125 2004 NR 80 NR 276 1.06 (0.51 to 2.21)‡ NS Prevalence HBV+ vs. HBV

No Psychiatric inpatient
veterans

Smoked crack cocaine Butterfield et al. 125 2004 NR 80 NR 276 1.18 (0.55 to 2.54)‡ NS Prevalence HBV+ vs. HBV

No Psychiatric inpatient
veterans

Alcohol use disorder Butterfield et al. 125 2004 NR 80 NR 276 0.93 (0.52 to 1.69)‡ NS Prevalence HBV+ vs. HBV

No Psychiatric inpatient
veteransTattoo Tattoo Tabibian et al. 121 2008 40 % 40 30 % 89 NR NS† Prevalence HBV+ vs. HBV

No Psychiatric inpatient
veterans

Tattoo Hwang et al. 1 24 2006 25 % 274 26 % 4

, 047 RR : 0.96 (0.73 to 1.25)† NS Prevalence HBV+ vs. HBV

No College students156Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Tattoo Butterfield et al. 126 1990 0 12 4.6 % 1

, 454 0.82 (0.05 to 14.06)†¶ 0.893¶ Prevalence HBV+ vs. HBV

No Obstetric population

Tattoo, number of, 1

- 2 Hwang et al. 124 2006 20 % 274 20 % 4

, 039 RR : 0.99 (0.74 to 1.32)† NS Prevalence HBV+ vs. HBV

- vs.

no tattoo No College students

Tatt oo, number of ≥3 Hwang et al. 124 2006 5 % 274 5 % 4

, 039 RR : 0.87 (0.50 to 1.50)† NS Prevalence HBV+ vs. HBV

- vs.

no tattoo No College students

Tattooed in professional setting Hwang e t al. 124 2006 21 % 274 22 % 4

, 035 RR : 0.93 (0.70 to 1.23)† NS Prevalence HBV+ vs. HBV

- vs.

no tattoo No College students

Tattooed in

non

professional setting Hwang et al. 124 2006 4 % 274 3 % 4

, 035 RR : 1.24 (0.69 to 2.23)† NS Prevalence HBV+ vs. HBV

- vs.

no tattoo No College students

Tattooed with

new or autoclaved needles only Hwang et al. 124 2006 18 % 267 21 % 3

, 920 RR : 0.87 (0.65 to 1.18)† NS Prevalence HBV+ vs. HBV

- vs.

no tattoo No College students

Tattooed with reused non

autoclaved needles Hwang et al. 124 2006 4 % 267 2 % 3

, 920 RR: 1.91 (1.11 to 3.30)† <0.05 Prevalence HBV+ vs. HBV

- vs.

no tattoo Yes College students157Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Tattooed with ink in single wells only Hwang et al. 124 2006 12 % 242 15 % 3

, 646 RR : 0.79 (0.55 to 1.15)† NS Prevalence HBV+ vs. HBV

- vs.

no tattoo No College students

Tattooed with ink in common wells Hwang et al. 124 2006 2 % 242 2 % 3

, 646 RR : 1.10 (0.50 to 2.41)† NS Prevalence HBV+ vs. HBV

- vs.

no tattoo No College studentsPiercing Piercing Tabibian et al. 121 2008 37.5 % 40 30 % 89 NR NS† Prevalence in HBV+ vs. HBV

No Psychiatric inpatient
veterans

Body piercing (other than ears) Hwang et al. 124 2006 16 % 268 21 % 4

, 008 RR : 0.74 (0.54 to 1.02)† NS Prevalence HBV+ vs. HBV

No College students

Number of body piercings 1

- 2 Hwang et al. 124 2006 14 % 266 17 % 3

, 975 RR : 0.77 (0

.55 to 1.08)† NS Prevalence HBV+ vs. HBV

- vs.

no piercing No College students

Number of body piercings ≥3 Hwang et al. 124 2006 2 % 266 3 % 3

, 975 RR : 0.55 (0.23 to 1.30)† NS Prevalence HBV+ vs. HBV

- vs.

no piercing No College students158Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

PopulationOther Professional manicure Hwang et al. 124 2006 56 % 272 54 % 4

, 033 RR : 1.08 (0.86 to 1.37)† NS Prevalence HBV+ vs. HBV

- vs.

no manicure No College students

Do not always wear gloves while embalming Turner et a l. 127 1989 NR 14 NR 94 RR : 9.8 (3.4 to 28.5)† NR Prevalence HBV+ vs. HBV

- vs. wears gloves Yes Embalmers in high

prev alence urban area

Do not always
wear gowns, aprons, shoe coverings, goggles, glasses, or face masks Turner et al. 127 1989 NR 14 NR 94 NR NR Prevalence HBV+ vs. HBV

- vs. does wear No Embalmers in high

prevalence urban area

Eat or drink while embalming Turner et al. 127 1989 NR 14 NR 94 RR : 1.8 (0.66 to 4.7)† NR Prevalence HBV+ vs. HBV

- vs. does not No Embalmers in high

prevalence urban area

Smoke while embalming Turner et al. 127 1989 NR 14 NR 94 RR : 1.6 (0.58 to 4.3)† NR Prevalence HBV+ vs. HBV

- vs. does not No Embalmers in high

prevalence urban area

* Odds ratios as reported in publication, u nless otherwise specified

** As reported in publication, unless otherwise specified

† Univariate, unadjusted ‡ Multivariate, adjusted for other factors ¶ Calculated by ECRI Institute NR

– Not reported159 

### Table 34

. HCV Identification of Behavioral Risk Factors DataCategory

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Potent ial Organ DonorsNon-injectionDrugs Alcohol

-

‘ Heavy ’ use Gasink et al. 102 2006 49.2 % 261 19.9 % 10,654 Not reported (NR) <0.001† Proportion in HCV+ vs. HCV

Yes Heart donors

Tobacco use, history of Gasink et al. 102 2006 69.0 % 261 35.4 % 10,654 NR <0.001† Proportion in HCV+ vs. HCV

Yes Heart donors

Potential Tissue DonorsSex Work Prostitution, history of Sanchez et al. 103 2006 NR 18 NR 56 NR NS Proportion in HCV+ vs. HCV

No Potential tissue donors, as reported by next of kinIncarceration Incarceration, history of Sanchez et al. 103 2006 NR 18 NR 56 NR NS Proportion in HCV+ vs. HCV

No Potential tissue donors, as reported by next of kin160Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

PopulationNon-injectionDrugs Illicit drug use Sanchez et al. 103 2006 NR 18 NR 56 4.65 (1.21 to 17.91) X 2 = 0.016 Proportion in HCV+ vs. HCV

Yes Potential tissue donors, as reported by next of kin

Alco hol use Sanchez et al. 103 2006 NR 18 NR 56 NR NS Proportion in HCV+ vs. HCV

No Potential tissue donors, as reported by next of kin

Cigarette smoking Sanchez et al. 103 2006 NR 18 NR 56 4.01 (1.11 to 14.65) X 2 = 0.024 Proportion in HCV+ vs. HCV

Ye s Potential tissue donors, as reported by next of kinTattoos andPiercing Tattoos, body piercing, or acupuncture Sanchez et al. 103 2006 NR 18 NR 56 NR NS Proportion in HCV+ vs. HCV

No Potential tissue donors, as reported by next of kinTravel Foreign travel Sanchez et al. 103 2006 NR 18 NR 56 NR NS Proportion in HCV+ vs. HCV

No Potential tissue donors, as reported by next of kin161Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Blood DonorsMSM Men: Number of lifetime male partners 1 Murphy et al. 105 2000 3 % 400 1 % 568 0.9 (0.2 to 4.4)‡ NS Proportion in HCV+ vs. HCV

Adjus ted for IDU with reference to 0 partners No Blood donors

Men: Number of lifetime male partners 2+ Murphy et al. 105 2000 6 % 400 1 % 568 1.1 (0.2 to 5.4)‡ NS Proportion in HCV+ vs. HCV

Adjus ted for IDU with reference to 0 partners No Blood donors

Men: Bisexual/ homosexual Murphy et al. 105 2000 8 % 758 2 % 1

, 039 1. 0 (0.3 to 3.0)‡ NS Proportion in HCV+ vs. HCV

Adjusted for IDU with reference to hetero

- sexual No Blood donors162Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

PopulationIDU Injection drug use in last 6 months Orton et al. 104 2004 2 9.2 % 65 0 % 225 61.46 (7.81 to 483.67) †¶ (Reported as undefined in original publication due to absence of factor in uninfected group) <0.001† Proportion in HCV+ vs. HCV

Yes Blood donors

Intravenous drug use Conry

Cantilena et al. 106 1996 42 % 248 2 % 131 12.5 (2.7 to 57.1)‡ 0.001 Proportion in HCV+ vs. HCV

Yes Blood donors initially positive on enzyme linked immunosorbent assay (EIA)

Injected drugs Murphy et al. 105 2000 51 % 758 1 % 1,039 49.6 (20.3 to 121.1)‡ Statisti

cally significant (SS) Proportion in HCV+ vs. HCV

- final multivariable logistic regression mod el Yes Blood donors

Injection drug use longer than 6 months ago only Orton et al. 104 2004 4.9 % 46 0.5 %% 225 10.9 (0.6 to 647)† 0.07 Proportion in HCV+ vs. HCV

No Blood donors163Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Injection steroid use longer than 6 mo nths ago only Orton et al. 104 2004 3.5 % 65 0.5 % 225 7.6 (0.4 to 448)† 0.12 HCV

- No Blood donors

Lived with injection drug

user Murphy et al. 105 2000 38 % 758 1 % 1,039 5.1 (2.9 to 8.8)‡ SS Proportion in HCV+ vs. HCV

Adjusted for IDU Yes Blood donors

Reside with an injection drug user in last 6 months Orton et al. 104 2004 7.7 % 65 0 % 225 Undefined (because zero controls reported this factor) <0.001† Proportion in HCV+ vs. HCV

Yes Blood donorsSex Work Received money for sex Murphy et al. 105 2000 7 % 758 1 % 1

, 039 3.0 (0.9 to 9.7)‡ SS Proportion in HCV+ vs. HCV

Adjusted for IDU Yes Blood donorsHigh-riskSexPartners Sex with i njection drug user in last 6 months Orton et al. 104 2004 18.5 % 65 1.8 % 225 12.5 (3.6 to 54)† <0.001 Proportion in HCV+ vs. HCV

Yes Blood donors164Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Sex wit h injection drug user in last 6 months Murphy et al. 105 2000 41 % 758 3 % 1,039 6.3 (3.3 to 12.0)‡ SS Proportion in HCV+ vs. HCV

A

djusted for IDU Yes Blood donors

Gave money for sex Murphy et al. 105 2000 15 % 758 6 % 1,039 1.5 (0.9 to 2.5)‡ SS Proportion in HCV+ vs

. HCV

Adjusted for IDU Yes Blood donors

Sex with hepatitis case Murphy et al. 105 2000 7 % 758 3 % 1 ,039 2.2 (1.1 to 4.5)‡ SS Proportion in HCV+ vs. HCV

Adjusted for IDU Yes Blood donors

Sex partner had hepatitis in last 6 months Orton et al. 104 2004 7.7 % 65 1.8 % 225 4.6 (1.0 to 24)† 0.03 Proportion in HCV+ vs. HCV

Yes Blood donors

Sex with transfusion recipient Murphy et al. 105 2000 5 % 758 3 % 1,039 2.5 (1.3 t o 5.0)‡ SS Proportion in HCV+ vs. HCV

Adjusted for IDU Yes Blood donors165Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

PopulationIncarceration Been in jail within 6 months of donation Orton et al. 104 2004 30.9 % 65 12.0 % 225 3.3 (1.6 to 6.6)† <0.001 Proportion in HCV+ vs. H CV

Yes Blood donors

Been in jail
at least 6 months before donation Orton et al. 104 2004 30.9 % 65 12.0 % 225 3.3 (1.6 to 6.6)† <0.001 Proportion in HCV+ vs. HCV

Yes Blood donors

In jail more than 3 days Murphy et

a l. 105 2000 22 % 758 2 % 1,039 5.0 (2.6 to 9.8)‡ SS Proportion in HCV+ vs. HCV

Adjusted for IDU Yes Bl ood donors

Imprisonment (history of) Conry

Cantilena et al. 106 1996 25 % 248 2 % 131 NR <0.001†;

NS‡ Proportion in HCV+ vs. HCV

Yes; Uni

variate only Blood donors initially positive on EIAOther Sex Practices Sexua l promiscuity (history of STD, sex with prostitute, >5 partners/ year) Conry

Cantilena et al. 106 1996 53 % 248 24 % 131 3.0 (1.5 to 5.9)‡ 0.002 Proportion in HCV+ vs. HCV

Yes Blood donors initially positive on EIA166Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

M

en: Number of lifetime female partners 1 Murphy et al. 105 2000 8 % 400 24 %% 568 0.8 (0.3 to 2.6)‡ NS Proportion in HCV+ vs. HCV

Adjusted for IDU with reference to 0 No Blood donors

Men: Number of lifetime female partners 2

- 10 Murphy et al. 105 2000 38 % 400 44 % 568 1.5 (0.6 to 4.0)‡ NS Proportion in HCV+ vs. HCV

Adjus ted for IDU with reference to 0 partners No Blood donors

Men: Number of lifetime female partners 11+ Murphy et al. 105 2000 51 % 400 24 % 568 1.7 (0.6 to 4.8)‡ NS Proportion in HCV+ vs. HCV

Adjusted for IDU with reference to 0 partners No Blood donors

Men: Not sexually active Murphy et al. 105 2000 3 % 400 6 % 568 0.7 (0.2 to 2.0)‡ NS Proportion in HCV+ vs. HCV

- with reference to hetero

- sexual No Blood donors167Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Women: Number of lifetime male partners 1 Murphy et al. 105 2000 13 % 351 32 % 463 1.2 (0.5 to 3.3)‡ NS Proportion in HCV+ vs. HCV

Adjusted for IDU with reference to 0 partners No Blood donors

Women: Number of lifetime male partners 2

- 10 Murphy et al. 105 2000 46 % 351 50 % 463 1.9 (0.7 to 5.0)‡ NS Proportion in HCV+ vs. HCV

Adjus ted for IDU with reference to 0 partners No Bloo d donors

Women: Number of lifetime male partners 11

- 49 Murphy et al. 105 2000 28 % 351 11 % 463 3.2 ( 1.1 to 9.1)‡ SS Proportion in HCV+ vs. HCV

Adjus ted for IDU with reference to 0 partners Yes Blood donors

Women: Number of lifetime male partners 50+ Murphy et al. 105 2000 8 % 351 1 % 463 8.8 (2.0 to 39.4)‡ SS Proportion in HCV+ vs. HCV

- with refer ence to 0 partners Yes Blood donors168Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Women: Not sexually active Murphy et al. 105 2000 3 % 351 4 % 463 0.9 (0.3 to 2.4)‡ NS Proportion with HCV+ vs. HCV

- adjusted for IDU and compared to hetero

- sexual No Bloo d donors

Two or more sexual partners in last 6 months Orton et al. 104 2004 21.5 % 65 4.9 % 225 5.3 (2.3 to 13)† <0.001 Proportion in HCV+ vs. HCV

Yes Blood donors

Women: Number of lifetime female partners >1 Murphy et al. 105 2000 6 % 351 2 % 463 1.3 (0.4 to 4.4)‡ NS‡ (Un

adjusted was SS) Proportion with HCV+ vs. HCV

- adj usted for IDU and compared to 0 lifetime female partners No (Once adjusted for IDU) Blood donors

Women: Number of lifetime female partners >2 Murphy et al. 105 2000 9 % 351 2 % 463 3.7 (1.2 to 11.1)‡ SS Proportion with HCV+ vs. HCV

- adj usted for IDU and compared to 0 lifetime female partners Yes Blood donors169Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Women: Sexual orientation bisexual/ homo sexual Murphy et al. 105 2000 16 % 351 4 % 463 2.3 (1.0 to 5.2)‡ NS Proportion with HCV+ vs. HCV

- adjus ted for IDU and compared to heterosexual No (when adjusted for IDU) Blood donorsNon-injection Drugs Snort drugs in last 6 months Orton et al. 104 2004 20.0 % 65 0 % 225 Undefined (because

zero controls reported this fact or) <0.001† Proportion in HCV+ vs. HCV

Yes Blood donors

Intranasal drugs longer than 6 months
ago Orton et al. 104 2004 17.4 % 52 6.6 % 225 3.0 (1.0 to 8.2)† 0.04† Proportion in HCV+ vs. HCV

Yes Blood donors

Intranasal cocaine use Conry

Cantilena et al. 106 1996 68 % 248 11 % 131 8.0 (3.9 to 16.5)‡ <0.001 Proportion in HCV+ vs. HCV

Yes Blood donors initially positive on EIA

Inhaled drugs Murphy et al. 105 2000 63 % 758 21 % 1,039 2. 2 (1.6 to 3.1)‡ SS Proportion in HCV+ vs. HCV

Adjusted for IDU Yes Blood donors

Friends use
str

eet drugs in last 6 months Orton et al. 104 2004 38.5 % 65 6.7 % 225 8.8 (4.2 to 18)† <0.001 Proportion in HCV+ vs. HCV

Yes Blood donors170Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

PopulationTattoo Tattoo in last 6 months Orton et al. 104 2004 4.6 % 65 0.5 % 225 11 (0.8 to 566)† 0.04 Proportion in HCV+ vs. HCV

Yes Blood donors

Tattoo Conry

Cantilena et al. 106 1996 21 % 248 4 % 131 NR p <0.001†;

NS‡ Proportion in HCV+ vs. HCV

Yes; uni

variate only Bl ood donors initially positive on EIA

Tattoo Murphy et al. 105 2000 27 % 758 5 % 1,039 3.9 (2.5 to 6.1 )‡ SS Proportion in HCV+ vs. HCV

- adjusted for IDU Yes Blood donorsPiercing Had body piercing in last 6 months Orton et al. 104 2004 4.6 % 65 2.2 % 225 2.1 (0.3 to 11)† 0.38 Proportion in HCV+ vs. HCV

No Blood donors

Ear piercing
among men Conry

Cantilena et al. 106 1996 30 % 139 0 % 83 NR <0.05‡ Proportion in HCV+ vs. HCV

Yes Blood donors initially positive on EIA (male only; factor
not significant
among women)

Pierced ears/ bo

dy parts Murphy et al. 105 2000 56 % 758 40 % 1,039 2.0 (1.1 to 3.7)‡ SS Proportion in HCV+ vs. HCV

- fi nal multivariable logistic regression model Yes Blood donors171Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

PopulationTravel Travel outside U.S. in last 6 months Orton et al. 104 2004 1.5 % 65 6.7 % 225 0.2 (0.01 to 1.5)† 0.13 Proportion in HCV+ vs. HCV

No Blood donors

Lived outside the U.S. Murphy et al. 105 2000 17 % 758 15 % 1,039 1.0 (0.7 to 1.5)‡ NS Proportion in HCV+ vs

. HCV

- adjusted for IDU No Blood donorsOther Religious scarification Murphy et al. 105 2000 8 % 758 2 % 1,039 2.8 (1.2 to 7.0)‡ SS Proportion in HCV+ vs. HCV

- final multivariable logistic regression model Yes Blood donors

Shared toothbrush/

razor Murphy et al. 105 2000 16 % 758 7 % 1,039 1.6 (1.0 to 2.5)‡ SS Proportion in HCV+ vs. HCV

- adjusted for IDU Yes Blood donors172Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Electrolysis hair removal Murphy et al. 105 2000 3 % 758 3 % 1,039 1.2 (0.6 to 2.6)‡ NS Proportion in HCV+ vs. HCV

- adjusted for IDU No Blood donors

General PopulationMSM Men who have sex with

men Hand and Vasquez 112 2005 5 % 320 6 % 307 NR 0.658† Proportion HCV+ vs. HCV

No Adults tested for HC V in health system because of clinical suspicionIDU Drug use

– Injection, lifetime Armstrong et al. 30 2006 45 % 114 0.7 % 5

, 254 148.9 (44.9 to 49.4)‡ SS No use (or marijuana only) HCV+ Yes General population aged 20 to 59 years

Injected drugs Fischer et al. 114 2000 27 % 11 2 % 1

, 369 26.47 (8.39 to 83.55) ‡ ¶ <0.001† Proportion in HCV+ vs. HCV

Yes Adults en rolled in HMO

Injection drug

use Hand and Vasquez 112 2005 53 % 320 5 % 307 20.1 (10.3 to 39.4)‡ <0.0001 Propor tion in HCV+ vs. HCV

Yes Adults tested for HCV in health system because of clinical suspicion

Intravenous drug use Kaur et al. 116 1996 66.6 % 6

, 121 5.2 % 528 23.34 (15.21 to 35.81) ‡ SS Proportion in HCV+ vs. HCV

Yes Volunteers from general population173Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Being at a social gathering with injecting drugs Nguyen et al. 113 2005 45.0 % 225 7.4 % 204 NR <0.001 Proportion HCV+ vs. HCV

- Yes Adults at general internal medicine clinic (controls) and h

epatology clinic (cases)

Seeing use of injecting drugs Nguyen et al. 113 2005 55.0 % 225 10.8 % 204 NR <0.001 Proportion HCV+ vs. HCV

- Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)Sex Work Female prostitutes Hand and Vasquez 112 2005 2 % 320 0 % 307 NR 0.028† Proportion HCV+ vs. HCV

- Yes Adults tested for HCV in health system bec ause of clinical suspicion

Exchanging sex for money Nguyen et al. 113 2005 17.1 % 225 2.0 % 204 NR <0.001† Proportion HCV+ vs. HCV

- Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)High-risk Sex Partners Sex with injecting drug

users Nguyen et al. 113 2005 37.8 % 225 3.4 % 204 5.39 (2.01 to 14.42)† <0.001 Proportion HCV+ vs. HCV

- Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)

Sex with intravenous drug users Kaur et al. 116 1996 45.7 % 408 4.7 % 5

, 373 7.29 (4.74 to 11.21)‡ NR Proportion in HCV+ vs. HCV

- Yes Volunteers from general population174Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Sex with prostitute Nguyen et al. 113 2005 20.7 % 225 1.5 % 204 9.76 (2.50 to 38.13)† <0.01† Proportion HCV+ vs. HCV

- Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)

Sex with prostitutes Hand and Vasquez 112 2005 3 % 320 0.7 % 307 NR†;

3.4 (0.6 to 18.9)‡ 0.014† ;
0.169‡ Proportion in HCV+ vs. HCV

- Yes; uni

- variate only Adults tested for HCV in health system because of clinical suspicionIncarceration Arrest ed, having been Nguyen et al. 113 2005 33.3 % 225 6.9 % 204 NR <0.001† Prevalence in HCV+ vs. HCV

- Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)Additional SexPractices Unprotected

sex Fischer et al. 114 2000 45 % 11 12 % 1

, 369 NR <0.001† Proportion in HCV+ vs. HCV

- Yes Adults enrolled in HMO

Number of sex partners

– 0 Nguyen et al. 113 2005 11.7 % 225 8.8 % 204 NR <0.01† Proportion with factor HCV+ vs. HCV

- Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases) Number of sex partners

– 1 Nguyen et al. 113 2005 7.2 % 225 17.2 % 204

Number of sex partners

– 2

- 9 Nguyen et al. 113 2005 32.4 % 225 46.6 % 204175Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Number of sex partners

– 10

- 49 Nguyen et al. 113 2005 37.8 % 225 25.0 % 204

Number of sex partners

– At least 50 Nguyen et al. 113 20 05 10.8 % 225 2.5 % 204

Number of sex partners 2

- 19 Armstrong et al. 30 2006 27 % 179 63 % 5

, 178 1.4 (0.3 to 6.0)‡ NR 0

- 1 partners prevalence of HCV+ No General population aged 20 to 59 years

Number of sex partners ≥20 Armstrong et al. 30 2006 39 % 179 14 % 5

, 178 5.2 (1. 5 to 18.2)‡ NR 0

- 1 partners prevalence of HCV+ Yes General population aged 20 to 59 years

Frequent sex partners Fischer et al. 114 2000 36 % 11 7 % 1

, 369 NR <0.001† Proportion in HCV+ vs. HCV

Yes Adults enrolled in HMO

Sex with multiple partners Kaur et al. 116 1996 13.5 % 542 6.5 % 5

, 923 2.24 (1.87 to 2.69)† NR Proportion in HCV+ vs. HCV

Yes Volunteers from general population

Sex with person of

same sex (not restricted to MSM) Nguyen et al. 113 2005 8.6 % 225 8.8 % 204 NR >0.99† Proportion HCV+ vs. HCV

No Adults at general internal medicine clinic (controls) and hepatology clinic (cases)176Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Age at first sexual intercourse 16

- 17 years (participants aged 20 to 59 years) Armstrong et al. 30 2006 27 % 126 30 % 4

, 928 NR <0.05† HCV+ with first sexual intercourse ≥18 years Yes General population
ag

ed 20 to 59 years

Age at first sexual intercourse 12

- 15 ye ars (participants aged 20 to 59 years) Armstrong et al. 30 2006 47 % 126 26 % 4

, 928 NR <0.005† HCV+ with first sexual intercourse ≥18 years Yes General population aged 20 to 59 years

Age at first sexual intercourse ≤11 ye ars (participants aged 20 to 59 years) Armstrong et al. 30 2006 11 % 126 2.5 % 4

, 928 NR <0.05† HCV+ with first sexual intercourse ≥18 years Yes General population aged 20 to 59 yearsNon-injectionDrugs Drug use

– noninjec tion (except marijuana) Armstrong et al. 30 2006 29 % 114 2.2 % 5

, 254 3.7 (1.7 to 7.9)‡ NR No drug use or only marijuana, HCV+ Yes General population aged 20 to 59 years177Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Snorting or inhaling non

prescription drugs Nguyen et al. 113 2005 55.4 % 225 18.1 % 204 NR <0.00† Proportion HCV+ vs. HCV

Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)

Inhaled cocaine Fischer et al. 114 2000 18 % 11 2 % 1

, 369 NR <0.05† Proportion in HCV+ vs. HCV

Yes Adults enrolled in HMO

Intranasal cocaine Hand and Vasquez 112 2005 39 % 320 14 % 307 NR†,

1.4 (0.8 to 2.4)‡ <0.0001†;

0.283‡ Proportion in HCV+ vs. HCV

Yes; uni

variate only Adults tested for HCV in health system because of clinical suspicion

Bein g at a social gathering with cocaine Nguyen et al. 113 2005 66.2 % 225 28.4 % 204 NR <0.001† Proportion HCV+ vs. HCV

Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)

Alcohol use

– none/missing weekly Nguyen et al. 113 2005 15.3 % 225 11.8 % 204 NR 0.12† Prevalence of factor in HCV+ vs. HCV

No Adults at general internal medicine clinic (controls) and hepatology clinic (cases) Alcohol use

– <1 drink weekly Nguyen et al. 113 2005 59.0 % 225 52.5 % 204

Alcohol use

– 1

- 5 drinks weekly Nguyen et al. 113 2005 15.3 % 225 27.9 % 204178Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

Population

Alcohol use

– More than 5 drinks weekly Nguyen et al. 113 2005 10.4 % 225 7.8 % 204

Alcoholism Fischer et al. 114 2000 18 % 11 9 % 1

, 369 NR NS † Proportion in HCV+ vs. HCV

No Adults enrolled in HMO

Moderate to heavy alcohol use (at least
2 u nits per day) Hand and Vasquez 112 2005 58 % 320 49 % 307 NR 0.034† Proportion in HCV+ vs. HCV

Yes Adults teste d for HCV in health system because of clinical suspicionTattoo Tattoo Nguyen et al. 113 2005 28.4 % 225 16.2 % 204 NR 0.003† Proportion HCV+ vs. HCV

Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)

Tattoo Fischer et al. 114 2000 36 % 11 6 % 1

, 369 NR <0.001† Proportion in HCV+ vs. HCV

Yes Adults enrolled in HMO

Tattoo Hand and Vasquez 112 2005 57 % 320 22 % 307 NR†;

2.9 (1.9 to 4.6)‡ <0.0001†;

<0.001‡ Proportion in HCV+ vs. HCV

Yes Adults tested for HCV in health system because of clinical suspicion179Category

Factor Citation YearPercentage ofInfectedwith FactorTotal NumberInfectedPercentage ofUninfected withFactorTotal NumberUninfected

Effect Size* p

- V

alue**ComparisonMadeAssociated inStudy?

PopulationPiercing Pierced ears Nguyen et al. 113 2005 59.0 % 225 73.5 % 204 NR 0.002† Proportion HCV+ vs. HCV

Yes Adults at g eneral internal medicine clinic (controls) and hepatology clinic (cases)

Pierced ears Hand and Vasquez 112 20 05 38 % 320 38 % 307 NR 0.998† Proportion HCV+ vs. HCV

No Adults tested for HCV in health system because of clinical suspicion

Body piercing Fischer et al. 114 2000 45 % 11 33 % 1

, 369 NR NS† Proportion HCV+ vs. HCV

No Adults enrolled in HMO

Body piercing Hand and Vasquez 112 2005 2 % 320 3 % 307 NR 0.737† Proportion in HCV+ vs. HCV

No Adults tested for HCV in health system because of clinic al suspicionOther No lifestyle risks Fischer et al. 114 2000 0 % 11 32 % 1

, 369 NR <0.05† Proportion in HCV+ vs. HCV

Yes Adults enrolled in HMO

* Odds ratios as reported in publication, unless otherwise specified

** As reported in publication, unless otherwise specified

† Univariat e, unadjusted ‡ Multivariate, adjusted for other factors ¶ Calculated by ECRI Institute180 

### Table 35

. HIV Identification of Behavioral Risk Factors Data

Category Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfectedwith FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison Made Associated in Study? Population

Potential Tissue DonorsSexWork Prostitution, history of Sanchez et al. 103 2006 Not reported (NR) 10 NR 56 NR Not significant (NS) Proportion in HIV+ vs. HIV No Potential tissue donors, as reported by next of kinIncarceration Incarceration

, history of Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV No Potential tissue donors, as reported by n ext of kinNon-IDU Illicit drug use Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Smoking history Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV No Potential tissue donors, as reported by next of kin

Alcohol use Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV No Potential tissue donors, as reported by next of kinTattoosandPiercing Tattoos, body piercing, or acupuncture Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV No Potential tissue donors, as reported by next of kinTravel Foreign travel Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV No Potential tissue donors, as reported by next of kin181 Category Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfectedwith FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison Made Associated in Study? Population

General PopulationMSM Male

- to

- male

sex McQuillan et al. 101 2006 52 % 21 4 % 2

, 418 26.0 (10.8 to 62.7)†¶ <0.001 Proportion in HIV+ vs. HIV

Yes General population

MSM, ever, men only Nguyen et al. 110 2008 53.8 % 13 8.3 % 577 15.11 (4.11 to 55.91)† SS Men who have had sex with women HIV+ vs. HIV

Yes General population of adults in New York City who have ever had sexIDU Injection drug

u

se Mehta et al. 109 2008 9 % 229 NR 16,467 1.17 (0.75 to 1.85)† NR Percent HIV+ vs. no injection drug use No Hospital inpatients and outpatients

Ever injected drugs McQuillan et al. 101 2006 13 % 30 2 % 4

, 938 7. 3 (2.5 to 21.6)†¶ 0.001 Proportion in HIV+ vs. HIV

Yes Gen eral population

Ever used a needle for drugs Nguyen et al. 110 2008 14.3 % 21 1.2 % 1

, 482 21.01 (3.99 to 110.64)† SS Never used needle Yes General population of adults in New York CityHigh-risk SexPartners Sex with HIV+
person Mehta et al. 109 2008 10 % 229 NR 16,467 3.25 (2.11 to 5.01)† NR No sex with HIV+ person in HIV+ Yes Hospital inpatients and outpat ients182 Category Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfectedwith FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison Made Associated in Study? PopulationOther Sex Practices Number of sex partners 1 Mehta et al. 109 2008 22 % 229 NR 16,467 0.79 (0.41 to 1.53)† NR 0 partners, HIV+ No Hospital inpatients and outpatients

N umber of sex partners 2

- 4 Mehta et al. 109 2008 34 % 229 NR 16,467 1.03 (0.55 to 1.95)† NR 0 partners, HIV+ No Hospital inpatients and outpatients

Number of sex partners 5

- 9 Mehta et al. 109 2008 12 % 229 NR 16,467 1.09 (0.54 to 2.20)† NR 0 partners, HIV+ No Hospital inpatients and outpatients

Number of sex partners ≥10 Mehta et al. 109 2008 10 % 229 NR 16,467 1.14 (0.55 to 2.36)† NR 0 partners, HIV+ No Hospital inpatients and outpatients

Number of sex partners

– D ata Missing Mehta et al. 109 2008 17 % 229 NR 16,467 0.92 (0.47 to 1.80)† NR 0 partners, HIV+ No Hospital inpatients and outpatients

Lifetime sex partners 0

- 1 McQuillan et al

. 101 2006 13 % 31 26 % 5

, 360 0.43 (0.15 to 1.2)†¶ 0.11 Proportion HIV+ vs. HIV

No General popul ation

Lifetime sex partners 2

- 49 McQuillan et al. 101 2006 55 % 31 71 % 5

, 360 0.50 (0.25 to 1.0 2)†¶ 0.55 Proportion HIV+ vs. HIV No General population

Lifetime sex partners 50+ McQuillan et al. 101 2006 32 % 31 4 % 5

, 360 11.3 (5.5 to 24.3)†¶ <0.001 Proportion HIV+ vs. HIV Yes General population

Multiple sex partners in past year Nguyen et al. 110 2008 30.0% 20 22.1% 1,34 6 1.41 (0.59 to 3.37)† NS Single sex partner past year No General population of adults in New York City who have ever had sex183 Category Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfectedwith FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison Made Associated in Study? Population

Sex partner same gender or both Mehta et al. 109 2008 16 % 229 NR 16,467 2.17 (1.49 to 3.15)† NR Prevalence of HIV+ with this factor vs. opposite gender only Yes Hospital inpatients and outpatients

Age at first intercourse <18 years McQuillan et al. 101 2006 77 % 31 58 % 5

, 342 2.4 (1.0 to 5.6)†¶ 0.038 Proportion in HIV+ vs. HIV

Yes General population

Condom use, past month Nguyen et al. 110 2008 33.3 3 59.2 238 0.32 (0.03 to 3.83)† NS Sometimes

or never used condoms No General population of adults in New York City who reported multiple sex partners during the past year and s exual activity during the past month

Condom use with current partner

– Sometimes Mehta et al. 109 2008 52 % 229 NR 16,467 1.14 (0.76 to 1.70)† NR Prevalence of condom use alw ays, HIV+ No Hospital inpatients and outpatients

Condom use with current partner

– Never Mehta et al. 109 2008 20 % 229 NR 16,467 0.75 (0.47 to 1.19)† NR Prevalence of condom use always, HIV+ No Hospital inpatients and outpatients

Condom use with current partner

– Missing Data Mehta et al. 109 2008 14 % 229 NR 16,467 1.54 (0.94 to 2.54)† NR Preva lence of condom use always, HIV+ No Hospital inpatients and outpatients184 Category Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfectedwith FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison Made Associated in Study? Population

A nal

- insertive

sex (men only)
<6 weeks ago Mehta et al. 109 2008 7% of

men 145 (men only) NR 9

, 589 1. 83 (0.94 to 3.57)† NR Did not have, HIV+ No Hospital inpatients and outpatients

A nal

- insertive

sex (men only) ≥6 weeks ago Mehta et al. 109 2008 14% of

men 145 (men only) NR 9

, 589 3.32 (2.01 to 5.48)† NR Did not have, HIV+ Yes Hospital inpatients and outpa tients

Anal

- insertive

sex (m

en only)

– Data m issing Mehta et al. 109 2008 28% of

men 145 (men only) NR 9

, 589 1.43 (0.97 to 2.11)† NR Did not have, HIV+ No Hospital inpatient s and outpatients

Anal

- receptive sex <6 weeks
ago Mehta et al. 109 2008 2 % 229 NR 16,467 2.29 (0.93 to 5.65)† NR Did not have, HIV+ No Hospital inpatients and outpatients

Anal

- receptive

sex ≥6 weeks
ago Mehta et al. 109 2008 6 % 229 NR 16,467 6.56 (3.73 to 11.5)† NR Did not have, HIV+ Yes Hospital inpatients and outpatients

Anal receptive

sex

– Data M issing Mehta et al. 109 2008 21 % 229 NR 16,467 1.70 (1.23 to 2.34)† NR Did not have, HIV+ Yes Hospital inpatients and outpatients

Vaginal sex <6 weeks ago Mehta et

a l. 109 2008 43 % 229 NR 16,467 0.33 (0.22 to 0.50)† NR Did not have, HIV+ No (protective) Hospital inpatients and outpatients185 Category Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfectedwith FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison Made Associated in Study? Population

Vaginal sex ≥6 weeks ago Mehta et al. 109 2008 32 % 229 NR 16,467 0.49 (0.32 to 0.74)† NR Did not have, HIV+ No (protective) Hospital inpatients and outpatients

Vaginal sex

– Data Missing Mehta et al. 109 2008 21 % 229 NR 16,467 0.56 (0.33 to 0.95)† NR Did not have, HIV+ No (protective) Hospital inpatients and outpatientsNon-injection Drugs Ever used cocaine/street drugs McQuillan et al. 101 2006 47 % 30 21 % 4

, 938 3.3 (1.6 to 6.9)†¶ <0.001 Proportion in HIV+ vs. HIV

Yes General population

Crack cocaine

use Alpert et al. 115 1996 NR 35 NR 840 NR‡ SS Proportion in HCV+ vs. HCV

Yes Adults at emergency department room

Alcohol and/or drug problem (as identified in health care database) Fischer et al. 114 2000 36 % 11 12 % 1

, 369 12.5 (2.3 to 69.0)† 0.004 Proportion in HCV+ vs. HCV

Yes Adults enrolled in HMO

* Odds ratios as reported in publication, unless otherwise specified

** As reported in publication, unless otherwise specified

† Univariate, unadjusted ‡ Multivariate, adjusted for other factors ¶ Ca lculated by ECRI Institute186 

### Table 36

. GRADE T able for Question 3 (Behavioral Risk F actors)

Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

Factors Identified in Original GuidelineMen who have Sex with Men (MSM) HBV 2 OBS 29,124 HBV was significantly associated with MSM in univariate analyses in two studies, one on the general population and one on college students. The college students st udy also performed an multivariate analysis and the association remained significant. 124 Low 0 0 0 0 0 1 0 0 Moderate

HCV 2 OBS 105,112 One blood donor study found a significa nt association between HCV and MSM upon univariate but not multivariate analysis. 105 A general popul ation study found no association at all in univariate analysis. 112 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV 2 OBS 101,110 HIV infection was significantly associated with MSM in the general population in two univariate analyses. Low 0 0 0 0 0 1 0 0 Moderate187 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfoundersInjection Drug Users (IDU) HBV 5 OBS 116,121,124

- 126 HBV was significantly associated with IDU in four studies, one of the general population 116 and three of special populations. 121,124,125 Three of these studies had large effect sizes, and the fourth came close. 124 The fifth study, another special popu lation study, did not find any association. This may be a statistical anomaly due to the very low prevalence of HBV and IDU in this obstetric population. 126 The general population study and one of the specia l population studies 125 performed multivariate analyses, the rest were univariate.
One of the special population studies also considered steroid injection but did not find a signi ficant relationship. 124 Low 0 0 0 0 0 0 0 0 Low

HCV 7 OBS 30,104

- 106,112,114,116 Three blood donor studies 104

- 106 and four general population studies 30,112,114,116 detected associations between IDU and HCV. All of these studies found large effect sizes. Two of the blood donor studies and three of general population studies 30,112,116 performed multiva riate analyses and determined IDU is an independent risk factor (the other studies performed univariate assessments only).

One of the blood donor studies also considered past steroid injection use and did not find a significant association with HCV. 104 Low 0 0 0 0 0 1 0 0 Moderate188 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

HIV 3 OBS 101,109,110 All three studies assessed IDU in the general population in univariate analyses. Two found a significant association with large effect sizes, 101,110 and the third did not find any association. 109 Low 0 0 0 0 0 0 0 0 LowSex Work HBV 3 OBS 103,121,125 None of the studies found an association between sex work (including sex bartering or sex for drugs) and HBV; however, one was a very low

- quality ti ssue donor study based upon next

- of

- kin interviews, 103 and the other two studied special populations. 121,125 Low 0 0

- 1 0 0 0 0 0 Very Low

HCV 4 OBS 103,105,112,113 The very low

- quality tissue donor study based upon next

- of

- kin data did not detect any association between HCV and sex work. The remaining three studies did. One multivariate

analysis blood donor study 105 and two univariate

analysis general populations studies 112,113 did detect significant associations. Low 0 0 0 0 0 0 0 0 Low

HIV 1 OBS 103 The very lo w

- quality tissue donor study based upon next

- of

- kin data did not detect any association between HCV and sex work. Low

- 1

- 1 0

- 1 0 0 0 0 Very Low189 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfoundersHigh-risk Sex Partners: IDUs HBV 4 OBS 116,117,121,124 In a multivariate analysis in the general
pop ulation, having a sex partner IDU was significantly associated with HBV. 116 In another general population study

, recent sex or household contact with an IDU was associated with rece nt HBV infection. 117 In univariate analysis it was significantly associated with HBV in one special population study 124 but in not another. 121 Low 0

- 1 0 0 0 0 0 0 Very Low

HCV 4 OBS 104,105,113,116 A univariate investigation of blood donors, 105

a multivariate investigation of blood donors, 104

a univariate investigation of people in the general population, 113 and a multivariate i nvestigation in a general population 116 all found a significant relationship between HCV and having sex with an IDU. In all four studies the effect size was large. Low 0 0 0 0 0 1 0 0 Moderate

HIV No Studies Identified - - - - - - - - - - NAHigh-risk Sex Partners:SexWorker HBV 1 OBS 121 Sex with a sex worker was not associated with HBV in a special population study. 121 Low 0

- 1

- 1

- 1 0 0 0 0 Very Low

HCV 3 OBS 105,112,11 3 Sex with a sex worker was associated with HCV in a multivariate analysis of blood donors 105 and i n two univariate analyses of general populations. 112,113 However, one of those general population studies also performed a multivariate analyses and did no t detect a relationship. 112 Low 0

- 1 0 0 0 0 0 0 Very Low190 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

HIV No Studies Identified - - - - - - - - - - NAHigh-risk Sex Partners: People with KnownInfection HBV 2 OBS 124,126 Of the two univariate analyses of special population studies, one study found a significant relationship between having a sexual partner with hepatitis and having HBV, 124 while the other did not

. 126 Low

- 1

- 1

- 1

- 1 0 0 0 0 Very Low

HCV 2 OBS 104,105 Two studies of blood donors, one with a multivariate analysis 105 and one with a univariate analysis, 104 found significant associations between having a sex partner with hepatitis and having HCV. Low 0 0 0 0 0 0 0 0 Low

HIV 1 OBS 109 On general population study performed a univariate analysis and found that the relationship between having a sex partner with HIV and having HIV was significant and large. 109 Low

- 1 0 0 0 1 0 0 LowIncarceration HBV 4 OBS 103,117,121,124 The tissue donor study based upon next

- of

- kin interview did not associate HBV with a history of incarceration. 103 Upon univariate analyses,

one general population study 117 and two special population studies did find a significant association. 121,124 However, the general population study also performed a multivariate analysis and did not find an association. 117 Low 0

- 1 0 0 0 0 0 0 Very Low191 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

HCV 4 OBS 103

- 106,113 The tissue donor study based upon next

- of

- kin interview did not associate HCV with a history of incarceration. 103 Three blood donor studies 104

- 106 found an association between HCV and history of incarceration, and of the two that performed multivariate analysis, 105,106 one found it was an independent risk factor. 105 Having ever been arrested was associated with HCV in the general population study. 113 Low 0 0 0 0 0 0 0 0 Low

HIV 1 OBS 103 T he tissue donor study based upon next

- of

- kin interview did not associate HIV with a history of incarceration. 103 Low

- 1

- 1 0

- 1 0 0 0 0 Very Low

Additional Potential Risk Factors Identified in the 2009 Literature SearchSex withMultiplePartners HBV 5 OBS

29,116,117,124,125 Various definitions of having multiple partners

w

ere associated with HBV in three general population s tudies 29,116,117 and two special population studies. 124,125 In all but one of these studies 124 multivariate analyses were performed. Low 0 0 0 0 0 0 1 0 Moderate192 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

HCV 6 OBS

30,1 04,105,113,114,116 As was the case for HBV, the studies testing the association of this factor with HCV defined “multiple” using different thresholds. A blood donor study found that having multiple partners was a risk factor for HCV among women but not m en in a multivariate analysis. 105 The remaining 5 studies are all general population studies that pe rformed univariate analyses and found associations between having multiple sex partners and having HCV. 30,104,113,114,116 Low 0 0 0 0 0 0 1 0 Moderate

HIV 3 OBS 101,109,1 10 All 3 studies performed univariate analyses on general populations using different definitions for “multiple” partners. The study with the highest threshold for defining “multiple” (>50) found an association with HIV, 101 while the other two studies (one investigating having at least 10 lifetime 109 partners and other investigating having “multiple” partners in the past year) did not. 1 10 Low 0

- 1 0 0 0 0 1 0 LowSame-Sex Partners, NotRestricted to MSM HBV No studies

- - - - - - - - - - NA

HCV 2 OBS 105,113 One blood donor study found a significant association between women who have sex with women and HCV infection, but in multivariate analysis this was only significant if the woman had had 2 or more same

- sex partners. One general population study did not find an association between same

- sex partners, not limited to MSM, in a univariate analysis. 113 Low 0

- 1 0

- 1 0 0 0 0 Very Low193 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

HIV 1 OBS 109 One general population study d id detect an association between HIV and having a same

- sex sex partner in a univariate analysis. 109 Low 0

- 1 0 0 0 1 0 0 LowAge at First Sexual Intercourse HBV 2 OBS 29,124 Age of 18 years or younger was not associated with HBV in general population multivariate analysis. 29 Age at first intercourse of 15 years or younger was associated with HBV infection in a special population univariate analysis. 124 Low 0

- 1 0 0 0 0 1 0 Low

HCV 1 OBS 30 In the general population, age of 17 years or younger was associated with HCV in a univariate analysis. 30 In that study, the size of effect was larger for people who were younger than 11 or 12

- 15 than for those 16

- 17 years old. Low 0

- 1 0 0 0 0 1 0 Low

HIV 1 OBS 101 Age of 18 years or younger was associated with HIV in a univariate analysis of a general population. 101 Low 0

- 1 0 0 0 1 0 0 LowNon-injectionIllicit Drugs HBV 5 OBS

29,103,121,124,125 HBV was not associated with illicit non

- injection drugs in the tissue donor study 103 or two special population studies. 121,125 A mult ivariate general population analysis 29 and univariate special population analysis 124 did find associations. Low 0

- 1 0 0 0 0 0 0 Very Low194 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

HCV 8 OBS 30,103

- 106,112

-
114 The tissue donor study did not find a n association between HCV and drug use as reported by next of kin. 103 Three blood donor studies did associate HCV with noninje ction drug use, 104

- 106 including in multivariate analyses in two of them. 105,106 In a general population univariate analyses, use of snorting or inhaling nonprescription drugs, 113 inhaling cocaine, 114 using intranasal cocaine, 112 and use of non

- injection drugs other than marijuana 30 were all associated with HCV. Two of these studies performed multivariate analyses, 30,112 and one did n ot find the factor to be an independent predictor of HCV. 112 Low 0 0 0 0 0 0 0 0 Low

HIV 2 OBS 101,115 HIV was associated with ever using cocaine or street drugs in a univariate analysis 101 and in a multivariate analysis 115 among members of the general population. Low 0 0 0 0 0 0 0 0 LowAlcohol HBV 2 OBS 103,125 HBV was not associated with alcohol use in a univariate analysis of tissue donors 103 or alcohol use disorder in a multivariate analysis of a special population. 125 Low 0 0 0

- 1 0 0 0 0 Very Low

HCV 5 OBS 102,103,112

- 114 HCV was associated with “hea vy” alcohol use in heart donors 102 and with having at least two units of alcohol per day in a general populat ion. 112 HCV was not associated with alcohol use among tissue donors 103 or having at least 5 alcoholic drinks weekly 113 or alcoholism 114 in general populations. All of these analyses were univariate. Low 0

- 1 0 0 0 0 0 0 Very Low195 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

HIV 2 OBS 103,114 HIV was associated with having an alcohol and/or (unspecified) drug problem in a general population 114

, but not with alcohol use among potential tissue donors. 103 Both of these analyses were univariate. Low 0

- 1 0

- 1 0 0 0 0 Very LowTobacco HBV 1 OBS 103 No association was found between cigarette smoking and HBV among tissue donors. 103 Low

- 1

- 1 0

- 1 0 0 0 0 Very Low

HCV 2 OBS 102,103 A history of tobacco use was associated with HCV in heart donors, 102 and cigarette smoking was

associated with HCV in tissue donors. 103 Both of these associations were made using univariate analyses. Low

- 1 0 0 0 0 0 0 0 Very Low

HIV 1 OBS 103 No association was found between cigarette smoking and HIV among tissue donors. 103 Low

- 1

- 1 0

- 1 0 0 0 0 Very LowTattoos and Piercing HBV 5 OBS

103,117 ,121,124,126 Tattoos, piercing, and acupuncture (as collectively analyzed as one outcome and reported by next

- of

kin) were not associated with HBV in tissue donors. 103

Tattoos were not associated with HBV in one general population study 117 or three special population studies. 121,124,126 Piercings were not associated with HBV in one general population study 117 or two special population studies. 121,124 All analyses were univariate. Low 0 0 0 0 0 0 0 0 Low196 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

HCV 7 OBS 103

- 106,112

- 114 Tattoos, piercing, and acupuncture (as collectively analyzed as one outcome and reported by next

- of

kin) were not associated with HBV in tissue donors. 103

3 blood donor studies 104

- 106 and three general population studies 112

- 114 detected significant associations between tattoos and HCV. Three performed multivariate anal yses, and one found that tattoos were not an independent predictor 106 while the other two did. 105,112
Of 3 blood donor studies, HCV was associated with ear piercing among men in one study 106 and pierced ears or body parts in another 105

in multivariate analyses, but not recent body piercing in a third with univariate analysis. 104 In univariate analyses of general populations, HCV was not associated with body piercing in two studies 112,114 but was associated with ear piercing in a third study. 113 Low 0 0 0 0 0 0 0 0 Low

HIV 1 OBS 103 Tattoos, piercing, and acupuncture (as collectively analyzed as one outcome and reported by next

- of

kin) were not associated with HBV in tissue donors. 103 Low

- 1

- 1 0

- 1 0 0 0 0 Very Low197 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfoundersInternational Travel HBV 2 OBS 103,117 International travel was not associated with HBV among tissue donors 103 or with recent HBV infection in a g eneral population. 117 Low 0 0 0

- 1 0 0 0 0 Very Low

HCV 3 OBS 103

- 105 International travel was not associated with HCV among tissue donors. 103 In blood donors neither recent travel outside the U.S. 104 nor ever having lived outside the U.S. 105 was associated with HCV. Low 0 0 0 0 0 0 0 0 Low

HIV 1 OBS 103 International travel was not associated with HIV among tissue donors. 103 Low

- 1

- 1 0

- 1 0 0 0 0 Very Low198 

### Table 37

. Prevalence of Behavioral Risk Factors

Category Risk Factor Citation Year Prevalence N = in population Population

Potential and Actual Organ DonorsDrugAbuse Unspecified ong oing substance abuse Hidalgo et al. 8 2001 5.5% 55 Parental potential living donors to their childrenAlcohol Heavy alcohol use Gasink et al. 102 2006 20% 10,915 Actual organ (heart) donorsTobacco History of tobacco use Gasink et al. 102 2006 36% 10,915 Actual organ (heart) donors

General PopulationMen whohave Sexwith Men Male

- to

- male sex McQuillan et al. 101 2006 3.7% 2

, 439 men General population

Men who have sex with men, history of Nguyen et al. 11 0 2008 9.3% 590 men General population in N.Y.C.Injection DrugUse Ever used a needle for drugs Nguyen et al. 110 2008 1.4% 1

, 50 5 General population in N.Y.C.

Lifetime injection dr ug use (participants aged 20

- 59) Armstrong et al. 30 2006 1.7% 5

, 3

68 General population, nationwide

Injection drug use Mehta et al. 109 2008 7.9% 16,696 Patients in urban medical care center

Injection drug use Kaur et al. 116 1996 3.5% 7

, 538 Volunteers from general population, mainly urban

No use of needle exchange program among injection drug

users Mehta et al. 109 2008 63.2% 1

, 258 Patients in medical care centerSex Work Exchanged sex for money or drugs Mehta et al. 109 2008 2.3% 16,696 Patients in an urban medica l care center199 Category Risk Factor Citation Year Prevalence N = in population PopulationHigh-risk SexPartners Sexual partner with HIV Mehta et al. 109 2008 3.6% 16,696 Patients in urban medical care center

Sex with IV drug user Kaur et al. 116 1996 5% 6, 5 62 Volunteers from general population, mainly urban

Sex with a commercial sex worker Mehta et al. 109 2008 7.4% 16,696 Patients in an urban medical care centerAdditional Sex Practices Sex with same or both genders (asked both men and women) Mehta et al. 109 2008 8.2% 15,586 Patients in urban medical care center

Lifetime number of se xual partners 10+ (participants aged 18

- 59) Armstrong et al. 30 2006 29% 5

, 357 General population, nationwide

Lifetime number of sexual partners 2+ McQuillan et al. 101 2006 74% 5

, 391 General population, nationwide

Lifetime number of sexual partners 2

- 49 Nguyen et al. 110 2008 7 4% 1

, 469 General population in N.Y.C.

Lifetime number of sexual partners 50+ McQuillan et al. 101 2006 3.5% 5

, 391 General population, nationwide

Lifetime number of sexual partners 50+ Nguyen et al. 110 2008 6.6% 1

, 469 General population in N.Y.C.

Sex with multiple partners Kaur et al. 116 1996 26% 7

, 325 Volunteers from general population, mainly urban

Sex with multiple partners during previous year Nguyen et al. 110 2008 22% 1

, 368 General population in N.Y.C.

Age at first intercourse younger than 18 years (participants aged 18

- 59) Armstrong et al. 30 2006 58% 5

, 054 General population, nationwide200 Category Risk Factor Citation Year Prevalence N = in population Population

Age at first intercourse younger than 18 years McQuillan et al. 101 2006 59% 5

, 373 General population, nationwideNoninjectionSubstanceAbuse Lifetime drug use other th an marijuana (participants aged 20

- 59) Armstrong et al. 30 2006 17% 5

, 683 General population, nationwide

Ever used cocaine/
street drugs McQuillan et al. 101 2006 21% 4

, 969 General population, nationwide

Ever used drugs, any Nguyen et al. 110 2008 18% 1,505 General population in N.Y.C.201 

### Table 38

. GRADE Table for Question 3 : Prevalence of Behavioral Risk Facto rs

Factor Quantity and Type of
Evidence FindingsStarting Grade Decrease GRADE Increase GRADE

GRADE of
Evidence
for
OutcomeStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseAssociated DespiteConfounders

Men who have sex with men 2 OBS* 101,110 In two general popula tion studies, one reported that 3.7% of men have sex with another man, 101 while the other repo rted that 9.3% have a history of having sex with another man. 128 High 0

- 1

- 1 0 0 0 0 0 Low

Injection drug abuse 4 OBS 30,109,110,116 All four studies assessed general populations. Reported prevalences of injection drug use were 1.4%, 110 1.7%, 30 3.5%, 116 and 7.9%. 109 The lower two estimates were derived from NHANES data, and the higher two were drawn from patients and volunteers in urban

areas. (Of the injection drug users in one study, 63.2% reported t hey did not use needle exchange programs. 109 ) High 0

- 1

- 1 0 0 0 0 0 Low

Sex Work 1 OBS 109 One general population study reported 2.3% of participants reported exchanging sex for money or drugs. 109 High 0

- 1

- 1 0 0 0 0 0 Low

High

- Risk Sex Partners: Injection drug

user 1 OBS 116 Among general population volunteers from a mainly urban area, 5% reported having sex with an injection drug use. 116 High 0

- 1

- 1 0 0 0 0 0 Low202 Factor Quantity and Type of
Evidence FindingsStarting Grade Decrease GRADE Increase GRADE

GRADE of
Evidence
for
OutcomeStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseAssociated DespiteConfounders

High

- Risk Sex Partners: Sex workers 1 OBS 109 In the same population, 7.4% reported sex with a commercial sex worker. 109 High 0

- 1

- 1 0 0 0 0 0 Low

Multiple Sex Partners: Multiple undefined 2 OBS 110,116 26% of volunteers in one study reported having sex with multiple partners, 116 while 22% of NHANES participants reported having multiple sex partners during the pre vious year. 110 High 0 0

- 1 0 0 0 0 0 Moderate

Multiple Sex Partners: At least 2 partners 2 OBS 101,129 74% reported having sex with at least two partners, 101 74% reported having sex with 2

- 49 partners. 110 High 0 0

- 1 0 0 0 0 0 Moderate

Multiple Sex Partners: At least 50 partners 2 OBS 101,110 In one study, 3.5% reported having at least 50 sex partners, 101 while in another 6.6% did. 110 High 0

- 1

- 1 0 0 0 0 0 Low

Age at first intercourse (<18 years) 2 OBS 30

, 101 The proportion of adults who reported having sex at age 18 or younger were 58% 30 and 59% 101 in two general population studies. High 0 0

- 1 0 0 0 0 0 Moderate

Same

- sex partner (not restricted to men) 1 OBS 109 8.2% of men and women reported having sex with same or both genders. 109 High 0

- 1

- 1 0 0 0 0 0 Low

Noninjection substance abuse: Ongoing 1 OBS 8 Among potential living donors, 5.5% had unspecified ongoing drug abuse. 8 High 0

- 1 0

- 1 0 0 0 0 Low203 Factor Quantity and Type of
Evidence FindingsStarting Grade Decrease GRADE Increase GRADE

GRADE of
Evidence
for
OutcomeStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseAssociated DespiteConfounders

Noninjection substance abuse: Lifetime 3 OBS 30,101,110 In the general population, 17% reported lifetime use of drugs other than marij uana, 30 18% reported ever having used any drugs, 110 and 21% reported ever using street drugs/cocaine. 101 High 0 0

- 1 0 0 0 0 0 Moderate

Alcohol 1 OBS 102 Among heart donors, 20% reportedly drank alcohol heav ily. 102 High

- 1

- 1 0 0 0 0 0 0 Low

Tobacco 1 OBS 102 Among heart donors, 36% reportedly used tobacco. 102 High

- 1

- 1 0 0 0 0 0 0 Low

*Observational study204 

## Question **4 : Results** 

In this section, data on non behavioral potential risk factors including signs and symptoms indicative of infection, potential exposure, co

- morbidities, and demographic factors are presented. Information regarding exclusionary factors listed in the 1994 guideline is presented first, and then information regarding additional factors for which at least two studies provided evidence regarding the same factor is presented. All of the data related to the identification of risk factors is provided in Table 39 (HBV),
Table 40 (HCV), Table 4 1 (HIV), and Table 42 (GRADE tables). Prevalence information is provided in
Table 43

.


### Exclusionary Criteria from 1994 Guideline
People with Hemophilia or Related Clotting Disorder who Received Clotting Factor Blood Products
The 1994 guideline excludes from donating “ Persons with hemophilia or related clotting disorders who
have received human

- derived clotting factor concentrates. ” We identified zero studies that studied
whe ther this factor was associated with an increased prevalence of infection. This may be due to the relative rarity of having hemophilia or a related blood clotting disorder in the populations included in the evidence base for these questions. However, we di d identify a large number of studies that considered the association between blood transfusions and infection regardless of any underlying disease. For more information, see Receipt of Blood Transfusion under Risk Factors Identified in the 2009 Literature
Search

.

Exposure to Infected or Suspected Blood
The 1994 guideline excludes from donating “ Persons who have been exposed in the preceding 12 months to known or suspected HIV

- infected blood through percutaneous inoculation or through contact with an

open wo und, nonintact skin, or mucous membrane. ”

Only one of the studies specifically inquired as to whether patients had been exposed to blood known or suspected to be infected. Among embalmers, Turner et al. did not find an association between needlestick injur y with exposure to recognized HBV infection during embalming and HBV infection. 127



### GRADE Summary: This evidence is ra ted as “very low” because of indirectness, imprecision, and lack of consistency.

Many of the studies did, however, ask about exposure to blood in general, including by needlestick injuries and in other accidents. See Nonspecific exposure below for informat ion on these factors.

Children

The nonbehavioral exclusion criteria for children are the same as listed in Question 3 . We did not identify any information regarding the two (above) nonbehavioral exclusion criteria in children or in children of
mothers wit h such factors, or any other clinical factors.205 

### Additional Potential Risk Factors Identified in the 2009 Literature Search
In addition to the factors identified in the 1994 guideline, we extracted data on all other reported risk
factors identified in the li terature

. The following sections describe the evidence regarding the various factors and infection rep orted by at least two studies.

Signs and Symptoms
An objective of this section was to identify nonbehavioral factors that could be predictive of infection

, especially acute infection during the window period before diagnostic tests could recognize the infection. However, extremely little data on such signs and symptoms were identified.

The only signs identified were associated with HCV infection. In blood donors, alanine aminotransferase (ALT) reactivity was associated with infection by Orton et al. 104 

### In a general young adult population (aged 18 to 49), serum ALT of >40 U/L was associated with HCV by Armstrong et al. 30 

### “ Elevated liver

enzyme ” was associated with HCV in adults comprising indivi duals at risk for HCV, and healthcare
workers enrolled in a health maintenance organization (HMO) in Fischer et al. 114 

### In addition, jaundice was associated with HCV in adults in a general medical clinic by Nguyen et al. 113



### GRADE Summary: Although several signs were reported, they are all different and therefore must be
considered in isolation. The association of HCV with jaundice, ALT reactivity, and elevated ALA were large effect sizes and therefore rated as low. The effect size for “elevated liver enzyme” was not large,
and therefore ra ted as very low.

Prevalence: In a general population, 9% of survey respondents had AL T >40 U/L. 30



### GRADE Summary of Prevalence: The prevalence estimate was rated as low due to indirectness and lack of proof of consistency.

Receipt of Blood Transfusion
Although no studies reported on risk in people with clotting disorders or who h ave received clotting factor blood products, many did investigate risk of infection associated with blood transfusion. Two of three studies associated blood transfusion with HBV, and all eight studies associated it with HCV.

HBV : Blood transfusion was ass ociated with HBV infection in a general population in Kaur et al., 116



### as was blood transfusion before 1991 among college students in Hwang et al. 124 

### Blood transfusion was not associated with HBV in the low prevalence obstetric patients study by Butterfield et al. (1990). 126



### HCV : All 8 studies that looked at this f actor did find some association with transfusion and HCV infection. Receiving a blood transfusion was independently associated with HCV in three studies of blood donors, Conry

- Cantilena et al., 106 

### Murphy et al. (2000 ), 105 

### and Murphy et al. (1996). 107 

### In Murphy et al. (2000), the association was only significant among donors who had never injected drugs. 105



### In three studies of the general population, blood transfusion was associated with HCV by Nguyen et al., 113 

### Hand and Vasquez, 112 

### and Kaur et al., 116 

### , and in the two studies that calculated multivariable models, 112,11 6 

### the association was independent. In the general population, Armstrong et al. found that the relationship between HCV and blood transfusion before 1992 was independent, 30 

### and Fischer et al. detected an association but did not test whether the risk factor was independent. 114 

### Sex with a blood transfusion recipient was also associated with HCV infection in Murphy et al. (2000). 105206 

### Some studies combined having received a blood transfusion with other outcom es. Being a blood transfusion recipient or donor (data not reported separately) as reported by next

- of

- kin was not associated with an increased risk of HBV, HCV, or HIV among potential tissue donors by Sanchez et al. 103 

### Either receiving a blood transfusion or having a household contact with a person who had was not associated with acute HBV by Alter et al. 117 

### We did not consider these outcomes sufficiently similar to group with receipt of blood transfusion only.

GRADE Summary: The evidence for HBV was mostly indirect, and downgraded to very low rat ing accordingly. For HCV, the evidence consistently pointed to an association with transfusion with large magnitude, and was rated as moderate.

Prevalence : Among general population survey respondents, 6% of those aged 20 to 59 years (in 2006) reported havi ng a blood transfusion before 1992, and 16% of those aged at least 60 years did. 30 

### Among volunteers from an urban area, 20% reported having ever had a blood transfusion. 116



### GRADE Summary of Prevalence: The evidence of these prevalence estimates were rated a s low due to indirectness and lack of proof of consistency.

Nonspecific Exposure
Although only one study asked participants whether they had ever been exposed to infected or potentially infected blood, many studies asked about exposure to blood without reg ard to any knowledge about the infection status of the blood. Besides hemodialysis, most of these factors were not found to be consistently associated with infection.

Accidental Needle Stick
According to data collected from next

- of

- kin, accidental needle s ticks were not associated with HBV, HCV, or HIV among potential tissue donors in Sanchez et al. 103



### In a general population stu dy by Kaur et al., needlestick injuries were actually associated with lower prevalence of HBV and HCV infection. 116 

### This may be because a substantial proportion of the enrollees

wer e healthcare workers, and in that study healthcare workers had a lower prevalence of HBV than the group as a whole. Needlestick injuries among healthcare worker blood donors in Conry

- Cantilena et al.
were not associated with HCV either. 106 

### However, “ bloody ” needlestick injuries in a medical setting was associated with an increased prevalence of HCV in Murphy et al. (2000). 105



### GRADE Summary: For all three viruses this evidence was rated as “very low

. ” For HBV this was due to lack of precision, for HCV it was due to inconsistency, and for HIV it was due to low quality

, imprecision, and lack of consistency.

Hemod ialysis
Most studies found an association between hemodialysis and HBV or HCV. Hemodialysis was associated with HBV among volunteers from the general population by Kaur et al. 116 

### and among college students by Hwang et al. 124 

### In studies that enrolled people from the general population, HCV infection was associated
wit h h emodialysis in Kaur et al., 116 

### and with “kidney dialysis” in Nguyen et al, 113 

### but not with hemodialysis in Hand and Vasquez

. 112 

### The duration of administration of dialysis was not specified.207 

### GRADE Summary: The evidence associating HBV with hemo dialysis was rated as “ moderate” because
the size of the association in the special population was large. For HCV, strength of evidence was low

.
Surgery
The relationship between surgery and infection was inconsistent. Based upon next

- of

- kin data for potential tissue donors, Sanchez et al. did not find any associations between HBV, HCV, or HIV and surgeries. 103 

### In the general population, surgery was associated with a lower HBV pr evalence by

Kaur et al., 116 

### and surgery during the last six months was not associated with acute HBV in Alter et al. 117


### Having surgery or a medical procedure in the six months before blood donation was not associated with
HCV in Orton et al., 104 

### and having a history of surgery was not associated with HCV in general population studies by Fischer et al. 114 

### or Kaur et al. 116 

### However, lifetime history of surgery or sutures was associated with elevated HCV prevalence in blood donors in Murphy et al. (2000). 105



### GRADE Summary: For all three viruses, the evidence was in consistent and rated as “very low.” For HIV
the eviden ce base was also of very low quality and imprecise.

O rgan and Corneal Transplantation Recipients

No organ transplantation studies were identified that met the inclusion critiera. Receipt of corneal transplantation was not associated with a greater risk of HBV , HCV, or HIV in the tissue donor study by
Sanchez et al. 103 

### , or with HBV among psychiatric inpatient veterans in the study by Tabibian et al. 121



### GRADE Summary : For all three viruses, the evidence was rated as very low due to i mprecision. For HCV and HIV the evidence was also of very low quality with no proof of consistency.

Acupuncture
Acupuncture during the last six months was not associated with an increased incidence of acute HBV in
Alter et al. 117 

### or increased prevalence of HBV among psychiatric inpatient veterans in Tabibian et al., 121 

### or with HCV among blood donors in Conry

- Cantilena et al. 106 

### or Murphy et al., 107 

### or people in a general population in Hand and Vasquez et al. 112



### GRADE Summary : For both HBV and HCV, the GRADE was not decreased and the evidence was rated
as low.

Dental Work

Dental work within the last six months was not associated with acut e HBV in Alter et al. 117 

### Dental work was not associated with HCV among blood donors in Murphy et al. 105 

### ; nor was having dental work in the
six months before donation in Orton et al. 104



### GRADE Summary: For HBV, the evidence was downgrad ed due to imprecision and rated as very low. For HCV, the evidence was not downgraded and was rated as low.

Blood Draws
Blood draws should not expose patients to blood (and is probably a proxy f or other risk factors).
Sanchez et al. did not find an associa tion between HIV testing and HIV, HBV, or HCV among tissue donors, based upon next

- of

- kin interviews. 103 

### However, Nguyen et al . (2005) did find an association between having had a blood test for HBV and having an HCV infection in a univariate analysis of adults in the general population. 113 

### Similarly, being a blood donor should not pose a direct infectious risk. In the208 

### same study, Nguy en et al. found that being a blood donor was associated with reduced risk of HCV, and that having been rejected as a blood donor was associated with an increased risk of HCV. 113



### GRADE Summary: Because evidence was imprecise for each of the viruses and also inco nsistent for HBV
and HIV , the evidence regarding blood draws was rated as “very low.”

Other Blood Exposure
Neither bloody object contact in Tabibian et al. 121 

### nor combat exposure in Butterfield et al. (2004) 125 

### were associated HBV among psychiatric inpatient veterans. Having been “ st uck ” or “ cut ” with a blood object was independently associated with HCV among blood donors in Murphy et al. (2000) 107 

### Among blood
donors in Orton et al. 104 

### blood exposure during fighting, by biting, at an accident site, or during a
manicure in the last six months was associated with HCV , but not during a haircut in the last six months

. Contact with blood was not associated with HCV in members of a general population study by Hand and Vasquez. 112



### We report these factors here because of their relevance but did not rate the GRADE for these “other” outcomes due to lack of replication of the various factors.

Household Exposur e Whether hepatitis infection among other household members was a risk factor for exposure was investigated in several studies, with inconsistent findings. Having household contact with someone with hepatitis was associated with HBV among college students in Hwang et al. 124 

### , as was a family history of HBV among Asian Americans in Lin et al. 123 

### Having a househ old member with hepatitis was not associated with HBV in an obstetric population in Butterfield et al.; 126 

### nor was being the wife of a man with HBV among Korean American church goers in Hann et al. 122 

### Among blood donors in Murphy et al., living with someone with hepatitis or havin g a relative with hepatitis was not associated with HCV infection, but living with a transfusion recipient was. 105 

### In general population studies, having at least

one family member treated for viral hepatitis was not associated with an i ncreased risk of HCV in
Fischer et al., 114 

### but having at least one family member with HCV was in Nguyen et al. 113



### Sharing a razor or toothbrush with an other household member was not associated with HBV members of the general population in Alter et al. 117 

### However, sharing a toothbrush or razor with person(s) unspecified

wa s associated with HCV among blood donors in Murphy et al. 105



### GRADE Summary : All of the evidence per taining to household exposure and HBV and HCV infection was inconsistent, and therefore rated as very low

. For HBV the ev idence was also indirect: all o f it came from special population studies.

Other Infections
Sexually transmitted infections were nearly universally associated with increased risk of HBV, HCV, or HIV. HBV surface antigen positivity was associated with HCV infection among heart donors in Gasink et
al. 102 

### Among college students, HBV infection was associated with having had a sexually transmitted disease (STD) in Hwang et al. 124 

### Among blood donors, HCV was significantly associated with history of STD in Conry

- Cantilena et al. 106 

### and Murphy et al. (2000), 105 

### and with having a STD within six months of donating in Orton et al., 104 

### and with seropositivity for other reactive infectious diseases in Orton et
al. 104 

### and Murphy et al. (1992). 107 

### Among people from general populations, having past treatment for209 

### STDs was not associated with HCV in Nguyen et al., 113 

### but having herpes simplex virus (HSV) infection was in Armstrong et al. 30 

### HIV infection was not associated with HCV infection upon univariate analysis of a general population in Hand and Va squez. 112 

### Diagnosis of STD in Mehta et al., 109 

### HSV

- 2 in McQuillan et al. (2006), 101 

### HSV

- 2 in Nguyen et al., 110 

### and syphilis or other infection not apparently
related to HIV in Alpert et al., 115 

### were all associated with HIV in general populations. Rabies exposure was not associated with any of the viruses in the tissue donor study by Sanche z et al

. 103



### GRADE Summary: For HBV and HIV, the evidence associating them with another infection was rated as
low. For HCV the evidence was rated as very low due to inconsistency.

Prevalence : Antibodies to HSV

- 2 were detected in 19% of general nati onwide population aged 18 to
49 years, 30 

### and 28% of New Yorkers. 110 

### STD diagnoses were reported by 18% of patients in an urba n medical car e center. 109



### GRADE Summary of Prevalence : The estimate of HSV

- 2 infection was rated as moderate due to indirectness. For unspecified STD it was rated as low due to indirectne ss and lack of proof of consistency.

Demographic Factors

Sex
Male sex was not consistently associated with an increased risk of infection

. Males had higher rates of HBV than women in studies that considered the general population, 116 

### psy chiatric inpatient veterans (of whom nearly all were male), 121 

### and Asian Americans, 123 

### but not Korean American church goers. 120 

### Among college students 124 

### females had higher rates of HBV, and among children who had received a blood transfusion, in Luban et al., rates were not significantly different. 118 

### Among heart transplant donors, being male was associated with an increased risk of HCV. 102 

### In one study of blood donors, being male was associated with an increased risk of HCV, 107 

### but among two others it was not. 104,106 

### In four general population studies, significantly higher proportions of males had HCV infection in four 30,108,113,116 

### out of
five studies. 114 

### Male sex was not associated with HIV in three general population studies. 109

- 111



### GRADE Summary: For HBV and HCV , the evidence was rated as very low due to inconsistent findings. For HBV, the eviden ce was also indirect because it was drawn primarily from special population studies. For HIV, the evidence was rated as low because lack of association was consistently found.

Age
Studies assessed the relationship between age and infection in a variety of different ways. While some used mean age, others used various cutoffs (such as older or younger than 30 years) or categorization (such as age by decade). Older age was associated with a greater rate of HCV among heart transplant donors in Gasink et al., 102 

### but inconsistently associated with HCV among blood donors, HCV or HIV in the general population, or HBV in s pecial subpopulations.

GRADE Summary: Evidence on age was collected using inconsistent methods among studies, clouding any potential relatio nship between age and infection . For HBV the evidence was inconsistent and came primarily from special population st udies, and was therefore rated as “very low.” The evidence for HCV
and HIV was also inconsistent and rated as very low.210 

### Race or Ethnicity, and National Origin



### HBV : Higher HBV prevalence in the general population was associated with non

- Hispanic Black
ethn icity compared with non

- Hispanic White ethnicity in McQuillan et al. 29 

### In the same study, being Mexican

- American was associated with no increase in pre valence compared with being non

- Hispanic white. In another general population study, the prevalence of HBV was lower among white and Hispanic individuals than other races. 116 

### The re st of the studies examined subpopulations. Prevalence was higher for African Americans compared to white people among psychiatric inpatient veterans in Butterfield et al. 125 

### and a mong college students in Hwang et al., 124 

### but not among inpatient veterans in Tabibian et al. 121 

### Hispanic or Latino ethnicity was not associated with HBV among psychiatric inpatient veterans in Tabibian et al. 121 

### or college students in Hwang et al. 124 

### Among college students in Hwang et al., Asian students had higher rat es of HBV. 124



### HBV was associated with birth in a Southeast Asian or African country in a general population study by Kaur et al. 116 

### but not in a study of Asian Americans by Lin et al. 123 

### Acute HBV was not associated with birth in an area with a high endemic rate of HBV or having a ho usehold contact with someone who was born in an endemic area in Alter et al. 117 

### Among Asian Americans, being born in the U.S. was found to be protective in children in Han n et al. 122 

### and in Asian Americans of any age in Lin et al. 123 

### Any international birth was associated with increased prevalence of HBV in McQuillan et al. 29



### HCV : Among heart donors in Gasink et al., ethnicity was not associated with HCV. 102 

### Among blood
do nors, two studies associated increased prevalence with “ black ” race 106,107 

### , and two studies found inconsistent relationships between Hispanic ethnicity and HCV. 104,107 

### However, black or Hispanic ethnicity was not associated with infection in general population studies

, 30,108,113 

### Orton et al. 104 

### found that being born in a country other than the U.S. was associated with HCV among blood donors, but Murphy et
al. 107 

### did not. McGinn et al. found an association between preferring to speak English or Spanish and

HCV. 108



### HIV : HIV was not associated with Asian 109,110 

### or Hispanic ethnicity 110,111 

### but was associated with Black ethnicity in two 109,110 

### of three 111 

### studies. Being a Spanish speaker was not associated with prevalence of HIV among public emergency room patients in Zetola et al. 111



### GRADE Summary: All of the evidence regarding race or ethnicity was rated as very low. For HBV this was because most of the data came from special subpopulation studies and because some information was inconsistent

. For HCV and HIV, most studies found no relationship between race or ethnicity and infection, but there were some inconsistencies . Very low evidence ratings for national origin/birthplace and preferred language were assigned for the same r easons.

Occupation
Unemployment was significantly associated with recent HBV infection in the general population in a multivariate analysis, in Alter et al. 117 

### Some of the studies investigated whether occupational exposure to blood was associated with hepatitis; however, findings were inconsistent. Being a healthcare worker with frequent blood exposure was associated with an increased prevalence of HBV in college students in Hwang et al. 124 

### , but being a healthcare worker was not associated with HBV in a general population studies by Kaur et al. 116 

### or McQuillan et al. 29 

### or having been a healthcare worker in psychiatric inpatient
veterans in Tabibian et al. 121 

### or a low

- prevalence obstetric population in Butterfield et al. 126 

### Among bloo d donors, occupational blood exposure was associated with HCV infection in Murphy et al., 105 

### but med ical211 

### or dental job or public safety job with frequent blood contact were not in Orton et al. 104 

### In the general population, work contact with blood was not associated with increased HCV in Fischer et al. 114



### , and being
a healthcare worker was actu ally associated with a lower rate of HCV in Kaur et al. 116 

### Services in the
armed forces was not associated with HBV in McQuillan et al. 29 

### or with HCV in either Fischer et al. 114 

### or Armstrong et al. 30 

### Having a job at a prison was associated with HCV in Nguyen et al. 113



### GRADE Summary : Most of the occupational information pertained to healthcare workers. Most evidence did not associate employme nt in healthcare with infection

. For HBV this finding was consistent and rated as low. An additional study considered the association between HBV and military service and did not find a relationship and was rated very low for imprecision. For HCV associations with health care job or job with blood exp osure was inconsistently related with HCV and was rated as very low due to inconsistency and imprecision. A lack of association between HCV and serving in the armed forces was found; this evidence was rated as very low due to imprecision. Findings associat ing HCV and working in public safety were inconsistent and therefore rated as very low.

Education
Inconsistent evidence suggests lower educational level attainment may be associated with infection. Less than a high school education was associated with a hi gher prevalence of HBV in the general population by McQuillan et al. 29 

### , but total years of education was not associated with HBV among psychiatric inpa tient veterans in Tabibian et al. 121 

### College students enrolled in 4

- year colleges had lower rates of

HBV than students enrolled in 2

- year colleges in Hwang et al. 124 

### Lower educational attainment was
associated with HCV in blood donors in Orton et al. 10 4 

### and Conry

- Cantilena et al. 106 

### and in the general population in Armstrong et al. 30 

### However, this association was not found in the general population by
McGinn et al. 108 

### or Nguyen et al. 113 

### An association between HIV and education was not detected in general population studies McQuillan et al. 101 

### or Mehta et al. 109



### GRADE Summary : The association between lower educational level and infection was i nconsistent for
HBV and H C V. For HBV the evidence was also indirect, and so it was rated as very low. For HCV, the
evidence was rated as very low because there was a dose

- response association. For HIV, information was
consistent but imprecise and therefore rated as very low.

Economic Factors
Being homeless was not associated with an increased risk of HBV among psychiatric inpatient veterans in
Tabibian et al. 121 

### Ever having been homeless was associated with an increased risk of HCV in adults attending general medicine or hepatology clinics in Nguyen et al. 113 

### and being homeless was associated with an increased preva lence of HIV in public hospital emergency room patients in Zetola et al. 111 

### Neither
income or nor living in poverty was associated with HCV in Nguyen et al. 113 

### or Armstrong et al. 30 

### or with
HIV in McQuillan et al. 101



### GRADE Summary : Economic factors were inconsistently associated with HCV and HIV, and imprecisely
associated with HBV and HCV. For all three virus es, the evidence w as rated as very low.

Health Insurance
Type of health insurance (Medicaid, Medicare, private, or self

- pay) was significantly associated with HCV in McGinn et al., a general populatio n study, with Medicaid patients having the highest rates of212 

### HCV. 108 

### Patients with no health insurance had higher prevalence of HIV in one study of hospital patients, Mehta et al., 109 

### but not in another such study, Zetola et al. 111



### GRADE Summary: The e vidence relating health insurance and infection was inconsistent for HCV and HIV and imprecise for HIV and therefore rated as very low for both.

Marital Status
Being married may be associated with a lower risk of infection. Being divorced or separated was associated with a higher prevalence of HBV in McQuillan et al., a general population study, than any
other status. 29 

### Being married was associated with a lower rate of HCV among blood donors in Murphy et
al. 105 

### and a lower prevalence of HIV in the gene ral population in McQuillan et al. 101 

### Marital status was
not associated with HBV infection amo ng psychiatric inpatient veterans in Butterfield et al. 125



### GRADE Summary : One study for each HCV and HIV found a relationship between being married and having a lower risk of infe ction and were rated as low. For HBV, infection was higher among divorced or single persons in a general population study. A special population study did not find any association
between marital status and infection, but since it was a special population s tudy we did not detract from
the GRADE and rated it as low.213 

### Evidence Tables for Question **4**

Table 39

. HBV Nonbehavioral Risk FactorsCategory

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Co

- Morbidity

Potential Tissue DonorsTransfusion Blood transfusion recipient or donor Sanchez et al. 103 2006 Not Reported (NR) 47 NR 56 NR Not significant (NS) Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kinNonspecific Exposure Accidental needle stick Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

History of transplant Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV

No Pot ential tissue donors, as reported by next of kin

Surgeries Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+

vs. HBV No Potential tissue donors, as reported by next of kin

HIV testing Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin214Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

PopulationOthers Liver disease Sanchez et al. 103 2006 NR 47 NR 5 6 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Treatment by physician in last 2 years Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Medical hospitalizations Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Psychiatric hospitalizations Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Medical illnesses Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Medications Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Toxic exposure Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Malaria
exposure or treat ment Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of k in215Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Chagas disease
exposure or treatment Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential ti ssue donors, as reported by next of kin

Rabies
exposure Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Heart disease Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Hypertension Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Kidney disease Sanchez et al. 103 2006 NR 4 7 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Gastro

intestinal disease Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Cancer history Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Diabetes history Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin216Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Pulmonary disease Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Rheumatologic disease Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Connective tissue disease Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Dermatologic disease Sanchez et

a l. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Neurologic d isease Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors, as reported by next of kin

Ocular disease Sanchez et al. 103 2006 NR 47 NR 56 NR NS Proportion in HBV+ vs. HBV No Potential tissue donors,
as repo rted by next of kin217Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

General PopulationTransfusion Blood transfusion Kaur et al. 116 1996 23 % 1

, 432 18.2 % 6

, 107 1.27 (1.04 to 1.57)‡ NR Proportion in HBV+ vs. HBV

Yes Volunteers from general population

Blood transfusion, history of, household
contact Alter et al. 117 1989 5 % 76 12 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adult s with no obvious cause of acute HBV and matched controlsNonspecific Exposure Needlestick injury Kaur et al. 116 1996 15.7 % 1

, 406 19.9 % 5

, 982 0.75 (0.64 to 0.87)† NR Proportion in HBV+ vs. HBV

No (protec

tive) Volunteers from general population (Note that a larger proportion of participants than would be expected in the general population were health care workers, and that in this population health care workers had significantly l ower HBV prevalence)

Hemodialysis Kaur et al. 116 1996 37.5 % 1

, 396 18.7 % 6

, 033 2.60 (1.14 to 5.96)† NR Proportion in HBV+ vs. HBV

Yes Volunteers from general population

Surgery Kaur et al. 116 1996 17.9 % 1

, 446 21.6 % 6

, 147 0.79 (0.70 to 0.89)† NR Proportion in HBV+ vs. HBV

No (protec

tive) Volunteers from general population218Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Surgery, last six months Alte r et al. 117 1989 4 % 76 3 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controls

Hospitalization, las t six months Alter et al. 117 1989 13 % 76 8 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controls

Ac upuncture, last six months Alter et al. 117 1989 1 % 76 0 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controls

Med ically

related injections, last six months Alter et al. 117 1989 16 % 76 17 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controls

Dental work,
any, last six months Alter et al. 117 1989 13 % 76 22 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population ad ults with no obvious cause of acute HBV and matched controls

Dental work, extensive, last six months Alter et al. 117 1989 5 % 76 6 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controlsOther Vaccinated for hepatitis B Kaur et al. 116 1996 7.8 % 1

, 356 22 % 8

, 509 0.40 (0.31 to 0.52)‡ NR Proportion in HBV+ vs. HBV

No (pro

tective) Volunteers from general population219Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Special PopulationExposureto InfectedBlood Needlestick injury with recognized HBV infection Turner et al. 127 1989 NR 14 NR 94 NR NR† Prevalence HBV+ vs. no injury No Embalmers in high

prevalence urban areaTransfusion Blood transfusion before 1991 Hwang et al. 124 2006 4 % 269 2.4 % 3

, 999 RR : 1.80 (1.04 to 3.11)† <0.05 Prevalence HBV+ vs. HBV

Yes College students

Blood transfusion Butterfield et al. 126 1990 0 % 1 2 2.5 % 1

, 454 1.54 (0.09 to 26.5)†¶ 0.77¶ Prevalence HBV+ vs. HBV

No Obstetric populationNonspecific Exposure Organ transplantation Tabibian et al. 121 2008 0 % 40 1 % 89 NR NS† Prevalence in HBV+ vs. HBV

No Psychiatric inpatient
veterans

Hemodialysis Hwang et al. 124 2006 0.7 % 270 0.0 5

% 4

, 045 RR : 7.96 (2.97 to 21.35)† <0.05 Prevalence HBV+ vs. HBV

Yes College students

Acupuncture Tabibian et al. 121 2008 15 % 40 17 % 89 NR NS† Prevalence in HBV+ vs. HBV

No Psychiatric inpatient
veterans

Bloody object
contact Tabibian et al. 121 2008 35 % 40 20 % 89 NR NS† Prevalence in HBV+ vs. HBV

No Psychiatric inpatient
veterans

Combat
exposure Butterfield et al. 125 2004 NR 8 0 NR 276 1.30 (0.63 to 2.67)‡ NS Prevalence HBV+ vs. HBV

No Psychiatric inpatient
veterans220Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Household contact with hepatitis Hwang et al. 124 2006 12 % 268 7 % 3

, 987 RR : 1.70 (1.19 to 2.42)† <0.05 Prevalence HBV+ vs. HBV

Yes College students

Household member with hepatitis Butterfield et al. 126 1990 0 12 1.3 % 1

, 454 2.96 (0.170 to 51.78)†¶ 0.46¶ Prevalence HBV+ vs. HBV

No Obstetric pop ulation

Wives of men surface antigen positive Hann et al. 122 2007 6.3 % H BsAg+, 57.1 % anti

HBs+ NR NR NR NR 0.23† Married equivalent
age group No Korean

- American church

goers

Family history of HBV (self

- report) Lin et al. 123 2007 NR 283 NR 2

, 880 RR : 1.9 (1.4 to 2.6)‡ SS Prevalence HBV+ vs. no history Yes Asian AmericansOther infection Sexually transmitted disease Hwang et al. 124 2006 29% 256 13% 3,924 RR: 2.48 (1.92 to 3.58) †;

OR: 1.61 (1.10 to 2.37)‡ <0.05 Prevalence HBV+ vs. HBV

Yes College studentsOther HBV Vaccination Lee et al. 120 2008 NR NR NR NR 0.12 (0.05 to 0.29)† SS Prevalence of HBV vs. no vaccine Yes, protec

tive Korean

- American church

goers

HBV Vaccination (self

- report) Lin et al. 123 2007 NR 283 NR 2

, 880 RR : 0.5 (0.3 to 0.8)‡ SS Prevalence HBV+ vs. no vaccine Yes, protec

tive Asian Americans221Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Demographics

General PopulationSex Male Kaur et al. 116 1996 58 % 1

, 416 35 % 6

, 275 2.14 (1.82 to 2. 51)‡ SS Proportion in HBV+ vs. HBV

Yes Volunteers from general populationAge Age >60 Kaur et al. 116 1996 35 % 1

, 356 19 % 5

, 853 1.22 (1.21 to 1.23)‡ SS Proport ion in HBV+ vs. HBV

in age <60 years Yes Volunteers from general populationRace Race White/Hispanic Kaur et al. 116 1996 65 % 1

, 302 84 % 5

, 764 0.32 (0.26 to 0.39)‡ SS Proportion in HBV+ vs. HBV

No (pro tec

tive) Volunteers from general population

Ethnicity Non

Hispanic Black McQuillan et al. 29 1999 NR 1

, 085 NR 20

, 180 3.9 (2.9 to 5.0)‡ SS Proportion in HBV+ vs. HBV

vs. Non

Hispanic White Yes General population

Ethnicity Mexican American McQuillan et al. 29 1999 NR 1

, 085 NR 20

, 180 0.7 (0.4 to 1.3) ‡ NS Proportion in HBV+ vs. HBV

vs. Non

Hispanic White No General population222Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

PopulationBirthplace Born in S.E. Asia or Africa Kaur et al. 116 1996 52 % 1

, 421 17.6 % 6

, 069 3.87 (2.81 to 5.34)‡ SS Proportion in HBV+ vs. HBV

Yes Volunteers from general population

Birth in an area with high endemic rate of HBV, household contact with someone with Alter et al. 117 1989 3 % 76 <1 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controls

Other than U.S. McQuillan et al. 29 1999 50 % 1

, 236 16.5 % 19,971 3.4 (2.0 to 5.8)‡ SS Proportion in HBV+ vs. HBV

Yes General populationOccupation Occupation Health Care Worker Kaur et al. 116 1996 11.6 % 1

, 453 21.5 % 6

, 185 0.48 (0.41 to 0.56)† SS Proportion in HBV+ vs. HBV

No (protecti ve) Volunteers from general population

Medical occupation McQuillan et al. 29 1999 5 % 955 4.7 % 15,451 1.07 (0.79 to 1.44)†¶ 0.67¶ Proportion in HBV+ vs. HBV

No General population aged at least 17 years

Health care employment, household contact with Alter et al. 117 1989 0 % 76 11 % 152 NR NS† Proportion in HBV+ vs. HBV

No General population adults with no obvious cause of acute HBV and matched controls

Military service,

ever McQuillan et al. 29 1999 13.2 % 961 14.6 % 15,568 0.89 (0.73 to 1.08)‡ 0.23 Proportion in HBV+ vs. HBV

No General population aged at least 17 years223Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Unemploy ed Alter et al. 117 1989 20 % 76 6 % 152 NR 0.01‡ Proportion in HBV+ vs. HBV

Yes General population adults with no obvious cause of acute HBV and matched controlsEducation Education: Less than high school McQuillan et

a l. 29 1999 56.4 % 1

, 081 40.9 % 15,431 1.5 (1.1 to 2.1)‡ SS Proportion in HBV+ vs. HBV

vs. some college Yes General population

Education: High school McQ uillan et al. 29 1999 24.3 % 1

, 081 31.0 % 15,431 1.1 (0. 9 to 1.5)‡ SS Proportion in HBV+ vs. HBV

vs. some college No General populationMarital Status Ma rital status: Divorced/ separated McQuillan et al. 29 1999 10.6 % 1

, 301 10.7 % 15,284 1.6 (1.1 to 2.2)‡ SS Proportion in HBV+ vs. HBV
vs. any other
status Yes General population aged at least 17 years224Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Children and AdolescentsBirthplace Korean

- born children: Carrier rate Hann et al. 122 2007 NR NR NR NR NR 0.022† U.S. born Yes Korean

- American church

goers, children

Korean

- born children: antibody rate Hann et al. 122 2007 NR NR NR NR NR <0.001† U.S. born Yes Korean

- American church

goers, children

Special PopulationsSex Male Tabibian et al. 121 2008 100 % 40 96.6 % 89 NR NS† Preva

lence in HBV+ vs. HBV

No Psychiatric inpatient
veterans

Male Hwang et

a l. 124 2006 32 % 274 39 % 4

, 047 RR : 0.77 (0.61 to 0.99)†;

OR : 0.69 (0.49 to 0.97)‡ <0.05 for both Preva

lence HBV+ vs. HBV

No, protecti

ve College students

Male Lin et al. 123 2007 NR NR NR NR RR : 2.1 (1.6 to 2.7)‡ SS Preva

lence HBV+ in Females Yes Asian Americans

Male Lee et al. 120 2008 NR 24 NR 609 1.69 (0.96 to 2.98)† NS Preva

lence HBV+ v s. HBV

No Korean Americans225Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

PopulationAge Age, mean Tabibian et al. 121 2008 48.9 mean 40 48.9

mean 89 NR NS† Mean age HBV+ vs. HBV

No Psychiatric inpatient
veterans

Age (continuous) Hwang et al. 124 2006 NR 269 NR 4

, 054 1.04 (1.03 to 1.06)‡ <0.05 Mean age in HBV+ vs. HBV

Yes College students

Age ≤ 20 years Hann et al. 122 2007 NR 377 NR 5

, 753 NR 0.0051† >20 years Yes Korean

- American church

goers
Age ≤ 30 years Lee et al. 120 2008 NR NR NR NR 0.072 (0.02 to 0.21) SS HBV+ vs. HBV

- in
age >50 years Yes, protecti

ve Korean

- American chu rch

goers

Age 30 to 49 years Lee et al. 120 2008 NR NR NR NR 0.287 (0.15 to 0.55)† <0.001 HBV+ vs

. HBV

- in
age >50 years Yes, protecti

ve Korean

- American church

goers

Age over 35 years Turner et al. 127 1989 NR 14 NR 94 RR : 3.6 (1.2 to 11.2)† NR HBV+ in <35 years Yes Embalmers in high

prevalence urban area

Age over 50 years Butterfield et al. 125 2004 NR 80 NR 276 1.27 (0.67 to 2.39)‡ NS Preva

lence HBV+ vs. HBV

No Psychiatr ic inpatient
veterans

Age 30

- 39 Lin et al. 123 2007 NR 283 NR 2

, 880 RR : 1.4 (0.7 to 2.6)‡ NS Preva

lence HBV+ in age <30 No Asian Americans226Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Age 40

- 49 Lin et al. 123 2007 NR 283 NR 2

, 880 RR : 1.5 (0.9 to 2.7)‡ NS Preva

- lence HBV+ in age <30 No Asian Americans

Age 50

- 59 Lin et al. 123 2007 NR 283 NR 2

, 880 RR : 1.0 (0.6 to 1.5)‡ NS Preva

- lence HBV+ in age <30 No Asian Americans

Age 60

- 69 Lin et al. 123 2007 NR 283 NR 2

, 880 RR : 0.9 (0.5 to 1.7)‡ NS Preva

- lence HBV+ in age <30 No Asian Americans

Age ≥70 Lin et al. 123 2007 NR 283 NR 2

, 880 RR : 0.6 (0.3 to 1.2)‡ NS Preva

- lence HBV+ in age <30 No Asian AmericansRace/Ethnicity Ethnicity, Caucasian Tabibian et al. 121 2008 40 % 40 55 % 89 NR NS† Preva

- lence in HBV+ vs. HBV

- No Psychiatric inpatient
veterans

Ethnicity, African

- A merican Tabibian et al. 121 2008 37.5 % 40 31 % 89 NR NS† Preva

- lence in HBV+ vs. HBV

- No Psychiatric inpat ient
veterans227Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

African

American Race Butterfield et al. 125 2004 NR 80 NR 276 2.79 (1.41 to 5.53)‡ <0.01 Preva

lence HBV+ vs. HBV

- vs. White Yes Psychiatric inpatient
veterans

B lack non

Hispanic Hwang et al. 124 2006 36 % 269 26 % 4

, 001 RR : 1.92 (1.44 to 2.56)†;

OR : 1.95 (1.34 to 2.84)‡ <0.05 for both Preva

lence HBV+ vs. HBV

- vs. White

non

Hispanic Yes College students

Ethnicity, Hispanic Tabibian et al. 121 2008 12.5 % 40 8 % 89 NR NS† Preva

lence in HBV+ vs. HB V

No Psychiatric inpatient
veterans

Hispanic or Latino Hwang et al. 124 2006 12 % 269 23 % 4

, 001 RR : 0.72 (0.48 to 1.08)†;

OR : 0.81 (0.49 to 1.34)‡ NS Preva

lence HBV+ vs. HBV

- vs. W

hite

non

Hispanic No College students228Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

Population

Asian Hwang et al. 124 2006 20 % 269 5 % 4

, 001 RR : 4.49 (3.26 to 6.19)†;

OR : 9.98 (6.01 to 16.55)‡ <0.05 for both Preva

lence HBV+ vs. HBV

- vs. W

hite

non

Hispanic Yes College studentsBirth-country Country of birth: East Asia, excluding China Lin et al. 123 2007 NR 283 NR 2

, 880 RR : 0.8 (0.6 to 1.1)‡ NS Preva

lence HBV+ vs

. born in China No Asian Americans

Country of birth: Southeast Asia/Pacific Islands Lin et al. 123 2007 NR 283 NR 2

, 880 RR : 1.2 (0.8 to 1.7)‡ NS Preva

lence HBV+ vs. born in Chi na No Asian Americans

Country of birth: United States Lin et al. 123 2007 NR 283 NR 2

, 880 RR : 0.05 (0.01 to 0.3)‡ SS Preva

lence HBV+ vs. born in China Yes, protec

tive Asian Am ericans229Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

PopulationOccupation Health care workers Tabibian et al. 121 2008 17.5 % 40 12.0 % 89 NR NS† Preva

lence in H BV+ vs. HBV

No Psychiatric inpatient
veterans

Healthcare

related job with frequent blood
exposure Hwang et al. 124 2006 7 % 270 4 % 3

, 987 RR : 1.83 (1.18 to 2.84)† <0.05 HBV

- Yes Colle ge students

Healthcare worker or spouse of Butterfield et al. 126 1990 8 % 12 7.5 % 1

, 454 1.07 (0.13 to 8.7)†¶ 0.947¶ Preva

lence HBV+ vs. HBV

No Obstetric populationEducation Education,
years Tabibian et al. 121 2008 13.5 mean 40 13.4

mean 129 NR NS† Mean
years education in HBV+ vs. HBV

No Psychiatric inpat ient
veterans

Enrolled in 2 year college Hwang et al. 124 2006 48 % 274 33 % 4

, 054 RR : 1.81 (1.44 to 2.27)†;

OR : 1.64 (1.13 to 2.40)‡ p <0.05 HBV
preva

lence vs. 4 year college Yes Col lege students230Category

Factor Citation YearPercentage ofInfected with FactorTotal NumberInfectedPercentage ofUninfectedwithFactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison MadeAssociated inStudy?

PopulationEconomic Homeless Tabibian et al. 121 2008 77.5 % 40 66 % 89 NR NS† Preva

lence in HBV+ vs. H BV

No Psychiatric inpatient
veterans

Independent or live with family (vs. homeless, institutional

ized, or other) Butterfield et al. 125 2004 NR 80 NR 276 0.82 (0.39 to 1.72)‡ N S Preva

lence HBV+ vs. HBV

No Psychiatric inpatient
veteransMaritalStatus Currently married Butterfield et al. 125 2004 NR 80 NR 276 1.67 (0.83 to 3 .40)‡ NS Preva

lence HBV+ vs

. HBV

No Psychiatric inpatient
veterans

* Odds ratios as reported in publication, unless otherwise specified

** As reported in publication, unless otherwise specified

† Univariate, unadjusted ‡ Multivariate, adjusted for other factors ¶ Calculated by ECR I Institute231 

### Table 40

. HCV: Nonbehavioral Risk FactorsCategory

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Signs and Symptoms

Blood DonorsSigns ALT reactive Orton et al. 104 2004 20 % 65 <1 % 225 47 (6.7 to 2

, 004)† <0.001 Proportion in HCV+ vs. HCV

Yes Blood donors

General Popul ationSigns Jaundice Nguyen et al. 113 2005 20.3 % 225 5.4 % 204 Not reported (NR) <0.001 Proportion HCV+ vs. HCV

Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)

Serum alanine aminotransferase levels <40 U/L Armstrong et al. 30 2006 49 % 220 92 % 12,900 NR Not significant ( NS ) † 0

- 39 U/L No G eneral
p

opulation aged 18 to 49 years

Serum alanine aminotransferase levels 40

- 79 U/L Armstrong et al. 30 2006 35 % 220 7 % 12,900 NR <0.005† 0

- 39 U/L Yes G eneral population aged 18 to 49 years

Serum alanine aminotransferase levels 80

- 119 U/L Armstrong et al. 30 2006 7 % 220 1 % 12,900 NR >0.05† 0

- 39 U/L Yes G eneral population aged 18 to 49 years232Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Serum alanine aminotransferase levels ≥120 U/L Armstrong et al. 30 2006 8 % 220 4 % 12,900 NR >0.05† 0

- 39 U/L Yes G eneral population aged 18 to 49 years

Elevated liver
enzyme Fischer et al. 114 2000 27 % 11 6 % 1

, 369 NR <0.05† Proportion in HCV+ vs. HCV

Yes Adults comprising individuals at risk for HCV and healthcareworker

s enrolled in HMO

Hepatitis

- related diagnoses (HAV, HBV, HIV, or el evated liver enzyme from health r ecord) Fischer et al. 114 2 000 NR 11 NR 1

, 369 13.9 (2.7 to 72.1)† 0.002 Proportion in HCV+ vs. HCV

Yes Adults comprising individuals at risk for HCV and healthcareworker

s enrolled in HMO

Co

- Morbidity

Potential Tissue DonorsTransfusion Blood transfusion recipient or donor Sanche z et al. 103 2006 NR 18 NR 56 NR NS Proportion in HCV+ vs. HCV

No Potential tissue donors, as reported by
next of kin233Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

PopulationNonspecific Exposure History of transplant Sanchez et al. 103 2006 NR 18 NR 56 NR NS Proportion in HCV+ vs. HCV No Potential tissue d

onors,

as reported by
next of kin

Accidental needle stick Sanchez et al. 103 2006 NR 18 NR 56 NR NS Proportion in HCV+ vs. H CV No Potential tissue donors,

as reported by
next of kin

Surgeries Sanchez et al. 103 2006 NR 18 NR 56 NR NS Proportion in HCV+ vs. HCV No Potential tissue donors,

as reported by
next of kin

HIV testing Sanchez et al. 103 2006 NR 18 NR 56 NR NS† P roportion in HCV+ vs. HCV No Potential tissue donors,

as reported by
next of kinOther Liver disease Sanchez et al. 103 2006 N R 18 NR 56 NR NS Proportion in HCV+ vs. HCV No Potential tissue donors,

as reported by
next of kin

Chest pain Sanchez et al. 103 2006 NR 18 NR 56 2.66 (0.96 to 7.38)† 0.054 Proportion in HCV+ vs. HCV Yes Potential tissue donors,

as reported by
next of kin234Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Cardiac medications Sanchez et al. 103 2006 NR 18 NR 56 2.84 (1.0 to 8.07)† 0.043 Proportion in HCV+ vs. HCV Yes Potential tissue donors,

as reported by
next of kin

Kidney stones Sanchez et al. 103 2006 NR 18 NR 56 5.48 (1.38 to 21.80)† 0.008 Proportion in HCV+ vs. HCV Yes Potential tissue donors, as reported by next of kin

Lung disease Sanchez et al. 103 2006 NR 18 NR 56 3.20 (0.98 to 10.41)† 0.044 Proportion in HCV+ vs. HCV Yes Potential tissue donors, as reported by next of kin

Treatme nt by physician in last 2 years Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue dono rs, as reported by next of kin

Medical hospitalizations Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by next of kin

Psychiatric hospitalizations Sanchez et al. 103 2006 NR 18 NR 56 NR N S† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by next of kin235Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Medical illnesses Sanchez et al. 103 20 06 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by next of kin

Medications Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next of kin

Toxic exposure Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next of kin

Malaria exposure or
treatment Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next of kin

Chagas disease
exposure or treatment Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next of kin

Rabies exposure Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next of kin236Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Heart disease Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next of kin

Hypertension Sanchez e t al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next of kin

Kidney d isease Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next o f kin

Gastrointestinal disease Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue don ors, as reported by
next of kin

Cancer history Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Pote ntial tissue donors, as reported by
next of kin

Diabetes history Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HC V+ vs. HCV No Potential tissue donors, as reported by
next of kin237Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Pulmonary disease Sanchez et al. 103 2006 NR 18 NR 56 NR NS † Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next of kin

Rheumatologic disease Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next of kin

Connective tissue disease Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next of kin

Dermatologic disease Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next of kin

Neurologic disease Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next of kin

Ocular disease Sanchez et al. 103 2006 NR 18 NR 56 NR NS† Proportion in HCV+ vs. HCV No Potential tissue donors, as reported by
next of kin238Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Potential and Actual Organ DonorsInfection HBV Surface Antig en Positive Gasink et al. 102 2006 0.4 % 261 0.03 % 10,654 NR 0.003† Proportion in HCV+ vs. HCV

Yes Heart trans plant donorsOther Diabetes mellitus Gasink et al. 102 2006 1.6 % 261 1.7 % 10,654 NR 0.86† Proportion in HCV+ vs. HCV No Heart transplant donors

Previous myocardial infarction Gasink et al. 102 2006 0 261 0.68 % 10,654 NR 0.18† Proportion in HCV+ vs. HCV No Heart transplant donors

Hypertension Gasink et al. 102 2006 15.2 % 261 11.3 % 10,654 NR 0.05† Proportion in HCV+ vs. HCV Yes Heart transplant donors

Creatinine >1.5 mg/dL Gasink et al. 102 2006 12.3 % 261 13.4 % 10,654 NR 0.60† Proportion in HCV+ vs. HCV No Heart transplant donors239Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Blood DonorsTransfusion Transfusion Conry

Cantilena et al. 106 1996 27 % 248 8 % 131 4.68 (3.44 to 6.36)†¶ <0.001‡ Proportion in HCV+ vs. HCV

Yes Blood donors initially positive
on enzyme

- linked immunosorbent assay (EIA)

Received blood transfusion Murphy et al. 105 2000 23 % 758 6 % 1

, 039 Non

- IDU : 10.9 (6.5 to 18.2) † ;

IDU : 0.9 (0.1 to 9.1) † Statistical

ly signifi

cant ( SS ) for non

IDU, NS for IDU Proportion in HCV+ vs. HCV

- final multivariable logistic regression mod el Yes, for

non

IDU Blood donors

Previous blood transfusion Murphy et al. 107 1996 13 % 3

, 126 5.9 % 859,272 2.8 (2.5 to 3.1)‡ SS Proportion in HCV+ vs. HCV

Yes Blood donorsNonspecific Exposure Needle stick among healthcare workers Conry

Cantilena et al. 106 1 996 4 % 248 2 % 131 NR >0.05† Proportion in HCV+ vs. HCV

No Blood donors initially positive on EIA

Bloody needle stick injury in medical
context Murphy et al. 105 2000 11 % 758 4 % 1,039 3.2 (1.9 to 2.6)‡ SS Proportion in HCV+ vs. HCV

adjusted for IDU Yes Blood donors240Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Stuck/cut with bloody object Murphy et al. 105 2000 11 % 758 4 % 1,039 2.1 (1.1 to 4.1)‡ SS Proportion in HCV+ vs. HCV

- final multivariable logistic regression model Yes Blood donors

Had s ame

- day surgery in the 6 months before donation Orton et al. 104 2004 9.2 % 65 6.3 % 225 1.5 (0.5 to 4.5)† 0.41 Proportion in HCV+ vs. HCV

No Blood donors

Had a medical and/or surgical procedure in the 6 months before d onation Orton et al. 104 2004 21.5 % 65 14.3 % 225 1.6 (0.8 to 3.3)† 0.16 Proportion in HCV+ vs. HCV

No Blood donors

Had surgery Murphy et al. 105 2000 74 % 758 64 % 1,039 1.7 (1.2 to 2.4)‡ SS Proportion in HCV+ vs. HCV

adjusted for IDU Yes Blood donors

Had sutures Murphy et al. 105 2000 77 % 758 65 % 1,039 1.7 (1.2 to 2.4)‡ SS Proportion in HCV+ vs. HCV

adjusted for IDU Yes Blood donors241Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Was hospitalized in the 6 mo nths before donation Orton et al. 104 2004 7.7 % 65 2.2 % 225 3.7 (0.8 to 16)† 0.05 Proportion in HCV+ vs. HCV

Yes Blood donors

Acupuncture
treatment Conry

Cantilena et al. 106 199 6 4 % 248 1 % 131 NR >0.05† Proportion in HCV+ vs. HCV

No Blood donors initially positive on EIA

Acupuncture Murphy et al. 105 2000 9 % 758 5 % 1,039 1.4 (0.8 to 2.4)‡ NS Proportion in HCV+ vs. HCV

adjusted for IDU No Blood donors

Had dental work in the 6 months before donation Orton et al. 104 2004 35.4 % 65 38.8 % 225 0.9 (0.5 to 1.5)† 0.61 Proportion in HCV+ vs. HCV

No Blood donors

Teeth cleaned 1

- 10 times Murphy et al. 105 2000 57 % 758 46 % 1,039 0.7 (0.3 to 1.4)‡ NS Proportion in HCV+ vs. HCV

adjusted for IDU with reference to never had cleaning No Blood donors2 42Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Teeth cleaned 11

- 20 times Murphy et al. 105 2000 23 % 758 33 % 1,039 0.5 (0.2 to 1.0)‡ NS Proportion in HCV+ vs. HCV

- adjusted for IDU with reference to never had cleaning No Blood donors

Teeth clea ned >20 times Murphy et al. 105 2000 11 % 758 12 % 1,039 0.6 (0.2 to 1.3)‡ NS Proportion in HCV+ vs. HC V

- adjusted for IDU with reference to never had cleaning No Blood donors

Tooth extraction Murphy et al. 105 2000 73 % 758 68 % 1,039 1.3 (0.9 to 1.8)‡ NS Proportion in HCV+ vs. HCV

- adjusted for IDU No Blood donors

In a fight with blood exposure last 6 months Orton et al. 104 2004 7.7 % 65 2.2 % 225 3.7 (0.8 to 16† 0.0 5 Proportion in HCV+ vs. HCV

- Yes Blood donors

By a bite with blood exposure last 6 months Orton et al. 104 2004 4.6 % 65 0 % 225 Un defined (because zero in uninfected group) 0.01 Proportion in HCV+ vs. HCV

- Yes Blood do nors243Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

During a haircut with blood exposure last 6 months Orton et al. 104 2004 23.1 % 65 13.8 % 225 1.9 (0.9 to 3.9)† 0. 11 Proportion in HCV+ vs. HCV

No Blood donors

During a manicure with blood exposure last 6 months (women only) Orton et al. 104 2004 20.0 % 30 3.8 % 105 5.2 (1.1 to 27) † 0.02 Proportion in HCV+ vs. HCV

Yes Blood donors

At accident site with blood exposure last 6 months Orton et al. 104 2004 6.2 % 65 1.3 % 225 4.9 (0.8 to 34) † 0.05 Proportion in HCV+ vs. HCV

Yes Blood donors

Lived with hepatitis

case Murphy et al. 105 2000 16 % 758 6 % 1

, 039 1.4 (0.9 to 1.5)‡ NS Proportion in HCV+ vs. HCV

adjusted for IDU No Blood donors

Relative with hepatitis Murphy et al. 105 2000 12 % 758 8 % 1

, 039 0.9 (0.6 to 1.5)‡ NS Proportion in HCV+ vs. HCV

adjusted for IDU No Blood donors

Lived with transfusion recipient Murphy et al. 105 2000 12 % 758 7 % 1

, 039 1.5 (1.0 to 2.3)‡ SS Proportion in HCV+ vs. HCV

adjusted for IDU Yes Blood donors244Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

PopulationOtherinfection Had a sexually transmitted diseas e (STD) in last 6 months before donation Orton et al. 104 2004 6.2 % 65 0 % 225 Un defined (because zero in control group had factor) 0.002† Proportion in HCV+ vs. HCV

Yes Blood donors

History of STD Conry

Cantilena et al. 106 1996 28 % 248 10 % 131 NR <0.001† Proportion in HCV+ vs. HCV

Yes Blood donors initially positive on EIA

STD Murphy et al. 105 2000 33 % 758 15 % 1

, 039 2.5 (1.8 to 3.5)‡ SS Proportion in HCV+ vs. HCV

adjusted for IDU Yes Blood donors

Other reactive infections diseas e markers (HIV, syphilis) Orton et al. 104 2004 8 % 65 0 % 225 Un defined (because zero in control group) <0.001† Proportion in HCV+ vs. HCV

Yes Blood donors

Seropositive for other infectious di seases (HTLV I and II, HIV , HBV

core) Murphy et al. 107 1996 NR 3

, 126 NR 859,272 10.4 (9.6 to 11.4)‡ SS Proportion in HCV+ vs. HCV

Yes Blood donors245Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

PopulationOther Receive d Hepatitis B Vaccine in last 6 months Orton et al. 104 2004 32.3 % 65 24.6 % 225 1.5 (0.8 to 2.7)† 0.21 Proportion in HCV+ vs. HCV

No Blood donors

Gamma globulin injection Murphy et al. 105 2000 22 % 758 16 % 1

, 039 1.6 (1.0 to 2.6)‡ SS Proportion in HCV+ vs. HCV

- final multivariable logistic regression model Yes Blood donors

History of hepatitis Orton et al. 104 2004 1.5 % 65 1.8 % 225 0.9 (0.02 to 10) † 1.00 Proportion in HCV+ vs. HCV

No Bloo d donors

History of liver disease Conry

Cantilena et al. 106 1996 31 % 248 5 % 131 NR <0.001† Proportion in HCV+ vs. HCV

Yes Blood donors initially positive on EIA246Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

General PopulationTransfusion Blood transfusion N guyen et al. 113 2005 43.2 % 225 13.7 % 204 8.62 (4.71 to 15.80)† <0.001 HCV

- Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)

Blood transfusion(s) Hand and Vasquez 112 2005 25 % 320 19 % 307 NR†;

3.2 (2.0 to 5.1)‡ 0.051†;

<0.001‡ Proportion in HCV+ vs. HCV

Yes Adults tested for HCV in health system because of clinical suspicion

Blood transfusion Kaur et al. 116 1996 14.6 % 559 7.1 % 6

, 170 4.09 (2.97 to 5.62)‡ NR Proportion in HCV+ vs. HCV

Yes Volunteers from general population

Transfusion, blood, before 19 92 Armstrong et al. 30 2006 14 % 128 5 % 5

, 665 2.6 (0.9 to 7.3)‡ <0.005 Propor tion in HCV+ vs. HCV

Yes General population aged 20 to 59
years

Transfusion, blood, before 1992, self

- reported Fischer et al. 114 2000 55 % 11 25 % 1

, 369 4.61 (3.42 to 6.21)†¶ <0.001 Proportion in HCV+ vs. HCV

Yes Adults comprising individuals at risk for HCV and healthcareworker

s enrolled in HMO247Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Tran sfusion, blood, before 1992,

as recognized in HMO database Fischer et al. 114 2000 0 % 11 <1 % 1

, 369 NR NS† Proportion in HCV+ vs. HCV

- No Adults comprising individuals at risk for HCV and healthcareworker s enrolled in HMONonspecific Exposure Needlestick injur y Kaur et al. 116 1996 6.4 % 543 8.9 % 5

, 982 0.70 (0.55 to 0.89)† NR Proportion in HCV+ vs. HCV

- No (pro

tec

tive) Volunteers from general population

– Note this population had a large proportion of healthcare workers who had a lower infection prevalence

Contact with blood Hand and Vasquez 11 2 2005 5 % 320 4 % 307 NR 0.798† Proportion in HCV+ vs. HCV

- No Adults tested for HCV in health system because of clinical suspicion

Surgery, any Fischer et al. 114 2000 91 % 11 78 % 1

, 369 NR NS† Proportion in HCV+ vs. HCV

- No Adults comprising individuals at risk for HCV and healthc areworker

s enrolled in HMO248Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Surgery Kaur et al. 116 1996 8.3 % 565 8.6 % 6

, 147 0.96 (0.80 to 1.16)† NS Proportion in HCV+ vs. HCV

No Volunteers from general population

Surgery

, ex ploratory Fischer et al. 114 2000 55 % 11 41 % 1

, 369 NR NS† Proportion in HCV+ vs. HCV

No Adults comprising individuals at risk for HCV and healthcareworker

s enrolled in HMO

Emergency department
treatment Nguyen et al. 113 2005 88.3 % 225 79.4 % 204 NR 0.02† Proportion HCV+ vs. HCV

Yes Ad ults at general internal medicine clinic (controls) and hepatology clinic (cases)

Hospitalization Nguyen et al. 113 2005 87.8 % 225 76.5 % 204 NR 0.003† Proportion HCV+ vs. HCV

Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cas es)

Kidney dialysis Nguyen et al. 113 2005 5.4 % 225 0.5 % 204 11.36 (1.15 to 86.5)†¶ 0.003† Proportion HCV+ vs. HCV

Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)249Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Hemodialysis Hand and Vasquez 112 2005 1 % 320 3 % 307 NR 0.068† Proportion in HCV+ vs. HCV

No Adults tested for HCV in health system because of clinical suspicion

Hemodialysis Kaur et al. 116 1996 42.3 % 544 8.1 % 6

, 033 10.95 (3.85 to 31.13)‡ NR Proportion in HCV+ vs. HCV

Yes Volunteers from general population

Acupuncture Hand and Vasquez 112 2005 2 % 320 0.7 % 307 NR 0.106† Proportion in HCV+ vs. HCV

No Adults tested for HCV in health system because of clinical suspicion

Family member treated for viral hepatitis Fischer et al. 114 2000 9 % 11 6 % 1

, 369 NR NS† Proportion in HCV+ vs. HCV

No Adults comprising individuals at risk for HCV and healthcareworker

s enrolled in HMO

At least one family member with HCV Nguyen et al. 113 2005 21 .2 % 225 6.9 % 204 NR <0.001† Proportion HCV+ vs. HCV

Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)250Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Had a blood test for HBV Nguyen et al. 113 2005 78.8 % 225 24.5 % 204 NR <0.001† Proportion HCV+ vs. HCV

Yes Adults at g eneral internal medicine clinic (controls) and hepatology clinic (cases)OtherInfection HIV positive Nguyen et al. 113 2005 1.8 % 225 1.5 % 204 NR >0.99† Proportion HCV+ vs. HCV

No Adults at general internal medicine clinic (controls) and hepatology clinic (cas es)

HIV positive Armstrong et al. 30 2006 3 % 134 0.5 % 5

, 549 NR Incon

clusiv e due to small number positives HCV

- Incon clus

ive Adults in general population aged 18 to 49 years

HIV positive Hand and Vasquez 112 2005 10 % 320 8 % 307 NR 0.351† Proportion in HCV+ vs. HCV

No Adults tested for HCV in health system because of clinical suspicion

HBV Positive, self

- report Nguyen et al. 113 2005 21.2 % 225 2.5 % 204 4.71 (1.49 to 14.83)† NR Proportion HCV+ vs. HCV

Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)251Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Herpes Simplex Virus Type 2 (HSV

- 2) Positive Armstrong et al. 30 2006 43 % 134 19 % 5

, 476 NR <0.005† Proportion HCV+ vs. HCV

Yes General population age 18 to 49 years

STD, past treatment for Nguyen et al. 113 2005 24.8 % 225 18.1 % 204 NR 0.10† Proportion HCV+ vs. HCV

No Adults at general internal medicine clinic (controls) and hepatology clinic (cases)Other Blood donor Nguyen et al. 113 2005 38.7 % 225 58.3 % 204 NR <0.001† Proportion HCV+ vs. HCV

No (prot ectiv e) Adults at general internal medicine clinic (controls) and hepatology clinic (cases)

Blood donor, rejected as Nguyen et al. 113 2005 28.4 % 225 16.2 % 204 2.57 (1.49 to 4.43)† 0.002 Proportion HCV+ vs. HCV Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cas es)

Vaccinated for hepatitis B Kaur et al. 116 1996 2.8 % 528 10 % 5

, 737 0. 37 (0.22 to 0.62)‡ NR Propo rtion in HCV+ vs. HCV

No (prot ectiv e) Volunteers from general population252Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Refu sed life insurance Nguyen et al. 113 2005 20.7 % 225 3.9 % 204 2.75 (1.05 to 7.25)† <0.001 Proportion HCV+ vs. HCV

Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)

Hepatitis diagnosis Fischer et al. 114 2000 36 % 11 4 % 1

, 369 NR <0.001† Proportion in HCV+ vs. HCV

Yes Adults comprising individuals at risk for HCV and healthcareworker

s enrolled in HMO

Moving motor vehicle accident Nguyen et al. 113 2005 15.3 % 225 5.4 % 204 NR <0.001† Proportion HCV+ vs. HCV

Yes Adults at general internal medicine clinic (co ntrols) and hepatology clinic (cases)

Diabetes mellitus Nguyen et al. 113 2005 14.4 % 225 9.8 % 204 NR 0.18† Proportion HCV+ vs. HCV

No Adults at general internal medicine clinic (controls) and hepatology clinic (cases)

Heart disease Nguyen et al. 113 2005 5.4 % 225 6.9 % 204 NR 0.55† Proportion HCV+ vs. HCV

No Adults at general internal medicine clinic (controls) and hepatology clinic (cases)253Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

“ Blood problems ” Nguyen et al. 113 2005 18.5 % 225 5.4 % 204 NR <0.001† Proportion HCV+ vs. HCV

Yes Adults at general internal medi cine clinic (controls) and hepatology clinic (cases)

Treated for chronic fatigue Fischer et al. 114 2000 18 % 11 10 % 1

, 369 NR NS† Proportion in HCV+ vs. HCV

No Adults comprising individuals at risk for HCV and healthcareworker

s enrolled in HMO

Injection of medication in Mexico H and and Vasquez 112 2005 22 % 320 27 % 307 NR 0.164† Proportion in HCV+ vs. HCV

No Adults tested for HCV in heal th system because of clinical suspicion

Demographics

Potential Organ DonorsSex Male Sex Gasink et al. 102 2006 80.1 % 261 31 % 10,654 NR <0.001 HCV

- Yes Heart transplant donorsAge Age, median and interquartile range Gasink et al. 102 2006 Median: 38 (IQR: 32

- 43) 261 Median: 29 (IQR: 20

- 41) 10,654 NR <0.001 HCV

- Yes Heart transplant donors254Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

PopulationRace/Ethnicity Ethnicity: White Gasink et al. 102 2006 87.7 % 261 85.5 % 10,654 NR 0.55 Proportions in HCV+ vs. HCV

No Heart transplant donors

Ethnicity: Black Gasink et al. 102 2006 10.7 % 261 12.3 % 1,304 NR

Ethnicity: Other Gasink et al. 102 2006 1.5 % 261 2.2 % 10,654 NR

Blood DonorsSex Male Sex Orton et al. 104 2004 54 % 65 54 % 225 1.0 (0.6 to 1.8)† 0.97 Proportion in HCV+ vs. HCV

No Blood donors

Ma le Sex Murphy et al. 107 1996 66 % 3,126 53 % 8 59,272 1.9 (1.8 to 2.1)‡ SS Proportion in HCV+ vs. HCV

Yes Blood donors

Female sex Conry

Cantilena et al. 106 1996 44 % 248 37 % 131 NR 0.17† Proportion in HCV+ vs. HCV

No Blood donors initially positive on EIAAge Mean age Orton et al. 104 2004 43 (mean age) 65 41 (mean age) 225 NR <0.001 Mean in HCV+ vs. HCV

No Blood donors

Mean age Conry

Cantilena et al. 106 1996 37 (mean age) 248 44 ( mean age) 131 NR <0.001† Proportion in HCV+ vs. HCV

Yes Blood donors initially positive on EIA255Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

PopulationRace/Ethnicity White non

- Hispanic Orton et al. 104 2004 84 % 65 89 % 225 1.6 (0.7 to 3.5)† 0.26 HCV+ race

“other ” No Blood do nors

Black race Conry

Cantilena et al. 106 1996 19 % 248 7 % 131 NR 0.002† Proportion in HCV+ vs. HCV

Yes Blood donors initially positive on EIA

Black race Murphy et al. 107 1996 17 % 3,126 7 % 859,272 1.7 (1.6 to 1.9)‡ SS Proportion in HCV+ vs. HCV

- with refe rence to white Yes Blood donors

Asian Murphy et al. 107 1996 1.8 % 3,126 3 % 859,272 0.4 (0.3 to 0.6)‡ SS Proportion in HCV+ vs. HCV

- with reference to white No (prot ectiv e) Blood donors

Hispanic Orton et al. 104 2004 5 % 65 7 % 225 0.6 (0.1 to 2.1)† 0.58 Proportio n in HCV+ vs. HCV

No Blood donors

Hispanic Murphy et al. 107 1996 8.4 % 3,126 6 % 859,272 1.3 (1.1 to 1.5)‡ SS Proportion in HCV+ vs. HCV

- with reference to white Yes Blood donorsBirthplace Foreign (not U.S. ) Orton et al. 104 2004 1.5 % 65 7.6 % 225 0.2 (0.0 to 1. 3)† 0.09 Proportion in HCV+ vs. HCV

No Blood donors256Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Foreign (not U.S. ) Murphy et al. 107 1996 6 % 3,126 6 % 859,272 2.8 (2.5 to 3.1)‡ SS Proportion in HCV+ vs. HCV

Yes Blood donorsOccupation Occupational blood
exposure Murphy et al. 105 2000 24 % 758 17 % 1,039 1.7 (1.2 to 2.3)‡ SS Proportion HCV+ vs. HCV

Yes Blood donors

Medical or dental job (frequent blood contact) Orton et al. 104 2004 9.2 % 65 3.6 % 225 2.8 (0.8 to 9.4)† 0.09 Proportion in HCV+ vs. HCV

No Blood donors

Public safety job (frequent blood contact) Orton et al. 104 2004 3.1 % 65 3.6 % 225 1.0 (0.1 to 5.4)† 1 .00 Proportion in HCV+ vs. HCV

No Blood donorsEducation High School/ GED or less Orton et al. 104 2004 48 % 65 28 % 225 4.76 (confidence intervals
not reported) <0.001 Test for trend among the three educational
strata Yes

– low level Blood donor

Associate/ vocational

- technical Orton et al. 104 2004 40 % 65 40 % 225 2.8

At least Bachelor ’ s degree Orton et al. 104 2004 12 % 65 32 % 225 1.0

No college education Conry

Cantilena et al. 106 1996 54 % 248 16 % 131 NR <0.001 Proportion in HCV+ vs. HCV

Yes Blood donors initially positive on EIA257Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

PopulationMaritalStatus Married Murphy et al. 105 2000 60 % 758 71 % 1

, 039 0.61 (0.50 to 0.75)†¶ <0.001 Proportion in HCV+ vs. HCV

Yes,
pro

tec

tive Blood donors

General Popula tionSex Male Nguyen et al. 113 2005 55.0 % 225 28.1 % 204 NR <0.001† Proportion HCV+ vs. HCV

Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)

Male McGinn et al. 108 2009 40 % 83 25 % 917 NR 0.02† Proportion in HCV+ vs. HCV

Yes In adult primary care clinic

Male Armstrong et al. 30 2006 64 % 238 48 % 14,841 NR <0.05† Proportion with HCV+ vs. HCV

Yes General population

Male Fischer et al. 114 2000 36 % 11 43 % 1

, 369 NR NS † Proportion with HCV+ vs. HCV

No Adults comprising individuals at risk for HCV and healthcareworker

s enrolled in HMO

Male Kaur et al. 116 1996 13.4 % 544 4.7 % 6

, 275 3.60 (2.66 to 4.87)‡ NR Proportion in HCV+ vs. HCV

Yes Volunteers from general population258Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

PopulationAge Age, mean and standard deviation McGinn et al. 108 2009 Mean : 52.9 (SD : 9.7) 83 Mean : 49.8 (SD : 14.7) 917 NR 0.01† Mean in HCV+ vs. HCV

Yes In adult primary care clinic

Age, decade of Birth 1910

- 1919 Nguyen et al. 113 2005 0 % 225 0.5 % 204 NR <0.001† Proportio n HCV+ vs. HCV

Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases) Age, decade of Birth 1920

- 1929 Nguyen et al. 113 2005 0.9 % 225 5.4 % 204

Age, decade of Birth 1930

- 1939 Nguyen et al. 113 2005 7.7 % 225 7.8 % 204

Age, d ecade of Birth 1940

- 1949 Nguyen et al. 113 2005 24.9 % 225 14.7 % 204

Age, decade of Birth 1950

- 1959 Nguyen et al. 113 2005 51.4 % 225 22.5 % 204

Age, decade of Birth 1960

- 1969 Nguyen et al. 113 2005 13.1 % 225 24.0 % 204

Age, decade of Birth 1970

- 1979 Nguyen et al. 113 2005 2.3 % 225 22.5 % 204

Age, decade of Birth 1980

- 1989 Nguyen et al. 113 2005 0 % 225 2.5 % 204259Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Age <50 years Fischer et al. 114 2000 55 % 11 26 % 1

, 369 NR NS † Proportion in HCV+ vs. HCV

No Adults comprising individuals at risk for HCV and healthcareworker

s enrolled in HMO

Age <60 years Kaur et al. 116 1996 12 % 520 19 % 5

, 853 0.53 (0.40 to 0.71)† NR Proportion in HCV+ vs. HCV

- with references to age <60 No (pro

tec

tive) Volunteers from general populati onRace or Ethnicity Ethnicity: White Nguyen et al. 113 2005 67.1 % 225 57.9 % 204 NR 0.15† Proportion HCV+ vs. HCV

No Adults at general internal medicine clinic (controls) and hepatology clinic (cases)

Ethnicity: Black Nguyen et al. 113 2005 23.9 % 225 30.2 % 204 NR

Ethnicity: Asian Nguyen et al. 113 2005 2.3 % 225 5.9 % 204 NR

Ethnicity: Latino Nguyen et al. 113 2005 3.6 % 225 3.0 % 204 NR

Ethnicity: Other Nguyen et al. 113 2005 3.2 % 225 3.0 % 204 NR260Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Ethnicity: White McGinn et al. 108 2008 11 % 83 10 % 917 NR 0.38† Proportion in HCV+ vs. HCV

No In adult primary care clinic

Ethnicity: Black McGinn et al. 108 2008 31 % 83 32 % 917 NR

Ethnicity: Other McGinn et al. 108 2008 0 % 83 5 % 917 NR

Ethnicity: Latino McGinn et al. 108 2008 58 % 83 53 % 917 NR

Ethnicity:

non

- Hispanic black Armstrong et al. 30 2006 42 % 252 26 % 13,691 1.9 (0.9 to 3.8)‡ N S Proporti on HCV+ vs. Non

Hispanic white No G eneral population aged 20 to 59 years

Ethnicity: Mexic an

- American Armstrong et al. 30 2006 23 % 252 32 % 13,691 2.6 (1.2 to 5.8)‡ SS Proportion HCV+ vs. Non

His panic white Yes G eneral population aged 20 to 59 years

White/Hispanic Kaur et al. 116 1996 7.9 % 507 9.2 % 5

, 764 0.57 (0.39 to 0.83)‡ NR Proportion HCV+ wi th reference to

“other ” Yes, protect ive Volunteers from general population261Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

PopulationNationality U.S. Citizen Nguyen et al. 113 2005 97.7 % 225 97.5 % 204 NR >0.99† Proportion HCV+ vs. HCV

- No Adults at general internal medicine clinic (controls) and hepatology clinic (case s)

Born outside of U.S. Armstrong et al. 30 2006 6 % 233 20 % 14,787 0.2 (0.0 8

- 0.7)‡ SS Born in U.S. HCV+ Yes G eneral population aged 20 to 59 years

Born in Southeast Asia/Africa Kaur et al. 116 1996 7.7 % 559 8.5 % 6

, 069 0.90 (0.50 to 1.64)† NS Proportion in HCV+ vs. HCV

- No Volunteers from general populationLanguage Preferred language

– English McGinn et al. 108 2008 89 % 83 79 % 917 NR 0.03† Proportion in HCV+ vs. HCV

- Yes In adult primary care clinic

Preferred language

– Spanish McGinn et al. 108 2008 11 % 83 20 % 917Occupation Work contact with blood Fischer et al. 114 2000 27 % 11 20 % 1

, 369 NR NS† Proportion in HCV+ vs. HCV

- No Adults comprising individuals at risk for HCV and healthcareworker

s enroll ed in HMO

Healthcare worker Kaur et al. 116 1996 2.9 % 568 10.3 % 6

, 185 0.26 (0.19 to 0.35)† SS Proportion in HCV+ vs. HCV

- Yes (prote ctive) Volunteers from general population262Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Arm ed forces Fischer et al. 114 2000 36 % 11 27 % 1

, 369 NR NS† Proportion in HCV+ vs. HCV

No Adults comprising individuals at risk for HCV and healthcareworker

s enrolled in HMO

Services in U.S. armed forces Armstrong et al. 30 2006 32 % 114 31 % 4

, 063 NR NS Prevalence HCV+ vs. HCV

No Men aged at least 20 years in general population

Job at prison Nguyen et al

. 113 2 005 7.7 % 225 1.5 % 204 NR 0.002† Proportion HCV+ vs. HCV

Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)Education Education

– less than 12 years Armstrong et al. 30 2006 62 % 172 43 % 8,634 NR <0.005† Proportion HBV+ with >12 years Yes Gene ral population aged at least 20 years263Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Education

– 6

th grade or less McGinn et al. 108 2008 10 % 83 11 % 917 NR 0.62† Proportion with level i n HCV+ vs. HCV

No In adult primary care clinic

Education

– 7

- 12 th grade McGinn et al. 108 2008 38 % 83 31 % 917

Education

– High school graduate McGinn et al. 108 2008 25 % 83 25 % 917

Education

– Some college McGinn et al. 108 2008 19 % 83 19 % 917

Educa tion

– At least a college degree McGinn et al. 108 2008 7 % 83 13 % 917

Education

– H igh school or less Nguyen et al. 113 2005 46.4 % 225 22.7 % 204 NR 0.15† Proportion HCV+ vs. HCV

No Adults at general internal medicine clinic (controls) and hepatology clinic (cases) Education

– Some college Nguyen et al. 113 2005 30.6 % 225 25.1 % 204

Education

– At least a college graduate Nguyen et al. 113 2005 23.0 % 225 52.2 % 204264Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

PopulationEconomic Factors Homeless, ever Nguyen et al. 113 2005 9.2 % 225 1.0 % 204 NR <0.001† Proportion HCV+ vs. HCV

Yes Adults at general internal medicine clinic (controls) and hepatology clinic (cases)

Annual Income <15,000 Nguyen et al. 113 2005 13.1 % 225 10.2 % 204 NR 0.90† Proportion HCV+ vs. HCV

No Adults at general internal medicine clinic (controls) and hepatology clinic (cases) Annual Income 15,000

- 25,000 Nguyen et al. 113 2005 12.6 % 225 11.7 % 204

Annual Income 25,000

- 40,000 Nguyen et al. 113 2005 15.9 % 225 19.9 % 204

Annual Income 40,000

- 75,000 Nguyen et al. 113 2005 26.2 % 225 29.1 % 204

Annual Income 75,000

- 100,000 Nguyen et al. 113 2005 18.7 % 225 14.3 % 204

Annual Income >100,000 Nguyen et al

. 113 2 005 13.6 % 225 14.8 % 204

Family income ≥2 times poverty threshold Armstrong et al. 30 2006 31 % 278 49 % 13,362 NR NS† Proportion HCV+ vs. HCV

No General population265Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Family income 1 to 1.9 times poverty threshold Armstrong et al. 30 2006 30 % 278 27 % 13,362 NR NS† Proportion HCV+ vs. HCV

No General populationOther Community

– Rural Nguyen et al. 113 2005 12.8 % 225 10.9 % 204 NR <0.001† Proportion HCV+ vs. HCV

Yes Adults at general inte rnal medicine clinic (controls) and hepatology clinic (cases)

Community

– Suburban Nguyen et al. 113 2005 52.6 % 225 30.6 % 204

Community

– Urban Nguyen et al. 113 2005 34.6 % 225 58.6 % 204

Insurance

– Medicaid McGinn et al. 108 2008 77 % 83 59 % 917 NR <0.001† Proportion with insurance type in HCV+ vs. HCV

Yes In adult primary care clinic

Insu rance

– Medicare McGinn et al. 108 2008 12 % 83 19 % 917266Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Insurance

– Private McGinn et al. 108 2008 10 % 83 21 % 917

Insurance

– Self Pay McGinn et al. 108 2008 1 % 83 1 % 917

Appointment type

– Scheduled McGinn et al. 108 2008 76 % 83 78 % 917 NR 0.86† Proportion with type in HCV+ vs. HCV

No In adult primary care clinic

Appointment type

– Urgen t Care McGinn et al. 108 2008 17 % 83 16 % 917

Appointment type

– Data Missing McGinn et al. 108 2008 7 % 83 6 % 917

Children and AdolescentsSex Male Luban et al. 118 2007 65 % 43 58 % 2,715 1.4 (0.7 to 2.5)†¶ 0.36¶ Proportion HCV+ vs. HCV

No Children who have received blood transf usionsRace/Ethnicity African American Luban et al. 118 2007 42 % 42 37 % 2,474 1.2 (0.7 to 2.3) †¶ 0.51¶ Propo rtion HCV+ vs. HCV No Children who have received blood transfusions

Asian Luban et al. 118 2007 0 % 42 1.5 % 2 ,474 0.7 (0.05 to 12.6) †¶ 0.85¶ Proportion HCV+ vs. HCV No Children who have received blood transfusions267Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue**Comparison madeAssociated in Study?

Population

Caucasian Luban et al. 118 2007 57 % 42 48 % 2,474 1.4 (0.8 to 2.7) †¶ 0.25¶ Proportion HCV+ vs. HCV No Children who have received blood transfusions

Hispanic Luban et al. 118 2007 0 % 42 3.4 % 2,474 0.3 (0.02 to 5.4) †¶ 0.44¶ Proportion HCV+ vs. HCV No Children who have received blood transfusions

* Odds ratios as reported in publication, unless otherwise specified

** As reported in publication, unless otherwise specified

† Univariate, unadjusted ‡ Multivariate, adjusted for other factors ¶ Calculated by ECRI Institute268 

### Table 41

. HIV : Nonbehavioral Risk FactorsCategory

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison M

adeAssociated in Study?

Population

Tissue Donors

Co

- MorbidityTransfusion Blood transfusion recipient or donor Sanchez et al. 103 2006 Not report

e

d (NR) 10 NR 56 NR Not significant (NS) Proportion in HIV+ vs. HIV

No Potential tissu e donors, as reported by next of kinNonspecific Exposure Accidental needle stick Sanchez et al. 103 2006 NR 10 NR 56 NR NS Pr oportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

History of transplant Sanchez et al. 103 200 6 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Surgeries Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kinOther Treatment by physician in last 2 years Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Liver disease Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Medical hospitalizations Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Psychiatric hospitalizations Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin269Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison M

adeAssociated in Study?

Population

Medical illnesses Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Medications Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Toxic exposure Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported b y next of kin

Malaria
exposure or treatment Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potentia l tissue donors, as reported by next of kin

Chagas disease
exposure or treatment Sanchez et al. 103 2006 NR 10 NR 56 NR NS Pr oportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Rabies
exposure Sanchez et al. 103 2006 NR 1 0 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Heart disease Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Hypertension Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Kidney disease Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Gastrointestina l disease Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin270Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison M

adeAssociated in Study?

Population

Cancer history Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Diabetes history Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Pulmonary disease Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Rheumatologic disease Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Connective tissue disease Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next o f kin

Dermatologic disease Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin

Neurologic disease Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potent ial tissue donors, as reported by next of kin

HIV testing Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HI V

No Potential tissue donors, as reported by next of kin

Ocular disease Sanchez et al. 103 2006 NR 10 NR 56 NR NS Proportion in HIV+ vs. HIV

No Potential tissue donors, as reported by next of kin271Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison M

adeAssociated in Study?

Population

General PopulationOther Infection STD, diagnosis of Mehta et al. 109 2008 25 % 229 NR 16,467 1.56 ( 1.15 to 2.11)† NR No STD, HIV+ Yes Hospital inpatients and outpatients

Herpes simplex virus

- 2 (HSV

- 2) antibody McQuillan et al. 101 2006 81 % 31 20 % 5

, 570 17.1 (6.9 to 41.9)†¶ <0.001 Proportion in HCV+ vs. HCV

Yes General population

HSV

- 2
serostatus Nguyen et al. 110 2008 71. 2 % 21 26.9 % 1

, 589 6.46 (2.30 to 18.10)† Statistically significant (SS) Negative Yes General population of adults in New York City

History of syphilis Alpert et al. 115 1996 NR 35 NR 840 NR‡ SS Proportion in HCV+ vs. HCV

Yes Adults at emergency department room

Infection not necessarily

r elated to HIV Alpert et al. 115 1996 NR 35 NR 840 NR‡ SS Proportion in HCV+ vs. HCV

Yes Adults at emergency department room

Demographics

General PopulationSex Male Mehta et al. 109 2008 63 % 229 NR 16,467 1 .30 (0.98 to 1.71)† NR Female HIV+ No Hospital inpatients and outpatients

Male Zetola et al. 111 2008 NR 15 NR 1

, 632 7.68 (0.98 to 60.26)‡ 0.053 Female HIV+ No Public hospital
emergenc y room patients

Male Nguyen et al. 110 2008 57.1 21 42.4 1

, 602 2.01 (0.91 to 4.40)† NS Female HIV+ No General population of adults in New York City272Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison M

adeAssociated in Study?

PopulationAge Age 18

- 30 Zetola et al. 111 2008 NR 15 NR 1

, 632 3.15 (1.03 to 9.61)‡ 0.044 Proportion HIV+ vs. HIV

- >46 years Yes Public hospital emergency room patients

Age 31

- 45 Zetola et al. 111 2008 NR 15 NR 1

, 632 0.76 (0.15 to 2.76)†; NR‡ 0.732†; NS‡ Proportion HIV+ vs. HIV

- >46 years No Public hospital emergency room patients

Age 25

- 39 Mehta et al. 109 2008 48 % 229 NR 16,467 3.22 (1.84 to 5.64)† NR Age 15

- 24, HIV+ Yes Hospital inpatients and outpatients

Age 40

- 54 Mehta et al. 109 2008 42 % 229 NR 1 6,467 3.39 (2.24 to 6.91)† NR Age 15

- 24 HIV+ Yes Hospital inpatients and outpatients

Age 55+ Mehta et al. 109 2008 4 % 229 NR 16,467 1.19 (0.50 to 2.85)† NR Age 15

- 24 HIV+ No Hospital inpatients and outpatients

Age 35 to 44
years Alpert et al. 115 1996 NR 35 NR 840 NR‡ SS Proportion in HCV+ vs. HCV

- Yes Adults at emergency department roomRace/Ethnicity Ethnicity, Black Mehta et al. 109 2008 44 % 229 NR 16,467 2.51 (1.61 to 3.93)† NR Proportion HIV+ vs. White Yes Hospital inpatients and outpatients

Black Zetola et al. 111 2008 NR 15 NR 1,632 1.01 (0.24 to 4.22) †; NR‡ 0.995†; NS‡ Proportion HIV+ vs. HIV

- vs. White No Public hospital emergency room patients

Black race/ethnicity Nguyen et al. 110 2008 55.0 20 20.9 1,578 5.53 (1.00 to 30.66)† SS White race/ethnicity HIV+ Yes General population of adults in New York City273Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison M

adeAssociated in Study?

Population

Ethnicity, Asian Mehta et al. 109 2008 0.4 % 229 NR 16,467 0.50 (0.07 to 3.68)† NR Proportion HIV+ vs. HIV

No Hospital inpatients and outpatients

Asian race/ethnicity Nguyen et al. 110 2008 5.0 20 13.0 1,578 1.12 (0.10 to 12.66)† NS White race/ethnicity HIV+ No General popula tion of adults in New York City

Ethnicity, Cape Verdean Mehta et al. 109 2008 4 % 229 NR 16,467 3.40 (1.16 to 7.15)† NR Proportion HIV+ vs. HIV

Yes Hospital inpatients and outpatients

Ethnicity, Haitian Mehta et al. 109 2008 13 % 229 NR 16,467 3.84 (2.24 to 6.60)† NR Proportion HIV+ vs. HIV Yes Hospital inpatients and outpatients

Ethnicity, Other/ Not reported Mehta et al. 109 2008 11 % 229 NR 16,467 3.43 (1.96 to 6.02)† NR Proportion HIV+ vs. HIV Yes Hospital inpatients and outpatients

Hispanic Zetola et al. 111 2008 NR 15 NR 1,632 2.07 (0.83 to 8.99)†;

NR‡ 0.253†; NS‡ Proportion HIV+ vs. White No Public hospital emergency room patients

Hispanic race/ethnicity Nguyen et al. 110 2008 30.0 20 36.0 1,578 2.07 (0.38 to 11.39)† NS White race/ethnicity HIV+ No General population of adults in New York CityLanguage Spanish speaker Zetola et al. 111 2008 NR 15 NR 1

, 632 0.58 (0.08 to 4.47)†;

NR‡ 0.559†; NS‡ English speakers HIV+ No Public hospital emergency room patients274Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison M

adeAssociated in Study?

PopulationEducation Less than high school McQuillan et al. 101 2006 39 % 31 32 % 5

, 889 1.4 (0.66 to 2.8)†¶ 0.41 Proportion in HIV+ vs. HIV

No General population

Less than high school Mehta et al. 109 2008 30 % 229 NR 16,467 1.41 (0.96 to 2.07)† NR At least high school/ GED , HIV+ No Hospital inpatients and outpatientsEconomicFactors Homeless Zetola et al. 111 2008 NR 15 NR 1

, 632 3.89 (1.32 to 11.45)‡ 0.014 Non

homeless HIV+ Yes Public hospital emergency room patients

Poverty Index <1 McQuillan et al. 101 2006 41 % 27 33 % 5

, 371 1.41 (0.65 to 3.0)†¶ 0.38 Proportion HIV+ vs. HIV

No General populationOther No health insurance Mehta et al. 109 2008 21 % 212 NR 16,467 1.66 (1.19 to 2.32)† NR Insured HIV+ Yes Hospital inpatients and outpatients

No health insurance Zetola et al. 111 2008 NR 15 NR 1

, 632 1.09 (0.38 to 3.12)†;

NS‡ 0.875†; NS‡ Insured HIV+ No Public hospital emergency room patientsMarital Status Married/ living together McQuillan et al. 101 2006 24 % 29 53 % 5

, 631 0.28 (0.12 to 0.60)†¶ 0.003¶ Proportion HIV+ vs. HIV

vs. Divorced, separated, never married Yes (Protec tive) General popul ation adults275Category

Factor Citation YearPercentage of Infectedwith FactorTotal Number InfectedPercentage ofUninfected with FactorTotal NumberUninfected

Effect Size* p

- V

alue** Comparison M

adeAssociated in Study?

Population

Children and AdolescentsSex Male D ’ Angelo et al. 119 1991 15 % 13 33 % 3,507 NR <0.05† Proportion HIV+ vs. HIV

No (pro

tective) Adolescents attending urban hospitalAge Age >15 years D ’ Angelo et al. 119 1991 NR 13 NR 3,507 NR <0.05† Proportion HIV+ vs. Age <15 Yes Adolescents attending urban hospital

* Odds ratios as reported in public ation, unless otherwise specified

** As reported in publication, unless otherwise specified

† Univariate, unadjusted ‡ Multivariate, adjusted for other factors ¶ Calculated by ECRI Institute276 

### Table 42

. GRADE T able for Question 4 ( N on behavioral Risk F actors)

Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

Factors Identified in Original GuidelineExposure to Infected orSuspected Blood HBV 1 OBS 127 One study of embalmers who had a needle stick injury during embalming did not find an association between needlestick injuries with known or suspected HBV positive blood and HBV infection

. 127 Low 0

- 1

- 1

- 1 0 0 0 0 Very Low

HCV No studies

- - - - - - - - - - N ot A pplicable (NA)

HIV

- - - - - - - - - - - NASigns and Symptoms HBV No studies

- - - - - - - - - - NA

HCV 1 OBS 113 Jaundice: Associated in one study 113 Low 0

- 1 0 0 0 1 0 0 Low

1 OBS 104 ALT Reactivity: Associated in one study. 104 Low 0

- 1 0 0 0 1 0 0 Low

1 OBS 30 AL T >40 U/L: Associated in one study 30 Low 0

- 1 0 0 0 1 0 0 Low

1 OBS 114 Elevated liver enzyme: Associated in one study 114 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV No studies

- - - - - - - - - - NA277 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfoundersReceipt of Blood Transfusion HBV 3 OBS 116,124,126 Blood transfusion was associated with HBV infection in a general population, 116 as was blood transfusion before 1991 in a special population. 124 Blood transfusion was not associated with HBV in another special population study. 126 Low 0 0

- 1 0 0 0 0 0 Very Low

HCV 8 OBS 30,105

- 107,112

- 114,116 All 8 studies associated having had a blood transfusion with HCV, and in eight of them the effect size was large. It was independently associ ated with HCV with large effect sizes in three blood donor studies 105

- 107 and two general population studies. 112,116 Two additional general population study performed univariate analyses only and found large effect sizes. 113,114 The remaining general population study found an independent association between having a blood tra ns fusion before 1992 and HCV, but the effect size was not large. 30 Low 0 0 0 0 0 1 0 0 Moderate

HIV No studies

- - - - - - - - - - NA278 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfoundersAccidental Needlestick with Unknown Blood HBV 2 OBS 103,116 According to data collected from a low

- quality next

of

- kin, accidental needle sticks were not associated with HBV among potential tissue donors. 103 A general population study found a lower prevalence of HBV among people who reported a needlestick. 116 Low 0 0 0

- 1 0 0 0 0 Very Low

HCV 4 OBS 103,105,106,116 According to data collected from a low

- quality next

of

- kin, accidental needle sticks were not associated with HCV among potential tissue donors 103 A general population study found a lower prevalence of H C V among people who reported a needlestick. 11 6 Among blood donors who work in a healthcare setting, needlestick injuries were not associated with HCV in one study, 106 but “bloody” needlestick injuries were in another. 105 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV 1 OBS 103 According to data collected from a low

- quality next

of

- kin, accidental needle sticks were not associated with HIV among potential tissue donors 103 Low

- 1

- 1 0

- 1 0 0 0 0 Very LowHemodialysis HBV 2 OBS 116,124 Hemodialysis was associated with HBV in one general population study 116 and one special population study. 124 Both analyses were univari ate, and the special population study had a large effect size. Low 0 0 0 0 0 1 0 0 Moderate

HCV 3 OBS 112,113,116 In g eneral population studies, “kidney dialysis” was associated with HCV in a univariate analysis in one study, 113 and hemodialysis was associated with HCV with a large effect size in multivariate analysis in a second study. 116 A third study did not find an association between hemodialysis and HCV. 112 Low 0 0 0 0 0 0 0 0 Low279 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

HIV No studies

- - - - - - - - - - NASurgery HBV 3 OBS 103,116,117 The tissue donor study did not associate having had surgery with HBV. 103 On e general population study found a lower prevalence of HBV among people who had surgery, 116 and another found no relationship. 117 Low 0

- 1 0 0 0 0 0 0 Very Low

HCV 5 OBS 103

- 105,114,116 The tissue donor study did not associate having had surgery with HCV. 103 One blood donor study did not find any association with recent surgery 104 and one general population study did not find any association with history of surgery. 114 However, one blood donor study did find an independent association between HCV and l ifetime history of surgery (or sutures). 105 A general population study found no association. 116 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV 1 OBS 103 The tissue donor study did not associate having had surgery with HIV. 103 Low

- 1

- 1 0

- 1 0 0 0 0 Very LowOrgan TransplantRecipients HB V 2 OBS 103,121 HBV was not associated with having an organ transplant in one very low

- quality study 103 or

a special population study. 121 Low 0 0 0

- 1 0 0 0 0 Very Low

HCV 1 OBS 103 HCV was not associated with having an organ transplant in one very low

- quality study. 103 Low

- 1

- 1 0

- 1 0 0 0 0 Very Low

HIV 1 OBS 103 HCV was not associated with having an organ
trans plant in one very low

- quality study. 103 Low

- 1

- 1 0

- 1 0 0 0 0 Very Low280 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfoundersAcupuncture HBV 2 OBS 117,121 Neither the general population study 117 nor the special population study 121 found an association between HBV and acupuncture. Low 0 0 0 0 0 0 0 0 Low

HCV 3 OBS 106,107,112 Acupuncture was not associated with HCV infection in two studies of blood donors 106,107 or one study of a general population. 112 Low 0 0 0 0 0 0 0 0 Low

HIV No studies

- - - - - - - - - - NADental Work HBV 1 OBS 117 Dental work within the last six months was not associated with acute HBV in one general population study. 117 Low 0 0 0

- 1 0 0 0 0 Very Low

HCV 2 OBS 104,105 Dental work was not associated with HCV among blood donors in one study 105

; nor was having dental work in the six months before donation in another. 104 Low 0 0 0 0 0 0 0 0 Low

HIV No Studies

- - - - - - - - - - NABlood Draws HBV 1 OBS 103 The tissue donor study did not find an association between HIV testing and HBV, based upon next

- of

kin interviews. 103 Low

- 1

- 1 0

- 1 0 0 0 0 Very Low

HCV 2 OBS 103,113 The low

- quality tissue donor study did not find an association between HIV testing and HCV, based upon next of

- kin interviews. 103 One general population study did find an association between having had a blood test for HBV and having an HCV infection. 113 The same study also found that being a bl ood donor was associated with reduced risk of HCV. 113 Low 0 0 0

- 1 0 0 0 0 Very Low281 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

HIV 1 OBS 103 The tissue donor study did not f ind an association between HIV testing and HIV, based upon next of

- kin interviews. 103 Low

- 1

- 1 0

- 1 0 0 0 0 Very LowHousehold Exposure HBV 5 OBS 117,122

- 124,126 Having household contact with someone with hepatitis was associated with HBV in a special population study 124

, as was a family history of HBV in another special population study. 123 However, having a household member with hepatitis was not associated with HBV in a third special population study; 126 nor was being the wife of a man with HBV in a fourth special population study. 122 Sharing a razor or toothbrush with a household member was not associated with HBV in a general population study either. 117 Low 0

- 1

- 1 0 0 0 0 0 Very Low

HCV 3 OBS 105,113,114 In one blood donor study, living with someone with hepatitis or having a relative with hepatitis was not associated wi th HCV , but living with a transfusion recipient and sharing a toothbrush or razor with person(s) unspecified was. 105 In general population studies, having at least one family member treated for viral hepatitis was not associated with an increased risk of HCV in one study, 114 but having at least one family member with HCV in another study

was. 113 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV No studies

- - - - - - - - - - NA282 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfoundersOther Infections HBV 2 OBS 102,124 HBV surf ace antigen positivity was associated with HCV infection among heart donors in one study. 102 HBV infection wa s associated with having had a sexually transmitted disease (STD) in a special population study. 124 Low 0 0 0 0 0 0 0 0 Low

HCV 6 OBS

30,104,106,107,112,113 HCV was significantly associated with history of STD in two blood donor studies 106,107 but not a general population study. 113 HCV was associated with having a STD within s ix months of donating in another blood donor study. 104 Herpes infection was associated with HCV in a general population study 30 In addition, HCV was associated with seropositivity for other reactive infectious diseases in two blood donor studies. 104,107 HIV infection was not associated with HCV infection upon univariate analysis of a gener al population study. 112 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV 4 OBS 101,109,110,115 In general population studies, HIV infection was associated with diagnosis of STD in one study

, 109 HSV

- 2 in two studies

, 101,110 and syphilis or other infection not apparently related to HIV in another study, 115 Low 0 0 0 0 0 0 0 0 Low283 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfoundersSex HBV 6 OBS

116,118,120,121,123,124 In one general population study 116 and 2 special population studies 121,123 males had higher prevalence of HBV. Two additional special populations studies found no differ ence 120 or a lower prevalence. 124 A study of children found no difference. 118 Low 0

- 1

- 1 0 0 0 0 0 Very Low

HCV 9 OBS 30,102,104,106

- 108,113,114,116 One organ donor stu dy found an increased prevalence of HCV in males. 102 Among blood donors it was in one study 107 but not in two others. 104,106 Four general population studies found an increased risk among males. 30,108,113,116 but one other did not. 114 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV 3 OBS 109

- 111 None of three general population studies associated male sex with an increased prevalence of HIV. 109

- 111 Low 0 0 0 0 0 0 0 0 LowAge HBV 8 OBS 116,120

- 125,127 Every study tested the a ssociation of HBV and age in different ways, and the results are inconsistent and difficult to compare. One general population study found an increased risk of HBV when >60 years. 116 The rest of the studies were special population studies. One found an association with mean age (with older people having greater prevalence of HBV) 124 while another did
not. 121 Increased prevalence was associated with
age younger than 20 years, 122 age over 35 years, 127 and age over 50 years. 125 In another study lower prevalence was found in people under 49 years. 120 The remaining study did not find any association between age and HBV. 123 Low 0

- 1

- 1 0 0 0 0 0 Very Low284 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

HCV 7 OBS

102,104,106,108,113,114,1

16 Every study tested the association of HCV and age in different ways, and the results are inconsistent and difficult to compare. The organ donor study found that HCV infection was associated with older median
age. 102 One of the blood donor studies associated HCV with older mean age, 104 the other did not. 106 In general population studies, HCV was associated with increased mean age 108 and decade of birth (with people born between 1940 and 1959 having the highest prevalence), 113 but not age less than 50 years 114 or age less than 60 years. 116 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV 3 OBS 109,111,115 The HIV studies also measured age in different ways, complicating comparison. In general these studies found young adults to be at the highest risk. One study found younger adults (aged 18 to 30) had increased pr evalence of HIV, 111 another found adults aged 25 to 40 had higher prevalence of HIV than younger people aged 15 to 24 years, 109 and the third found increased prevalence among adults aged 35 to 44 years. 115 Low 0

- 1 0 0 0 0 0 0 Low285 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfoundersRace or Ethnicity HBV 2 OBS 116,121 White or Hispanic race was associated with lower HBV prevalence in a general population study in a multivariate analysis 116 but not in a special population study. 121 Low 0

- 1 0

- 1 0 0 0 0 Very Low

4 OBS 29,121,124,125 Non

- Hispanic Black race was associated with a higher prevalence of HBV in a general population study multivariate analysis 29 a nd two special population studies 124,125 but not another special population study. 121 Low 0 0

- 1 0 0 0 0 0 Very Low

3 OBS 29,121,124 Being Mexican

- American was not associated with a different prevalence of HBV than non

- Hispanic White race in a multivari ate analysis of a general population study. 29 In special population studies, Hispanic ethnicity 121 and Hispanic or Latino ethnicity 124 were not associated with HBV infection. Low 0 0

- 1 0 0 0 0 0 Very Low

1 OBS 124 A special population study found an increased prevalence of HBV among Asian Americans compared with non

- Hispanic White Americans. 124 Low 0

- 1

- 1 0 0 0 0 0 Very Low

1 OBS 117 Among African American, Caucasian, Asian, and Hispanic children who received blood transfusions, the prevalence was not significantly different. Low 0 0 0

- 1 0 0 0 0 Very Low286 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

HCV 7 OBS 30,102,104,106

-

108,113 Because about half of the studies combined races in analyses (their results presented first), the different analyses are reported together here. The different analysis metho ds complicate side

- by

- side comparison, but the evidence rating would always be ‘very low’ for these studies. (These results are all presented in the same row because of overlap within the studies.) In organ donors, no relation between race and HCV infectio n was detected. 102 Three general population studies did not find any relation either. 30,108,113

White r ace was not associated with a difference in rate of HCV compared with other races. 104

Black race was associated with increased rates of HCV compared to Whites in two studies. 106,107 Being Asian was associated with having a lower prevalence of HCV compared to Whi tes among blood donors. 107 Among blood donor s, one study found that Hispanics had a higher risk of HCV than Whites, 107 but another did not. 104 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV 3 OBS 109

- 111 In univariate analyses, two general population studies found increased prevalence of HIV among people of Black race 109,11 0 but a third did not. 11 1 Low 0

- 1 0 0 0 0 0 0 Very Low

2 OBS 109,110 In univariate analyses, neither of two general population st udies found a difference in HIV prevalence in Whites and Asians. 109,110 Low 0 0 0

- 1 0 0 0 0 Very Low287 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfoundersNational Origin/Birthplace HBV 5 OBS

29,116,117,122,123 National origin and birthplace were reported differently among studies and most factors cannot be considered side

- by

- side. How ever, since the rating for any factor in this group will be ‘very low’ and there is some overlap among studies, we present the findings together. In multivariate analysis of general populations, HCV was associated with being born in Southeast Asia or Afric a in one study. 116 A special population study found children born in Korea had higher prevalence of HBV than children born in the U.S. 122 Other special population studies did not find significantly different rates of Asian Americans born in East Asia (exc luding China) or Southeast Asia or Pacific Islands compared to Asian Americans born in China. 123 Birth in an area with a high endemic rate or household exposure to someone born i n a high endemic rate was not in another general population study. 117 In multivariate analyses, a general population study 29 and a special population study 123 found that being born in the U.S. was associated was lower prevalence of HBV. Low 0

- 1

- 1 0 0 0 0 0 Very Low288 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

HCV 5 OBS

30,104,107,113,116 One blood donor study did not associate foreign birth with HCV, 104 but another did in a multivariate analysis. 107 A general population study found people born outside of the U.S. had a lower prevalence of HCV. 30 Birth in Southeast Asia or Africa was not associated with an increased prevalence of HCV in another general population study. 116 A general population study found no ass ociation between HCV and U.S. citizenship. 113 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV No studies

- - - - - - - - - - NAPreferred Language HBV No studies

- - - - - - - - - - NA

HCV 1 OBS 108 One general population study found an association between preference of English or Spanish and HCV. 108 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV 1 OBS 111 One general population study found no difference in prevalence of HIV among Spanish speakers. 111 Low 0

- 1 0

- 1 0 0 0 0 Very Low289 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfoundersOccupation HBV 6 OBS

29,116,117,121,124,126 Occupation as a health care worker was protective against HBV in one general population study 116 and not associated with HBV in another general population study 29 or a special population study. 121 However, having a healthcare

- related job with frequent blood exposure was associated with HBV in one special population study. 124 Another general population study did not associate healthcare employment or household contact with someone who is a health care worker with HBV, 117 and a special populatio n study did not associate being a health care worker or the spouse of one with HBV. 126 Low 0 0 0 0 0 0 0 0 Low

1 OBS 29 Ever being in the mili t ary was not associated with HBV in a general population study. 29 Low 0 0 0

- 1 0 0 0 0 Very Low

HCV 2 OBS 105,114 In any occupation, occupational blood exposure was associated with HCV among blood donors in one study, 105 but work contact with blood was not associated with HCV in a general population study. 114 Low 0

- 1 0

- 1 0 0 0 0 Very Low

2 OBS 104,116 Medical or dental job with frequent blood contact was not associated with HCV in one blood donor study 104 and was associated with lower prevalence of HCV in a general population study. 116 Low 0

- 1 0

- 1 0 0 0 0 Very Low

2 OBS 30,114 Neither of two gene ral population studies associated ever having served in the armed forces with HCV. 30,114 Low 0 0 0

- 1 0 0 0 0 Very Low290 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfounders

2 OBS 104,113 Public safety job with frequent blood contact was not associated with HCV in one blood donor study. 104 Another study did associate having a job at a prison with having HCV. 113 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV No studies

- - - - - - - - - - NAEducation HBV 3 OBS 29,121,124 Having less than a high school education was associated with HBV in one general population study, compared with some college. 29 In special population studies, one found a higher prevalence of HBV among students in 2

- year colleges compared to those in 4

- year colleges, 124 and the other study found

no r elationship between years of education and HBV. 121 Low 0

- 1

- 1 0 0 0 0 0 Very Low

HCV 5 OBS 30,104,1 06,108,113 One blood donor study associated less education with HCV, 104 and another associated having no college education with having HCV. 106 One general population study associ ated having fewer than 12 years of education with having HCV, 30 but two othe rs found no association between educational attainment and HCV. 108,113 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV 2 OBS 101,109 Neither of two general population studies found an association bet ween having less than a high school education and having H I V. 101,109 Low 0 0 0

- 1 0 0 0 0 Very Low291 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfoundersEconomic Factors HBV 2 OBS 121,125 One special population study did not associate homelessness with HBV. 121 Another special population study did not associate homelessness, institutionalization, or other non

- independent living arrangement with HBV. 125 Low 0 0

- 1

- 1 0 0 0 0 Very Low

HCV 2 OBS 30,113 In a general population, ever having been homeless was associated with an increased risk of HCV. 113 In the same study, annual inc ome was not associated with HCV. Another general population study did not find any association with family poverty level and HCV. 30 Low 0

- 1 0

- 1 0 0 0 0 Very Low

HIV 2 OBS 101,111 Being homeless was associated with an increased prevalence of HIV in one general population study. 111 In another general population study, havin g a poverty index of less than one was not associated with HIV. 101 Low 0

- 1 0 0 0 0 0 0 Very L owHealth Insurance HBV No studies

- - - - - - - - - - NA

HCV 1 OBS 108 One general popu lation study associated insurance with HCV infection, with people on Medicaid having the highest prevalence. 108 Low 0

- 1 0 0 0 0 0 0 Very Low

HIV 2 OBS 109,111 One general population study found a higher prevalence of HIV among peopl e with no insurance 109 but a second did not. 111 Low 0

- 1 0

- 1 0 0 0 0 Very Low292 Factor Virus Quantity and Type of Evidence Findings Starting Grade Decrease Grade Increase Grade

GRADE of Evidence for OutcomeOverall QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseAssociated DespiteConfoundersMarital Status HBV 2 OBS 29,125 Being divorced or separated was associated with a higher prevalence of HBV than any other status in
one gen eral population study. 29 Being currently married was not associated with any difference in HBV prevalence than any other status in one special populati on study. 125 Low 0 0 0 0 0 0 0 0 Low

HCV 1 OBS 105 Being married was associated with a lower risk of HCV in one blood donor study. 105 Low 0 0 0 0 0 0 0 0 Low

HIV 1 OBS 101 Being married or cohabitating was associate d with a lower risk of HIV in one general population study. 101 Low 0 0 0 0 0 0 0 0 Low293 

### Table 43

. Prevale nce of Nonbehavioral Risk Factors among Potential Organ Donors

Category Risk Factor Citation Year Prevalence Number of Participants Population

General Population

Serum alanine aminotransferase level >40 U/L Armstrong e t al. 30 2006 9% 13,113 General population, nationwide

Transfusion Blood tra nsfusion before 1992 (participants aged 20

- 59 years) Armstrong et al. 30 2006 6% 5

, 733 General population, nationwide

Blood transfusion before 1992 (participants aged
at least 60 years) Armstrong et al. 30 2006 16% 2

, 916 General population, nationwide

Blood transfusion Kaur et al. 116 1996 20% 7

, 539 Volunteers from general populat ion, mainly urban

Herpes simplex virus infection Antibodies to herpes simplex type 2 (HSV

- 2) (ages 18

- 49) Armstrong et al. 30 2006 19% 5

, 610 General population, nationwide

Seropositive for HSV

- 2 Nguyen et al. 110 2008 28% 1

, 613 General population in N.Y.C.

S TDs STD diagnosis Mehta et al. 109 2008 18% 16,696 Patients in urban medical care center294 

### Table 44

. GRADE for Question 4 : Prevalence of Nonbehavioral Risk Factors

Factor Quantity and Type
of Evidence FindingsStarting Grade Decrease GRADE Increase GRADE

GRADE of
Evidence for
OutcomeStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseAssociated DespiteConfounders

Serum alanine

a mino

transferase (ALA) level
>40 U/L 1 OBS* 30 In o n

e general population study, 9% of participants had ALA >40 U/L. 30 High 0

- 1

- 1 0 0 0 0 0 Low

Blood transfusion 2 OBS 30,116 In one general population study, the prevalence of ever having received a blood transfusion was 20%. 116

In a nother, 6% of participants aged 20

- 59 years had received a blood transfusion before 1992, and 16% of participants aged at least 60 had. 30 Hig h 0

- 1

- 1 0 0 0 0 0 Low

Other infection: HSV

- 2 2 OBS 30,110 Two studies assessed the prevalence of herpes simplex virus

2 (HSV

- 2) in general populations. In one, 19% of people aged 18

- 49 tested positive. 30 In the other, 28% of adults did. 110 High 0 0

- 1 0 0 0 0 0 Moderate

Other infection: Other STD 1 OBS 109 Another study found that 18% of adults had had a STD diagnosis. 109 High 0

- 1

- 1 0 0 0 0 0 Low

* Observational study295 

## Question **5 . Wha**  **t are the test characteristics of the screening methods** 
**available to detect HIV, HBV, and HCV**  **in potential solid organ donors? Do test characteristics differ in particular populations and**  **with donor** 
**clinical status (i.e., heart beating**  **vs. non**  **- heart beating donors OR adult** 

**vs. pediatric donors)?** 

The purpose of this question is to summarize information and evidence on 35 diagnostic tests of interest, as designated by CDC. A list of these tests of interest is p resented in 

### Table 4 of the introductory section. Tests of interest include immunoassay tests and nucleic acid tests (NAT) currently used in the U.S. by Organ Procurement Organizations (OPOs), as well as, fourth

- generation HIV and HCV antibody/antigen tests currently in use outside of the U.S. T he p24 antigen test for HIV was not included because it is no longer used by OPOs. Additionally, a n HCV antigen assay used in Europe was not included because the assay was licensed after the literature search was conducted

. In this question, the following information is
addressed:

**•** U.S. FDA approval

**•** Test format: type of test

**•** Specimen collection: In particular, whether approved for use in non

- heart

- beating donors , which is primarily a considerat ion for testing tissue donors. Heart

- beating potential organ donors are not
deceased donors for the purposes of using these tests.

**•** Window period: The duration of time between infection and when the test can detect infection

**•** Turnaround time: The duration of time required for the test to be performed

**•** Diagnostic performance characteristics: In particular, sensitivity and specificity. Measures of diagnostic performance are described in greater detail under Analysis Methods.

To address this question, informatio n will be provided in the following order: literature search methods and results; list of included peer

- reviewed studies and gray literature; samples and study methods of peer

reviewed publications ; analysis methods used in this question ; study assessment; methods of risk of bias and GRADE assessment of peer

- reviewed publications ; results summary

, followed by data extraction
tables and GRADE tables.

Peer

- reviewed publications and other types of information, as appropriate (see next paragraph), were only
inc luded if they presented information specific to the tests of interest as listed in Table 4

. Information regarding any other tests was excluded unless the other test was used in reference to a test of interest.
Info rmation must have been reported for each test individually, not as part of a multiple

- test algorithm, because the focus of this question is on the performance of individual tests. Highly selected data sets (such as seroconversion panels, or HIV

- 2 genetic d iversity panels) were not included for the assessment of diagnostic performance due to both spectrum bias and lack of relevance to performance of the test in the U.S. in potential organ donors. Because they are influenced by disease prevalence, predictive values and likelihood ratios were only to be collected from studies that calculated them from data from reasonably relevant populations to the U.S. (such as clinical applications in a general population, or on296 

### blood donors, not serial dilutions or other la boratory sets, or samples selected for being unusual or representative of an endemic area).

Initial searches of bibliographic databases were for diagnostic instruments for HBV, HCV, or HIV. Once the list of included tests was generated, additional searches were performed specifically by each test’s name. The focus of these searches was to identify clinical literature regarding window period, turnaround time, and diagnostic performance characteristics. Because this strategy did not identify information for a ll of the listed tests, we also searched gray literature sources including FDA product labeling information,

p ackage inserts, manufacturer’s W eb sites, and additional sources including the World Health Organization (WHO). FDA approval information was searc hed for all tests as well. We used these sources for information on turnaround time and window period but not other diagnostic characteristics (e.g., sensitivity and specificity), because these sources of information generally do not report sufficient
info rmation to enable assessment of the study design, quality, and other factors that impact the outcomes and the strength of the evidence. This is a particular concern given the potential for inaccuracy in these
various sources of literature. Where data from sources other than clinical literature were used for the other characteristics, the source is clearly noted in the extraction tables.

Three hundred and forty

- eight potentially relevant articles were identified by the bibliographic searches.
Most were exclu ded for not reporting on a test on the list of interest (including earlier generations of tests of interest). Most of the rest were excluded for not addressing an outcome of interest. Ultimately, 45 peer

reviewed publications, each presenting at least one outcome for at least one data set, were included. Included publications, including data sets from those publications, and the outcomes they address are listed alphabetically by author in Table 45 . This table also i ncludes information on what test(s) of interest the publications investigated and which data sets were included. Ninety nine pieces of gray literature were reviewed for potentially useful data. These included literature from manufacturers’ Web sites (40), the internet (6), the Food and Drug Administration (FDA) (23), agencies in the United Kingdom (14), agencies from Australia (13), and items from the World Health Organization (3). Data from 26 pieces of gray literature reporting window period or turnaround time were included. These sources of information
are listed in Table 46

. Basic information on test format and approved uses were extracted from FDA approval documents and, for tests not approved in the U.S., manuf acturers’ Web sites.297 

### Table 45

. Included Data Sets from Peer

- reviewed Publications

Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Aboud et al. 130 2006 HIV 4th generation Vironostika HIV Uni

- Form II Ag/AB Blood donations and diagnostic test samples (clinical HIV submissions, antenat al syphilis submissions) combined (Tanzania) 

Aghokeng et al. 131 2004 HIV 4th generation Genscreen plus HIV Ag/Ab Blood donations (Cameroon) 

Anderson et al. 132 1995 HCV EIA Abbott HCV EIA 2.0 Blood donations (U

. S

. ) 

Bamaga et al. 133 2006 HCV NAT COBAS AmpliScreen HCV 2.0 Blood donations (Saudi Arabia) 

Additional Information 

HIV NAT COBAS AmpliScreen HIV 1.5 Blood donations (Saudi Arabi a) 

Additional Information 

Barbe et al. 134 1994 HIV EIA, 3 rd generation Abbott recombinant HIV

- 1/HIV

- 2 3rd generation EIA Prenatal screening test samples (France)  Specificity

False

- reactive EIA results Over

- selected

HIV positive samples , archived (France)  Sensitivity

Seroconversion samples (Commercial) 298 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Barrera et al. 135 1995 HCV EIA

, 3

rd generation Ortho HCV v3 ELISA Seroconversion samples (U.S.) 

Bourlet et al. 136 2005 HIV 4th generation AxSYM Ag/Ab Combo Diagnostic samples (France) 

Seroconversion panels (commercial) 

VIDAS DUO ULTRA Diagnostic samples (France) 

Seroconversion panels (commercial) 

Busch et al. 137 2005 HIV NAT COBAS AmpliScreen HIV

- 1 v. 1.5 Seroconversion samples (U.S.) 

HCV NAT COB AS AmpliScreen HCV v.2.0 Seroconversion samples (U.S.) 

HCV/HIV NAT ProCleix HIV

1/HCV Seroconversion samples (U.S.) 299 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Candotti et al. 138 2003 HCV NAT, HIV NAT ProCleix HIV

1/HCV Blood donors ( U.K. ) No reference standard

Known positive samples with various subtypes O verly selected / specificity not appropriately reported (above)

Additional information 

Seroconversion panels (commercial) 

Denoyel et al. 139 2004 HCV EIA Advia Centaur HCV Assay Blood donors and hospitali zed patients (France, Germany)  Specificity

Known positives (Commercial samples)  Sensitivity

Seroconversion panels (Commercial) 

Interference samples Overly selected

Diepersloot et al. 140 2000 HBsAg AxSYM HB sAg C linical submissions (U

. S

. ) 

Galel et al. 141 2002 HCV EIA Abbott HCV EIA 2.0 Blood donations (U

. S

. ) 

Ortho HCV EIA 3.0 Blood donations (U

. S

. ) 300 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Huzly et al. 142 2008 anti

- HBs Advia Centaur anti

- HBsAg Patients and healthcare worke rs (Germany) 

Additional Information 

Iqbal et al. 143 2005 HIV 4th generation Vironostika HIV Uni

- Form II Ag/AB Diagnostic samples (India) 

Commercial known

- status samples 

Seroconversion panel (in

- house) Window period not reported

Jackson et al. 144 2002 HCV NAT, HIV NAT ProCleix HIV

- 1/ HCV High risk individuals (U.S.) 

Katsoulidou et al. 145 2004 HCV NAT, HIV NAT ProCleix HIV/HCV HCV and HIV patients (Greek) Analytic sensitivity only

Seronegative blood donors (Greek) Sensitivity not reported ; study must report both sensitivity and specificity to be included

Seroconversion panels (Greek) 

HCV/HIV Co

- infection (Greek) O verly selec ted

Various genotypes (Greek) O verly selected301 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Kita et al. 146 2009 HCV EIA Ortho EIA 3.0 Diagnostic samples (Japan) 

Seroconversion panel (Commercial) 

Advia Centaur HCV Diagnostic samples (Japan) 

Seroconversion panels (Commercial) 

Kleinman et al. 147 2005 NAT HBV COBAS AmpliScreen HBV test Blood donations (U

. S

. ) 

Kolk et al. 148 2002 HCV NAT, HIV NAT ProCleix HIV

- 1/HCV Seroconversion panels (Commercial) 

Kwon et al. 149 2006 HIV 4th generation ARCHITECT HIV Ag/Ab Combo Diagnostic samples with known status (Korea) 

p24 antigen subtype panel and p24 antigen sensitivity panel (Commercial) O verly sel ected

Seroconversion panels (Commercial) 

Low titer antibody panel (Commercial) Overly selected302 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

HIV antibody panel including various subtypes (Commercial) Overly selected

– diagnostic samples with known status used preferenti ally

AxSYM HIV Ag/Ab Combo Diagnostic samples with known status (Korea) 

p24 antigen subtype panel and p24 antigen sensitivity panel (Commercial) O verly selected

Seroconversion panels (Commercial) 

Low titer antibody pan el (Commercial) Overly selected

HIV antibody panel including various subtypes (Commercial) Overly selected

– diagnostic samples with known status used preferentially

Laperche et al. 150 2005 HCV NAT, HCV 4th generation COBAS AmpliScreen HCV v. 2.0 Seroconversion panels (Commercial) 

Blood donations (France) No reference standard

Monolisa HCV Ag/Ab Ultra S eroconversion panels (Commercial) 

Blood donations (France) No reference standard303 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Laperche et al. 151 2005 HCV 4 th generation Monolisa HCV Ag/Ab Ultra Seroconversion samples (France) 

Laycock et al. 152 1997 HCV EIA Abbott HCV v. 2.0 Potential cornea donors, most of whom positive on previous test (U.S.) 

Leon et al. 153 1993 HCV EIA Abbott HCV EIA 2.0 Unselected high

- risk individuals plus known positives from archive (Spain) 

Ly et al. 154 2007 HIV 4 th generatio n ARCHITECT HIV Combo Negative samples (French)  Specificity

Positive samples from various HIV endemic areas of the world, including mosaics and subtypes  Sensitivity

Seroconversion panels (Commercial) 

COBAS Core HIV Combi EIA Negative samples (French)  Specificity

Positive samples from various HIV endemic areas of the world, including mosaics and subtypes  Sensitivity

Seroconversion panels (Commercial) 304 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Genscreen Ag/Ab HIV Ultra Negative samp les (French)  Specificity

Positive samples from various HIV endemic areas of the world, including mosaics and subtypes  Sensitivity

Seroconversion panels (Commercial) 

VIDAS HIV DUO Quick Seroconversion panels (Commercial)  Sensitivity and specificity not assessed for this test in the publication

VIDAS HIV DUO Ultra Negative samples (French)  Specificity

Positive samples from various HIV endemic areas of the world, including mosaics and subtypes  Sensitiv ity

Seroconversion panels (Commercial) 

Ly et al. 155 2006 HBV EIA Advia Centaur HBsAg Reference HBsAg panel (France) and HBsAg mutants (commercial)  No other outc omes of interest reported

Ly et al. 156 2004 HIV 4 th generation AxSYM HIV Ag/Ab Combo Positive samples from various HIV endemic areas of the world, including mosaics and subtypes  Sensitivity

Negative samples  Specificity305 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Seroconversion pane l (Commercial) 

Genscreen Plus Ag/Ab Positive samples from various HIV endemic areas of the world, including mosaics and subtypes  Sensitivity

Negative samples  Specificity

Seroconversion panel (Commercial) 

Murex HIV Ag/Ab Combo Positive samples from various HIV endemic areas of the world, including mosaics and subtypes  Sensitivity

Negative samples  Specificity

Seroconversion panel (Commercial) 

Vironostika Uni

Form II Ag/Ab Positi ve samples from various HIV endemic areas of the world, including mosaics and subtypes  Sensitivity

Negative samples  Specificity

Seroconversion panel (Commercial) 306 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Ly et al. 157 2001 HIV 4 th generation Vironostika HIV Uni

- Form II Ag/AB Seroconversion panels (Commercial) 

Addi tional information 

HIV

- 1 p24 antigen panel infected with HIV

- 1 M subtype B (Commercial) Overly selected

Ly et al. 158 20 01 HIV 4 th generation AxSYM HIV Ag/Ab Combo Panel with various HIV subtypes, including group M subtypes A, B, C, D, CRF A/e, F, G, group O (Commercial) Sensitivity not reported ; study must report both sensitivity and specificity to be included

Se roconversion panel (Commercial) 

Murex HIV Ag/Ab Combo Panel with various HIV subtypes, including group M subtypes A, B, C, D, CRF A/e, F, G, group O (Commercial) Sensitivity not reported ; study must report both sensitivity and specificity t o be included

Seroconversion panel (Commercial) 

VIDAS HIV DUO ULTRA Panel with various HIV subtypes, including group M subtypes A, B, C, D, CRF A/e, F, G, group O (Commercial) Sensitivity not reported ; study must report both sensitivit y and specificity to be included

Seroconversion panel (Commercial) 307 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Owen et al. 159 2008 HIV EIA , 3 rd generation Genetics System (GS)
HIV

- 1/HIV

- 2
p

lus ) EIA Blood and plasma donors, including some international donors selected for being representative of non

- subtype

- B HIV

- 1 (78% U.S. ) 

Seroconversion panels (Commercial) 

HIVAB HIV

1/HIV

- 2 (rDNA)
EIA Blood and plasma donors, incl uding some international donors selected for being representative of non

- subtype

- B HIV

- 1 (78% U.S. ) 

Seroconversion panels (Commercial) 

HIV NAT COBAS AmpliScreen HIV

- 1 Test 1.5 Blood and plasma donors, including some international dono rs selected for being representative of non

- subtype

- B HIV

- 1 (78% U

. S

. )  Seroconversion not reported for this test

Romano et al. 160 2005 HBV NAT COBAS AmpliScreen H BV v. 2.0 Blood donors ( Probably Italian, unclear in publication ) No reference standard

Blood donors with previous negative test results elevated ALT , chronic HCV No reference standard308 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

HBV DNA nucleic acid panel (Commercial) O verly selected

Seroconversion panels (Commercial) 

Saville et al. 161 2001 HIV 4 th generation VIDAS HIV DUO ULTRA Mixed set comprised of U

. S

. blood donors (35%), U.S. clinical samples (18%), high

- incidence population in Trinidad (40%), STD clinic attendees in Bahamas (3%), confirmed HIV

- 1 group 0 from Cameroon (0.4%), confirmed HIV

- 2 samples from Cote d’Ivoire (0.4%), p24 antigen

only (0.3%)
Diagnostic performance reported for all samples together, and sample groups separately  For U.S. sample, PPV & NPV only reported for patients seek ing HIV tests (population may have different prevalence than potential organ donors).

Seroconversion panel 

Seyoum et al. 162 2005 HIV 4 th generation Viron ostika HIV Uni

- Form II Ag/AB Blood donors (Ethiopia) 

Sickinger et al. 163 2004 HIV 4 th generat ion AxSYM Ag/Ab Combo Blood donors  Specificity

Hospital patients  Specificity309 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Commercial panels tested together: Infected with HIV

- 2 group M subtypes; Non

- staged individuals infected with unknown HIV

- 1 subtypes; Individuals with HIV

- 2 living in endemic areas; High

- risk individuals; interference panel  Sensitivity

Seroconversion panels 

Sun et al. 164 1999 HCV NAT AmpliScreen HCV 2.0 Blood donors No outcomes of interest reported

Known positive, genotypes 1a, 1b, 2, 2b, 3a, 5a, 6a, from archives No outcomes of interest reported

Seroconversion panel (Commercial) 

Van Binsbergen et al. 165 1998 HIV 4 th generation Vironostika HIV Uni

- Form II Ag/AB HIV

- 1 sub

- typed samples with A through F, and grou p O (Yaounde and Cameroon) Overly selected (sub

- types only)

Samples with human anti

- mouse antibody Overly selected ; not clinical samples

Seroconversion panels (Commercial) 310 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Van Binsbergen et al. 166 1999 HIV 4 th generation Vironostika HIV Uni

- Form II Ag/AB Worldwide HIV

- 1 Performance Panel, including various subgroups (group M subtypes A through F, and group O) (Commercial) Specificity not reported ; study must rep ort both sensitivity and specificity to be included

Seroconversion panels (Commercial) 

Vargo et al. 128 2002 HCV NAT, HIV NAT ProCleix HIV/HCV Known positive HIV

- 1 samples (Commercial)  Sensitivity

Known positive HCV samples (Commercial)  Sensitivity

Co

- infected HIV

- 1/HCV samples  Sensitivity

Negative samples  Specificity

Seroconv ersion panels (Commercial) 

Vrielink et al. 167 1995 HCV EIA Ortho 3.0 HCV EIA Volunteer random blood donors (Dutch) 

Vrielink et al. 168 1995 HCV EIA Ortho 3.0 HCV EIA Blood donor samples submitted for characterization because of initial positive result, p atients with

non

- A non

- B hepatitis , m ultiply

transfused patients  Sensitivi ty311 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Positive blood donors’ serial dilutions No outcomes of interest

First

- time blood donors  Specificity

Weber et al, 169 2002 HIV 4 th generation VIDAS D UO ULTRA Seroconversion panels 

Dilutions of cell culture supernatants with different HIV

- 1 subtypes (incl. B, E, F, G, H, O) Overly selected, not clinical samples

Interference panel O verly selected

Additional Information 

Weber et al. 170 2002 HIV 4 th
gener ation COBAS Core HIV Combo EIA Seroconversion panels 

Acute infection panels O verly selected

Known positive samples from patients in different stages of HIV

- 1 and HIV

- 2 Overly selected

Sub typed samples from different
geograp hical locations Overly selected

Dilutions of cell culture supernatants from cells infected with different HIV

- 1 subtypes Overly selected312 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

P

erformance panels , low

- titer or mixed titer (Commercial) Overly selected

Blood donor sam ples , unselected (European)  Specificity

Diagnostic samples , unselected (European)  Sensitivity

Interference panel O verly selected

Willoughby et al. 171 1989 HIV 4 th generation Coulter HIV

- 1 p24 Ag Assay Blood donors , known seropositive samples, spinal cord fluid, interference samples No other outcomes reported

Additional Information 

Yang et al. 172 2001 HIV NAT COBAS AmpliScreen HIV

- 1 v.1.5 Known negative blood donors Specificity not reported ; study must report both sensitivity and specificity to be included

Seroconversion panel 

Group M subtype panel Overly selected

Interference panel Overly select ed313 Citation Year Test Category Index T est(s) Data Set (s) Outcomes Included

Reason Sample Set Excluded Diagnostic Performance Window Period Turn

a round TimeSensitivity &SpecificityPredictiveValuesLikelihoodRatios

Yang et al. 173 1999 HIV NAT AmpliScreen HIV

- 1 v .1.5 Genotype panel Overly selected

Blood donors, seronegative Sensitivity not reported ; study must report both sensitivity and specificity to be included

Interference panels O verly selected

Seroconversion panels 314 

### Tabl e 46

. Included Data Sets from Gray Literature

Citation Year Test Category Test(s) of I nterest Data Set(s) Included Outcomes Included

Literature T ype Window Period Turn

around

Time

Abbott Laboratories 174 Download 9/2009 4 th generation HIV EIA ARCHITECT HIV Ag/Ab Combo (None)  Manufacturer W eb site product information (Seroconversion also reported but only for selected 3 or 31 panels,

so not included)

BioMerieux Diagnostics 175 Downloaded 9/2009 HIV 4

th generation VIDAS HIV DUO ULTRA 16 seroconvers ion panels  Manufacturer W eb site product information

BioMerieux Diagnostics 176 Downloaded 9/2009 HIV 4

th generation VIDAS HIV DUO QUICK 25 seroconversion panels  Manufacturer W eb site product information

Burgess and Perry 177 2008 4 th generation HIV EIA ARCHITECT HIV Ag/Ab Combo Assay AxSYM HIV Ag/Ab Combo GENSCREEN Ultra HIV Ag/Ab Murex HIV Ag/Ab Combination

Vironostika HIV Uni

- Form II Ag/Ab 20 seroconversion panels, with comparative data for 18 of them   Independent public health laboratory evaluation

Burgess et al. 178 2001 4 th generation HIV EIA AxSYM HCV version 3.0 22 seroconversion panels  Independent public health laboratory evaluation

Cooray et al. 179 20 03 4 th generation HIV EIA AxSYM HIV Ag/Ab Combo Murex HIV Ag/Ab Combination Genscreen PLUS HIV Ag/Ab

Vironostika HIV Uni

- Form Ag/Ab 35 seroconversion panels   Independent public health laboratory evaluation315 Citation Year Test Category Test(s) of I nterest Data Set(s) Included Outcomes Included

Literature T ype Window Period Turn

around

Time

Coulter Corporation 180 Downloaded 9/2009 HCV 4

th generation Coulter HIV

- 1 p24 Antigen Assay 5 seroconversion panels  Manufacturer W eb site product information

Curtis et al. 181 2006 4 th generation HIV EIA Genscreen ULTRA HIV Ag/Ab Murex HIV Ag/Ab Combo

Vironostika HIV Uni

- Form Ag/Ab 21 seroconversion panels   Independent public health laboratory evaluation

Dean et al. 182 2006 HCV 4

th generation MONOLISA HCV Ag/Ab ULTRA 19 seroconversion panels  Independent public health laborat ory evaluation

Delieu et al. 183 2001 4 th generation HIV EIA Murex HIV Ag/AB Combination EIA 39 seroconversion panels   Independent public health laboratory evaluation

FDA approval documentation 184 Package insert approved 5/2007 HCV NAT COBAS AmpliScreen HCV Test 9 seroconversion panels  FDA documentation including package insert

FDA approval documentation 185 Package insert approval 8/2007 HB V NAT COBAS AmpliScreen HBV Test Ortho HBsAg 40 seroconversion panels  FDA documentation including package insert

FDA approval documentation 186 Package insert approved 12/2004 HBV HBc ADVIA Centaur HBc 7 seroconversion panels  FDA documentation inclu ding package insert

FDA approval documentation 187 Package insert approved 10/2005 HBV Core PRISM HBcore None reported  FDA documentation including package insert316 Citation Year Test Category Test(s) of I nterest Data Set(s) Included Outcomes Included

Literature T ype Window Period Turn

around

Time

FD A approval documentation 188 Package insert approved 12/2004 HCV assay ADVIA Centaur HCV Assay

Ortho HCV v. 3 23 seroconversion panels  FDA documentation including package insert

FDA approval documentation 189 Package insert approved 5/2005 HBV HBsAg ADVIA Centaur HBsAg 6 seroconversi on panels  FDA documentation including package insert

FDA approval documentation 190 Package insert approved 7/2004 3 rd generation HI V EIA HIVAB HIV

- 1/HIV

- 2 (rDNA) EIA 9 seroconversion panels  FDA documentation including package insert

FDA approval information 191 Package insert approved 2/2002 HIV/HCV NAT ProCleix HIV

- 1/HCV Assay 10 HIV seroconversion panels
10 HCV seroconversion panels  FDA documentation including package insert

FDA approval information 192 Current package insert approved 5/2007 HIV NAT COBAS AmpliScreen HIV

- 1 Test

Coulter HVI

- 1 p24 Ag test 41 seroconversion panels  FDA documentation including package insert

FDA approval information 193 Package insert approved 1/2003 HBsAg EIA Genet ic Systems HBsAg EIA 3.0 21 seroconversion panels  FDA documentation including package insert

FDA approval information 194 Package insert approved 20

06 HBsAg Assay AxSYM HBsAg Assay 15 seroconversion panels  FDA documentation including package insert317 Citation Year Test Category Test(s) of I nterest Data Set(s) Included Outcomes Included

Literature T ype Window Period Turn

around

Time

FDA approval information 1 95 Package insert approved 8/2003 3 rd generation HIV EIA Genetic Systems HIV

- 1/HIV

- 2 Plus O EIA 50 seroconversion panels  FDA documentation including package insert

Innogenetics 196 Downloaded 9/2009 HCV 4 th generation Innotest HCV Ab IV

Ortho HCV 3.0 30 seroconversion panels  Manufacturer W eb site product information

Ortho

- Clinical Diagnostics 197 Downloaded 9/2009 HBV HBsAg Genetic Systems HBsAg EIA 3.0 21 seroconversion panels  Manufa cturer W eb site product information

White and Perry 198 2003 HBc Ortho HBc ELISA Test System 4 seroconversion panels  Independent public health laboratory evaluation

World Health Organization 199 2004 4 th generation EIA Enzygnost HIV In tegral II Genscreen Plus HIV Ag/Ab Murex HIV Ag/Ab Combination

Vironostika HIV Uni

- Form II Ag/Ab 8 seroconversion panels   Independent public health laboratory evaluation318 

### Samples **and Study Methods in Peer** 

**- reviewed Publications** 

Table 47 shows a summary of the general study and sample characteristics for each of the included peer

reviewed publications. We sometimes refer to the tested blood sets as samples because not all came from clinical populations (most wer e purchased from laboratory supply companies). Publications were first categorized by whether or not the test(s) of interest are currently in use by U.S. O.P.Os. Test s were further categorized as immunoassays (e.g., EIA) or nucleic acid tests (NAT). All we re further subdivided by which virus(es) they are intended to detect. (Where studies addressed tests of interest from more than one category, the study information is repeated for each category. The test pertinent to the category is bolded.)

For each of t he publications, information regarding the national origin of the samples, the sources(s) of the samples, how the samples were selected, references standard(s) employed, and source(s) funding (if reported) is listed. Many of these studies were conducted in ternationally, and some conducted domestically used international samples. Although most of the commercial samples were purchased from U.S. companies, many of those U.S.

- purchased panels had samples from all over the world. None of the sources of samples w ere potential organ donors. Publications used samples from a variety of sources (and often, multiple sources within the same publication), including clinical samples from routine screening or diagnosis, blood donor samples, and commercially purchased or ar chived known

- status samples and seroconversion panels. Correspondingly, the prevalence of infection ranged widely, from a very small fraction of 1% to over 60% (not including seroconversion panels or all known

- positive sets). Some sample sets were unselect ed (i.e., part of a consecutive or randomly selected sample), while others were selected for known characteristics (e.g., known infection or known non

- infection, known seroconversion). All samples appear to have been drawn from living individuals, with the exception of one publication. None appear to have specifically studied pediatric populations. Everything from previous

- generation EIA to NAT to exhaustive algorithms were employed as reference standards. Well

- defined commercially purchased samples did not always have the reference standard explicitly described in the study, but those that did typically used multiple confirmatory analyses and quantitative analyses to determine the sample status. Some studies report funding from the manufacturer and some app ear to have been publicly funded through federal health organizations, but for most the funding source was not reported.

In gray literature, window periods were always determined relative to other tests using seroconversion panels. Methods used to determin e turnaround time were not reported.319 

### Table 47

. General Study and Sample Characteristics of Peer

- reviewed Studies

Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

Tests currently in use in U.S. Organ Procurement Organization (OPO): Immunoassays

HIV EIA 3

rd generation Abbott recombinant HIV

- 1/HIV

- 2 3

rd generation EIA Barbe et al. 134 1994 France O bstetric sample s ( n = 1

, 546 ) (for specificity)

Prevalence 0.05%
HIV positive samples (n
= 7) (for sensitivity)

S eroconversion samples (8 samples) Unselected prenat al screening at an OB / GYN office

Seroconversion and infected samples selected for known properties Known status for seroconversion panel

For clinical samples, bioMerieux Vidas test with Western blot (WB) confirmation No None reported

Genetics Syst em (GS)
HIV

- 1/HIV

- 2 plus EIA;

HIVAB HIV

- 1/HIV

- 2 (rDNA) EIA (Abbott);

COBAS AmpliScreen HIV

- 1 Test 1.5 Owen et al. 159 2008 Mostly U.S., also Cameroon and unspecified international samples with

non

- subtype

- B HIV

- 1 Tested together: U

. S

. blood donors (n
= 997)

, international donors (n
= 97).

s

amples from Cameroon (n
= 114)

HIV

- 2 specimens from Ivory Coast (n
= 32) and commercial HIV

- 2 specimens (n
= 2) Prevalence 56% (53%
HIV

- 1, 2% HIV

- 2)

Seroconversion panels (15 panels, 183 specimens) For defined properties (at left); all commercially purchased Known status for seroconversion and purchased panels For negatives,

consensus negative with other screening
tests

Confirmation o f positives with Western blot No Not reported, but all authors affiliated with Centers for Disease Control (CDC)320 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

HBsAg AxSYM HBsAg Diepersloot et al. 140 2000 U

. S

. Clinical submissions for HBV tests (n
= 200)

Prevalence: 6% Not reported, but study stat es selection was prospective Abbott Imx and DPC IMMULITE
assays

AxSYM total anti

- HBV core assay for discrepancies No None reported

anti

- HBs Advia Centaur anti

HBsAG Huzly et al. 142 2008 Germany Patients and

h

ealthcare workers (n
= 200)

Prevalence of surface antigen (including vaccinated individuals 73%); Core antigen 12% Unselected Bitros anti

- HBs

Roche Elecs ys anti

- HBs

Liasion anti

- HBs

Abbo tt Architect anti

- HBs

ETI

- AB

- AUK

- 3
Enzygnost anti

- HBs

Monolisa anti

- HBS

AxSYM AUSAB No None reported321 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

HCV EIA Abbott HCV EIA 2.0 Anderson et al. 132 1995 U.S. Blood donors (n
= 21, 431)

Prevalence 0.6% Unselected Ortho Anti

- HCV 2.0

For confirmation of positives, Matrix HCV

anti

- HCV RIBA

- I I

PCR No None reported

Laycock et al. 152 1997 U.S. Potential cornea donors (n
= 101)

Prevalence: 62% Selected from archives, but apparently not for any particular char acteristics Matrix

- HCV RIBA No Grants from Mid

- America Transplant Association and Research to Prevent Blindness Inc.

Leon et al. 153 1993 Spain H igh

- risk individuals (n
= 398)

Prevalence 2%
Known p ositive blood donat ion s from archive (n
= 102)
Overall prevalence 22% High

- risk individuals unselected (men who have sex with men, inmates, “mentally retarded”)

B lood donors who were known to have tested positive on first generation HCV ELISA test All samples tested by 11 m ethods, Negatives by

consensus

Those reactive in at least one also tested with supplemental assays to confirm positives No Not reported, but performed at a national microbiology
center322 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

Abbott HCV EIA 2.0

Ortho HCV EIA 3.0 Galel et al. 141 2002 U

. S

. Blood donors (n
= 5.5 ×10 6 ) Previously negative COBAS AmpliScreen HCV test 2.0 No Not r eported. Abbott performed PRISM testing, Roche Molecular provided RNA testing and equipment

Advia Centaur HCV Assay Denoyel et al. 139 2004 Noncommercial samples from Europe or U.S.

Seroconversion samples commercial Seroconversion panels (20 panels)
For specificity, blood donors (n = 5

, 015) and people (n = 213)

Prevalence 0.4% For sensitivity, samples presumed infected (n = 472) Commercial panels and positives selected for known properties

. Blood donors and hospitalized patients

u nselected Commercial panels: Known samples

Blood donors and hospitalized patients: Abbott AxSYM 3.0 and verification of positives with RIBA immunoblot testing No None reported323 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

Advia Centaur HCV

Ortho 3.0 EIA Kita et al. 146 2009 Clinical samples from Japan.

Seroconversion panels purchased from U

. S

. companies. Clin ical submissions for HCV tests (n
= 500)

Prevalence: 2.6% Commercially purchased seroconversion p anels (2 series) Clinical s amples appear to be unselected.

Seroconversion panels selected seroconversion Panels : known
status. Clinical samples compared among other tests to define negativity (Ortho Quick Chaser HCV Ab, VITROS HCV, Ortho HCV Ab PA Test II, Imx HCV Dainapak

- II, Architect HCV, Lumipulse IT Ortho HCV, Lumipulse Presto HCV) and confirmatory analyses t o define positivity (RIBA III, or RNA PCR) No None reported

Ortho 3.0 HCV EIA Barrera et al. 135 1995 U.S. Serial specimens from individuals who developed post

transfusion HCV (n
= 21) For seroconversion Known status No None r eported, but most of the authors employed at Ortho Diagnostic Systems324 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

Vrielink et al. 167 1995 The Netherlands Blood bank archives (n
= 2,153)

Prevalence <1% Unselected blood donors For specificity, Ortho 2.0 HCV EIA For sensitivity

, Ortho 2.0 HCV EIA, PCR, RIBA

- 2 No None reported

Vrielink et al. 168 1995 The Netherlands Tested together: Repeatedly positive blood donors (403 samples), non

- A non

B hepatitis patients (212 samples)

, multiply

- transfused patients (253 samples), unselected first

- time donors (1,055 samples )

Prevalence 21% For properties at left PCR, RIBA

- 2 No None reported

Tests currently in use in U.S. Organ Procurement Organizations (OPO): NAT

HIV NAT COBAS AmpliScreen HCV 2.0; COBAS AmpliScreen HIV 1.5 Bamaga et al. 133 2006 Saudi Arabia Blood donors (n
= 3,288) Prevalence: 0.2% Unselected blood donors Abbott AxSYM HCV 3.0, Enzygnost HIV No None reported325 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

COBAS AmpliScreen HIV

- 1,

COBAS Ampli Screen HCV, ProCleix HIV

- 1/HCV Busch et al. 137 2005 U.S. Archived plasma donations with confirmed viremia and/or seroconversion (12 HIV seroconversion panels, 12 HCV seroconversion panels) Serial samples available at least two weeks before samples became quantifiable, with short collection intervals (less than one week) Known

- status seroconversion panels (no

n

egative samples) No Funded in part by National Heart, Lung, and Blood Institute
contracts.

Genetics System (GS)
HIV

- 1/HIV

- 2 plus ) EIA;

HIVAB HIV

- 1/HIV

- 2 (rDNA) EIA (Abbott);

COBAS AmpliScreen HIV

- 1 Test 1.5 Owen et al. 159 2008 Mostly U.S., also Cameroon and unspecified international samples with

non

- subtype

- B HIV

- 1 Tested together: U

. S

. blood donors (n
= 997)

, international donors (n
= 97).

s

amples from Cam eroon (n
= 114)

HIV

- 2 specimens from Ivory Coast (n
= 32) and commercial HIV

- 2 specimens (n
= 2)

Prevalence 56% (53% HIV

- 1, 2% HIV

- 2)

Seroconversion panels (5 panels,
183 specimens) For defined properties (at left); all commercially purchased Known status for seroconversion and purchased panels For negatives,

consensus negative with other screening
tests

Confirmation of positives with Western blot No Not reported, but all authors affiliated with Centers for Disease Control (CDC)

COBAS AmpliScreen HIV

- 1 v. 1.5 Yang et al. 173 1999 Commercial panels Seroconve rsion panels (10 panels) For seroconversion Known status No None reported, but all authors affiliated with Roche Molecular Systems, Inc.326 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

Yang et al. 172 2001 Commercial panels Seroconversion panels (10 panels) For seroconversion Known status No None reported, but all authors af

filiated with Roche Molecular Systems, Inc.

HCV NAT COBAS AmpliScreen HCV 2.0;

COBAS AmpliScreen HIV 1.5 Bamaga et al. 133 2006 Saudi Arabia Blood donors (n
= 3,288) Prevalence: 0.2% Unselected blood donors Abbott AxSYM HCV 3.0, Enzygnost HIV No None reported

COBAS AmpliScreen HIV

- 1,

COBAS AmpliScreen HCV, ProCleix HIV

- 1/HCV Busch et al. 137 2005 U.S. Archived plasma donations with confirmed viremia and/or seroconversion (1 2 HIV seroconversion panels, 12 HCV seroconversion panels) Serial samples available at least two weeks before samples became quantifiable, with short collection intervals (less than one week) Known

- s

tatus seroconversion panels (no negative samples) No Fund ed in part by National Heart, Lung, and Blood Institute
contracts.

COBAS AmpliScreen HCV v. 2.0

Monolisa HCV Ag/Ab Ultra Laperche et al. 150 2005 Commercial seroconversion panels from U

. S

. companies Commercial

seroco nversion panels (10 panels,
107 samples) S eroconversion panels for defined properties (seroconversion) For seroconversion No Not reported, appears to be French public

source32 7 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

COBAS AmpliScreen HCV 2.0 Sun et al. 164 1999 Commercial panels Commercial seroconversion panels (5 panels) For seroconversion Known status No None reported, but all authors affiliated with Roche Molecular Systems, Inc.

HBV NAT COBAS AmpliScreen HBV Kleinman et al. 147 2005 U

. S

. Blood donors (n
= 581,790)

Prevalence: 0.02% All donors meeting standard criteria incl uded HBsAg Auszyme and anti

- HBc EIA (Abbott Laboratories) or HBsAg test system 2 and anti

- HBc tota l (Ortho Clinical Diagnostics).

D iscordant results : ID NAT with the AmpliScreen HBV test, alternative NAT, and DNA quantification. No Roche Molecular Systems

Romano et al. 160 2005 Commercial Seroconversion panels (5 panels) (commercial) For seroconversion Known status No None reported328 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

HIV

- 1 and HCV NAT COBAS AmpliScreen HIV

- 1,

COBAS AmpliScreen HCV, ProCleix HIV

1/HCV Busch et al. 137 2005 U.S. Archived plasma donations with confirmed viremia and/or seroconversion (12 HIV seroconversion panels, 12 HCV seroconversion panels) Serial samples available at least two weeks before samples became quantifiable, with short collection intervals (less than one week) Known

- status

seroconve rsion panels (no negative samples) No Funded in part by National Heart, Lung, and Blood Institute
contracts.

ProCleix HIV

- 1 /HCV Candotti et al. 138 2003 Commercial Commercial seroconversion panels (2 panels) For seroconversion Known status No National Blood Service NAT steering committe e and Chiron Corporation

Jackson et al. 144 2002 U.S. H igh

- risk individuals ’ archived samples (n
= 539)

Prevalence: 2.2% HIV only, 48% HCV only, 2% co

- infected At high risk for HIV and HCV “ Standard ” serological test

, p24 antigen test, alternative NAT, follow up if needed No Not reported, but 3 co

- authors employed at Gen

- Probe Inc.

Katsoulidou et al. 145 2004 Greece Seroconversion panels from dialysis patients (25 panels) For seroconversion Known status No None report ed, but Chiron Corp. provided reagents.

Kolk et al. 148 2002 Commercial Commercial seroconversion panels (26 panels HIV,
24 panels HCV) For seroconversion Known status No In part by National Heart, Lung, and Blood Institute. Authors employed at Gen

- Probe Inc.329 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

Vargo et al. 128 2002 U.S.

Commercial B lood donors (n
= 191,200) for specificity

Commercial:
Positive samples (n
= 2,015: 1,040 HIV infected, 1,015 HCV infected)) for sensitivity

Seroconversion panels (10 panels
HIV

- 1 and 10 HCV) Blood donors appear to be unselected

Panels for seroconversion S erology, with WB and/or immunofluoresce nce and/or p24 Ag test for HIV and RIBA for HCV to confirm positives

Panels and infected samples: Known status Yes Not reported but some authors affiliated with Chiron Corp.

Tests currently not in use in U.S. Organ P rocurement Organization (OPO): Fourth Generation Immunoassays

HIV 4

th generation EIA ARCHITECT HIV Ag/Ab Combo,

AxSYM HIV Ag/Ab Combo Kwon et al. 149 2006 Korea

C ommercial Korean samples in collection at university laboratory (143 infected, 412 uninfected)

Three commercial seroconversion panels (n
= 21) Panels selected for defined properties (positive, negative, seroconversi on) Known status for commercial panels Negatives by other Ab/Ag test

consensus Clinical samples Western blot confirmed. No None reported330 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

ARCHITECT HIV Combo

Cobas Core HIV Combi

Genscreen Ag/Ab HIV Ultra

VIDAS HIV DUO Quick

VIDAS HIV DUO Ultra Ly et al. 154 2007 France

Commercial Lab archives: For specificity: HIV negative samples (1,005)
For sensitivity: known positive samples from endemic areas (669)

Seroconver sion panels (24 panels), commercial For known characteristics (positive, negative, seroconversion) Known status for commercial panels and positives
Samples were considered negative if all samples run were negative No None reported

AxSYM Ag/Ab Combo

VID AS DUO ULTRA Bourlet et al. 136 2005 Serum samples from France

Commercial panels Serum samples submitted to university hospital microbio logy department (n
= 1,443)

Prevalence: 0.8%
Commercial panel:

S eroconversion panels (14 panels,

n = 112) Serum samples consecutive.

Seroconversion panels selected for define d properties (seroconversion). Panels known
status. Serum sample positives confirmed by Western blot or HIV

- 1 antigen
assay or HIV

- 1 RNA assay

Ne gative if all three 4

th generation tests of interest negative. No None reported331 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

AxSYM HIV Ag/Ab Combo,

Genscreen Plus Ag/Ab

Murex HIV Ag/Ab Combo,

Vironostika Uni

- Form II Ag/Ab Ly et al. 156 2004 Including U

. S

. , France, Cameroon, G hana, Uganda, U.K., Brazil, S outh Africa, Thailand, Argentina 25 seroconversion panels (176 samples)
Antibody positive samples (669 samples) for sensitivity Unselected negatives (1,005 samples) (for specificity) For defined properties (positive, negative, seroconversion) Known status No None reported

AxSYM Ag/Ab Combo Sickinger et al. 163 2004 Various pan els purchased from U.S., Ger many.

B lood donations and diagnostic samples possibly German because diagnosis confirmation held to German standards. Commercial panels

t ested together for sensitivity: HIV

- 1+ (n
= 453),
HIV

- 2 from endemic area (n
= 108),
HIV+ not staged or genotyped (n
= 107)

HIV

- 1 group O (n
= 19)

HIV

- 1 with p24 Ag (n
= 50)

Blood donors (n
= 7,900) (specificity)

D iagnostic submissions (n
= 1,939) (specificity) Known properties (positive, negative, or seroconversion) Panels known
status.

Blood donors and diagnostic popula tion RNA test, with AmpliCore HIV

- 1 Monitor RNA test

, Lav Blot I or Lav Blot II for confirmation No Not reported, but all authors affiliated with Abbott332 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

COBAS Core HIV Combo EIA Weber et al. 170 2002 >10 countries, including Cameroon, Germany, Luxembourg, Belgium, Portugal, Switzerland, South Africa, Thailand, and Zimbabwe Commercial
seroconversion panels (94 panels, 709 sera)
Assessed together for specificity: blood donor samples (n
= 7,579), daily routine samples (n
= 303), sa mples from hospital ized patients (n=997), potentially interfering

s

amples (n
= 1,222)
Assessed together for sensitivity: acute positives (n
= 32),
HIV

- 1 positive (n
= 620), HIV

- 1 subtyped (n
= 462),
HIV

- 2 positive (n
= 462), HIV p24 Ag/Ab positive (n
= 120), commercial performance panel (n
= 102) For known status (positi ve, negative, seroconversion) or variations of positive types (at left) Seroconversion panels known
status Negative with respect to alternate screening assays or negative WB, or WB indeterminate and p24 Ag negative

Positives confirmed by WB No Roche Diagno stics provided reagents, analyzers, and financial support for testing WB and confirmation
assays

Coulter HIV

- 1 p24 Ag Assay Willoughby et al. 171 19 89 U.S. Seropositive samples (from 34 individuals) For seroconversion Known status No National Institutes of Health333 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

Genscreen plus HIV Ag/Ab Aghokeng et al. 131 2004 Cameroon Blood donors (n
= 503)

Prevalence: 56

% confirmed positive Unclear whether samples were selected for any particular characteristic but HIV prevalence was high (56% confirmed)

Intended to represent group M genetic diversity Specificity determined with reference to 8 other tests: 4 rapid assays,
Enzygnost HIV Integral, Wellcozyme HIV Recombinant,

HIV Blot 2.2,

INNO

- LIA.

Positives

c

onfirmed with Inno

- Lia HIV Confirmation or HIV Blot 2.2 No National French agency for AIDS research334 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

Saville et al. 161 2001 U S, Trinidad, the Bahamas, Cote d'Ivorie, Cameroon Mixed set comprised of U.S . diagnostic samples (n = 503)

U.S. blood donors (n
= 1,010)

H igh

- i ncidence population in Trinidad (n
= 1,141)

S TD clinic attendees in Bahamas (N
= 83)

Confirmed HIV

- 1 group 0 from Cameroon (n
= 10)

Confirmed HIV

- 2 (n
= 16)

C ommercial panels : 1 panel HI V

- 1 group M antigen reactive (n
= 9) Prevalence (without seroconversion panel): 4.5%
Seroconversion panel (10 panels with

n = 74) Mostly unse lected donors or patients
Archived positives

C ommercially available seroconversion panel Known status (for
p

anel an d known samples)
Genetic Systems HIV

- 1 and HIV

- 2 ELISA, or rDNA EIA and HIV AG

1 monoclonal p24 assay by Abbott, with additional reference tests WB and/or RT

- PCR to investigate discrepancies and confirm positives Yes Funded by bioMerieux

VIDAS HIV DUO UL TRA Weber et al. 169 2002 Commercial panels Commercial seroconversion panels (16 panels) For seroconversion Known status No Roche Diagnostics provided test kits and financial
supp ort335 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

Murex HIV Ag/Ab Combo,

VIDAS HIV DUO ULTRA,
prototype AxSYM HIV Ag/Ab combo Ly et al. 158 2001 Commercial panels Seroconversion
pa nels (19 panels) For seroconversion Known samples No Not reported, but
most co

- authors employed at Abbot Laboratories

Vironostika HIV Uni

- Form II Ag/AB Aboud et al. 130 2006 Tanzania Submitted for diagnostic HIV testing (n
= 361) or an tenatal testing (n
= 511) in hospital lab, or by blood donors (n
= 508)

Prevalence: 22% overall confirmed Not reported, appears to be all samples from

sources For negative, other tes ts: Enzygnost anti

- HIV 1/2 Plus Vir onostika HIV Uni

- Form II plus O

Murex H IV antigen/antibody.

To confirm positives Inno

- Lia antibody assay

. For discrepancies, Innotest p24 Ag
assay. No Financial support from Swedish International Development Agency (SIDA), Department of Research Cooperation

Some materials provided by tests

man ufacturers

Iqbal et al. 143 2005 India Clinical samples from AIDS counseling
center (n = 264)

Prevalence: 48% Clinical samples unselected Western Blot Blinded to patient infection status None reported336 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

Ly et al. 157 2001 C ommercial panels Seroconversion panels, commercial (30 panels,
175 samples) Sel ected for defined properties (seroconversion) Known status No None reported, but manufacturers supplied panels and kits

Seyoum et al. 162 2005 Ethiopia (n
= 408) Bl ood donors

Prevalence: 3.4% Unselected Amplicor DNA PCR

ExaVir Load Test for HIV reverse transcriptase (v.2)
Amplicor HIV

- 1 RNA test for discrepancies, or other antibody
tests No Collaboration of several public health services, Red Cross, and a University department

Van Binsbergen et al. 165 1998 Commercial panels Commercial seroconversion panels (7 panels,
41 samples) Selected for defined properties (seroconversion) Known status No None reported. All but one author affiliated with Organon

- Tekn ika (manufacturer at time of publication)

Van Binsbergen et al. 166 1999 Commercial Seroconversion panels (10 panels) For seroconversion Known samples No Not reported, but all authors affili ated with Organon

- Teknika (manufacturer
at time of publication)337 Virus/ Test Type Index T est(s) Citation Year National Origin of Included Samples Source(s) of Included Samples How S e lected (Enrollment) Reference Standard(s) Blinding (Masking) Clearly Stated Funding Source

HCV 4

th generation EIA Monolisa HCV Ag/Ab Ultra Laperche et al. 151 2005 France Blood donors (n
= 12), Hemodialysis patients (n
= 23) Selected for defined properties ( a ll in seroconversion ) Known status (Based upon tests and follow

- up) No Not reported. All authors appear to be affiliated with public sources in France.

COBAS AmpliScreen HCV v. 2.0

Monolisa HCV Ag/Ab Ultra Laperche et al. 150 2005 Commercial

seroconv ersion
p

anels from U.S. companies Commercial

sero conversion panels (10 panels,
107 samples) For seroconversion Known status No Not reported, appears to be French public

source338 

### Analysis Methods

The characteristics of interest for this question are turnaround ti me, window period, and diagnostic performance. The methods used to assess each of these outcomes differ. The following paragraphs define those characteristics and explain the procedures used to collect information regarding them. In data extraction tables, data are presented separately for each test because results may vary by test, even within the same generation.

Turnaround Time
Turnaround time is the duration of time required for a sample to be fully assessed. As this information was sparsely reported in clinical literature, we also extracted relevant data from other sources, particularly review articles and grey literature including primary technology assessments and package insert
information. Where no other data were available we also extracted similar information such as “run time.” Note that “run time” is only the analytic component of turnaround time and does not include time needed for specimen preparation and ost

- analytic reporting time. These instances are clearly noted in the data
tables.

Window Period
Window period refers to the duration of time between infection and test positivity. The information regarding window periods comes from using the test of interest on seroconversion panels. Seroconversion panels are series of blood draws from patien ts who eventually become seropositive. They are typically collected from people at high risk for infection. Although a few investigators studied their own in

- house seroconversion panels, most such panels were purchased from laboratory supply companies. The se tests enable estimation of time to positive test result from first blood collection. However, the first day of blood collection may not coincide with the day of infection. Also, these samples are typically collected at irregular intervals, not daily. Th ese limitations cloud the estimation of the period of time between infection and when the test detects infection. Studies generally reported the difference in window period between two tests (e.g., Test 2 detected infection an average of 5 days later than Test 1). This type of information comprises the information in the results section on window period. No information was identified that captured absolute window periods using actual samples.

Diagnostic Performance
The most commonly used study design to eva luate the accuracy of a diagnostic test i s the diagnostic cohort study, in which a ll enrolled patients are examined with both the diagnostic test of interest and the accepted reference standard test. “Accuracy” is defined as the proportion of times the tes t of interest correctly categorizes an individual as having disease or not. The accepted reference standard test accurately categorizes the patient as having infection or not. ( A reference standard capable of determining
the true infec tion status of the pa tient is sometimes referred to as the “gold standard.” ) The accuracy of
the test of interest is determined with reference to the infe ction status of the patient, as determined by the reference standard, as shown in Table 48 . The information in this table can be used to calculate sensitivity and specificity of the test of interest , and where the prevalence of disease in the tested data set is similar to the prevalence in the target population

, can be used to determin e predictive values and likelihood ratios (these terms are defined in the text following the table).339 

### Table 48

. Determining Diagnostic Performance

True Status (Reference Standard)

Infected Not Infected

Test of interest Positive True Positive False Positive

Negative False Negative True Negative

However, because there are no perfect test s for the diagnosis of HBV, HCV, or HIV, no true single gold standard test currently exists. True disease state would be most accurately deter mined using information from more than one source (e.g., confirmatory tests, clinical assessment), possibly with repeat testing at a
follow

- up time to confirm negatives (after a window p eriod has passed). However, for the purposes of identifying as much in formation as possible for inclusion in this report, data were collected without regard to the accuracy of the reference standard (although studies that employ poor reference standards will be downgraded for study design and quality) . It is important to bea r this in mind when assessing the
extracted data because the reference standard influences diagnostic performance data

. This is particularly true when a more sensitive test is compared to a less sensitive test. For instance, if the test of interest is

more sensitive than the reference standard and no additional discriminatory tests are performed, positives that the test of interest catches but the reference standard misses will be misclassified as false positives and specificity will be underestimated . (For this r eason we refer to these outcomes as measures of “Diagnostic Performance” rather than “Diagnostic Accuracy.”) In the data extraction tables, t he reference standard used is always presented alongside the diagnostic performance data. Where more than on e set of information is reported for a particular test of interest, greatest heed should be paid to the statistic
det ermined using the most accurate reference standard (s)

. Commonly used diagnostic performance measures are calculated from the type of inform ation provided in
Table 48 and include sensitivity and specificity, predictive values, and likelihood ratios. Sensitivity is the

propo rtion of people with the infection (as determined by the reference standard) tha t the test of interest correctly recognizes as positive. A test with high sensitivity will rarely misclassify people with the disease as not having the disease (the test has a low rate of false

- negatives). Specificity is the proportio n of people
without in fection (as determined by the reference standard) that the test of interest correctly recognizes as negative. A test with high specificity will rarely misclassify people without the disease as diseased ( it has
a low rate of false

- positives). Sensitivity an d specificity are both expressed on a scale of 0% to 100%

, with greater values showing more agreement between the test of interest and the reference standard, and a
value of 50% being correct as frequently as random guessing. However, knowing the sensitivi ty and specificity of a test does not tell you whether a particular patient with a positive or negative test is
infected or not.

Other measures of diagnostic performance are more clinically applicable. The positive predictive value (PPV) of a test is the p robability of a patient having the disease following a positive test result. The negative predictive value (NPV) is the probability of a patient not having the disease following a negative
test result. Likelihood ratios indicate how much more likely patien ts with the disease are to have that particular result than patients without the disease . Positive likelihood ratios (PLR) indicate how much more likely people with infection are to have a positive test result, and negative likelihood ratios (NLR)340 

### indicate how much more people with infection are to have a negative result. Values of greater than one suggest infection, and values of less than one suggest not having infection. Unlike sensitivity and specificity, predictive values and likelihood ratios are infl uenced by the prevalence of the disease in the population of patients being tested. For this reason, we did not report (or calculate) predictive values or likelihood ratios from data not applicable to potential organ donors.

Diagnostic performance measures typically involve a trade

- off between counterpart metrics. For instance, increasing sensitivity (catching more of the true positives) may be at the expense of decreasing specificity (more false positives too). Acceptable thresholds for diagnostic performa nce and trade

- off between sensitivity and specificity will vary by intended use of the test.



### Assessment of Peer

**- reviewed Studies** 

We assessed the design and risk of bias (quality) of the peer

- reviewed studies and rated the strength of the evidence using gui delines proposed by the GRADE working group (Schunemann et al. (2008) 2 

### ; also
available online th rough links found at the GRADE W eb site.) We assessed studies reporting diagnostic characteristics using these protocols. It is likely that there is an inte raction between study design and study limitations/risk of bias, with the lower

- rated studies providing less reliable results. Where multiple studies report data on the same test, the study or studies with the fewest detractions on quality should be
consid ered more reliable.

We did not assess turnaround time because most of that information was not evidence

- based. We did not assess window period in this manner either, because much of the information came from sources other than peer

- reviewed publications a nd insufficient information was reported to assess them in full, and because there was no information directly pertinent to absolute window period.

Study Design
According to the GRADE diagnostics rating guidance, study design should initially be considered “high” quality if the study assesses patients with diagnostic uncertainty (e.g., unknown infection status) and comparison of results of test of interest with an appropriate reference standard. 2 

### The following paragraphs
describe the standards we used t o determine appropriateness of reference standard and diagnostic uncertainty. Studies that fulfilled both of these criteria were initially rated as “high.” Studies that fulfilled only one were initially rated as “moderate.” For evidence bases comprised of more than one study, we used the median number of items to determine the overall initial GRADE rating. Individual study design
factors are itemized in Table 49

.
Reference Standard

As described in the Methods sectio n, the correctness of the reference standard in deeming whether or not the sample is infected influences the diagnostic characteristics reported in that study, because all
characteristics are calculated with reference to that standard. When a reference sta ndard mis

- categorizes the true status of samples, correct identification of samples by the test of interest will be considered wrong. An example of a test that is not reasonable could be an earlier generation of the test of interest.
Because a first

- genera tion EIA should be less sensitive than a third generation test, it is an inappropriate reference standard and will lead to positive samples identified by the more sensitive 3 rd 

### generation that were not recognized by the older test being misclassified as fa lse positives rather than true positives. If the older test has more frequent false positives, the sensitivity of the newer test will be underestimated.341 

### Although another EIA may be an appropriate reference standard for specificity (to confirm negatives), a NAT or Western blot (WB) would have been more appropriate reference standards for sensitivity (to confirm positives) or to resolve discrepancies between the EIAs. However, because no single test is always correct, the most accurate way to determine the tr ue status of the sample is to use multiple testing methods, including using additional tests to resolve discrepant findings between the test of interest and the reference test, and to confirm positives. Clinical information could also contribute to the def initive status. In addition, to determine whether either the reference test or the test of interest may have both misclassified an infected sample as negative, samples should be drawn again after completion of a window period. Such practices could provide a very convincing and definitive reference standard by which to judge the characteristics of the test of interest. Well

- characterized commercially purchased samples (such as from a laboratory supply company) should also provide a very accurate reference

st andards. Commercial samples are typically characterized using a variety of tests, including confirmatory tests and quantitative tests for positive samples.

Diagnostic Uncertainty
Diagnostic uncertainty pertains to whether the infection status of a sample i s known before study enrollment. Selecting individuals based upon their infection status is likely to cause spectrum bias. Spectrum bias is mostly an issue of external validity; however, it may also bias diagnostic performance characteristics. If only pati ents who are either infected or uninfected are selected for inclusion, the study results generally suggest the test is more accurate than it really is. Spectrum bias would be best controlled for by enrolling an unselected (preferably consecutive or random) group of potential organ donors. Other unselected populations, such as general populations or blood donors, may provide reasonable substitutes, although these populations may differ in unknown way from potential organ donors (the characteristics of whom h ave been poorly described), including prevalence of infection and severity of disease. When test performance is measured within a cohort of individuals with unknown disease status representative of the target population, the study is assessing “clinical” p erformance. Such studies minimize the potential influence of spectrum bias and provide the best approximation of real

- world use.
Studies that only assessed sensitivity or specificity (or only positive or negative likelihood ratios or predictive values) wer e excluded from the evidence base. We included studies that reported both sensitivity and specificity with the intent of assessing both counterpart statistics derived from testing the same set of samples, to assess “clinical” diagnostic performance. Howeve r, some studies assessed sensitivity in known infected samples only and specificity in known uninfected samples only. Characterized infected and uninfected samples were purchased from laboratory supply companies or retrieved from laboratory archives. This type of a study is assessing “analytic” performance. Such studies may not accurately represent the performance of the test in real

- world use (typically, overestimation can be expected) and are ripe for spectrum bias. They may also be susceptible to further potential bias if no blinding occurs, especially if investigators have a vested interest in any particular test(s). Because the true status of the samples is already known, these analytic studies have some of the same limitations as other retrospective st udies.342 

### Table 49

. Study Design Items for Diagnostic Performance

Virus / Test Type Test Trade Name Manufacturer Cite Study Design Factor Satisfied Individual Study Design Rating GRADE Study Design Starting Point for Test Referen ce Standard Diagnostic Uncertainty

Tests currently in use in U.S. Organ Procurement Organization (OPO): Immunoassays

HIV 3

rd generation EIA Genetics System (GS) HIV

- 1/HIV

- 2 Plus 0 EIA Bio

- Rad Laboratories Owen et al. 2008 159 

- Moderate Moderate

HIVAB HIV

- 1/HIV

- 2 (rDNA) EIA Abbott Laboratories Barbe et al. 1994 134 

- Moderate Moderat e

Owen et al. 2008 159 

- Moderate

HBV (H B sAg; the surface antigen) Abbott AxSYM H B sAg Assay Abbott Laboratories Diepersloot et al. 2000 140   High H igh

Abbott PRISM HB sAg Abbott Laboratories No studies

- - - -

ADVIA Centaur HB sAg Assay Siemens Healthcare Diagnostics Huzly et al. 2008 142 

- Moderate Moderate

Genetic Systems (GS) HBsAg EIA 3.0 Bio

- Rad Laboratories No studies

- - - -

HBV (anti

- HBs; antibodies to the surface antigen) Ortho Antibody to H B sAg ELISA Test System 3 Ortho Clinical Diagnostics No studies

- - - -

HBV (anti

- HBc; antibodies to the core

a ntigen) Abbott PRISM HBcore Abbott Laboratories No studies

- - - -

ADVIA Centaur HBc Total Assay Siemens Healthcare Diagnostics No studies

- - - -343 Virus / Test Type Test Trade Name Manufacturer Cite Study Design Factor Satisfied Individual Study Design Rating GRADE Study Design Starting Point for Test Referen ce Standard Diagnostic Uncertainty

AxSYM Core 2.0 Abbott Laboratories No studies

- - - -

CORZYME Abbott Laboratories No studies

- - - -

Ortho HBc ELISA Test System Ortho Clinical Diagnostics No studies

- - - -

HCV Abbott HCV EIA 2.0 Abbott Laboratories Anderson et al. 1995 132 -  Moder ate High

Laycock et al. 1997 152   High

Leon et al. 1993 153   High

ADVIA Centa ur HCV assay Siemens Healthcare Diagnostics Denoyel et al. 2004 139 

- Moderate High

Kita et al. 2009 146   High

AxSYM Anti

- HCV Abbott Laboratories No studies

- - - - Ortho HCV Version 3.0 ELISA Test System Ortho Clinical Diagnostics Kita et al. 2009 146   High High

Vrielink et al. 1995 167   High

Vrielink et al. 1995 168 

- Moderate344 Virus / Test Type Test Trade Name Manufacturer Cite Study Design Factor Satisfied Individual Study Design Rating GRADE Study Design Starting Point for Test Referen ce Standard Diagnostic Uncertainty

Tests currently in use in U.S. Organ Procurement Organization (OPO): NAT

HIV NAT COBAS AmpliScreen HIV

- 1 Test v. 1.5 Roche Diagnostics Bamaga et al. 2006 133 -  Moderate Moderate

Owen et al. 2008 159 

- Moderate

HCV NAT COBAS AmpliScreen HCV Test version. 2.0 Roche Diagnostics Bamaga et al. 2006 133 -  Moderate Moderate

HBV NAT COBAS Ampli S creen HBV Test Roche Diagnostics Kleinman et al. 2005 147   High High

HCV and HIV

- 1 NA T ProCleix HIV

- 1/HCV Assay Gen

- Probe Incorporated Jackson et al. 2002 144

– HIV   High Moderate

Vargo et al. 2002 128

– HIV 

- Moderate

Jackson et al. 2002 144

– HCV   High

Vargo et al. 2002 128

– HCV 

- Moderate

Vargo et al. 2002 128

– Co

- infected 

- Moderate345 Virus / Test Type Test Trade Name Manufacturer Cite Study Design Factor Satisfied Individual Study Design Rating GRADE Study Design Starting Point for Test Referen ce Standard Diagnostic Uncertainty

Tests not in use in U.S. Organ Procurement Organization (OPO): 4 th generation Ag/Ab Immunoassays

HIV 4

th generation ARCHITECT HIV Combo Abbott Laboratories Kwon et al. 2006 149 

- Moderate Moderate

Ly et al. 2007 154 

- Moderate

AxSYM HIV Ag/Ab Comb o Abbott Laboratories Bourlet et al. 2005 136   High Moderate

Kwon et al. 2006 149 

- Moderate

Ly et al. 2007 156 

- Moderate

Sickinger et al. 2007 163 

- Mode rate

COBAS Core HIV Combi Roche Diagnostics Ly et al. 2007 154 

- Moderate Moderate

Weber et al. 2002 170 

- Moderate

Coulter HIV

- 1 p24 Antigen Assay Coulter Corporation No studies

- - - - Enzygnost HIV Integral II Siemens Healthcare Diagnostics No studies

- - - -

Genscreen Plus HIV Ag/Ab Combo Bio

- Rad Laboratories Aghokeng et al. 2004 131   High High

Ly et al. 2007 156 

- Moderate

Genscreen HIV Ultra Ag

- Ab Assay Bio

- Rad Laboratories Ly et al. 2007 154 

- Moderate Moderate346 Virus / Test Type Test Trade Name Manufacturer Cite Study Design Factor Satisfied Individual Study Design Rating GRADE Study Design Starting Point for Test Referen ce Standard Diagnostic Uncertainty

Modular HIV Comb i Roche Diagnostics No studies

- - - - Murex HIV Ag/Ab Combo Ab bott Laboratories Ly et al. 2007 156 

- Moderate Moderate

VIDAS DUO QUICK bioMerieux Clinical Diagnostics No studies

- - - -

VIDAS DUO ULTRA bioMerieux Clinical Diagnostics Bourlet et al. 2005 136   Hi gh High

Ly et al. 2007 154 

- Moderate

Saville et al. 2001 161   High

Vironostika HIV Uni

- Form II Ag/Ab bioMerieux Clinical Diagnostics Aboud et al. 2006 130   High High

Iqbal et al. 2005 143

*   High

Ly et al. 2007 156 

- Moderate

Seyoum et al. 2005 162   High

HCV 4

th generation INNOTEST HCV Ab IV Innogenetics N V No studies

- - - - Monolisa HCV Ag/Ab Ultra Bio

- Rad Laboratories No studies

- - - -

Murex 4.0 Abbott Laboratories No studies

- - - -

* Iqbal et al. reported outcomes for two data sets, which are both shown in Table 56 . However, for the purposes of assessment of the evidence base (to eliminate double

- influence of one study on the overall rating), the diagnostic data set is represented here.347 

### Limitations (Risk of Bias/Quality)
In addition to study design, we ass essed the limitations of each study using three more items. To assess the limitations of the included studies that report diagnostic performance outcomes, we asked the following three questions:

**•** Enrollment: Was there enrollment of consecutive/all, or rando m sample, of eligible patients ?

**•** Data loss : Is data loss minimal?

**•** Blinding: Was blinding performed for both the test of interest and the reference standard?
Failure to apply a reference standard to all samples was basis for exclusion (e.g., if all negatives were assumed to be true negatives), so we did not assess that factor.

The following paragraphs describe the criteria used to determine whether a particular study had a limitation. Itemized limitation assessment for all included studies is provided in Table 50 . Studies with one or more limitations are detracted one point in GRADE. If the majority of studies in a multiple

- study evidence base have one or more limitations, the strength is likewise detracted one point i n GRADE. Following these paragraphs, itemized assessment for each study is provided in Table 50

.

Enrollment
Enrollment of all eligible patients, a consecutive series of patients, or a random selection of patients o r blood samples minimizes the threat of sampling bias. Samples that are “unselected” with unknown status also satisfy this criterion. Selecting panels for a particular characteristic (i.e., known infected or known uninfected) does not satisfy this item reg ardless of the method used to select them because such sample sets are highly selected and prone to selection bias.

Data Loss
Although there may be no attrition in diagnostic cohort studies, data may be excluded from the evidence
base when the true status of the sample is inconclusive. Ideally, researchers would deal with conflicting or inconclusive test results by performing additional tests on the sample. Samples that remain inconclusive may have low antibody titers or amounts of nucleic acid and were pos sibly collected during a window period. Re

- testing at a later date (to allow for a window period to pass) could help to establish definitive status. Rather than perform these additional tests to reconcile conflicting results with true status, some
studies simply exclude the inconclusive samples from the data set. Data may also be excluded if there are errors in collecting the samples or performing the test. If enough data sets are excluded to impact the outcome statistics, diagnostic performance is likely t o be overestimated. We considered this criterion not satisfied if more than 5% of data are lost due to any cause.

Blinding
Blinding is a commonly recognized way to protect against diagnostic bias when interpreting results. Although qualitative assessment o f a sample should require little interpretation, lack of blinding could lead to miscategorization. Knowing the sample status could lead to misclassification of incorrect results as inconclusive (possibly resulting in the exclusion of that sample), especial ly if the result is close to the threshold or if it leads the researcher to recognize an error was made. This c ould be a particular problem

if the investigator has a potential conflict of interest with the study findings.348 

### Table 50

. Quality Assessment of Question 5 : Diagnostic Characteristics

Virus / Test Type Test Trade Name Manufacturer Cite Limitation Item Met Number of Items Satisfied Starting Grade Adjustment for Quality Enrollment Data Loss (Excessive Exclusions) Blinding

Tests currently in use in U.S. Organ Procurement Organization (OPO): Immunoassays

HIV 3

rd generation EIA Genetics System (GS)
HIV

- 1/HIV

- 2 Plus 0 EIA Bio

- Rad Laboratories Owen et al. 2008 159  

- 2

- 1

HIVAB HIV

- 1/HIV

- 2 (rDNA)
EIA Abbott Laboratories Barbe et al. 1994 134  

- 2

- 1 Owen et al. 2008 159  

- 2

HBV (H B sAg; the surface antigen) Abbott AxSYM H B sAg Assay Abbott Laboratories Diepersloot et al. 2000 140  

- 2

- 1

Abbott PRISM HB sAg Abbott Laboratories No studies

- - - - -

ADVIA Centaur HB sAg Assay Siemens Healthcare Diagnostics Huzly et al. 2008 142  

- 2

- 1

Genetic Systems (GS) HBsAg EIA 3.0 Bio

- Rad Laboratories No studies

- - - - -

HBV (anti

- HBs; antibodies to the surface antigen) Ortho Antibody to H B sAg ELISA Test System 3 Ortho Clinical Diagnostics No studies

- - - - -

HBV (anti

- HBc; antibodies to the core antigen) Abbott PRISM HBcore Abbott Laboratories No studies

- - - - -

ADVIA Centaur HBc Total Assay Siemens Healthcare Diagnostics No studies

- - - - -349 Virus / Test Type Test Trade Name Manufacturer Cite Limitation Item Met Number of Items Satisfied Starting Grade Adjustment for Quality Enrollment Data Loss (Excessive Exclusions) Blinding

AxSYM Core 2.0 Abbott Laboratories No studies

- - - - -

CORZYME Abbott Laboratories No studies

- - - - -

Ortho HBc ELISA Test System Ortho Clinical Diagnostics No studi es

- - - - -

HCV Abbott HCV EIA 2.0 Abbott Laboratories Anderson et al. 1995 132  

- 2

- 1 Laycock et al. 1997 152  

- 2

Leon et al. 1993 153  

- 2

ADVIA Centaur HCV assay Siemens Healthcare Diagnostics Denoyel et al. 2004 139 - 

- 1

- 1 Kita et al. 2009 146  

- 2

AxSYM Anti

- HCV Abbott Laboratories No studies

- - - - -

Ortho HCV Version 3.0 ELISA Test System Ortho Clinical Diagnostics Kita et al. 2009 146  

- 2

- 1 Vrielink et al. 1995 167  

- 2

Vrielink et al. 1995 168 

### - 

- 1350 Virus / Test Type Test Trade Name Manufacturer Cite Limitation Item Met Number of Items Satisfied Starting Grade Adjustment for Quality Enrollment Data Loss (Excessive Exclusions) Blinding

Tests currently in use in U.S. Organ Procurement Organization (OPO): NAT

HIV NAT COBAS AmpliScreen HIV

- 1 Test v. 1.5 Roche Diagnostics Bamaga et al. 2006 133  

- 2

- 1 Owen et al. 2008 159  

- 2

HCV NAT COBAS Ampl iScreen HCV Test version. 2.0 Roche Diagnostics Bamaga et al. 2006 13

3  

- 2

- 1

HBV NAT COBAS Ampli S creen HBV Test Roche Diagnostics Kleinman et al. 2005 147  

- 2

- 1

HCV and HIV

- 1 NAT ProCleix HIV

- 1/HCV Assay Gen

- Probe Incorporated Jackson et al. 2002 144

– HIV  

- 2

0 Vargo et al. 2002 128

– HIV    3

Jackson et al. 2002 144

– HCV  

- 2

Vargo et al. 2002 128

– HCV    3

Vargo et al. 2002 128

– Co

- infected    3351 Virus / Test Type Test Trade Name Manufacturer Cite Limitation Item Met Number of Items Satisfied Starting Grade Adjustment for Quality Enrollment Data Loss (Excessive Exclusions) Blinding

Tests not in use in U.S. Organ Procurement Organization (OPO): 4 th generation Ag/Ab Immunoassays

HIV 4

th gene ration ARCHITECT HIV Combo Abbott Laboratories Kwon et al. 2006 149 - 

- 1

- 1 Ly et al. 2007 154 - 

- 1

AxSYM HIV Ag/Ab Combo Abbott Laboratories Bourlet et al. 2005 136  

- 2

- 1

Kwon et al. 2006 149 - 

- 1

Ly et al. 2007 156 - 

- 1

Sickinger et al. 2007 163 - 

- 1

COBAS Core HIV Combi Roche Diagnostics Ly et al. 2007 154 - 

- 1

- 1

Weber et al. 2002 170 - 

- 1

Coulter HIV

- 1 p24 Antigen Assay Coulter Corporation No studies

- - - - -

Enzygnost HIV Integral II Siemens Healthcare Diagnostics No studies

- - - - -352 Virus / Test Type Test Trade Name Manufacturer Cite Limitation Item Met Number of Items Satisfied Starting Grade Adjustment for Quality Enrollment Data Loss (Excessive Exclusions) Blinding

Genscreen Plus HIV Ag/Ab Combo Bio

- Rad Laboratories Aghokeng et al. 2004 131  

- 2

- 1

Ly et al. 2007 156 - 

- 1

Genscreen HIV Ultra Ag

- Ab Assay Bio

- Rad Laboratories Ly et al. 2007 154 - 

- 1

- 1

Modular HIV Comb i Roche Diagno stics No studies

- - - - -

Murex HIV Ag/Ab Combo Abbott Laboratories Ly et al. 2007 156 - 

- 1

- 1

VIDAS DUO QUICK bioMerieux Clinical Diagnostics No studies

- - - - -

VIDAS DUO ULTRA bioMerieux Clinical Diagnostics Bourlet et al. 2005 136  

- 2

- 1

Ly et al. 2007 154 - 

- 1

Saville et al. 2001 161    3

Vironostika HIV Uni

- Form II Ag/Ab bioMerieux Clinical Diagnostics Aboud et al. 2006 130  

- 2

- 1

Iqbal et al. 2005 143

*  

- 2

Ly et al. 2007 156 - 

- 1353 Virus / Test Type Test Trade Name Manufacturer Cite Limitation Item Met Number of Items Satisfied Starting Grade Adjustment for Quality Enrollment Data Loss (Excessive Exclusions) Blinding

Seyoum et al. 2005 162  

- 2

HCV 4

th generation INNOTEST HCV Ab IV Innogenetics NV No studies

- - - - - Monolisa HCV Ag/Ab Ultra Bio

- Rad Laboratories No studies

- - - - -

Murex 4.0 Abbott Laboratories No studies

- - - - -

* Iqbal et al. reported outcomes for two data sets, which are both shown in Table 55 . However, for the purposes of assessment of the evidence base (to eliminate double

- influence of one study on the overall rating), the diagnostic data set is represented here.354 

### Additional Considerations

Consistenc y Although in some instances several studies addressed the same test of interest, different reference standards and samples were used. Differences in these two fundamental study design factors can be expected to lead to differences in outcomes and to dicta te generalizability. In this respect, each study should probably best be considered in isolation. For this reason we did not downgrade for inconsistency, although we do summarize multiple studies to provide an overall picture of the tests’ performances.

Di rectness
In the assessment of diagnostic technologies, GRADE assessment of directness pertains to whether direct measures of diagnostic performance (e.g., patient

- oriented clinical outcome) or indirect measures of diagnostic performance (e.g., intermediate or surrogate outcomes such as sensitivity and specificity) are reported. In this assessment, all data were indirect. However, the purpose of the question was to assess “test characteristics,” specifically including sensitivity and specificity. Detracting points because the study addresses the question of interest is inappropriate; therefore, we did not.

Precision
Lack of precision is typically measured by 95% confidence intervals (CI) of outcome statistics. Because not all studies reported CI or data neces sary to calculate CI, we considered the factor that influences precision instead, number of samples assessed. As most of the sample sets assessed were large (only four had 200 or fewer samples) and the smaller evidence bases had an over

- representation of i nfection compared with real

- world prevalence, we did not detract for precision.

Publication Bias
Because traditional methods of publication bias assessment are not useful for small evidence bases and evidence bases for which quantitative assessment is inap propriate, such as those addressing each test of interest, we assessed the potential for publication bias by considering whether at least half of the studies for a particular test were funded by the test’s manufacturer. If studies with significant findings are more likely to be published, and if only manufacturers funded the published studies, it is possible that independently funded studies with non

- significant findings were never published. The main limitation of this method is that most of the studies di d not report a funding source.

Full GRADE assessments are shown in Table 56 , after the Results section and tables.



### Results

Although a large number of peer

- reviewed publications and pieces of gray literature were i ncluded, little (or no) data addressed each of the individual studies of interest. Only one study may have collected samples from deceased individuals (corneal donors) . None of the studies appear to have focused on pediatric use. Due to this, it was not po ssible to determine differential test performance among populations or by donor clinical status.

The following sections provide summaries of results. Full results data are provided in the tables following
these sections.355 

### Turnaround Time

Information on the time required to full y administer diagnostic tests was sparse. For most of the test categories, no data were identified, despite consulting multiple sources for data. Available turnaround times are summarized by test type in Table 51 . Full data extraction on turnaround time on a per

- test basis
is shown in Table 4

. 

### Table 51

. Summary of Turnaround Times

Test Category Turnaround Time

Tests currently in use in U.S. Organ Procurement Organizations (OPO): Immunoassays

HIV, 3 rd generation EIA No data

HBsAg EIA 29 minutes for Advia Centaur (not reported for any of the others)

Anti

- HBs EIA No data

Anti

- HBc EIA No data

HCV, 2 nd or 3 rd generation EIA No dat a
Tests currently in use in U.S. Organ Procurement Organizations (OPO): NAT

HIV NAT 2 hours

HCV NAT 2 hours

HBV NAT No data

HCV and HIV

- 1 NAT Combined 6 hours

Tests not in use by U.S. Organ Procurement Organizations (OPO): 4 th generation Ag/Ab Immuno assays

HIV 4 th generation Ag/Ab EIA 26 minutes to 4 hours, depending on test brand

HCV 4 th generation Ag/Ab EIA 190 minutes for one test brand356 

### Window Period
Due to the limitations of using seroconversion panels to attempt to determine absolute window p eriods (previously defined as the duration between being infected and testing positive), we summarized the window periods relative to other tests. We report mean differences in time to detection among tests, and where reported, the range of time to detecti on. “Mean range” refers to the range of means when more than one study reported this data. These data were extracted from peer

- reviewed publications and gray literature including independent laboratory assessments and product labeling information.
This inf ormation is presented in Table 52 . Full data extraction on window periods and additional related information on a per

- test basis is shown in Table 4

. 

### Table 52

. Summary of Window Periods and Related Data

Test Category Window Period

Tests currently in use in U.S. Organ Procurement Organizations (OPO): Immunoassays

HIV, 3 rd generation EIA Positive mean 12

- 1 4 days before Western blot, but in one panel a t the same time as Western blot

HBsAg EIA Positive range of 0

- 7 days before other unnamed licensed test

Anti

- HBs EIA Positive range of 14

- 18 days after NAT
Positive later than HBsAg EIA on some samples

Anti

- HBc EIA Positive 1

- 4 weeks after HBsAg, coinci dent with symptom onset

HCV, 2 nd or 3 rd generation EIA Positive mean of 30

- 35 days after RNA test, and overall range of time to detect infection 4

- 118 days
Tests currently in use in U.S. Organ Procurement Organizations (OPO): NAT

HIV NAT* Positive rang e of 2

- 15 days before Ab test
Positive range 7

- 10 days before p24 Ag test Positive range of 0

- 28 days before Ag test alone

HCV NAT* Positive mean range of 25

- 85 days (and where reported absolute range 5

- 186 days) before confirmed 3 rd generation Ab test (a nd a mean of 113 days before 2

nd generation Ab test) Positive mean 5 days (range : 0

- 24 days) before 4 th generation test

HBV NAT Positive mean range 10 to 15 days (overall range where reported 4

- 18 days) before HBsAg (single

- sample procedure)

Tests not in use by U.S. Organ Procurement Organizations (OPO): 4 th generation Ag/Ab Immunoassays

HIV 4 th generation Ag/Ab EIA Positive means of 1.4 to 2 days after PCR Positive means of 1.5 to several days before 3 rd generation

HCV 4 th generation Ag/Ab EIA Positi ve mean of 5 days (range : 0

- 24 days) after NAT, a mean of 4.8 days (range: 0

- 32 days) after PCR, and a mean of 30 days after RNA assay

Positive mean of 2 6 days (range : 0

- 72 days) before 3 rd generation

*Includes data from combined HIV/HCV NAT357 

### Diagnostic Pe rformance
All of the extracted diagnostic performance data were sensitivity and specificity, drawn from clinical and analytic performance studies. Predictive values and likelihood ratios from potentially generalizable populations were not reported. We did not calculate these values because the prevalence of infection among potential solid organ donors has not been clearly defined. A summary of sensitivity and specificity data by test category are shown in Table 53

. The summarized data are point estimates. Where multiple estimates were reported, the lowest and highest (range of) values are reported. Full data extraction per test by name is shown in Table 55

.

The last column o f Table 53 shows the median GRADE assessment for the evidence base for the test category; full GRADE assessments for each test are shown in Table 56 . In brief, reasons for GRADE detraction most commonly included lack of blinding and lack of diagnostic uncertainty. Inappropriate reference standard was encountered less frequently, but could have strong effects on the outcomes (see HIV NAT and HCV NAT summary statistics in the table below). No studies had substantial data loss.
Table 56 also notes whether each statistic was calculated from an analytic study or a clinical study.



### Table 53

. Summary of Sensitivity and Specificity Data (Range of Reported Point Estimates)

Test Category Sensitivity Specificity GRADE ( Table 56 )

Tests currently in use in U.S. Organ Procurement Organizations (OPO): Immunoassays

HIV, 3 rd generation EIA 99.4% to 100% 97.7% to 99.7% Low

HBsAg EIA 100% 97.9% to 99.4% Low to Moderate

Anti

- HBs EIA No data No data

-

Anti

- HBc EIA No data No data

-

HCV, 2 nd or 3 rd generation EIA 73.2% to 100% 92.7% to 99.9% Moderate

Tests currently in use in U.S. Organ Procurement Organizations (OPO): NAT *

HIV NAT* * 92.6% to 100% 96.9% to 100% Low

HCV NAT * * 99.3% to 99.6% 97.4% to 99.6% Low

HBV NAT 84.8% 100% Very Low

Tests not in use by U.S. Organ Procurement Organizations (OPO): 4 th generation Ag/Ab Immunoassays

HIV 4 th generation Ag/Ab EIA 100% (all) 82.5% to 100% (Most >99%) Low to Moderate

HCV 4 th generation Ag/Ab EIA No data No data

-

*Includes data from combined HIV/HCV test

**

Summary table does not include data from Bamaga et al. due to lack of sufficient ly accurate reference standard for determining sensitivity and specificity. Data from that study are shown in the evidence tables.358 

### Table 54

. Overview of Diagnostic Tests

Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

Tests Currently in Use by U

. S

. Organ Procurement Organizations (OPOs) : Immunoassays

HIV 3

rd generation EIA Genetics System (GS)
HIV

- 1/HIV

- 2 Plus 0 EIA Bio

- Rad Laboratories 8/5/2003 EIA Living (serum, plasma),

Deceased donor (serum) From 15 seroconversion panels, at least half of the results were positive about 1 4 days before Western blot. 159 In the package labeling in the FDA approval document , data are reported on use in 50 seroconversion panels, compared with FDA licensed HIV

- 1/HIV

- 2 EIAs and a licensed HIV

- 1 Western blot. Compared with (unnamed) kit 1, it detected infection sooner 74% of the time and at the same t ime in the remainder. Compared with (unnamed) kit 2 (in only 46 of the panels), it detected HIV sooner 18% of the time, at the same time 70% of the time, and later 12% of the time. Compared with the Western blot it became positive sooner in 74% and at the same time in 26%. 195 -

HIVAB HIV

- 1/HIV

- 2 (rDNA) EIA Abbott Laboratories 7/22/2004 EIA Living (serum, plasma),

Deceased donor ( serum) In 7 of 8 seroconversion panels, positive responses were obtained 4 to >9 days sooner than Western blot, and at the same time in the eighth. 134
From 15 seroconversion panels, at least half of the test results were positive about 12 days before Western blot. 159
In the pack age insert, on 9 seroconversion panels this test detected antibod y at the same time or sooner than the Abbott HIVAB HIV

- 1 EIA (three times positive when Abbott was inconclusive, and one time inconclusive when Abbott was negative) . In one of the panels it detected HIV two bleeds (8 days) before Western blot. 190 -

HBV (H B sAg; the surface antigen) Abbott AxSYM H B sAg Assay Abbott Laboratories 6/1/2006 original approval; 2/5/2007 manufac

turing change; 12/ 19/2007 labeling change Micro

particle EIA Living (serum, plasma) In its FDA Summary of Safety and Effectiveness Data and Product Label, AxSYM HBsAg detected infection 3 to 7 days earlier than a (unnamed) FDA

- licensed reference in 5 out of 15 seroconversio n panels, and on the same day in the remaining 10. 194 -359 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

Abbott PRISM H B sAg Abbott Laboratories 7/18/2006 ChLIA Living (serum, plasma),

Deceased don or (serum) - -

ADVIA Centaur HB sAg Assay Siemens Healthcare Diagnostics 5/26/2005 original approval; 3/4/2009
process change EIA Living (serum, plasma) In the product label, in 6 seroconversion panels this test was positive at the same time as the (unnam ed) reference assay in 5 serials, and two bleeds sooner in the remaining serial. 189 29 15

5 to 30

142 minutes

Genetic Systems (GS) HBsAg EIA 3.0 Bio

- Rad Laboratories 1/23/2003 EIA Living (serum, plasma)

Deceased donor (serum) As reported on its package in sert, on 21 seroconversion panels, the GS HBsAg EIA 3.0 detected infection at the same time or earlier than the two unnamed licensed EIA comparison tests. 193 -

HBV (anti

- HBs; antibodies to the surface antigen) Ortho Antibody to H B sAg ELISA Test System 3 † Ortho Clinical Diagnostics 4/23/2003 EIA Serum, plasma In the FDA product label for Co bas AmpliScreen HBV test, on 40 seroconversion panels Orth o H BsAg System 3 detected HBV

a median of 14 to 18 days later than the NAT, depending on preparation method. 185 In company marketing materials for Genetic Systems HBsAg EIA, the window period for the GS test and this Ortho test was the same for 10 of 21 commercial seroconversion panels. For the remaining 11, GS detected reactive results sooner. 197 -360 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

HBV (anti

- HBc;

a ntibodies to the core antigen) Abbott AxSYM Core 2.0 Abbott Laboratories 9/8/2006 original approval; 2/5/2007 manufacturin g and packaging change Micro

particle EIA Living (serum, plasma) - -

Abbott PRISM HBcore Abbott Laboratories 10/13/2005 ChLIA Living (serum, plasma) The product label states, “Anti

- HBc appears in the serum of patients infected with HBV one to four weeks after the appearance of HBsAg, at the onset of symptoms.” 187 -

ADVIA Centaur HBc Total Assay Siemens Healthcare Diagnostics 12/22/2004 ChLIA Living (serum, plasma) The product labeling reports that, in a study of 7 seroconversion panels, the Advia Centaur detected infection at the same time as the ( unnamed) reference in 6 panels and one day sooner in the seventh. 186 -

CORZYME† Abbott Laboratories 3/19/1991 initial approval EIA Living (serum, plasma) - -

Ortho HBc ELISA Test System † Ortho Clinical Diagnostics 4/18/1991 EIA Living (serum, plasma) In a U.K. Health Protection Agency

- sponsored evaluation of the ORTHO HBc ELISA Test System, the test was evaluated in four seroconversion panels. All evaluated HBc tests detected the same number of samples. 198 -361 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

HCV Abbott AxSYM Anti

HCV Abbott Labora tories 2/5/2004 initial; 6/30/2004; 12/3/2004, 12/14/2004, 1/31/2005, 2/5/2007

manu

facturing changes; 2/22/2008 labeling changes Micro

particle EIA Living (serum) In an independent laboratory evaluation sponsored by the U.K. Medical Devices Agency, AxSYM HCV v.3 and six other HCV tests were evaluated. On 22 seroconversion panels and 2 performance panels AxSYM detected HCV a mean of 1.6 days after the most sensitive assay for a given panel (ranking #2 out of all the tests), compared with 1.1 for Vitros ECi anti

- HCV (which ranked first). 178 In an evaluation sponsored by the U.K. Health Protection Agency on 19 seroconversion panels, the Monolisa HCV Ab/Ab Ultra detected infection a mean of 4.8 days after PCR at a 0.5 threshold, and 7.5 days after PCR at a 1.0 threshold. For either threshold the range of days to detection was 0

- 32. By comparison, AxSYM HCV v. 3.0 detected HCV a mean of 19.7 days (range: 0

- 38) after PCR. 182 -

Abbott HCV EIA 2.0 Abbott Laboratories 7/22/2004 EIA Liv ing (serum, plasma),

Deceased donor (serum) Of 19 blood donors who were RNA

- positive but initially EIA

- 2 antibody negative, EIA

- 2 was positive at follow

- up a median of 63 days later , but 4 of the samples were still not EIA

- 2 reactive on the last follow

- u p sample available (at 23 days, 93 days, 317 days, and 190 days, respectively)

. For comparison, 8 of the donors were EIA

- 3 positive at initial test , 9 more were reactive at first follow

- up, and all were reactive by second follow

- up. So, by the last follow

- up time EIA

- 3 was positive for all donors, but for 4 of them EIA

- 2 was never reactive within the duration of the study. Intervals between blood draws were long, the authors noted. 141 -362 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

ADVIA Centaur HCV
assay Siemens Healthcare Diagnostics 12/22/2004 initial; 3/4/2009

manu

facturing
process change; 4/9/2009 trade name labeling change ChLIA Living (serum, plasma) Advia detected infection a mean of 34.6 days (range: 6 to 182 days) from the initial draw date on 20 panels. 139 In a study with two panels, Advia detected infection on bleed day 11 on one and day 28 on the other. 146 In its FDA submission of Summary of Safety and Effectiveness data, on 23 seroconversion panels, Advia Centaur was “at least as sensitive in the detection of seroconversion for HCV as commercially available assays,” compared with published data.
In the same document, on 20 seroconversion panels Centaur detected HCV on the same day as Ortho HCV v. 3.0 in 14 series, three days later in one, and a mea n of 3.25 days sooner on the remaining 4. 188 -363 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

Ortho HCV Version 3.0 ELISA Test System Ortho Clinical Diagnostics 5/20/1996; changes to package insert and indications 2/9/2009 EIA Living (serum, plasma),

Deceased donor (serum, EDTA) 8 of 19 blood donors who were RNA

- positive but initially EIA

- 2 antibody negative were EIA

- 3 reactive

. 17 of the 19 were reactive when recalled for additional testing a median of 34 (range : 5 to 70) days later , and all were reactive by the next follow

- up . This includes 4 who were EIA

- 2 negative for the entire duration of the study, with blood last tested at 23 days, 93 days, 190 days, and 317 days,

re

spectively. . Intervals between blood draws were long, the authors noted. 141

The me an time to detect infection i n transfusion recipients was 74 days post

- transfusion(range : 26 to 118 days). 15/21 cases were detected in the same bleed by Ortho 3.0 and the second generation version. In the other 5, this test detected infection a mean of 2 6 days (range : 20 to 34 days) earlier than the second generation version. 135

In a study with two panels, this test detected infection on bleed day 11 day on one and day 14 on the other. 146 In the FDA product label for COBAS AmpliScreen HCV Test 2.0, on 9 seroconversion panels it detected HCV a mean of 32 days before seroconversion, defined as positive results on both Ortho 3.0 EIA and Chiron RIBA 3.0. 184 In its FDA submission of Summary of Safety and Effectiveness data and product label, on 20 seroconversion panels Centaur detected HCV on the same day as Ortho HCV v. 3.0 in 14 series, three days later in one, and a mean of 3.25 days sooner on the remaining 4. 188 -364 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

Tests Currently in Use by U.S. Organ Procurement Organizations (OPOs) : Nucleic Acid Tests (NAT)

HIV NAT COBAS AmpliScreen HIV

- 1 Test v. 1.5 Roche Diagnostics 12/20/2002 initial approval; 12/19/2003 expanded indications; 3/9/2005 expanded indications; 5/23/2007 changes in labeling and directi ons PCR Living (plasma);

Deceased donor (serum, plasma) Based upon modeling, the window period was about 12 hours (95% CI : 5 to 19 hours) less than the Gen

- Probe TMA HIV

- NAT
test. 137
In 10 seroconversion panels, this test was positive 2 to 14 days (range) days before antibody seroconversion and 0 to 28 days (range) before p24 antigen test. 172
In 10 seroconversion panels, this test was positive 7 to 17 days before antibody seroconversion tested with anti

- HIV

- 1 Ortho Anti

HIV1/2 Test. 173 According to its FDA product label, AmpliScreen HIV Test v.1.5 detected HIV a mean of 12 days before Abbott HIV

- 1

- 2 antibody test on 41 seroconversion panels, 6.8 days before the Abbott p24 antigen test o n 40 panels, and 4.4 days before the Coulter p24 antigen test on 38 panels, using the multiprep procedure.
As reported in its FDA product label, this test detected HIV a mean of 14.2 days before Abbott HIV

- 1

- 2 antibody test on 41 panels, 8.3 days before t he Abbott p24 ant igen test on 40 panels, and 5.8 days before the Coulter p24 antigen test on 38 panels using the standard processing procedures. 192 Also reported in its FDA product label, COBAS HIV

- 1 Test v. 1.5 was evaluated on 10 plasma seroconversion panels. COBAS v.1.5 recognized HIV a mean of 12 days b efore Abbott HIV

- 1/2, 7.5 days bef ore Abbott HIV

- 1 p24 Antigen, and 4.3 days before Coulter HIV

- 1 Antigen test. 192 One s tudy reported the turnaround time of two hours. 133365 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

HCV NAT COBAS A mpliScreen HCV Test version . 2.0 Roche Diagnostics 12/3/2002 original approval; 5/13/2004 expanded indications; 3/9/2005 expanded indications; 5/22/2007 labeling PCR Living (plasma),

Deceased donor (serum, plasma) Based upon modeling, the window period was abou t 14 hours (95% CI : 10 to 9 hours) less than the Gen

- Probe TMA HCV

- NAT
test. 137

In 4 of 5 seroconver sion panels, the AmpliScreen test returned positive results 23 to 32 days before seroconversion panels. In the other panel, it detected infection later 164 On 44 blood donor samples in the window period, this test returned positive results a mean of 5.1 days (range: 0 to 24 days) before Monolisa HCV Ag

- Ab testing. 150 In the FDA product label for COBAS AmpliScreen HCV Test 2.0, on 9 seroconversion panels it detected HCV a mean of 32 days before seroconversion, defined as positive results on both Ortho 3.0 EIA and Chiron RIB A 3.0. 184 One study reported the turnaround time as two hours. 133

HBV NAT COBAS Ampli S creen HBV Test Roche Diagnostics 4/21/2005 original approval; 8/2/200 5 additional indications;

8/16/2007 labeling changes PCR Living (plasma),

Deceased donor (serum, plasma) Using 5 seroconversion panels this test was positive a mean of 10 days (range : 4 to 18 days) before HBsAg in single

- sample procedure; mean 3.7 days (0 to 11) with minipool. 160 In the FDA product label, in 40 seroconversion panels this test had a window period of 15 (SD : 17) days fewer than Ortho 3 for HBsAg using mult iprep procedure and 20 (SD : 17) days fewer using the standard preparation. 185 -366 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

HIV

- 1 a nd HCV NAT ProCleix HIV

- 1/HCV Assay Gen

- Probe Incorporated 2/27/2002 initial approval; 6/4/2004 expanded indications TMA Living (plasma),

Deceased donor (serum, plasma) Based upon modeled data and compared with AmpliScreen, the window period with ProCleix for HI V is an estimated 12 hours (95% CI: 5 to 19 hours) less, and for HCV it was an estimated 14 hours (95% CI: 5 to 19 hours). 137

HIV: In two seroconversion panels, ProCleix was positive 7 to 10 days before p24 antigen and 12 to 14 days before an antibody test for HIV. 138 In 26 seroconversion panels, ProCleix was positive for HIV at a mean of 10.2 bleed days (range : 0 to 61), compared with 12 .3 (range: 1 to 61) for PCR, 16.9 (range : 1 to 67) for HIV

- 1 antigen, and 24.5 (range : 9 to 74) for HIV

- 1 antibody. The window period was reduced by a mean of 14.6 (SD : 6.2) days compared with antibody testing and a mean of 6.6 (SD : 4.4) days compared with antigen testing. 148 In 10 HIV seroconversion panels, ProCleix tested neat was positive a median of 12 days (neat) or 10 days (diluted 1:16) before antibody test (HIV 1/2 antibody assay by Abbott). It was positive a median of 7 days (neat) or 3 days (diluted) before p24 antigen test (Abbott or Coulter). The discriminatory assay was positive a median of 12 days before the antibody test and 6 days before the antigen test. 128 In its product label, on 10 HIV seroconversion panels ProCleix detected infection a median of 10 d ays before Abbott HIV

- 1/2 and 3 da ys before the Abbott or Coulter p24 antigen test in a 1:16 dilution. The discriminatory assay tested neat detected infection a median of 12 days before the antibody test and 6 days before the antigen tests. ProCleix recognized HIV before the comparators in 8 panels and at the same time as the other two. 191 One study reported an “experienced operato r” required 6 hours to perform two HIV/HCV tests, and 6.5 hours to perform three. 138367 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

HCV:
In 2 seroconversion panels, one of the HCV panels had “similar” findings; the other had an 85 day difference between detection of HCV RNA and confirmed 3 rd generation antibody test. 138 In 25 seroconversion panels, ProCleix detected HCV a mean of 113.2 (Standard Deviation [SD] : 98.7) days before a 2 nd generation anti

- HCV assay and 80.5 (SD : 55.9) days before a 3 rd

-

generation
assay. 145 (The window period for HIV was not reported in the article.)
In 24 seroconversion panels, ProCleix detected HCV at a mean of 12 days (rang e : 0 to 140) compared with 13. 35 for PCR (of the 20 panels tested, range : 0 to 140) and 37.9 (range: 5 to 186) for antibody test. Compared with an anti body test, this test had a

mean reduction of 25.8 (SD: 15.5) day reduction in detection

. 148 In 10 HCV seroconversion panels, ProCleix (including the discriminatory assay) was positive a median of 25 days before the antibody test (Ortho 3.0). 128 In its product label, on 10 HCV seroconversion panels, ProCleix detected HCV sooner than the Ortho HCV 3.0 ELISA or the Abbott Anti

- HCV 2.0 for every series, and a median of 25 earlier whether diluted or not

. 191

Tests not currently in use in U.S. Organ Pro curement Organization (OPO): 4 th generation Immunoassays

HIV 4

th generation ARCHITECT HIV Combo Abbott Laboratories Not FDA Approved Micropart icle ChLIA (CMIA) Serum or plasma In 24 seroconversion panels, ARCHITECT HIV Combo was positive at mean of 13.1 d ays (range : 1 to 37). 154 In 3 panels, it was positive on day 8 in two and day 23 on the third. 149 In an evaluation funded by the U.K. Health Protection Agency on 18 seroconversion panels, the mean delay (range) in days of the Architect HIV Ag/Ab Combo was 0.9 (0

- 6) compared with the m ost sensitive assay. (For AxSYM HIV Ag/Ab Combo this was 0.6 (0

- 7); Genscreen Ultra HIV Ag

- Ab 1.5 (0

- 7); Murex HIV Ag/Ab Combo 4.8 (0

- 53); Vironostika HIV Uni

- Form II Ag/Ab 8.6 (0

- 57)). 177 Run time 26 minutes 154
Or, 29 minutes
per company marketing materials 174
Or, 30 minutes in an independent evaluation 177368 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

AxSYM HIV Ag/Ab Combo Abbott Laboratories Not FDA Approved Micro

particle EIA Serum or plasma In 24 seroconversion panels, AxSYM HIV Ag/Ab Combo was positive at mean of 14.8 days (range: 1 to 37). 156 In 19 seroconversion panels, it was positive at a mean of 13.2 days (range: 1 to 35). 158 In 14 seroconversion panels it detected HIV at a mean of 24.6 days (range: 7 to 50). 136 In 3 seroconversion panels it detected HIV at 15, 23, and 34 days. 149 In 25 seroconversion panels, it detected HIV a mean of 0.44 days (range: 0

- 5 days) after the first assay (which varied by panel). 156 This was 2

- 3 days before the 3 rd

-

generation assays. In 22 panels, compared with a 3 rd generation test (AxSYM gO), the window period was reduced by a mean of 6.15 days. 1 63 It was positive first by 1 to 2 bleeds in 18 of the panels, and equal in the other 4. In an evaluation funded by the U.K. Health Protection Agency on 18 seroconversion panels, the mean delay (range) in days of the Architect HIV Ag/Ab Combo was 0.9 (0

- 6

) compared with the most sensitive assay. (For AxSYM HIV Ag/Ab Combo this was 0.6 (0

- 7); Genscreen Ultra HIV Ag

- Ab 1.5 (0

- 7); Murex HIV Ag/Ab Combo 4.8 (0

- 53); Vironostika HIV Uni

- Form II Ag/Ab 8.6 (0

- 57)). 177 In an evaluation by the U.K. Medicines and Healthcare products Regulation Agency of 35 seroconversion panels, AxSYM Ag/Ab combo was always the first positive test out of the other tested 4

th and 3 rd generation as says. By comparison, the mean (range) of days longer for positivity by Murex HIV Ag/Ab Combination were 2.4 (0

- 53), Genscreen PLUS HIV Ag

- Ab were 3.6 (0

- 53), and Vironostika HIV Uni

- Form II Ag/Ab 5.9 (0

- 57). 179

In an evaluation of th e Genscreen ULTRA HIV Ag

- Ab funded by the U.K. Health Protection Agency, in 21 seroconversion panels, this test detected HIV a mean of 1 day (range: 0

- 6) after AxSYM (the earliest test). By comparison, Murex HIV Ag/Ab Combination detected HIV a mean of 3.8 days (range: 0

- 53) days later, and Vironostika HIV Uni

- Form II Ag/Ab detected HIV a mean of 7.3 (range: 0

- 57) days later. 181 Run time 40 minutes 154

Time to completion about 2 hours for 90 specimens in a Health Protection Agency evaluation

. 179369 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

COBAS Core HIV Combi Roche Diagnostics Not FDA Approved EIA Of 24 seroconversion panels, COBAS Core Combi only recognized HIV in 23 of the sample sets. Of those 23, the mean time to positive test result was 16.8 days (overall range 1 to never within panel set). 154 In 94 seroconversion pan els, compared with 3 rd generation tests the window period was reduced by 3.6 to 5.7 days. 170 In 87 panels in the same study, it detected HIV a mean of 2.75 days after RT

- PCR. 170 Run time 75 minutes 154

Coulter HIV

- 1 p24 Antigen Assay Coulte r Corporation Not FDA Approved EIA Plasma,

serum, or tissue culture
super

natants In the package insert, on 5 seroconversion panels the Coulter test detected HIV antigen prior to antibodies (tested by Abbott HIVAB
HIV

- 1 antibody EIA test) on 4 tests, by 21 days, 23 days, 42 days, and 28 days. In the other panel, antigen was not detected. 180 The package insert also reported on findings on 31 seroconversion panels by “independent investigators.” Window period was compared with Abbott HIVAB HIV

- 1/HIV

- 2 (rDNA) EIA and GS HIV

- 1/HIV

- 2 EIA, and several investigational tests. The Coulter test detected antigen prior to seroconversion in 80.6% of panels, and at the same time in 9.7%. Of the three remaining panels, one was not RNA

- positive eith er. The Coulter test reportedly detect antigen at the same time as the investigational tests detected RNA in the
rest. 180
As reported in its FDA product label, this test detected HIV a mean of 14.2 days before Abbott HIV

- 1

- 2 antibo dy test on 41 panels, 8.3 days before the Abbott p24 antigen test on 40 panels, and 5.8 days before the Coulter p24 antigen test on 38 panels using the standard processing procedures. 192
Also reported in its FDA product label, COBAS HIV

- 1 Test v. 1.5 was evaluated on 10 plasma seroconversion panels. COBAS v.1.5 recognized HIV a mean of 12 d ays before Abbott HIV

- 1/2, 7.5 days before Abbott HIV

- 1 p24 Antigen, and 4.3 days before Coulter HIV

- 1 Antigen test

. 192 Total test time 4 hours. 171370 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

Enzygnost HIV Integral II Siemens Healthcare Diagnostics Not FDA Approved EIA Serum, plasma In a WHO/UNAIDS evaluation, Enzygnost HIV Integral II detected HIV a mean of 1 day (range: 0 to 2) earlier than Enzygnost HIV 1/2 Plus, using 8 seroconversion series. By comparison, means were 0.9 for Genscreen Plus HIV Ag/Ab,

- 0.9 for Murex HIV Ag /Ab Combination, and

- 0.7 for Vironostika HIV Uni

- Form II Ag/Ab. 199 Total time 2 hours 50 minutes for 96 sera, according to WHO/UNAIDS report 15. 199

Genscreen Plus HIV Ag/Ab Combo Bio

- Rad Laboratories Not FDA Approved EIA Se rum, plasma In an evaluation by the U.K. Health Protection Agency on 18 seroconversion panels, the mean delay (range) in days of the Architect HIV Ag/Ab Combo was 0.9 (0

- 6) compared with the most sensitive assay. (For AxSYM HIV Ag/Ab Combo this was 0.6 (0

- 7); Genscreen Ultra HIV Ag

- Ab 1.5 (0

- 7) ; Murex HIV Ag/Ab Combo 4.8 (0

- 53); Vironostika HIV Uni

- Form II Ag/Ab 8.6 (0

- 57)). 177 In an evaluation funded by the U.K. Medica l Devices Agency of 38 seroconversion panels, the Murex Combo test detected HIV a mean of 3.9 days (range : 0 to 20) before the most sensitive antibody test. By comparison, the mean (range) was 2.76 (0 to 20) for Genscreen PLUS HIV Ag

- Ab and 0.34 (

- 9 to 20) for Vironostika Uni

Form II Ag/Ab. 183 In an evaluation funded by the U.K. Medicines and Healthcare products Regulation Agency of 35 seroconversion panels, AxSYM Ag/Ab combo was always the first positive test out of the oth er tested 4 th and 3 rd generation assays. By comparison, the mean (range) of days longer for positivity by Murex HIV Ag/Ab Combination were 2.4 (0

- 53), Genscreen PLUS HIV Ag

- Ab were 3.6 (0

- 53), and Vironostika HIV Uni

- Form II Ag/Ab 5.9 (0

- 57). 179 In a WHO/UNAIDS evaluation on 8 seroconversion panels, Genscreen Plus HIV Ag/Ab was positive a mean of 0.9 days (range:

- 0.1 to 1.75 days) earlier than the reference assay, Enzygnost HIV1/2 Plus. By comparison, means were

- 1 for Enzygnost HIV Integral II,

- 0.9 for Genscreen Plus,

- 0.9 for Murex HIV Ag/Ab Combination, and

- 0.7 for Vironostika HIV Uni

- Form II Ag/Ab. 199 Total time 3 hours for 96 tests, according to WHO/UNAIDS report 15 199

Or 152 minutes in an indepen dent laboratory evaluation. 181371 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

Genscreen HIV Ultra Ag

Ab Assay Bio

- Rad Laboratories Not FDA Approved EIA In 24 seroconversion panels, Genscreen HIV Ultra Ag

- Ab was positive at mean of 18.3 days (range: 1 to 37). 154 In an evaluation of the Genscreen ULTRA HIV Ag

- Ab funded by the U.K. Health Protection Agency, in 21 seroconversion panels, this test detected HIV a mean of 1 day (range: 0

- 6) af ter AxSYM (the earliest test). By comparison, Murex HIV Ag/Ab Combination detected HIV a mean of 3.8 days (range: 0

- 53) days later, and Vironostika HIV Uni

- Form II Ag/Ab detected HIV a mean of 7.3 (range: 0

- 57) days later. 181 Approxi mate time to completion 152 minutes, according to the U.K. Health Protection Agency. 181

Modular HIV Comb i Roche Diagnostics Not FDA Approved EIA Of 24 seroconversion panels, Modular Combi only recognized HIV in 23 of the sample se ts. Of those 23, the mean time to positive test result was 15.4 days (overall range 1 to never within panel set). 154372 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

Murex HIV Ag/Ab Combo Abbott Laboratories N ot FDA Approved EIA Serum, plasma Of 24 seroconversion panels, Murex Combo only recognized HIV in 23 of the sample sets. Of those 23, the mean time to positive test result was 14.6 days (overall range 1 to never within panel set). 154 In 19 seroconversion panels, it recognized HIV in 16 of the sample sets. Of those 16, the mean time to positive test was 15 d ays (overall range 1 to never within panel set). 158 In 25 seroconversion panels it recognized HIV a mean of 0.92 days (range : 0

- 15 days) after the first assay (which varied by panel). 156 This was about 1. 5 days before the 3 rd generation assays.
In an evaluation funded by the U.K. Health Prote ction Agency on 18 seroconversion panels, the mean delay (range) in days of the Architect HIV Ag/Ab Combo was 0.9 (0

- 6) compared with the most sensitive assay. (For Ax SYM HIV Ag/Ab Combo this was 0.6 (0

- 7); Genscreen Ultra HIV Ag

- Ab 1.5 (0

- 7); Murex HIV Ag/Ab Combo 4.8 (0

- 53) ; Vironostika HIV Uni

- Form II Ag/Ab 8.6 (0

- 57)). 177
In an evaluation by the U.K. Medical Devices Agency of 38 seroconversion panels, the Murex Combo test detected HIV a mean of 3.9 days (range : 0 to 20) before the most sensitive antibody test. By comparison, the mean (range) was 2.76 (0 to 20) for Genscreen PLUS HIV Ag

- Ab and 0.34 (

- 9 to 20) for Vironostika Uni

- Form II Ag/Ab. 183
In an evaluation funded by the U.K. Medicines and Healthcare products Regulation Agency of 35 seroconversion panels, AxSYM Ag/Ab combo was always the first positive test out of the other tested 4 th and 3 rd generation assays. By comparison, the mean (range) of days longer for positivity by Murex HIV Ag/Ab Combination were 2.4 (0

- 53), Ge nscreen PLUS HIV Ag

- Ab were 3.6 (0

- 53), and Vironostika HIV Uni

- Form II Ag /Ab 5.9 (0

- 57). 179 In an evaluation of the Genscreen ULTRA HIV Ag

- Ab funded by the U

. K

. Health Protection Agency, in 21 seroconversion panels, this test detected HIV a mean of 1 day (range : 0

- 6) after AxSYM (the earliest test). By co mparison, Murex HIV Ag/Ab Combination detected HIV a mean of 3.8 days (range : 0

- 53) days later, and Vironostika HIV Uni

- Form II Ag/Ab detected HIV a mean of 7.3 (range : 0

- 57) days later. By comparison, means were

- 1 for Enzygnost HIV Integral II,

- 0.9 for Genscreen Plus HIV Ag/Ab,

- 0.7 for Vironostika HIV Uni

- Form II Ag/Ab. 181 Total time to run assay 2 hours 55 minutes according to WHO/UNAIDS report 15. 199

Run time 120 minutes 183

Time to completion 140 minutes, as reported in a U.K. Medical Devices Agency report373 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

VIDAS DUO QUICK bioMerieux Clinical Diagnostics Not FDA Approved EIA In 24 seroconversion panels, VIDAS DUO QUICK was positive
at mean of 13.2 bleeding days (range : 1 to 37). 154

On the manufacturer W eb site, on 25 seroconversion panels there was a mean delay of 1.44 days in HIV detection compared to an RNA test. 176 Run time 80 minutes 154

VIDAS DUO ULTRA bioMerieux Clinical Diagnostics Not FDA Approved EIA In 14 seroconversion panels, VIDAS DUO ULTRA was positive at a mean of 23.5 days (range : 2 to 47) 136 In 24 seroconversion panels, it was positive at mean of 13.5 days (range: 1 to 30). 154 In 19 seroconversion panels, it was positive a mean of 16.2 days (range: 1 to 35). 158 In 16 seroconversion panels, it was positive at a mean of 2.31 days (range: 0 to 20) after RT

- PC R. 169 Compared with the most sensitive antibody test in the test’s information enclosure, on 10 seroconversion panels it detected HIV one bleed earlier in 2 cases, 2 bleeds earli er in 3, 3 bleeds earlier in 4, and 5 bleeds earlier in 1. 161 On the same panels compared with the most sensitive antigen test, it tested infection at the same time in 7 panels, 4 bleeds earlier in 1, 1 bleed earlier in 1, and 1 bleed later in the other. 161 On the company W eb site, in 16 seroconversion panels this test detected infect ion at a mean of 2.13 bleeding days (range: 0

- 20) compared with 2.38 (range: 0

- 22) for an antigen test. 175 Run time 120 minutes 154,169

Vironostika HIV Uni

For m II Ag/Ab bioMerieux Clinical Diagnostics Not FDA Approved EIA Serum, plasma Of 24 seroconversion panels, Vironostika Uni

- Form II Ag/Ab only recognized infection in 21. Of those 21, the mean time to positivity was 19.3 days (range 1 to never within panel set). 156 Of 19 seroconversion panels, it only recognized HIV in 16. Of those 16, the mean time to positivity was 15.6 days (overall range 1 to never within panel set). 158 Of 7 seroconversion panels, it was positive on day bleed 7, 15, 47, 26, 9, 18, and 27, respectively. It was always positive before Western blot and was positive from 0 to 37 days before the Total time to perform assay 2 hours 15 minutes, according to WHO/UNAIDS report 15. 199

Run time 90 minutes 154,157374 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

3

rd generation Vironostika test. 165 In 10 seroconversion panels this test was found to have a window period shortened by 6.2 days compared with the 3 rd generation Vironostika test. This is 2.2 days longer than a HIV

- 1 p24 antigen
assay. 166 Modeling from the same study suggests a total window period of 18 days. 166 In 30 seroconversion panels, it missed 3 positives. Of the rest, it detected HIV at a mean of 17 .1 days (overall range 0 to never). 157 On the same panels th ree 3 rd generation tests all missed either 3 or 4 positives, and had means detection at 17.6 days, 20.3 days, and 23.3 days. In 25 seroconversion panels, it detected HIV a mean of 2.6 days (range : 0 to 19 days) after the most sensitive assay (which varied by panel). 156 This was about the same as one 3 rd generation assay and a day sooner than another 3 rd generation assay. In an evaluation by the U.K. Health Protection Agency on 18 seroconversion panels, the mean delay (range) in days of the Architect HIV Ag/Ab Comb o was 0.9 (0

- 6) compared with the most sensitive assay. (For AxSYM HIV Ag/Ab Combo this was 0.6 (0

- 7); Genscreen Ultra HIV Ag

- Ab 1.5 (0

- 7); Murex HIV Ag/Ab Combo
4.8 (0

- 53); Vironostika HIV Uni

- Form II Ag/Ab 8.6 (0

- 57)). 177 In an evaluation funded by the U.K. Medical De vices Agency of 38 seroconversion panels, the Murex Combo test detected HIV a mean of 3.9 days (range: 0 to 20) before the most sensitive antibody
test. By comparison, the mean (range) was 2.76 (0 to 20) for Genscreen PLUS HIV Ag

- Ab and 0.34 (

- 9 to 20) for Vironostika Uni

Form II Ag/Ab. 183 In an evaluation by the U.K. Medicines and Healthcare products Regulation Agency of 3 5 seroconversion panels, AxSYM Ag/Ab combo was always the first positive test out of the other tested 4 th and 3 rd generation assays. By comparison, the mean (range) of days longer for positivity by Murex HIV Ag/Ab Combination were 2.4 (0

- 53), Genscreen PLU S HIV Ag

- Ab were 3.6 (0

- 53), and375 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

Vironostika HIV Uni

- Form II Ag/Ab 5.9 (0

- 57). 179 In an evaluation of the Genscreen ULTRA HIV Ag

- Ab by the U

. K

. Health Protection Agency, in 21 seroconversion panels, this test detected HIV a mean of 1 day (range : 0

- 6) after AxSYM (the earliest test). By comparison, Murex HIV Ag/Ab Combination detected HIV a mean of 3.8 days (range : 0

- 53) days later, and Vironostika HIV Uni

Form II Ag/Ab detected HIV a mean of 7.3 (range : 0

- 57) days later

. 181 In a WHO/UNAIDS evaluation on 8 seroconversion panels, Vironostika HIV Uni

- Form II Ag/Ab was positive a mean of 0.6 days (range :

- 0.2 to 1.5 days) earlier than the reference assay, Enzygnost HIV1/2 Plus. By comparison, means were

- 1 for Enzygn ost HIV Integral II,

- 0.9 for Genscreen Plus HIV Ag/Ab,

- 0.9 for Murex HIV Ag/Ab Combination. 199

HCV INNOTEST HCV Ab IV Innogenetics NV Not FDA Approved EIA Serum, plasma In company marketing materials, on 30 seroconversion panels the Innotest HCV Ab IV had a total delay of 22 days for the detection of HCV, compared with 122 days for Ortho 3.0 test (a 3 rd generation

assa y). 196 -376 Virus Test Trade Name Manufacturer FDA Approval Format* Speci men Collection Window Period Turn a round Time

Monolisa HCV Ag/Ab Ultra Bio

- Rad Laboratories Not FDA Approved EIA In 10 seroconversion panels, there was a mean delay in positivity between the Monolisa HCV Ag /Ab Ultra and MP

- NAT of 5.1 days (range: 0 to 24 days). 150 Compared with Prism HCV EIA (Abbott) (3 rd generation EIA) , this was a reduction of 26.8 days (range: 0 to 72 days). 150

In non

- commercial conversion panels of 23 hemodialysis patients, there Monolisa Ultra detected HCV a mean of 21.6 days before the most sensitive antibody test (which varied by panel). 151 The mean delay of the Monolisa after RNA assay was 30.3 days. The mean delay after the trak

- C antigen assay was 27.9 days
compar ed with the HCV core Ag quantification assay and 16.3 days compared with the HCV Ag blood screening assay. 151 In an evaluation funded by the U.K. Health Protection Agency on 19 seroconversion panels, the Monolisa HCV Ab/Ab Ultra de tected infection a mean of 4.8 days after PCR at a 0.5 threshold, and 7.5 days after PCR at a 1.0 threshold. For either threshold the range of days to detection was 0

- 32. By comparison, AxSYM HCV v. 3.0 detected HCV a mean of 19.7 days (range : 0

- 38) after PCR. 182 Approximate time to completion 190 minutes,

as reported by study funded by U.K. Health Protection Agency. 182

Murex 4.0 Abbott Laboratories Not FDA Approved EIA

- -

* ChLIA: Chemiluminescent immunoassay; EIA: Enzyme Immunoassay; PCR: Polymerase chain reaction; TMA: Transcription

- mediated amplification

† No FDA approval documentation found377 

### Table 55

. Diagnostic Characteristics

Virus/ T ype Test Trade Name Manufacturer Cite Study Type Sensitivity Specificity Data Loss Comments

Samples Reference Sensitivity Samples Reference Specificity

Tests currently in use in U.S. Organ Procurement Organization (OPO): Immunoassays

HIV 3 rd generation EIA Genetics System (GS)
HIV

- 1/HIV

- 2 Plus 0 EIA Bio

- Rad Laboratories Owen et al. 2008 159 Analytic 621 infected Other serological tests, nucleic acid
tests (NAT), Western blot (WB) for confirmation 99.8% 513 un

infected Other serological tests, NAT, WB 99.4% None Positives not tested in duplicate

HIVAB HIV

1/HIV

- 2 (rDNA) EIA Abbott Laboratories Barbe et al. 1994 134 Analytic 7 infect ed Archived samples 100% 1

, 546 negative Repeat testing, BioMerieux Assay, WB 99.74% None

Owen et al. 2008 159 Analytic 621 infected Other serological tests, NAT, WB for confirmation 99.4% 513 un

infected Other serological tests, NAT, WB 97.7% None Positives not tested in duplicate

HBV (HBsAg; the surface antigen) Abbott AxSYM HBsAg Assay Abbott Laboratories Diepersloo t et al. 2000 140 Clinical 200 Abbott IMx and DPC IMMULITE
assays. Discrepanci es by confirmatory
assay 100% 200 Abbott IMx and DPC IMMULITE assays 99.4% None

Abbott PRISM HBsAg Abbott Laboratories None identified - - - - - - - - -378 Virus/ T ype Test Trade Name Manufacturer Cite Study Type Sensitivity Specificity Data Loss Comments

Samples Reference Sensitivity Samples Reference Specificity

ADVIA Centaur HBsAg Assay Siemens Healthcare Diagnostics Huzly et al. 2008 142 Analytic 139 Consensus by >6 of 9 assays 100% 47 (exclude vacci

nated) Consensus by >6 of 9 assays 97.9% Not all patients included for calculation of sensitivity and specificity due to vaccination history. Patients unselected at enrollment but included for sensitivity or specificity retrospec

tively based
upon vaccination history

Genetic Systems (GS) HBsAg EIA 3.0 Bio

- Rad Laboratories None identif ied - - - - - - - - -

HBV (anti

- HBs; antibodies to the surface antigen) Ortho Antibody to HBsAg ELISA Test System 3 Ortho Clinical Diagnostics None identified - - - - - - - - -

HBV (anti

- HBc; antibodies to the core antigen) Abbott PRISM HBcore Abbott Lab oratories None identified - - - - - - - - -

ADVIA Centaur HBc Total Assay Siemens Healthcare Diagnostics None identified - - - - - - - - -

AxSYM Core 2.0 Abbott Laboratories None identified - - - - - - - - -

CORZYME Abbott Laboratories None identifie d - - - - - - - - -

Ortho HBc ELISA Test System Ortho Clinical Diagnostics None identified - - - - - - - - -379 Virus/ T ype Test Trade Name Manufacturer Cite Study Type Sensitivity Specificity Data Loss Comments

Samples Reference Sensitivity Samples Reference Specificity

HCV Abbott HCV EIA 2.0 Abbott Laboratories Anderson et al. 1995 132 Clinical 21,432 Ortho Anti

HCV 2.0 73.2% (64.6% to 80.7%)* 21,432 Ortho Anti

HCV 2.0 99.9% (99.9% to 100%* None Positives tested in duplicate

Additional
tests were used but results reported with respect to the 2.0 EIA reported

Laycock et al. 1997 1 52 Clinical 101 Matrix HCV RIBA 100% 101 Matrix HCV RIBA 92.7% None

Leon et al. 1993 153 Clinical 496 Consensus by 11 tests plus supple

mental confirmatory
assays 85.7% (80.5% to 89.9%)* 496 Consensus by 11 tests 99.8% (99.7% 99.9%)* 4 indeterminate (0.8%)

ADVIA Centaur HCV
assay Siemens Healthcare Diagnostics Denoyel et al. 2004 139 Analytic 472 presumed infected Abbott AxSYM 3.0, verification of positives with Chiron RIBA 3.0 100% (99.18 % to 100%) 5

, 228 Abbott AxSYM 3.0 99.9% (99.78% to 99.97%) For sensitivity, 3.4% (16 samples) excluded. For specificity, 0.08% (4 samples) excluded. Based upon repeated testing

Kita et al. 2009 146 Clinical 500 Consensus of 9 screening assays and PCR 100% (85.8% to 100%)* 500 Consensus of 9 screening assays and PCR 94.4% (91.1% to 96.3%)* None PCR used as reference standard instead of RIBA here to avoid da ta loss380 Virus/ T ype Test Trade Name Manufacturer Cite Study Type Sensitivity Specificity Data Loss Comments

Samples Reference Sensitivity Samples Reference Specificity

AxSYM Anti

HCV Abbott Laboratories No studies

- - - - - - - - -

Ortho HCV Version 3.0 ELISA Test System Ortho Clinical Diagnostics Kita et al. 2009 146 Clinical 500 Consensus of 9 screening assays and PCR 100% (89.7% to 100%)* 500 Consensus of 9 screening assays and PCR 95.5% (93.2% to 97.2%) None PCR used as reference standard instead of RIBA here to avoid data loss

Vrielink et al. 1995 167 Clinical 2

, 153 Ortho 2.0, PCR, and RIBA

- 2 100% 2

, 153 Ortho 2.0 99.7% (99.4% to 99.9%) No data loss (because PCR used as reference standard instead of RIBA)

Vrielink et al. 1995 168 Analytic 868 high probability infected Murex 3.0 EIA and Abbott 3.0 EIA

, PCR confirmation 100% 1,055 un

selected Murex 3.0 EIA and Abbott 3.0 EIA 99.9% No data l oss (because PCR used as reference standard instead of RIBA)

Tests currently in use in U.S. Organ Procurement Organization (OPO): NAT

HIV NAT COBAS AmpliScreen HIV

- 1 Test v. 1.5 Roche Diagnostics Bamaga et al. 2006 133 Clinical 3

, 288 Enzygnost HCV (EIA) 7.7% (0% to 52.8%)
(Note : EIA used as reference standard) 3

, 288 En zygnost HCV (EIA) 100% (99.9% to 100%) None 0.5 was added to TP and FP (which were zero) to enable calculation.

Owen et al. 2008 159 Analytic 621 infected Ot her
assays, NAT, WB 92.6% 513 un

infected Other
assays, NAT, WB 96.9% None381 Virus/ T ype Test Trade Name Manufacturer Cite Study Type Sensitivity Specificity Data Loss Comments

Samples Reference Sensitivity Samples Reference Specificity

HCV NAT COBAS AmpliScreen HCV Test version. 2.0 Roche Diagnostics Bamaga et al. 2006 133 Clinical 3

, 288 AxSYM 3.0 HCV EIA 20% (8.4% to 36.9%)
(Note : EIA used as reference standard) 3

, 288 AxSYM 3.0 HCV EIA 99.4% (99% to 99.6%) None

HBV NAT COBAS AmpliScreen HBV Test Roche Diagnostics Kleinman et al. 2005 147 Clinical 581,790 HB sAg, anti

- HBc, and follow

- up if discordant 84.8% (79.2% to 100%)* 581,790 HBsAg, anti

HBc, and follow

- up if discordant 100% (100% to 100%)* None

HCV and HIV

- 1 NAT ProCleix HIV

- 1/HCV Assay Gen

- Probe Incorporated Jackson et al. 2002 144

– HIV Clinical 530 Serology, p24 antigen (Ag), alternate NAT, re

- test at follow up if inconclusive 100% (85.2% to 100%)* 530 Serology, p24 Ag, alternate NAT, re

- test at follow up if inconclusive 100% (99.3% to 100%)* 1.7% data loss due to 9 inconclusive samples Tested neat

Vargo et al. 2002 128

– HIV Analytic 1 ,040 infected Clinical
status 99.9% (99.4% to 100%) 192,288 Serology, with WB and/or immunofluor

escence (IFA), if needed 99.67% (99.55% to 99.77%) overall 44 (2%) of all samples used in sensitivity in this study (for both viruses)

were excluded Positives tested neat

Jackson et al. 2002 144

– HCV Clinical 520 Serology, alternate NAT, re

- test at follo w

- up if inconclusive 99.3% (97.3% to 99.9%) 520 Serology, alternate NAT, re

- test at follow

- up if inconclusive 97.4% (94.4% to 99.0%) 3.5% data loss due to 19 inconclusive samples382 Virus/ T ype Test Trade Name Manufacturer Cite Study Type Sensitivity Specificity Data Loss Comments

Samples Reference Sensitivity Samples Reference Specificity

Vargo et al. 2002 128

– HCV Analytic 1

, 015 infected Clinical
status 99.6% (98.9% to 99.9%) 192,288 Serology, RIBA, follow

- up if needed 99.6% 44 (2%) of all samples used in sensitivity in this study (for both viruses)

were excluded Tested neat

Vargo et al. 2002 128

– Co

infected Analytic 180 co

infected Clinical
status 100% (98% to 100%) 192,288 Serology (as above for HIV and HCV separately) 100% 44 (2%) of all samples used in sensitivity in this study (for both viruses)

were excluded Tested neat

Tests currently not in use in U.S. Organ Procurement Organization (OPO): 4 th generation Immu noassays

HIV 4 th generation EIA ARCHITECT HIV Combo Abbott Laboratories Kwon et al. 2006 149 Analytic 149 infected Known

s amples 100% 412 un

infected Known samples 99.6% None

Ly et al. 2007 154 Analytic 553 infected 10 other 4 th generation assays and 2 3

rd generation assays, WB,
p

24 Ag, and PCR confirmation 100% 1

, 005 un

infected 10 other 4 th genera

tion assays and 2 3 rd genera

tion a ssays 99.9% initially reactive, 100% repeatedly reactive None

AxSYM HIV Ag/Ab Combo Abbott Laboratories Bourlet et al. 2005 136 Clinical 1

, 443 2 other assays plus confirmation 100% 1

, 443 2 other
assays 99.65% None

Kwon et al. 2006 149 Analytic 149 infected Known samples 100% 412 un

infected Known samples 98.0% None383 Virus/ T ype Test Trade Name Manufacturer Cite Study Type Sensitivity Specificity Data Loss Comments

Samples Reference Sensitivity Samples Reference Specificity

Ly et al. 2007 156 Analytic 669 infected Known samples characterize d genetically or by p24 Ag or WB 100% 1

, 005 un

infected 8 screening
assays, or WB neg ative or indetermi

nate and p24 Ag negative 99.8% initially reactive, same for repeatedly reactive None

Sickinger et al. 2007 163 Analytic 453 infected Known samples 100% 1

, 938 (hospitali

zed patients) RNA and “marker” negative 99.90% None

7

, 900 (blood donors) RNA and “marker” negative 99.87% None

COBAS Core HIV Combi Roche Diagnostics L y et al. 2007 154 Analytic 669 infected 10 other 4 th generation assays and 2 3

rd genera

tion assays, WB, p24 Ag, and PCR confirmation 100% 1

, 005 un

infected 10 othe r 4 th generation assays and 2 3

rd generation
assays 99.3% initially reactive, 99.4% repeatedly reactive None

Weber et al. 2002 170 Analytic 1

, 641 infected WB, p24 Ag, RNA assay 100% (99.82% to 100%) 10,031 negative (including inter

ference) Other

sc

reening
assays all negative, or WB negativ e, or WB indetermi

nate and p24 Ag negative 99.73% (99.61% to 99.82%) None

Coulter HIV

- 1 p24 Antigen Assay Coulter Corporation - - - - - - - - -384 Virus/ T ype Test Trade Name Manufacturer Cite Study Type Sensitivity Specificity Data Loss Comments

Samples Reference Sensitivity Samples Reference Specificity

Enzygnost HIV Integral II Siemens Healthcare Diagnostics - - - - - - - - -

Genscreen Plus HIV Ag/Ab Co mbo Bio

- Rad Laboratories Aghokeng et al. 2004 131 Clinical 503 Another EIA, 1 discrimina

tory assay, 2 confirmatory
assays 100% (99.6% to 100%) 503 Another EIA, 1 discrimina

tory assay, 2 confirmatory
assays 95%, or 82.5% (79.2% to 85.8%) with indetermi

n ate samples included None when indeterminate samples included. 8.4% (42) of the samples were indeter

minate.

Ly et al. 2007 156 Analytic 669 infected Known samples character

ized genetically or by p24 Ag or WB 100% 1

, 00 5 un

infected 8 screening

assa ys, or WB negative or indetermi

n ate and p24 Ag negative 99.9% initial, 99.9% repeat None

Genscreen HIV Ultra Ag

Ab Assay Bio

- Rad Laboratories Ly et al. 2007 154 Analytic 669 infected 10 other 4 th genera

tion assays and 2 3 rd genera

tion assays and PCR 100% 1

, 005 un

infected 10 other 4 th genera

tion assays and 2 3 rd genera

tion assays 99.7% initially reactive, 99.8% repeatedly reactiv e None

Modular HIV Combi Roche Diagnostics - - - - - - - - -

Murex HIV Ag/Ab Combo Abbott Laboratories Ly et al. 2007 156 Analytic 669 infected Known samples characterize d genetically or by p24 Ag or WB 100% 1

, 005 un

infected 8 screening

assa ys, or WB negati ve or indetermi

n ate and p24 Ag negative 99.5% initially reactive, 99.6% for repeatedly reactive None385 Virus/ T ype Test Trade Name Manufacturer Cite Study Type Sensitivity Specificity Data Loss Comments

Samples Reference Sensitivity Samples Reference Specificity

VIDAS DUO QUICK bioMerieux Clinical Diagnostics - - - - - - - - -

VIDAS DUO ULTRA bioMerieux Clinical Diagnostics Bourlet et al. 2005 136 Clinical 1

, 443 2 other assays plus confirmation
tests 100% 1

, 443 2 other
assays 99.86% None

Ly et al. 2007 154 Ana lytic 669 infected 10 other 4 th generation assays and 2 3

rd generation assays and PCR 100% 1

, 005 un

infected 10 other 4 th genera

tion assays and 2 3 rd genera

tion assay s 98.8% initial, 99.5% repeatedly reactive None

Saville et al. 2001 161 Clinical 2

, 773 Antibody screening, p24 Ag, confirma tory assays, NAT 100% 2

, 773 Antibody screening, p24 Ag, confirmatory assays, NAT 99.5% 0.1% (3 s amples) excluded be because
not “fully resolved.”

Vironostika HIV Uni

- Form II Ag/Ab bioMerieux Clinical Diagnostics Aboud et al. 2006 130 Clinical 1

, 380 Another EIA and confirmation 100% (98.8% to 100%) 1

, 380 Another EIA 99.4% (98.8% to 99.8%) None

Iqbal et al. 2005 143 Clinical 264 WB 100% (100% to 100%) 264 WB 99.3% (97.8% to 100%) 0.4% (1 sample) excluded for being indetermi nate

Iqbal et al. 2005 143 Analytic 104 infected WB 100% 100 un

infected WB 100% None This set not included in GRADE
assessment (clinical set above included instead)386 Virus/ T ype Test Trade Name Manufacturer Cite Study Type Sensitivity Specificity Data Loss Comments

Samples Reference Sensitivity Samples Reference Specificity

Ly et al. 2007 156 Analytic 669 infected Known samples characterize d geneticall y or by p24 Ag or WB 100% 1

, 005 un

infected 8 screening
assays, or WB negative or indetermi

nate and p24 Ag negative 97.21% initially reactive, 99.6% for repeatedly reactive None

Seyoum et al. 2005 162 Clinical 408 NAT and ExaVir Load
test 100% 408 NAT and ExaVir Load
test 99.2% None

HCV 4 th
gene ration EIA INNOTEST HCV Ab IV Innogenetics NV - - - - - - - - -

Monolisa HCV Ag/Ab Ultra Bio

- Rad Laboratories - - - - - - - - -

Murex 4.0 Abbott Laboratories - - - - - - - - -387 

### Table 56

. GRADE Table for Question 5 : Diagnostic Performance (Sensitivity/Specificity)

Virus Test Trade Name Manufacturer Quantity and Type of Evidence Findings (Poi nt Estimates) Starting GRADE (Study Design Table 49 ) Decrease GRADE GRADE for Evidence for OutcomeQuality(Table49)ConsistencyDirectnessPrecisionPublicationBias

Tests currently in use in U.S. Organ Procurement Organization (OPO): Immunoassays

HIV 3

rd generation EIA Genetics System (GS) HIV

- 1/ HIV

- 2 Plus 0 EIA Bio

- Rad Laboratories 1 A* 159 Sensitivity: 99.8%A**
Specificity: 99.4%A

Main limitations: lack of diagnostic uncertainty,

no blinding Moderate

- 1 0 0 0 0 Low

HIVAB HIV

- 1/HIV

- 2 (rDNA) EIA Abbott Laboratories 2 A 134,159 Sensitivity: 99.4%A 159 and 100%A 134 Specificity: 97.7%A 159 and 99.74%A 134

Main limitation s: lack of diagnostic uncertainty, no blinding. Study design and quality assessment equal for the two studies. Moderate

- 1 0 0 0 0 Low

HBV (H B sAg; the surface antigen) Abbott AxSYM H B sAg Assay Abbott Laboratories 1 CDx† 140 Sensitivity: 100%C‡
Specific ity: 99.4%C Main limitation: no blinding High

- 1 0 0 0 0 Moderate

Abbott PRISM HB sAg Abbott Laboratories No studies

- - - - - - - -388 Virus Test Trade Name Manufacturer Quantity and Type of Evidence Findings (Poi nt Estimates) Starting GRADE (Study Design Table 49 ) Decrease GRADE GRADE for Evidence for OutcomeQuality(Table49)ConsistencyDirectnessPrecisionPublicationBias

ADVIA Centaur HB sAg Assay Siemens Healthcare Diagnostics 1 A 142 Sensitivity: 100%A
Specificity: 97.9%A

Main limitations: lack of diagnostic uncertainty,

no blinding Moderate

- 1 0 0 0 0 Low

Genetic Systems (GS) HBsAg EIA 3.0 Bio

- Rad Laboratories No studies

- - - - - - - -

HBV (anti

- H Bs; antibodies to the surface antigen) Ortho Antibody to H B sAg ELISA Test System 3 Ortho Clinical Diagnostics No studies

- - - - - - - -

HBV (anti

- HBc; antibodies to the core antigen) Abbott PRISM HBcore Abbott Laboratories No studies

- - - - - - - -

AD VIA Centaur HBc Total Assay Siemens Healthcare Diagnostics No studies

- - - - - - - -

AxSYM Core 2.0 Abbott Laboratories No studies

- - - - - - - -

CORZYME Abbott Laboratories No studies

- - - - - - - -

Ortho HBc ELISA Test System Ortho Clinical Dia gnostics No studies

- - - - - - - -389 Virus Test Trade Name Manufacturer Quantity and Type of Evidence Findings (Poi nt Estimates) Starting GRADE (Study Design Table 49 ) Decrease GRADE GRADE for Evidence for OutcomeQuality(Table49)ConsistencyDirectnessPrecisionPublicationBias

HCV Abbott HCV EIA 2.0 Abbott Laboratories 3 CDx 132,152,153 Sensitivity: 73.2%C 132

, 85.7%C 153 , 100%C 152 Specificity: 92.7%C 152

, 99.8%C 153 , 99.9%C 132 Main limitations: one study less appropri ate reference standard, no blinding in
any.

Anderson et al. 132 used a less reliable reference standard. All other factors in study design and limitatio ns assessment the same for all three studies. High

- 1 0 0 0 0 Moderate

ADVIA Centaur HCV
assay Siemens Healthcare Diagnostics 1 A 139

1 DxC 146 Sensitivity: Both 100% Specificity: 94.4%C 146

, 99.9%A 139 Main limitations: one study suboptimal enrollment methods, no bli nding in either. Denoyel et al. 139 did not report appr opriate enrollment methods. All other study design and limitations assessments were the same. High

- 1 0 0 0 0 Moderate

AxSYM Anti

- HCV Abbott Laboratories No studies

- - - - - - - -390 Virus Test Trade Name Manufacturer Quantity and Type of Evidence Findings (Poi nt Estimates) Starting GRADE (Study Design Table 49 ) Decrease GRADE GRADE for Evidence for OutcomeQuality(Table49)ConsistencyDirectnessPrecisionPublicationBias

Ortho HCV Version 3.0 ELISA Test System Ortho Clinical Diagnostics 2 CDx 146,167 1 A 168 Sensitivity: All three 100%C
Specificity: 95.5%C 146

, 99.7%C 167 , 99.9%A 168

Main limitations: one study lack of diagnostic uncertainty, one study suboptimal enrollment methods, no blind ing.

Vrielink et al. 168 did not use samples with diagnostic uncertainty or report adequate enrollment methods. The rest of the study design and limitations assessment factors were the same for all three studies. High

- 1 0 0 0 0 Moderate391 Virus Test Trade Name Manufacturer Quantity and Type of Evidence Findings (Poi nt Estimates) Starting GRADE (Study Design Table 49 ) Decrease GRADE GRADE for Evidence for OutcomeQuality(Table49)ConsistencyDirectnessPrecisionPublicationBias

Tests currently in use in U.S. Organ Procurement Organization (OPO): NAT

HIV NAT COBAS AmpliScreen HIV

- 1 Test v. 1.5 Roche Diag nostics 1 DxC 133

1 A 159 Sensitivity: 7.7%C 133 and 92.6%A 159 Specificity: 96.9%A 159 and 100%C 133 Main limitations: one study inappropriate reference standard, other lack of diagnostic uncertainty, neither blinded

The main difference in findings appears to be due to the use of a reference standard inappropriate to calculate sensitivity in Bamaga et al. 133 Moderate

- 1 0 0 0 0 Low

HCV NAT COBAS AmpliScreen HCV Test version. 2.0 Roche Diagnostics 1 CDx 133 Sensitivity: 20%C
Specificity: 99.4%C

Main limitations: inappropriate reference standards, no blinding Moderate

- 1 0 0 0 0 Low

HBV NAT COBAS Ampli S creen HBV Test Roche Diagnostics 1 CDx 147 Sensitivity: 84.8%C
Specificity: 100%C

Main limitations:

no blinding, potential for publication bias Moderate

- 1 0 0 0

- 1 Very Low392 Virus Test Trade Name Manufacturer Quantity and Type of Evidence Findings (Poi nt Estimates) Starting GRADE (Study Design Table 49 ) Decrease GRADE GRADE for Evidence for OutcomeQuality(Table49)ConsistencyDirectnessPrecisionPublicationBias

HCV and HIV

- 1 NAT ProCleix HIV

- 1/ HCV Assay Gen

- Probe Incorporated 1 CDx 144

1 A 128 HIV Sensitivity: 99.9%A 128 and 100%C 144 Specificity: 99.67%A 128 and 100%C 144

HCV
Sensitivity: 99.3%C 144 and 99.6%A 128 Specificity: 97.4%C 144 and 99.6%A 128 Main limitations: one study lack of diagnostic uncertainty, one study

no blinding, p otential for publication bias

. Vargo et al. 128 did not have diagnostic uncertainty, and Jackson et al. did not have blinding. The stud ies were on the same for the rest of the study design and limitations assessment factors. Moderate 0 0 0 0

- 1 Low393 Virus Test Trade Name Manufacturer Quantity and Type of Evidence Findings (Poi nt Estimates) Starting GRADE (Study Design Table 49 ) Decrease GRADE GRADE for Evidence for OutcomeQuality(Table49)ConsistencyDirectnessPrecisionPublicationBias

Tests currently not in use in U.S. Organ Procurement Organization (OPO): 4 th generation Immunoassays

HIV 4

th generation ARCHITECT HIV Combo Abbott Laboratories 2 A 149,154 Sensitivity: Both 100%A
Specificity: 99.6%A 149 and 100%A 154

Main l imitations: lack of diagnostic uncertainty, suboptimal enrollment methods, no blinding.
The study design and limitations assessments were the same for both studies. Moderate

- 1 0 0 0 0 Low394 Virus Test Trade Name Manufacturer Quantity and Type of Evidence Findings (Poi nt Estimates) Starting GRADE (Study Design Table 49 ) Decrease GRADE GRADE for Evidence for OutcomeQuality(Table49)ConsistencyDirectnessPrecisionPublicationBias

AxSYM HIV Ag/Ab Combo Abbott Laboratories 1 CDx 136

3 A 149,156 ,163 Sensitivity: All 100%
Specificity: 98%A, 149 99.65%C, 136 99.8 %A, 156 99.9%/99.87%A 163 (last two from same study, different data sets)

Main limitations: two studies lack o f diagnostic uncertainty and/or suboptimal enrollment methods, all studies no blinding.

Bourlet et al. 136 had diagnostic uncertainty and appropriate enrollment methods while the rest did not. The stud ies were the same on all other study design and limitations assessment factors. Moderate

- 1 0 0 0 0 Low395 Virus Test Trade Name Manufacturer Quantity and Type of Evidence Findings (Poi nt Estimates) Starting GRADE (Study Design Table 49 ) Decrease GRADE GRADE for Evidence for OutcomeQuality(Table49)ConsistencyDirectnessPrecisionPublicationBias

COBAS Core HIV Combi Roche Diagnostics 2 A 154,170 Sensitivity: Both 100%A
Specificity: 99.3%A 154 and 99.73%A 170

Main limitations: lack of diagnostic uncertainty,

one study suboptimal enrollment methods, both no blinding.

The two studies were the same for study design and limitations assessment. Moderate

- 1 0 0 0 0 Low

Coulter HIV

- 1 p24 Antigen Assay Coulter Corporation No studies

- - - - - - - -

Enzygnost HIV Integral II Siemens Healthcare Diagnostics No studies

- - - - - - - -396 Virus Test Trade Name Manufacturer Quantity and Type of Evidence Findings (Poi nt Estimates) Starting GRADE (Study Design Table 49 ) Decrease GRADE GRADE for Evidence for OutcomeQuality(Table49)ConsistencyDirectnessPrecisionPublicationBias

Genscreen Plus HIV Ag/Ab Combo Bio

- Rad Laboratories 1 DxC 131

1A 156 Sensitivity: Both 100%
Specificity: 82.5%C, 131 99.9%A 156 Main limitations: One study lack of diagnostic uncertainty, one suboptimal enrollment methods, neither blinded. Ly et al. 156 did not have diagnostic uncertainty or report appr opriate enrollment methods. All other study design and limitation assessment factors were the same. High

- 1 0 0 0 0 Moderate

Genscreen HIV Ultra Ag

- Ab Assay Bio

- Rad Laboratories 1 A 154 Sensitivity:100%A
Specificity: 99.8%A

Main limitations: lack of diagnostic uncertainty, suboptimal enrollment methods, blinding Moderate

- 1 0 0 0 0 Low

Modular HIV Comb i Roche Diagnostics No studies

- - - - - - - -397 Virus Test Trade Name Manufacturer Quantity and Type of Evidence Findings (Poi nt Estimates) Starting GRADE (Study Design Table 49 ) Decrease GRADE GRADE for Evidence for OutcomeQuality(Table49)ConsistencyDirectnessPrecisionPublicationBias

Murex HI V Ag/Ab Combo Abbott Laboratories 1 A 154 Sensitivity: 100%A
Specificity: 99.6%A

Main limitations: lack of diagnostic uncertainty, suboptimal enrollment methods, bl inding Moderate

- 1 0 0 0 0 Low

VIDAS DUO QUICK bioMerieux Clinical Diagnostics No studies

- - - - - - - -

VIDAS DUO ULTRA bioMerieux Clinical Diagnostics 2 DxC 136,161

1 A 154 Sensitiv ity: All 100%
Specificity:99.5%C, 154 99.5%A, 161 99.86%C 136 Main limitations: one study lack of diagnostic uncertainty, one study suboptimal enroll ment methods, two studies lack of blinding Ly et al. 154 did not have diagnostic uncertainty or report appropriate enrollment methods. None of the studies besides S aville et al. 161 used blinding. All othe r study design and limitation assessment factors were the same. High

- 1 0 0 0 0 Moderate398 Virus Test Trade Name Manufacturer Quantity and Type of Evidence Findings (Poi nt Estimates) Starting GRADE (Study Design Table 49 ) Decrease GRADE GRADE for Evidence for OutcomeQuality(Table49)ConsistencyDirectnessPrecisionPublicationBias

Vironostika HIV Uni

- Form II Ag/Ab bioMerieux Clinical Diagnostics 3 CDx 130,143,162

1 A 156 Sensitivity: All 100%
Specificity: 99.2%C

, 162 99.3%C, 143 99.4%C, 130 99.6%A 156 Main limitations: one study lack of diagnostic uncertainty, no blinding Ly et al. 156 did not have diagnostic uncer tainty or report appr opriate enrollment methods. All other study design and limitation assessment factors were the same. High

- 1 0 0 0 0 Moderate

HCV 4

th generation INNOTEST HCV Ab IV Innogenetics NV No studies

- - - - - - - -

Monolisa HCV Ag/Ab Ultra B io

- Rad Laboratories No studies

- - - - - - - -

Murex 4.0 Abbott Laboratories No studies

- - - - - - - -

* A: Analytic study

** A: Analytic sensitivity/specificity

† CDx: Clinical diagnostic cohort ‡ C: Clinical sensitivity/specificity399 

# Evidence Reviews: **III**

**. Donor interventions to decrease**  **transmission of HIV, HBV,or HCV from infected donors**

**Question 6**  **. Which do no**  **r interventions reduce the probability of pathogen transmission from an organ donor**  **infected with HIV, HBV, or** 

**HCV to a previously uninfected r**  **ecipient?**

Two publications of the same study of virus inactivation in organs met the inclusion criteria. 200,201



### The study described kidney perfusion technique s that may pot entially inactivate h epatitis C

. The study
methods and results are shown in Table 57 and Table 58 , respectively. The study procured kidneys from HCV positive deceased donors, and investigated the virus

- reducing capacity of four inactivation protocols :

**•** The first ( called “ standard ” by the authors ) involved initial flushing with 1.0L of University of Wisconsin ( U/W ) solution, 20 hours of pulsatile perfu sion, and another U/ W flushing.
U/W solution is “ a normokalemic, intracellular colloid injected into vi tal organs during harvesting to preserve function before transplantation ”

. 202



### • The second ( called “ enhanced ” ) involved a second pulsatile perfusion and addition al flushings.

**•** The third involved 24 hours of pulsatile perfusion at a lower flow rate

**•** The fourth ( “ ultrafiltered ” ) involved the filtration of used perfusate during the perfusion process.

The results ( Table 58 ) sh owed that all four methods substantially reduc ed the viral load. The best results were found with the enhanced pulsatile perfusion, for which 99.7% of the HCV viral particles had been removed within 15 minutes after the start of the second perfusion.

Regar ding study quality ( Table 59 ) , there was no control group that did not receive inactivation; no

“ patients ” were actually enrolled. A pplying the GRADE system ( Table 60 ) resu lted in a grade of Low

. This was based on the fact that it was only a single study , and there was no non

- inactivated control group

, but it did find a large magnitude of effect as well as a dose response association

.400 

### Table 57

. Inacti vation M ethods in Zucker et al. (1994)

Kidney D onor Inactivation P rocedure Procedural Steps

Donor 1, Deceased HCV positive Standard pulsatile perfusion 1) Flushed with 1.0 L of U/W solution
2) 20 hours of perfusion on a Waters MOX

- 9 pulsatile perfusion ap paratus using 1.0 L of silica gel

- treated plasma at between 4

- 6 degrees Celsius at a flow rate of approximately 400mL/minute
3) Again flushed with 1.0 L of U/W solution

Donor 2, Deceased HCV positive Enhanced pulsatile perfusion Steps 1

- 2 of the standard procedure, and then:
3) Three additional flushes with 1.0 L of U/W solution
4) Another 20 hours of perfusion using 1.0 L of silica gel

- treated plasma at between 4

- 6 degrees Celsius at a flow rate of approximately 400mL/minute
5) Again flushed with 1.0 L of U/W solution

Donor 3, Deceased HCV positive

, Kidney 1 Pulsatile perfusion, without ultrafiltration of perfusate 1) Flushed with 1.0 L of U/W solution
2) 24 hours of perfusion on a Waters MOX

- 9 pulsatile perfusion apparatus using 1.0 L of silica gel

- tre ated plasma at between 6 degrees Celsius at a flow rate of 200mL/minute

Donor 3 , Deceased HCV positive, Kidney 2 Pulsatile perfusion, with ultrafiltration of perfusate 1) Flushed with 1.0 L of U/W solution
2) 24 hours of perfusion on a Waters MOX

- 9 pulsat ile perfusion apparatus using 1.0 L of silica gel

- treated plasma at between 6 degrees Celsius at a flow rate of 200mL/minute, with ultrafiltration of perfusate using a high

- flow hollow

- fiber filter with a molecular weight cut

- off of 300k daltons401 

### Table 58

. Inactivation R esults in Zucker et al. (1994)

Total Viral Burden BEFORE I nactivation When the Viral Load was M easured Total Viral B urden AFTER I nactivation % of Viral Copies that had been R emoved

Standard Pulsatile Renal Preservat ion P rocedure

4.78 x 10 5 After the first 4 hours of pulsatile perfusion 1.28 x 10 5 73%

Enhanced Pulsatile Renal Preservation P rocedure

247 x 10 5 After the full 20 hours of the first pulsatile perfusion 60.5 x 10 5 76%

247 x 10 5 After the 3 additional U /W flushes and 15 minutes after the start of the second pulsatile perfusion 0.74 x 10 5 99.7%

Pulsatile Renal Preservation Procedure, without Ultrafiltration of P erfusate

160 x 10 5 After the first 1 hour of pulsatile perfusion 120 x 10 5 25 %

160 x 10 5 Aft er the full 24 hours of pulsatile perfusion 50 x 10 5 69%

Pulsatile Renal Preservation Procedure, with Ultrafiltration of P erfusate

160 x 10 5 After the first 1 hour of ultrafiltered pulsatile perfusion 60 x 10 5 63%

160 x 10 5 After the full 24 hours of ul trafiltered pulsatile perfusion 15 x 10 5 91%



### Table 59

. Question 6 : Quality A ssessment

Study 6a 6b 6c 6d 6e 6f 6g 6h

Zucker et al. (1994) 200,201  

A checkmark (  ) means that the study met the quality criterion for t his Question; the lack of a checkmark means that the study either did not meet the criterion, or it was unclear whether the study met the criterion. The criteria specific to this Question were:

6a. Were the patients randomly assigned to treatments?

6b. Was the st udy planned prospectively (i.e., before any data were collected)

6c. Were all consecutive patients enrolled (or a random sample of eligible patients)?

6d. Were the two groups comparable at baseline? (age, sex, comorbidities, indi cation for transplant, previous dur ation on waitlist)

6e. If not, were statistical adjustments performed to control for baseline differences?

6f. Were the two groups treated concurrently? 6g. Did at least 85% of the study enrollees provide data?

6h. Was the between

- group difference in study completion rat es less than 15%?402 

### Table 60

. GRADE T able for Question 6 (I nactivation)

Comparison Outcome Quantity and T ype of Evidence FindingsStarting Grade Decrease GRADE Increase GRADE

GRADE of Evidence for OutcomeStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDoseResponseConfounders wouldreduce the effect

Inactivating vs. not inactivating pathogens in solid organs Viral burden One study 200,201 The four inactivation procedures reduced viral bu rden 69%% to 99.7% Low

- 1

- 1 0 0 0 +1 +1 0 Low403 

# Evidence Reviews: IV **. Potential risks and benefits of transplanting, or not transplanting,**  **solid organs from donors positive for HIV, HBV, or HCV** 

**Question 7** 

**. How do the clinical outcomes of recipients of**  **organs from**
**donors infected with HIV, HBV, or HCV**  **compare to those who remain on the transplant list?** 

This question involves whether the long

- term health of a recipient will be better if 1) an organ from a known infected donor is transplanted, or 2) the pa tient remains on the waiting list for an organ from an uninfected donor. Transplanting an organ from an infected donor incurs the chance of a new infection, in addition to the usual risks of organ transplantation (e.g., graft failure, graft

- vs. host diseas e). However, remaining on the waiting list also entails risks, primarily the risk of death before an organ becomes available. Even if an organ from an uninfected donor become available, transplantation pr ocedural risks will still apply, and these risks wou ld be slightly higher at that time because the recipient would be older.

This question should not be confused with Question 8, which considers clinical outcomes after the transplantation of organs from at

- risk donors with unknown infection status.

Our orig inal inclusion criteria for this question ( Table 2 ) required a waitlist control group; only one study met those original criteria: Abbott et al. (2004). 82 

### This study involved the transplantation of kidneys from deceased donors known to have been infected with HCV; its methods and results are detailed in the next section. Due to the paucity of evidence, we r elaxed the initial inclusion criteria to include:

**•** Studies of recipients who were negative before transplant that compared the clinical outcomes
after receiving an organ from a positive donor vs. receiving an organ from a negative donor

**•** Studies of recipient s who were positive before transplant that compared clinical outcomes after receiving an organ from a positive donor vs. receiving an organ from a negative donor

This expansion yielded 7 and 22 additional publications, respectively; they are listed in Table 64

. Although these comparisons do not involve the waitlist, they are still relevant. When a potential organ recipient does not receive an organ because it is from a known positive donor, the recipient remains on the waitlist for an organ from a negative donor. This hoped

- for organ may or may not become available before the patient dies. The comparison group “receiving an organ from a negative donor” represents the realization of this hope, so it estimates a relati vely good waitlist outcome.

The use of organs from infected donors may be more acceptable for recipients who are already positive before transplant, because disease transmission is less important (although dual infection with a different genotpye is possib le). Their outcomes may be quite different from the outcomes of recipients who were negative before transplant, which is why we considered the two types of recipients separately.

Some centers may reserve organs from infected donors only for the most ill re cipients. For example, Haji et al. (2004) 77 

### stated that “at our institution, an HC V

- seropositive donor was used when, in the judgment of the transplant team, the recipient was critically ill and not a candidate for mechanical404 

### ventricular assist device or had a significant complication while on the ventricular assist device.” 77


### (page 278 ) Based on this practice, a simple comparison of survival times between those who received organs from infected donors and those who received organs from uninfected donors would be biased against the former group. Thus, a better analysis would attempt to control for pre

- transplant differences so that the comparison is more balanced.



### Org **ans from Positive Donors Compared to Remaining on the Waitlist**

Abbott et al. (2004) 82 

### considered the clinical scenario of a patient with end

- stag e renal disease (ESRD) on dialysis, and a kidney from a deceased HCV+ donor becomes available to this patient. Authors used retrospective data on Medicare beneficiaries in the United States Renal Data System who had been on the kidney transplant waiting li st between 4/1/1995 and 7/31/2000. Of the 38,270 potential recipients:

**•** 389 patients (1%) were transplanted with kidneys from deceased HCV+ donors (abbreviated DHCV+). Of these 389 recipients, 201 of them (52%) were HCV+ before the transplant.

**•** 16,106 patien ts (42%) were transplanted with kidneys from deceased HCV

- donors . Of these recipients, 508 of them (3%) were HCV+ before the transplant.

**•** 17,044 patients (45%) were not transplanted during the study period. The pre

- transplant HCV status of these recipients was not reported.

**•** 4,731 patients (12%) were transplanted prior to dialysis, or transplanted with an organ other than a kidney, or transplanted with any kidney from a living donor (neither separate counts not outcome data were reported for these patients). The pre

- transplant HCV status of these recipients was not reported.

A critical question is whether these groups of patients were similar before the transplantations occurred.

If they were not, then pre

- transplant factors (e.g., age, or amount of time alre ady on waitlist) could explain subsequent differences in mortality rates. In this study, there were some differences between
the 389 patients who received kidneys from DHCV+ and the full group of patients (all reported
characteristics are listed in Table 61 below). The only characteristic with a particularly large difference

at baseline involved race: 58% of recipients of organs from DHCV+ donors were African

- American,

as compared to only 30.4% of the full group of enrolled patients. Several of the other differences were statistically significant (due to the extremely large number of enrolled patients), but the actual size of the baseline differences were not generally large.

The authors performed adjusted analyses to control for pre

- transplant differences. Any variable that was statistically significantly associated with mortality (defined as p <0.10) was adjusted for: recipient age, recipient race, cause of end

- stage renal disease (ESRD), year of first dialysis, pr esence of congestive heart failure, ischemic heart disease, peripheral vascular disease, serum albumin level, Medicare claims for

access

- related complications, and Medicare HCV claims at the time of listing.

The mortality analyses contained an important l imitation: if an organ from any donor other than a
deceased HCV+ donor was transplanted, all subsequent survival times were excluded from the analysis. Therefore, the mortality from remaining on the waitlist was only up to the point of receiving an alterna te kidney. A more comprehensive approach would have included post

- transplant survival times for those who did eventually receive kidneys from alternate donors.405 

### Authors compared the adjusted mortality rates of kidney recipients from a DHCV+ donor to waitlis t patients. The reported results are shown in Figure 11 . The adjusted hazard ratio of 0.76 (95% confidence interval 0.60 to 0.96) indicated reduced mortality after receiving a kidney from a deceased HCV+ donor

as c ompared to being on the waitlist.

Authors did not directly compare the mortality rates of recipients of kidneys from HCV+ donors to recipients of kidneys from HCV

- donors. However, they did report a comparison between receiving a kidney from any deceased donor (regardless of donor HCV status) and being on the waitlist. This comparison favored transplantation substantially (adjusted hazard ratio of 0.47; 95% CI: 0.43 to 0.50). Thus, the mortality advantage of receiving a kidney more than doubled when recipi ents of HCV

- donor kidneys were included in the analysis (i.e., the 24% mortality advantage in the primary analysis increased to a 53% advantage).

The GRADE evidence profile appears in Table 63 . The grade was Very Low, which was due to three factors: 1) the study did not randomly assign recipients to groups; 2) the study excluded survival data after the transplantation of any kidney that was not a kidney from a d eceased HCV+ donor; and 3) that there was only one stu dy. If either of the latter two factors were removed, the rating would still be

“ Very Low ”

.406 

### Table 61

. Baseline Characteristics in the Abbott et al. (2004) Study

Characteristic DHCV+ (N = 389) Full Group of Enrolled Patients (N = 3 8,270) Between

- group Difference in Percentage P oints (p.p.), or Hedges ’ g

% male 75.3% 61.3% 14 p.p.

% African

- American 58.4% 30.4% 28 p.p. ; Large difference at baseline

% with diabetes as the cause of end

stage renal disease 29.8% 35.3% 5 p.p.

% with hypertension 77% 73.9% 4 p.p.

% with congestive heart failure 15.9% 13.8% 2 p.p.

% ischemic heart disease 9.7% 8.9% 1 p.p.

% with smoking history 8.4% 5.3% 3 p.p.

% with hemodialysis (not peritoneal) 86.1% 80.5% 6 p.p.

% with peripheral vascular disea se 4.4% 5.3% 1 p.p.

% with Medicare claims for HCV at the time of listing 5.4% 0.5% 5 p.p.

% with positive HCV serology by UNOS 51.7% Not reported Not calculable

% with Medicare claims for access 17.7% 14.2% 3.5 p.p.

Mean Age 51.2 (SD: 11.3) 47.6 (SD: 13.8) g = 0.26

Mean Body Mass Index 26.0 (SD: 5.5) 26.7 (SD: 6.2) g = 0.11

Mean Serum albumin (gm/dL) 3.2 (SD: 0.7) 3.4 (SD: 0.7) g = 0.29

Mean Hematocrit 28.2 (SD: 5.8) 27.9 (SD: 5.7) g = 0.05

Note : Shaded cells represent baseline characteristics that differed by 15+ percentage points, or differed by 0.4+ on the scale of Hedges’ g. Hedges’ g is the difference between means divided by the pooled standard deviation. The difference in percentage points, and values for Hedges’ g, were calculated by ECRI I nstitute
SD

– Standard deviation407 

### Figure 11

. Adjusted Mortality Results of Transplanting Kidneys from DHCV+ Donors Compared to the Waitlist



## 0 0.5 1 1.5 2 Adjusted hazard ratio* 0.76

Note : T he horizontal bars represent the reported 95% confidence interval around the adjust ed hazard ratio. The fact that the confidence intervals was fully below 1.0 indicates that the adjusted hazard ratio was statistically significantly in favor of receiving a kidney from a DHCV+ donor ov er being on the waitlist.

* Variables adjusted for incl uded recipient age, recipient race, cause of end

- stage renal disease, year of first dialysis, presence of con gestive heart failure,

ischemic heart disease, peripheral vascular disease, serum albumin level, and Medicare claims for access

- related complicatio ns and Medicare claims for access

related complications HCV408 

### Organs from Positive Donors Compared to Organs from Negative Donors W hen the Recipients were Negative Before T ransplant

We included seven publications (five unique studies) that made this compar ison. One study involved HBV, and four involved HCV. General study characteristics are listed in the upper portion of Table 64 , and details of methods appear in the upper portion of Table 65

.
Regarding quality (the upper portion of Table 67 ), none of the studies were randomized or prospective, but all five treated the groups concurrently, and three studies enrolled patients consecuti vely. Two studies reported data on at least 85% of the enrolled patients and also had less than a 15% difference in completion rates between groups. For baseline comparability of groups (upper portion of Table 66 ), only two of the five studies reported any specific characteristics to enable a comparison (the Fong et al. [ 2002 ] 55 

### study of HBV, and the Haji et al. [ 2004 ] 77,79 

### study of HCV). Our analyses of between

- group compar ability identified three large differences at baseline (identified as gray cells in the upper portions of Table 66 ). For Fong et al. (2002) 55 

### , the rate of donor death due to stroke was substantially higher in the D+ group (51% than the D

group (36%). For Haji et al. ( 2004) 77,79 

### , the percentage of donors who were male was greater in the D+ group (74%) than in the D

- group (57%), and also the mean recipient age was greater in the D+ group (age 57) than
in the D

- group (age 52).

One way to address the problem of differing pre

- transplant characteristics is to perform statistical adjustments of the results. Only one of the five studies (Abbott et al. 2003) 83,84 

### clearly performed such adjustments. The methods section of the Haji et al. ( 2004) 77,79 

### study reported some use of Cox regression

“to adjust for significant covariates ” , but authors did not report whether the reported hazard ratio of 2.8 was adjusted or unadjusted.

All study results appear in the upper portion of Ta ble 68 , and pertinent plots are in Figure 12 . The points appear without confidence intervals because studies did not report enough information to permit such calculation, which is also why no meta

- analyses of thes e results were possible. Note that in the figure, the data generally fall below the 45 degree line, suggesting shorter survival among those who received D+ organs than those who received D

- organs. However, the lack of demonstrated group comparability, and the possibility that in some studies the pre

- transplant prognosis was poorer for recipients of D+ organs, make it difficult to interpret these raw results. The one study that controlled for baseline differences (Abbott et al. 2003) 83,84 

### ) found a significantly shorter survival of those who received D+ organs (adjusted hazard ratio of 2.25; see footnote to the figure). The Haji et al. ( 2004) 77,79 

### study, which may have controlled for baseline differences, also reported shorter survival for recipients of D+ organs (see Table 68 ).

Regarding different g enotypes of HBV and HCV, none of the five studies reported donors' genotypes, or stated whether recipient survival was different by donor genotype.

The GRADE evidence profiles appear in Table 63 . We graded the evi dence as Very Low for all of these evidence bases, except for the comparison of recipient survival of HCV+ and HCV

- organs, which we graded as Low. None of these studies had randomized recipients to groups, and several had pre

- transplant
differences betwee n groups that were not statistically adjusted for. The single “Low” GRADE (for recipient survival comparing HCV+ and HCV

- donors) was due to the large effect magnitudes found in those three
studies.409 

### Figure 12

. Clinical Outcomes of Negative Recipients: Positive vs. Negative Donors, any Pathogen, any Organ

0 10 20 30 40 50 60 70 80 90 100

0 10 20 30 40 50 60 70 80 90 100 

### Survival %

after D+ transplant

Survival %
after D

- transplant

Graft survival of HBV

- recipients after kidney transplant

Graft survival of HCV

- recipients after liver transplant

Patient survival of HBV

- recipients after kidney transplant

Patient survival of HCV

- recipients after liver transplant

Patient survival of HCV

- recipients after heart transplant s

s s

Note : The diagonal line represents no difference in survival between those who received an organ from a positive donor and those who received an organ from a negative donor. Point s above the diagonal line favor recipients of organs from positive donors, whereas points below the diagonal line favor recipients of organs from negative donors. This figure only includes studies that reported graft or survival data as percentages, and it only includes the longest followup timepoint from each study. The full data are provided in Table 68 . None of the plotted studies reported confidence intervals. Studies with a lower case ‘s’ next to the point repo rted that the comparison of full survival curves was statistically significant; all other studies either did not report whether the difference was statistically significant, or reported that the difference was not statistically significant. One of the stud ies did not report results on a percentage scale, and so its results do not appear in the plot. This was the Abbott et al. (2003) 83,84 study, which found an adjusted hazard ratio of death of 2.25 (95% CI: 1.56 to 3.24) i n favor of recipients of organs from HCV

- donors.410 

### Organs from Positive Donors Compared to Organs from Negative Donors When the Recipients were Positive Before T ransplant

We included 22 publications (17 unique studies) that made this comparison. Three studi es involved HBV only, 13 studies involved HCV only, and one study provided separate data on both HBV and HCV. General study characteristics are listed in the lower portion of Table 64 , and details of methods appear s in the lower portion of Table 65

.
Regarding quality (the lower portion of Table 67 ) , none of the studies were randomized or prospective, but all 17 treated the groups con currently, and 13 studies enrolled patients consecutively. Ten studies reported data on at least 85% of the enrolled patients and also had less than a 15% difference in completion rates between groups.

For baseline comparability of groups, 10 of the 17 st udies (two of HBV and eight of HCV) reported specific characteristics to enable a comparison . These 10 studies reported 128 characteristics that could be compared (listed in the lower portions of Table 66 ), and we classified 27 of these 128 were as large differences (reproduced below in Table 62 ). In the HBV studies, the differences involved rates of donor HCV (HBV+ donors were more likely to also be HCV+), donor and recipie nt age (both were higher in D+ groups), and race (D+ donors were more likely to be African

- American and less likely to be Caucasian

- American).

In the HCV studies, we noticed two types of consistent differences: donor/recipient ages (which were higher

in D+ groups) and the recipient’s amount of time on the waitlist (which was much shorter in the D+ groups:

9.9 months vs. 17.7 months in Woodside et al. (2003) 85 

### , and 9 months vs. 29 months in Mandal et al. (2000)

. 86411 

### Table 62

. Large Pre

- transplant Differences between Recipients of D+ and D

- Organs in Studies of Pre

- transplant Positive Recipients

Study Char acteristic Mean (SD) or % for R ecipients of D+ O rgans Mean (SD) or % for R ecipients of D

- O rgans Difference in Percentage P oints, or Hedges ’ g

Recipients Infected Before Transplant; Comparison of Clinical Outcomes after HBV+ Donor vs. HBV

- Donor

Fong et al. (2002) 55 Donor % HCV+ 22% ( 31/140) 5% ( 105/2093) 17 p.p.

Recipient % African

- American 56% ( 78/140) 39% ( 816/ 2093) 17 p.p.

Donor age 42.7 ( SD: 13.9) 34.9 ( SD: 18.2) g = 0.43

Madayag et al. (1997) 56 Recipient % Caucasian

- American 26% ( 12/45) 49% ( 22/45) 23 p.p.

Recipient age 49.1 ( SD: 11.8) 43 .6 ( SD: 11.8) g = 0.47

Recipients Infected Before Transplant; Comparison of Clinical Outcomes after HCV+ Donor vs. HCV

- Donor

Woodside et al. (2003) 85 CMV % donor/recipient pairs with both CMV+ 70% ( 14/20) 55% ( 11/20) 15 p.p.

Recipient % anti

- HBc+ 20% ( 4/20) 35% ( 7/20) 15 p.p.

Recipient % Caucasian

- American 15% ( 3/20) 35% ( 7/20) 20 p.p

.

Recipient % Hispanic

- American 35% ( 7/20) 5% ( 1/20) 30 p.p.

Recipient % male 80% ( 16/20) 65% ( 13/20) 15 p.p.

Recipient Triple drug therapy % 100% ( 20/20) 80% ( 16/20) 20 p.p.

Recipient time on waitlist (months) 9.9 ( SD: 8) 17.7 ( SD: 14.8) g = 0.66412 Study Char acteristic Mean (SD) or % for R ecipients of D+ O rgans Mean (SD) or % for R ecipients of D

- O rgans Difference in Percentage P oints, or Hedges ’ g

Mandal et al. (2000) 86 Donor % CMV+ 87% ( 16/18) 50% ( 5 /10) 37 p.p.

Recipient % with diabetes 28% ( 5/18) 10% ( 1/10) 18 p.p.

Recipient % being retransplanted 28 % (5 /18) 60 % (6 /10) 32 p.p.

AB mismatch 3.2 ( SD: 0.8) 2.3 ( SD: 0.9) g = 1.08

Cold ischemia time (hrs) 28 ( SD: 8.5) 22 ( SD: 9.5) g = 0.68

Donor age 46 ( SD: 8.5) 35 ( SD: 19) g = 0.84

DR mismatch 1.6 ( SD: 0.8) 1.3 ( SD: 0.3) g = 0.45

Recipient age 48 ( SD: 8.5) 44 ( SD: 6.3) g = 0.51

Recipient time on waitlist (months) 9 ( SD: 12.7) 29 ( SD: 9.5) g = 1.71

Morales et al. (1995) 87 Recipient % abnormal liver histology 31% ( 7/24) 50% ( 20/40) 19 p.p.

Recip ient % anti

- HBc+ 50% ( 12/24) 23% ( 9/40) 27 p.p.

Recipient % renal disease: chronic glomerulonephritis 55% ( 13/24) 35% ( 14/40) 20 p.p.

Recipient pre

- transplant number of transfusions 7 ( SD: 8) 21 ( SD: 39) g = 0.45

Salizzoni et al. (2001) 88 Donor age 62.6 ( SD: NR) 53.7 ( SD: NR) g = 0.49

Testa et al. (1998) 89 Recipient % male 50% ( 11/22) 73% ( 84/115) 23 p.p.

Note : This table onl y includes pre

- transplant differences that met our criteria for “large”, which was a Hedges’ g of 0.4 or more for continuous data, or a difference in percentage points of 15 or more. These differences were calculated by ECRI Institute. The full list of rep orted baseline characteristics is in Table 66

.413 

### One way to address the problem of differing pre

- transplant characteristics is to perform statistical adjustments of the results. Only four of the 17 studies did this ( Fong et al. [ 2002 ] 55 

### , Madayag et al. [ 1997 ] 56



### , Abbott et al. [ 2003 ] 83,84 

### , and Marroquin et al. [2001]). 90



### All study results appear in the lower portion of Table 68 , and pertinent plots are in Figure 13

, Figure 14 , and Figure 15 . The points appear without confidence intervals because studies did not report enough information to permit such calculation; this also explains why no meta

- analyses of these resul ts were possible. The HBV plot ( Figure 13 ) shows no consistent trend: two data points favored the D+ group, three data points favored
the D

- group, and four data points suggested equivalence. Restricting the analys is to the two HBV studies that used statistical adjustments to control for baseline prognosis, one study (Madayag et al. [1997] 56 

### ) found poorer graft survival in the D+ group, and the other study (Fong et al. [2002] 55 

### ) found no large differences in either graft survival or patient s urvival.

The two HCV plots ( Figure 14 for kidney transplants, and Figure 15 for liver transplants) each suggest a small but consistently better survival for recipients of D+ organs than recipients of D

- organs; one cannot determine the statistical significance of this effect due to insufficient reporting. Restricting the analysis to the
two HCV studies that used statistical adjustments to control for baseline prognosis, the y found conflicting
results. Whereas Abbott et al. (2003) 83,84 

### found shorter survival in the D+ group (adjusted hazard ratio 2.04), Marroquin et al. (2001) 90 

### found longer survival in the D+ group (adjusted odds of patient survival at two years was 0.51) (results of these two studies are not p lotted because the results were not reported as percentages; see the footnote to the figure).

Regarding different genotypes of HBV, none of the four studies reported donors' genotypes, or stated whether recipient survival different by donor genotype. For H CV genotypes, two studies 88,91 

### attempted to investigate the impact of genotype, but they did not draw conclusions due to the paucity of data. A third study 92 

### provided pre

- tran pslant genotypes for all donors and recipients, as well which which genotype predominated for each donor

- recipient pair. Recipient survival was unaffected by whether the predominant genotype was from the donor or was already present in the recipient. None of the other studies attempted analyses by HCV genotype.



### GRADE Assessment of **Clinical Outcomes After Receiving Organs from Infected Donors**
The GRADE evidence profiles (HBV graft survival; HBV patient survival; HCV graft survival; and HCV patient survival) appear in Table 63 . We graded the evidence as Very Low for all four pathogen/outcome combinations, due to the lack of randomization to groups and the pre

- transplant differences between groups.414 

### Figure 13

. Clinical Outcomes of Positive Recipients: Positive vs. Negative Donors, HBV, Kidney or Liver

0 10 20 30 40 50 60 70 80 90 100

0 10 20 30 40 50 60 70 80 90 100 

### Survival %

after D+ transplant

Survival %
after D

- transplant

Graft survival of HBV+ recipients after kidney transplant

Graft survival of HBV+ recipients after liver transplant

Patient survival of HBV+ recipients after kidney transplant

Patient survival of HBV+ recipients after liver transplant s

s

Note : The diagonal line represents no difference in survival between those who received an organ from a positive donor and those who received an o rgan from a negative donor. Points above the diagonal line favor recipients of organs from positive donors, whereas points below the diagonal line favor recipients of organs from negative donors. This figure only includes studies that reported graft or sur vival data as percentages, and it only includes the longest followup timepoint from each study. The full data are provided in Table 68 . None of the plotted studies reported confidence intervals. Studies with a lowe r case ‘s’ next to the point reported that the comparison of full survival curves was statistically significant; all other studies either did not report whether the difference was statistically significant, or reported that the difference was not statistic ally significant.415 

### Figure 14

. Clinical Outcomes of Positive Recipients: Positive vs. Negative Donors, HCV, Kidney

0 10 20 30 40 50 60 70 80 90 100

0 10 20 30 40 50 60 70 80 90 100 

### Survival %

after D+ transplant

Survival %
after D

- transplant

Graft survival of HCV+ recipients after kidney transplant

Patient survival of HCV+ recipients after kidney transplant

Note : The diagonal line represents no difference in survival between those who received an organ from a positive d onor and those who received an organ from a negative donor. Points above the diagonal line favor recipients of organs from positive donors, whereas points below the diagonal line favor recipients of organs from negative donors. This figure only includes st udies that reported graft or survival data as percentages, and it only includes the longest followup timepoint from each study. The full data are provided in Table 68 . None of the plotted studies reported confidenc e intervals. Studies with a lower case ‘s’ next to the point reported that the comparison of full survival curves was statistically significant; all other studies either did not report whether the difference was statistically significant, or reported that the difference was not statistically significant. One of the studies did not report results on a percentage scale, and so its results do not appear in the plot. This was the Abbott et al. (2003) 83,84 study, which found a n adjusted hazard ratio of death of 2.04 (95% CI: 1.20 to 3.45) in favor of recipients of negative organs.416 

### Figure 15

. Clinical Outcomes of Positive Recipients: Positive vs. Negative Donors, HCV, Liver

0 10 20 30 40 50 60 70 80 90 100

0 10 20 30 40 50 60 70 80 90 100 

### Survival %

after D+ transplant

Survival %
after D

- transplant

Graft survival of HCV+ recipients after liver transplant

Patient survival of HCV+ recipients after liver transplant s

Note : The diagonal line rep resents no difference in survival between those who received an organ from a positive donor and those who received an organ from a negative donor. Points above the diagonal line favor recipients of organs from positive donors, whereas points below the diag onal line favor recipients of organs from negative donors. This figure only includes studies that reported graft or survival data as percentages, and it only includes the longest followup timepoint from each study. The full data are provided in Table 68 . None of the plotted studies reported confidence intervals around the data. Studies with a lower case ‘s’ next to the point reported that the comparison of full survival curves was statistically significant; all othe r studies either did not report whether the difference was statistically significant, or reported that the difference was not statistically significant. One of the studies did not report results on a percentage scale, and so its results do not appear in th e plot. These was the Marroquin et al. (2001) 90 study, which found an adj usted two

- year odds of graft failure of 0.88, in favor of recipients of positive organs, and an adjusted two

- year odds of patient death of 0.51, also in favor of recipients of positive organs.417 

### Table 63

. GRADE Table for Question 7 (Clinical Outcomes of Known Positive Organs vs. Waitlist or Known Negative O rgans )

Comparison Outcome Quantity and Type of E vidence FindingsStarting Grade Decrease GRADE Increase GRADE

GRADE of Evidence for Outcome Overall GRADE of Evidence BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseConfounderswouldreduce the effect

Receiving an HCV+ organ compared to remaining on the waitlist Recipient survival One observational study 82 Adjusted hazard ratio 0.76 (95% CI: 0.6 to 0.96) (in favor of transplantation over the waitlist) Low

- 1

- 1 0 0 0 0 0 0 Very Low Very Low

Receiving an HBV+ organ

co mpared to receiving a negative organ for recipients who were NEGATIVE before transplant Graft survival One observational study 55 Results favored receiving an organ from a negative donor: 1 year: D+ 87%, D

- 88% 2 yrs.: D+ 78%, D

- 83% 3 yrs: D+ 72%, D

- 77% Low

- 1

- 1 0 0 0 0 0 0 Very Low

Very Low Recipient survival One observational study 55 Results favored receiving an organ from a negative donor:
1 year: D+ 94%, D

- 94% 2 yrs.: D+ 90%, D

- 92 % 3 yrs: D+ 86%, D

- 90% Low

- 1

- 1 0 0 0 0 0 0 Very Low418 Comparison Outcome Quantity and Type of E vidence FindingsStarting Grade Decrease GRADE Increase GRADE

GRADE of Evidence for Outcome Overall GRADE of Evidence BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseConfounderswouldreduce the effect

Receiving a HCV+ organ compared to receiving a negative organ for recipients who were NEGATIVE before transplant Graft survival Three observational studies

16,83,84,93,94 No statistically significant difference was reported by any of the three studies. Low

- 1 0 0 0 0 0 0 0 Very Low

Low Recipient survival Three observational studies

16,77,79,83,84 Two of the three studies reported results in favor of receiving an organ from a negative donor. The third study found a statistically nonsignificant result. Low

- 1 0 0 0 0 +1 0 0 Low419 Comparison Outcome Quantity and Type of E vidence FindingsStarting Grade Decrease GRADE Increase GRADE

GRADE of Evidence for Outcome Overall GRADE of Evidence BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseConfounderswouldreduce the effect

Receiv ing an HBV+ organ compared to receiving a negative organ for recipients who were POSITIVE before transplant Graft survival Four observational studies 55,56,91,9

5

- 97 Only one of the four studies reported any statistically significant difference. This study found that if the kidney donor was living, results slightly favored receiving an organ from an HBsAg+ donor, whereas if the kidney donor was deceased, results favored receiving an organ from an HBsAg

- donor. Low

- 1

- 1 0 0 0 0 0 0 Very Low

Very Low Recipient survival Three observational studies 55,91,95

-

97 Only one of the three studies reported any statistically significant difference. This study found that if the kidney donor was living, there was no statistically significant difference, whereas if the kidney donor was dec eased, results favored receiving an organ from an HBsAg

- donor. Low

- 1

- 1 0 0 0 0 0 0 Very Low420 Comparison Outcome Quantity and Type of E vidence FindingsStarting Grade Decrease GRADE Increase GRADE

GRADE of Evidence for Outcome Overall GRADE of Evidence BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseConfounderswouldreduce the effect

Receiving a HCV+ organ compared to receiving a negative organ for recipients who were POSITIVE before transplant Graft survival 13 observational studies 12,16,83

- 94,98,99 No statistically significant difference was reported by any of the 13 studies. Low

- 1 0 0 0 0 0 0 0 Very Lo w

Very Low Recipient survival 11 observational studies 12,16,83

- 92,98 On ly 2 of the 11 studies found any statistically significant difference. One of the two favored recipients of organs of positive donors, and the other favored recipients of organs of negative donors. Low

- 1 0 0 0 0 0 0 0 Very Low

Note : The shaded rows deno te recipient survival, which was considered a “critical” outcome. Graft survival is unshaded because it was not considered “c ritical” for the purpose of evidence grading.421 

### Additional Evidence Tables for Question **7**

Table 64

. Question 7 : General Information about Included Studies

Study Country Center(s) or Program(s) Organ Number of Centers Transplantation Dates Funding

Recipients Negative Before Transplant; Comparison of Clinical Outcomes After HBV+ Donor vs. HBV

- Donor

Fong et al. ( 2002) 55 USA UNOS Scientific Renal Transplant Registry Kidney UNOS 1994 to 1999 NR

Recipients Negative Before Transplant; Comparison of Clinical Outcomes After HCV+ Donor vs. HCV

- Donor

Abbott et al. (2003) 83,84 USA United States Renal Data System (USRDS) Kidney USRDS Jan

- 96 to May

- 01 NR

Velidedeoglu et al. (20 02) 93,94 USA University of Pennsylvania (Penn), Philadelphia, PA, and UNOS Liver 1 Jan

- 95 to Dec

- 99 NR

Shah et al. (1993) 12,16 USA Univ ersity of Pittsburgh School of Medicine, Pittsburgh, PA Liver 1 Mar

- 86 to Mar

- 90 NR

Haji et al. (2004) 77,79 USA Clevela nd Clinic, Cleveland, OH Heart 1 Jul

- 93 to Dec

- 98 NR

Recipients Positive Before Transplant; Comparison of Clinical Outcomes After HBV+ Donor vs. HBV

- Donor

Fong et al. (2002) 55 USA UNOS Scientific Renal Transplant Registry Kidney UNOS 1994 to 1999 NR

Madayag et al. (1997) 56 USA U ni versity of Maryland, Baltimore, MD Kidney 1 Jan

- 92 to Jul

- 96 NR

Lai et al. (1996) 95

- 97 Taiwan National Taiwan University, Taip ei, Taiwan Kidney NR Jul

- 81 to Jan

- 94 NR

Saab et al. (2003) 91 USA Dumont

- UCLA Liver Transplant Center, L os Angeles, CA Liver 1 Jan

- 90 to Apr

- 01 NR422 Study Country Center(s) or Program(s) Organ Number of Centers Transplantation Dates Funding

Recipients Positive Before Transplant; Comparison of Clinical Outcomes After HCV+ Donor vs. HCV

- Donor

Kasprzyk et al. (2007) 98 Poland Medical University of Wroclas, Wroclas, Poland Kidney NR Jul

- 94 to Jul

- 06 NR

Abbott et al. (2003) 83,84 USA USRDS Kidney USRDS Jan

- 96 to May

- 01 NR

Woodside et al. (2003) 85 USA University of Texas Medical Branch, Galveston, TX Kidney 1 Jul

- 92 to Jul

- 00 NR

Mandal et al. (2000) 86 USA Joh ns Hopkins Hospital, Baltimore, MD Kidney 1 Jan

- 97 to Jun

- 99 NR

Ali et al. (1998) 99 USA Washington Hospital Center, Washington, DC Kidney 1 Feb

- 91 to Sep

- 96 NR

M orales et al. (1995) 87 Spain Hospital 12 de Octubre, Madri d, and Hospital Clinic, Barcelona Kidney 2 Mar

- 90 to Dec

- 92 Parti ally supported by FIS grant No. 94/1002

Saab et al. (2003) 91 USA Dumont

- UCLA Liver Transplant Center, Los Angeles, CA Liver 1 Jan

- 90 to Apr

- 01 NR

Velidedeoglu et al. (2002) 93,94 USA University of Pennsylvania, Philadelphia, PA, and UNOS Li ver 1 for Penn data, many for UNOS data Jan

- 95 to Dec

- 99 NR

Marroquin et al. (2001) 90 USA UNOS Scientific Renal Transplant Registry Liver UNOS Apr

- 94 to Jun

- 97 NR

Salizzoni et al. (2001) 88 Italy S. Giovanni Battista Hospital, Torino, Italy Liver 1 Jul

- 98 to Dec

- 99 NR

Vargas et al. (1999) 92 USA Thomas E. Starzl Transplantation Institute, Pittsburgh, PA Liv er 1 Feb

- 92 to May

- 05 NR

Testa et al. (1998) 89 USA Baylor University Medical Center, Dallas, Texas Liver 1 Jul

- 85 to Jul

- 95 NR423 Study Country Center(s) or Program(s) Organ Number of Centers Transplantation Dates Funding

Shah et al. (1993) 12,16 USA Uni versity of Pittsburgh School of Medicine, Pittsburgh, PA Liver 1 Mar

- 86 to Mar

- 90 NR

NR

– Not reported424 

### Table 65

. Question 7 : Details of Study Methods

StudyProspectiveConsecutive

Duration of F ollow

- upN Enrolled forD+N Enrolled forDDefinition of Positivity Specific Test U sed

Recipients Negative Before Transplant; Comparison of Clinical Outcomes after HBV+ Donor vs. HBV

- Donor

Fong et al. (2002) 55 No Yes NR 763 24

, 661 anti

- HBc+ NR

Recipients Negative Before Transplant; Comparison of Clinical Outc omes after HCV+ Donor vs. HCV

- Donor

Abbott et al. (2003) 83,84 No Yes Mean : 33 (SD : 20) 280 34

, 151 anti

- HCV “ Presumably ELISA ”

Velidedeoglu et al. (2002) 93,94 No Y es For Penn sylvania data, the

mean followup was 23.4 months

. For UNOS data, the

mean followup was 22.4 months. 29 7

, 811 “ HCV+ ” NR

Shah et al. (1993) 12,16 No No NR 25 375 anti

- HCV ELISA2

Haj i et al. (2004) 77,79 No No Mean : 50 months (SD : 23) 34 183 anti

- HCV ELISA2

Recipients Positive Before Transplant; Compa rison of Clinical Outcomes after HBV+ Donor vs. HBV

- Donor

Fong et al. (2002) 55 No Yes NR 140 2

, 093 anti

- HBc+ NR

Madayag et al. (1997) 56 No Yes Mean : 24 (R ange : 2

- 64) 45 45 Donor anti

- HBc+ and HBsAg

- ; Recipient had prior HBV infection or had been vaccinated Abbott tests

Lai et al . (1996) 95

- 97 No Yes NR 25 42 HBsAg Austria II and Ausab (Abbott)425 StudyProspectiveConsecutive

Duration of F ollow

- upN Enrolled forD+N Enrolled forDDefinition of Positivity Specific Test U sed

Saab et al. (2003) 91 No NR For HBV+ recipients,

mean follow

- up for patien t survival data was 2.3 years (R ange : 0

- 8.7), and for graf t survival data was 2.0 years (R ange : 0

- 8.7).

For HC V+ recipients,

mean follow

- up for patient survival data was 2.6 years (R ange : 0

- 5.8), and for graf t survival data was 1.8 years (R ange : 0

- 5.8)

. 74 42 anti

- HBc+ NR

Recipients Positive Before Transplant; Comparison of Clinical Outcomes after HCV+ Donor vs. HCV

- Donor

Kasprzyk et al. (2007) 98 No Yes Range : 12

- 156 60 199 anti

- HCV NR

Abbott et al. (2003) 83,84 No Yes Mean : 33 (SD : 20) 593 1

, 932 anti

- HCV “ Presumably ELISA ”

Woodside et al. (2003) 85 No Yes Mean : 26 months (R ange : 0.4

- 119) for those who received a positive organ, and 3 4 months (R ange : 0.2

- 66) for those who received a negative
organ 20 20 “ seropositive ” NR

Mandal et al. (2000) 86 No Yes Median: 16, Mean: 15 (standard error of the mean: 2), Range: 3

- 33 18 10 anti

- HCV and HCV

- RNA+ HCV RNA measured by PCR

Ali et al. (1998) 99 No Yes Mean : 36, R ange : 12

- 60 28 16 anti

- HCV NR426 StudyProspectiveConsecutive

Duration of F ollow

- upN Enrolled forD+N Enrolled forDDefinition of Positivity Specific Test U sed

Morales et al. (1995) 87 NR Yes Mean : 26 months (SD : 8) for those who received a positive organ, and 30 months (SD : 10) for those who received a negative organ 24 40 anti

- HCV ELISA2 (Ortho) and RIBA (Chiron)

Saab et al. (2003) 91 No NR For HBV+ recipients,

mean follow

- up for patien t survival data was 2.3 years (R ange : 0

- 8.7), and for graf t survival data was 2.0 years (R ange : 0

- 8.7).

For HCV+ recipients,

me an follow

- up for patient surviva l data was 2.6 years (Range: 0

- 5.8), and for graft survival data was 1.8 years (R ange : 0

- 5.8) 27 212 anti

- HCV NR

Velidedeoglu et al. (2002) 93,94 No Yes For Penn data, the

mean followup was 23.4 months

. For UNOS data, the

mean followup was 22.4 months. Penn : 13;

UNOS : 190 Penn : 103;

UNOS :

5

, 053 Penn: “ HCV+ ”;

UNOS: Donors were anti

- HCV+, and of recipi ents, 96% were anti

- HCV+ and 4% were RIBA+ and/or HCV

- RNA+ NR

Marroquin et al. (2001) 90 No Yes Median was 34 months for those who received a positive organ, and 37 months for those who received a negative organ 96 2

, 827 “ HCV+ ” NR427 StudyProspectiveConsecutive

Duration of F ollow

- upN Enrolled forD+N Enrolled forDDefinition of Positivity Specific Test U sed

Salizzoni et al. (2001) 88 No NR Mean: 12, R ange : 1

- 25 12 103 anti

- HCV NR

Vargas et al. (1999) 92 No Yes NR 23 169 anti

- HCV ELISA3 (Abbott)

Testa et al. (1998) 89 No Yes Mean : 40 months (R ange : 12

- 58) for those who received a positive organ, and 36 months (R ange : 17

- 135) fo r those who received a negative organ 22 115 anti

- HCV ELISA1 until 1990, then ELISA2

Shah et al. (1993) 12,16 No No NR 5 111 anti

- HCV ELISA2

NR

– Not reported428 

### Table 66

. Question 7 : Pre

- transplant Patient Characteristics

Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Recipients Negative Before Transplant; Comparison of Clinical Outcomes After HBV+ Donor vs. HBV

- Donor

Fong et al. (2002) 55 Donor % African

- American 17% (130/763) 10% (2

, 466/24

, 661) 7 p.p.

Donor % death due to stroke 51% (389/763) 36% (8

, 878/24

, 661) 15 p.p. Large difference
at baseline

.
Donor % HCV+ 11% (84/763) 2% (493/24

, 661) 9 p.p.

Donor % male 42% (320/763) 41% (10

, 111/24

, 661) 1 p.p.

Recipient % African

- American 34% (259/763) 25% (6

, 165/24

, 661) 9 p.p.

Recipient % Asi an

- American 5% (38/763) 3% (740/24

, 661) 2 p.p.

Recipient % HCV+ 11% (84/763) 5% (1

, 233/24

, 661) 6 p.p.

Recipient % male 63% (481/763) 61% (15

, 043/24

, 661) 2 p.p.

Recipient % being retransplanted 12% (92/763) 13% (3

, 206/24

, 661) 1 p.p.

Mean Cold is chemia time (hours) 22.1 (SD: 8.5) 20.6 (SD: 8.2) g = 0.18

Mean Donor age 40.5 (SD: 16) 33.7 (SD: 18.1) g = 0.38429 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Number of HLA mismatches 3.7 (SD: 1.6) 3.4 (SD: 1.8) g = 0.17

Mean Recipient age 47.8 (SD: 13.1) 45.5 (SD: 14.2) g = 0.16

Recipient duration of dialysis (months) 38.1 (SD: 34.6) 36.6 (SD: 36.9) g = 0.04

Recipient Peak Panel Reactive Antibody 13.2 (SD: 24.3) 14 (SD: 25.8) g = 0.03

Recipients Negative Before Transplant; Comparison of Clinical Outcomes After HCV+ Donor vs. HCV

- Dono r
Abbott et al. (2003) 83,84

, Velidedeoglu et al. (2002) 93,94 These studies did not report pre

- transplant characteristics comparing those who received organs from in fected donors vs. those who received organs from uninfected donors

Shah et al. (1993) 12,16 Study only reported that “No statistical difference in disease indication for OLTx was evident betw een the 4 study groups”

Haji et al. (2004) 77,79 % “Cause” was dilated cardiomyopathy 32% (11/34) 34% (62/183) 2 p.p.

% “Cause” was ischemic cardiomyopathy 62% (21/34) 56% (102/183) 6 p.p.

% “Cause” was something else 5% (2/34) 9% (16/183) 4 p.p.

Donor % male 74% (25/34) 57% (104/183) 17 p.p. Large difference
at baseline

. Recipient % male 76% (26/34) 79% (145/183 ) 3 p.p.

Mean Donor age 39 (SD: 9) 35 (SD: 14) g = 0.3430 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Mean Recipient age 57 (SD: 10) 52 (SD: 11) g = 0.46 Large difference
at baseline

. Mean Recipient average biopsy score 1.31 (SD: 0.65) 1.51 (SD: 0.66) g = 0.3

Mean number of recipient episode s of acute rejection before this transplant 1.7 (SD: 1.5) 1.8 (SD: 1.6) g = 0.06

Recipients Positive Before Transplant; Comparison of Clinical Outcomes After HBV+ Donor vs. HBV

- Donor

Lai et al. (1996) 95

- 97

, Saab et al. (2003) 91 Th ese studies did not report pre

- transplant characteristics comparing those who received organs from infected donors vs. those who received organs from uninfected donors

Fong et al. (2002) 55 Donor % African

- American 26% (36/140) 13% (272/2

, 093) 13 p.p.

Donor % death due to stroke 47% (66/140) 37% (774/2

, 093) 10 p.p.

Donor % HCV+ 22% (31/140) 5 % (105/2

, 093) 17 p.p. Large difference
at baseline

.
Donor % male 34% (48/140) 42% (879/2

, 093) 8 p.p.

Recipient % African

- American 56% (78/140) 39% (816/2

, 093) 17 p.p. Large difference
at baseline

. Recipient % Asian

- American 16% (22/140) 10% (209/2

, 0 93) 6 p.p.

Recipient % being retransplanted 8% (11/140) 10% (290/2

, 093) 2 p.p.

Recipient % HCV+ 35% (49/140) 21% (440/2

, 093) 14 p.p.431 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Recipient % male 73% (102/140) 64% (1

, 340/2

, 093) 9 p.p.

Mean Cold ischemia time (hours) 20.6 (SD: 8.2) 20.7 (SD : 8.7) g = 0.01

Mean Donor age 42.7 (SD: 13.9) 34.9 (SD: 18.2) g = 0.43 Large difference
at baseline

.
Mean number of HLA mismatches 4.3 (SD: 1.4) 3.7 (SD: 1.7) g = 0.36

Mean Recipient age 49.7 (SD: 10.7) 46.5 (SD: 14) g = 0.23

Mean Recipient dur ation of dialysis (months) 42.1 (SD: 31.3) 44.2 (SD: 40.2) g = 0.05

Mean Recipient Peak Panel Reactive Antibody 14.3 (SD: 23.6) 14.3 (SD: 25.6) g = 0

Madayag et al. (1997) 56 Donor % de ceased 69% (31/45) 58% (26/45) 11 p.p.

Donor % living related 29% (13/45) 40% (18/45) 11 p.p.

Recipient % anti

- lymphocyte therapy 40% (18/45) 33% (15/45) 7 p.p.

Recipient % Asian

- American 60% (27/45) 49% (22/45) 11 p.p.

Recipient % Caucasian

- Am erican 26% (12/45) 49% (22/45) 23 p.p. Large difference
at baseline

. Recipient % other race 13% (6/45) 2% (1/45) 11 p.p.432 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Recipient % HCV+ 31% (14/45) 31% (14/45) 0 p.p.

Recipient % high

- risk behavior 13% (6/45) 18% (8/45) 5 p.p.

Recipient % hist ory of alcohol abuse 13% (6/45) 7% (3/45) 6 p.p.

Recipient % intraoperative or postoperative transfusion 85% (38/45) 81% (36/45) 4 p.p.

Recipient % male 68% (31/45) 62% (28/45) 6 p.p.

Recipient % Simultaneous kidney

- pancreas transplant 2% (1/45) 2 % (1/45) 0 p.p.

Recipient % with pre

- transplant transfusion 60% (27/45) 47% (21/45) 13 p.p.

Mean Recipient age 49.1 (SD: 11.8) 43.6 (SD: 11.8) g = 0.47 Large difference
at baseline. Dispersion reported as “+/

- ” but authors did not specify what this w as; ECRI Institute estimated the SD for each group to be 11.8 based on the reported p = 0.03 for ANOVA

Recipient date of transplant The study intentionally matched patients on this characteristic433 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Recipient Pre

- transplant HBV serology The study intent ionally matched patients on this characteristic

Type of organ transplanted The study intentionally matched patients on this characteristic

Recipien ts Positive Before Transplant; Comparison of Clinical Outcomes After HCV+ Donor vs. HCV

- Donor

Kasprz yk et al. (2007) 98

, Abbott et al. (2003) 83,84

, Ali et al. (1998) 99

, Saab et al. (2003) 91 These studies did not report pre

- transplant characteristics comparing those who received organs from infected donors vs. those who received organs from uninfected donors

Woodside et al. (2003) 85 % Immunosuppressive induction therapy 90% (18/20) 80% (16/20) 10 p.p.

CMV % donor/recipient pairs with both CMV

- 5% (1/20) 5% (1/20) 0 p.p.

CMV % donor/recipient pairs with both CMV+ 70% (14/20) 55% (11/20) 15 p.p. Large difference
at baseline

. CMV % donor/recipient pairs with only donor+ 0% (0/20) 10% (2/20) 10 p.p.

CMV % donor/recipient pairs with only recipient+ 20% (4/20) 20 % (4/20) 0 p.p.

CMV % donor/recipient pairs with unknown recipient status 5% (1/20) 0% (0/20) 5 p.p.

Donor % anti

- HBc+ 20% (4/20) 20% (4/20) 0 p.p.

Donor % HBsAg+ 0% (0/20) 0% (0/20) 0 p.p.434 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Recipient % anti

- HBc+ 20% (4/20) 35% (7/20) 15 p.p

. Large difference
at baseline

. Recipient % African

- American 50% (10/20) 45% (9/20) 5 p.p.

Recipient % Asian

- American 0% (0/20) 10% (2/20) 10 p.p.

Recipient % Caucasian

- American 15% (3/20) 35% (7/20) 20 p.p. Large difference
at baseline

. Recipie nt % Hispanic

- American 35% (7/20) 5% (1/20) 30 p.p. Large difference
at baseline

. Recipient % HBsAg+ 0% (0/20) 0% (0/20) 0 p.p.

Recipient % male 80% (16/20) 65% (13/20) 15 p.p. Large difference
at baseline

. Recipient % being retransplanted 15% (3/2 0) 15% (3/20) 0 p.p.

Recipient % with 1 prior transplant 5% (1/20) 10% (2/20) 5 p.p.

Recipient % with 2 prior transplants 5% (1/20) 5% (1/20) 0 p.p.

Recipient % with 3 prior transplants 5% (1/20) 0% (0/20) 5 p.p.

Recipient Triple drug thera py % 100% (20/20) 80% (16/20) 20 p.p. Large difference
at baseline

.435 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Mean Cold ischemia time (hours) 24.3 (SD: 9.8) 21.5 (SD: 2.7) g = 0.39 ECRI Institute estimated the SDs using the reported SEMs and Ns

Mean Recipient age 44 (SD: 13.4) 45 (SD: 44.7) g = 0.03 ECRI Institute estimated the SDs using the reported SEMs and Ns

Mean Recipient time on waitlist (months) 9.9 (SD: 8) 17.7 (SD: 14.8) g = 0.66 Large difference
at baseline. ECRI Institute estimated the SDs using the reported SEMs and Ns

Mandal et al. (2000) 86 Donor % CMV+ 87% (16/18) 50% (5/10) 37 p.p

. Large difference
at baseline

. Donor % history of alcohol abuse 5% (1/18) 10% (1/10) 5 p.p.

Donor % prior cocaine snorting or selling of drugs NR NR NC

Recipient % African

- American 66% (12/18) 60% (6/10) 6 p.p.

Recipient % CMV+ 83% (15/18) 7 0% (7/10) 13 p.p.

Recipient % male 66% (12/18) 80% (8/10) 14 p.p.

Recipient % with diabetes 28% (5/18) 10% (1/10) 18 p.p. Large difference
at baseline.436 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Recipient % with hypertension 33% (6/18) 40% (4/10) 7 p.p.

Recipient % being retransplante d 28% (5/18) 60% (6/10) 32 p.p. Large difference
at baseline.

Mean AB mismatch 3.2 (SD: 0.8) 2.3 (SD: 0.9) g = 1.08 Large difference
at baseline. ECRI Institute estimated the SDs using the reported SEMs and Ns

Mean Cold ischemia time (hours) 28 (SD: 8. 5) 22 (SD: 9.5) g = 0.68 Large difference
at baseline. ECRI Institute estimated the SDs using the reported SEMs and Ns

Mean Donor age 46 (SD: 8.5) 35 (SD: 19) g = 0.84 Large difference
at baseline. ECRI Institute estimated the SDs using the reported SEMs and Ns

Mean DR mismatch 1.6 (SD: 0.8) 1.3 (SD: 0.3) g = 0.45 Large difference
at baseline. ECRI Institute estimated the SDs using the reported SEMs and Ns437 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Mean Recipient age 48 (SD: 8.5) 44 (SD: 6.3) g = 0.51 Large difference
at baseline. ECRI Institu te estimated the SDs using the reported SEMs and Ns

Mean Recipient duration of dialysis (months) 88 (SD: 152.7) 79 (SD: 66.4) g = 0.07 ECRI Institute estimated the SDs using the reported SEMs and Ns

Mean Recipient Terminal creatinine (mg/dL) 0.9 (SD: 0 .8) 0.9 (SD: 0.6) g = 0 ECRI Institute estimated the SDs using the reported SEMs and Ns. One of the reported SDs was 0, which is not reasonable, therefore we used the SD from the other group

Mean Recipient time on waitlist (months) 9 (SD: 12.7) 29 (SD: 9 .5) g = 1.71 Large difference
at baseline. ECRI Institute estimated the SDs using the reported SEMs and Ns

Morales et al. (1995) 87 Recipient % abnormal liver histology 31% (7/24) 50% (20/40) 19 p.p. Large diffe rence at baseline.

Recipient % anti

- HBc+ 50% (12/24) 23% (9/40) 27 p.p. Large difference
at baseline.438 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Recipient % chronic active hepatitis 0% (0/24) 10% (4/40) 10 p.p.

Recipient % chronic liver disease 4% (1/24) 5% (2/40) 1 p.p.

Recipient % chronic persistent hepatitis 17% (4/24) 8% (3/40) 9 p.p.

Recipient % elevated ALT 54% (13/24) 50% (20/40) 4 p.p.

Recipient % HBsAg+ 8% (2/24) 3% (1/40) 5 p.p.

Recipient % hemosiderosis 0% (0/24) 5% (2/40) 5 p.p.

Recipient % history of drug abuse 0% (0/24) 0% (0/40) 0 p.p.

Recipient % HIV+ 0% (0/24) 0% (0/40) 0 p.p.

Recipient % male 67% (16/24) 60% (24/40) 7 p.p.

Recipient % mild elevated ALT 50% (12/24) 45% (18/40) 5 p.p.

Recipient % PCR+ 71% (17/24) 79% (32/40) 8 p.p.

Reci pient % renal disease: arterial hypertension 8% (2/24) 7% (3/40) 1 p.p.

Rec ipient % renal disease: chronic glome rulonephritis 55% (13/24) 35% (14/40) 20 p.p. Large difference
at baseline.439 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Rec ipient % renal disease: chronic in terstitial nephritis 29% (7/24) 33% (13/40) 4 p.p.

Recipient % renal disease: cystic disease 0% (0/24) 5% (2/40) 5 p.p.

Recipient % ren al disease: other 8% (2/24) 20% (8/40) 12 p.p.

Recipient % RIBA+ 100% (24/24) 100% (40/40) 0 p.p.

Recipient % being retransplanted 8% (2/24) 20% (8/40) 12 p.p.

Mean Recipient age 47 (SD: 12) 44 (SD: 14) g = 0.23

Mean Recipient duration of dialy sis (months) 72 (SD: 53) 75 (SD: 49) g = 0.06

Mean Recipient pre

- transplant number of transfusions 7 (SD: 8) 21 (SD: 39) g = 0.45 Large difference
at baseline.

Velidedeoglu et al. (2002) 93,94 Recip ient % UNOS status 1 23.1% (3/13) 15.4% (16/103) 7.7 p.p. Only reported comparative characteristics for the Penn data, not for the UNOS data

Recipient % UNOS status 2A 15.4% (2/13) 24.2% (25/103) 8.8 p.p. Only reported comparative characteristics for the Penn data, not for the UNOS data440 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Recipient % UNOS status 2B 61.5% (8/13) 60.4% (62/103) 1.1 p.p.

Mean Cold ischemia time (hours) 8.5 (SD: 3.2) 8.5 (SD: 3) g = 0 ECRI Institute estimated the SDs using the reported SEMs and Ns. Only reported comparativ e characteristics for the Penn data, not for the UNOS data

Mean Donor age 36.5 (SD: 8.7) 36.9 (SD: 16.2) g = 0.03 ECRI Institute estimated the SDs using the reported SEMs and Ns. Only reported comparative characteristics for the Penn data, not for the UN OS data

Mean Recipient age 52.6 (SD: 8.3) 50.2 (SD: 8.1) g = 0.3 ECRI Institute estimated the SDs using the reported SEMs and Ns. Only reported comparative characteristics for the Penn data, not for the UNOS data441 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Mean Warm ischemia time (hours) 51 (SD: 15.1) 50.6 (SD: 42.6) g = 0.01 ECRI Institute estimated the SDs using the reported SEMs and Ns. One of the reported SDs was 0, which is not reasonable, therefore we used the SD from the other group. Only reported comparative characteristics for the Penn d ata, not for the UNOS data

Marroquin et al. (2001) 90 ABO % incompatibili ty 4.2% (4/96) 1.3% (37/2

, 827) 2.9 p.p.

Donor % cause of death: cardiovascular
event 1% (1/96) 3.2% (90/2

, 827) 2.2 p.p.

Donor % cause of death: cerebrovascular accident 46.9% (45/96) 39.8% (1

, 125/2

, 827) 7.1 p.p.

Donor % cause of death: head trauma 45.8% (44/96) 50.6% (1

, 430/2

, 827) 4.8 p.p.

Donor % cause of death: other 6.3% (6/96) 6.4% (181/2

, 827) 0.1 p.p.

Donor % male 68.8% (66/96) 63.3% (1

, 789/2

, 827) 5.5 p.p.

Recipient % hepatocellular carcinoma 8.3% (8/96) 3.1% (88/2

, 827) 5.2 p.p.442 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Re cipient % male 67.6% (65/96) 68.5% (1

, 936/2

, 827) 0.9 p.p.

Recipient % use of vasopressor 68.7% (66/96) 67% (1

, 894/2

, 827) 1.7 p.p.

Recipient % being retransplanted 4% (4/96) 10% (277/2

, 827) 6 p.p.

Recipient % year of transplant 1997 (the last
year of study enrollment) 21% (20/96) 15% (424/2

, 827) 6 p.p.

Mean Cold ischemia time (hours) 9.4 (SD: NR) 8.8 (SD: NR) g = 0.07 Dispersion not reported, but
p >0.05 reported. E CRI Institute estimated Hedges’ g using an estimated SD of 8.2 for both groups, wh ich was based on pooling on other studies’ reported SDs for this characteristic.443 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Mean Donor age 38.5 (SD: NR) 35.8 (SD: NR) g = 0.15 Dispersion not reported, but
p >0.05 reported. EC RI Institute estimated Hedges’ g using an estimated SD of 18 for both gr oups, which was based on pooling on other studies’ reported SDs for this characteristic.

Mean Recipient age 49.5 (SD: NR) 48.6 (SD: NR) g = 0.06 Dispersion not reported, but
p >0.05 reported. E CRI Institute estimated Hedges’ g using an estimated SD of
14 .1 for both groups, which was based on pooling on other studies’ reported SDs for this characteristic.

Mean Recipient creatinine mg/dL 1.2 (SD: NR) 1.2 (SD: NR) NC Dispersion not reported, but
p >0.05 reported

Mean Recipient hospital stay (days) 18.7 ( SD: NR) 27.1 (SD: NR) NC Dispersion not reported, but
p >0.05 reported444 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Mean Recipient ICU stay (days) 11.5 (SD: NR) 15.1 (SD: NR) NC Dispersion not reported, but
p >0.05 reported

Mean Recipient weight (kg) 73.6 (SD: NR) 72.9 (SD: NR) NC Dispersion not reported, but
p >0.05 reported

Mean Warm ischemia time (hours) 45.9 (SD: NR) 46.8 (SD: NR) NC Dispersion not reported, but
p >0.05 reported

Salizzoni et al. (2001) 88 Mean Donor age 62.6 (SD: NR) 53.7 (SD: NR) g = 0.49 Large diffe rence at baseline. These are medians. Dispersion not reported, but authors stated there was “n o significant difference”. ECRI Institute estimated Hedges’ g using an estimated SD of 18 for both groups, which was based on pooling on other studies’ reported S Ds for this characteristic.445 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Mean Recipient coagulation time (INR) 1.2 (SD: NR) 1.2 (SD: NR) NC These are medians. Dispersion not reported, but authors stated there was “no significant difference”

Mean Recipient hepatic enzymes ALT (U/L) 24 (SD: NR) 22 (SD: NR) NC These are medians. Dispersion not reported, but authors stated there was “no significant difference”

Mean Recipient hepatic enzymes AST (U/L) 24 (SD: NR) 21 (SD: NR) NC These are medians. Dispersion not reported, but authors stated there

was “no significant difference”

Mean Recipient platelet concentration (10 9 /L) 177 (SD: NR) 215 (SD: NR) NC These are medians. Dispersion not reported, but authors stated there was “no significant difference”

Mean Total ischemia time (hours) 10.3 (SD: NR) 9 .8 (SD: NR) NC Dispersion not reported, but authors stated there was “no significant difference”446 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Mean Warm ischemia time (hours) 0.6 (SD: NR) 0.53 (SD: NR) NC These are medians. Dispersion not reported, but authors stated there was “no significant differ ence”

Vargas et al. (1999) 92 Recipient % male 74% (17/ 23) 85% (144/169) 11 p.p.

Mean Recipient age 51.1 (SD: 10.4) 49.5 (SD: 11.7) g = 0.14 SD of the age of recipients of infecte d organs was calculated by ECRI Institute based on Table 1 of the article. SD of the age of recipients of uninfected organs

was c alculated by ECRI Institute using the reported SEM of 0.9 and the N for that group which was 169447 Study Characteristic Mean (SD) or % for Recipients of D+ Organs Mean (SD)

or % for Recipients of D

- Organs Difference in percentage points (p.p.), or Hedges’ g Comments

Testa et al. (1998) 89 Recipient % male 50% (11/22) 73% (84/115) 23 p.p. Large difference
at baseline.

Mean Recipient age 48.2 (SD: NR) 47.1 (SD: NR) g = 0.08 Neither SD nor SEM were reported, and

no statistical test reported. ECRI Institute estimated Hedges’ g using an estimated SD of 14.1 for both
groups, w hich was based on pooling on other studies’ reported SDs for this characteristic.

Shah et al. (1993) 12,16 Study only reported that “No statistical difference in disease indication for OLTx w as evident between the 4 study groups”

Note : Shaded cells denote comparisons for which the groups differed at baseline by 15 or more percentage points (dichotomous outcomes) or for wh ich the groups differed at baseline by Hedges’ g of 0.4 or more (continu ous measures). Hedges’ g is the difference between means divided by the pooled standard deviation. This was calculated by ECRI Institute.

NC

– Not calculable NR

– Not reported
p.p.

– P ercentage points SD

– Standard deviation SE M

– Standard error of the mea n448 

### Table 67

. Question 7 : Quality Assessment

Study 7a 7b 7c 7d 7e 7f 7g 7h

Recipients Negative Before Transplant; Comparison of Clinical Outcomes After HBV+ Donor vs. HBV

- Donor Fong et al. (2002) 55  
Recipients Negative Before Transplant; Comparison of Clinical Outcomes After HCV+ Donor vs. HCV

- Donor

Abbott et al. (2003) 83,84     
Velidedeoglu et al. (2002) 93,94  
Shah et al. (1993) 12,16 
Haji et al. (2004) 77,79   
Recipients Positive Before Transplant; Comparison of Clinical Outcomes After HBV+ Donor vs. HBV

- Donor Fong et al. (2002) 55   
Madayag et al. (1997) 56     
Lai et al. (1996) 95

- 97  
Saab et al. (2003) 91 
Recipients Positive Before Transplant; Comparison of Clinical Outcomes After HCV+ Donor vs. HCV

- D onor Kasprzyk et al. (2007) 98    
Abbott et al. (2003) 83,84     
Woodside et al. (2003) 85    
Mandal et al. (2000) 86    
Ali et al. (1998) 99    
Morales et al. (1995) 87    
Saab et al. (2003) 91 
Velidedeoglu et al. (2 002) 93,94   
Marroquin et al. (2001) 90      
Salizzoni et al. (2001) 88 
Vargas et al. (1999) 92     
Testa et al. (1998) 89    
Shah et al. (1993) 12,16 

A checkmark (  ) means that the study met the quality criterion for this Question; the lack of a checkmark means that the study either did not meet the criterion, or it was unclear whether the study met the criterion. The criteria specific to this Question were:

7a. Were the patients randomly assigned to treatments?

7b. Was the study planned prospectively (i.e., before any data were collected)

7c. Were all consecutive patients enrolled (or a random sam ple of eligible patients)?

7d. Were the two groups comparable at baseline? (age, sex, comorbidities, indication for transplant, previous duration on waitlis t)

7e. If not, were statistical adjustments performed to control for baseline differences?

7f. Were the two gro ups treated concurrently? 7g. Did at least 85% of the study enrollees provide data?

7h. Was the between

- group difference in study completion rates less than 15%?449 

### Table 68

. Question 7 : Reported D ata

Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Recipients Negative Before Transplant; Comparison of Clinical Outcomes After HBV+ Donor vs. HBV

- Donor

Fong et al. (2002) 55 Graft survival 12 87% (N = Not reported [NR]) 88% (N = NR) None Overall graft survival curve:

p = 0.009 for D+R

- vs. D

- R

- ;

p = 0.06 for D

- R+ vs. D

- R

- ;

p = 0.69 for D+R+ vs. D

- R

Surviva l percentages estimated by ECRI Institute from Figure 1 in the article

Graft survival 24 78% (N = NR) 83% (N = NR) None Overall graft survival curve:
p = 0.009 for D+R

- vs. D

- R

- ; p = 0.06 for D

- R+ vs. D

- R

- ; p = 0.69 for D +R+ vs. D

- R

Surviva l percentages estimated by ECRI Institute from Figure 1 in the article

Graft survival 36 72% (N = NR) 77% (N = NR) None Overall graft survival curve:
p = 0.009 for D+R

- vs. D

- R

- ; p = 0.06 for D

- R+ vs. D

- R

- ; p = 0.69 for D+R+ vs. D

- R

Surviva l percentages estimated by ECRI Institute from Figure 1 in the article

Patient survival 12 94% (N = NR) 94% (N = NR) None Overall patient survival curve:
p = 0.01 for D+R

- vs. D

- R

Survival percentages estimated by ECRI Institute from Figure 2 i n the article450 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Patient survival 24 90% (N = NR) 92% (N = NR) None Overall patient survival curve:

p = 0.01 for D+R

- vs. D

- R

Surviva l percentages estimated by ECRI Institute from Figure 2 in the article

Patient survival 36 86% (N = NR) 90% (N = NR) Non e Overall patient survival curve:

p = 0.01 for D+R

- vs. D

- R

Surviva l percentages estimated by ECRI Institute from Figure 2 in the article

Recipients Negative Before Transplant; Comparison of Clinical Outcomes After HCV+ Donor vs. HCV

- Donor

Abbott et a l. (2003) 83,84 Graft survival NA Relative risk was 0.97 (95% CI: 0.6 to 1.56) (very slightly in favor of recipients of positive organs) None n.s.

Patient survival, hazard ratio of death NA Unadjusted hazard ratio of death was 2.30 (95% CI: 1.75 to 3.26) in favor of recipients of negative organs. None Significant

Patient survival, hazard ratio of death NA Adjusted hazard ratio of death was 2.25 (95% CI: 1.56 to 3.24) in favor of recipients of negative
organs. Donor age, recipient age, HLA mis match, elevated creatinine
at 1 year post

transplantation,
years of dialysis before transplantation, and albumin level. Significant451 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Velidedeoglu et al. (2002) 93,94
UNOS d ata Graft survival 12 80.9% (N = 29) 82.3% (N = 7,811) None NR

Graft survival 36 69.2% (N = NR) 76% (N = NR) None NR

Graft survival 60 69.2% (N = NR) 70.1% (N = NR) None NR

Shah et al. (1993) 12,16 Graft survival 24 60% (N = NR) 69% (N = NR) None n.s.

Patient survival 24 60% (N = NR) 75% (N = NR) None n.s.452 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Haji et al. (2004) 77,79 Patient survival 12 80% (N = NR) 96% (N = NR) Not reported. The methods section reported the use of Cox regression “to adjust for significant covariates”, but authors did not report whether the hazard ratio of 2.8 was adjus ted or unadjusted. They did report that “By univariate Cox regression, re cipient and donor age, ischemia time, cumulative episodes of rejection, standard biopsy score, donor and recipient cytomegalovirus seropositivity, and post

- transplant cytomegalovirus infect ion were not significant (All p

- values >0.1) in determining mortality in our patient population.” (page 280) Overall p

- value for the survival

curves was reported as
p = 0.004 in favor of D

- recipients Confounding by indication: “ At our institution, a n HCV

- seropositive donor was used when, in the judgment of the transplant team, the recip ient was critically ill and
not a candidate for mechanical
ventr icular assist device (recurrent stroke, infections)” (page 278) However, one criterion for inclusion in the analysis was that all patients must have been discharged home successfully i.e., went home in stable condition. Surviva l percentages estimated by ECRI Institute from Figure 1 in the article453 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Patient survival 36 78% (N = NR) 92% (N = NR) Not reported. The methods section reported the use of Cox regression “to adjust for significant covariates”, but authors did not report whether the hazard ratio of 2.8 was adjusted or unadjusted. They did report that “By univariate Cox regression, recipient and donor a ge, ischemia time, cumulative episodes of rejection, standard biopsy score, donor and recipient cytomegalovirus seropositivi t y, and post

- transplant cytomegalovirus infect ion were not significant (All p

- values >0.1) in determining mortality in our patient
p opulation.” (page 280) Overall p

- value for the survival

curves was reported as
p = 0.004 in favor of D

- recipients Surviva l percentages estimated by ECRI Institute from Figure 1 in the article454 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Patient survival 60 59% (N = NR) 88% (N = NR) Not reported. T he methods section reported the use of Cox regression “to adjust for significant covariates”, but authors did not report whether the hazard ratio of 2.8 was adjusted or unadjusted. They did report that “By univariate Cox regression, recipie nt and donor age

, ischemia time, cumulative episodes of rejection, standard biopsy score, donor and recipient cytomegalovirus seropositivity, and post

- transplant cytomegalovirus infect ion were not significant (All p

- values >0.1) in determining mortality in our patient
pop ulation.”(page 280) Overall p

- value for the survival

curves was reported as
p = 0.004 in favor of D

- recipients Surviva l percentages estimated by ECRI Institute from Figure 1 in the article

Patient survival,
rate Mean : 50 months (SD : 23) 68% (23/34) 85% (155/183) None Relative risk or mortality: 2.8 (95% CI: 1.3

- 5.7;
p = 0.006) in favor of D

- recipients455 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Recipients Positive Before Transplant; Comparison of Clinical Outcomes After HBV+ Donor vs. HBV

- Donor

Fong et al. (2002) 55 Graft survival 12 91% (N = NR) 86% (N = NR) Adjusted for previous transplant, recipient age, recipient race, peak panel reactive antibody, recipient HCV, duration of dialysis, donor age, cold ischemia time, donor race, cause of donor death, ABDRMM (definition of this acronym not provided) NR Percentage estimated by ECRI Institute from Figure 1 in the publication

Graft

sur vival 24 80% (N = NR) 83% (N = NR) Adjusted for previous transplant, recipient age, recipient race, peak panel reactive antibody, recipient HCV, duration of dialysis, donor age, cold ischemia time, donor race, cause of donor death, ABDRMM (definition of th is acronym not provided) NR Percentage estimated by ECRI Institute fr om Figure 1 in the publication

Graft survival 36 68% (N = NR) 75% (N = NR) Adjusted for previous transplant, recipient age, recipient race, peak panel reactive antibody, recipient HCV, duration of dialysis, donor age, cold ischemia time, donor race, cause of donor death, ABDRMM (definition of this acronym not provided) NR Percentage estimated by ECRI Institute from Figure 1 in the publication456 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Patient survival 12 95% (N = NR) 94% (N = N R) Adjusted for previous transplant, recipient age, recipient race, peak panel reactive antibody, recipient HCV, duration of dialysis, donor age, cold ischemia time, donor race, cause of donor death, ABDRMM (definition of this acronym not provided) NR Perc entage estimated by ECRI Institute from Figure 1 in the publication

Patient survival 24 94% (N = NR) 91% (N = NR) Adjusted for previous transplant, recipient age, recipient race, peak panel reactive antibody, recipient HCV, duration of dialysis, donor ag e, cold ischemia time, donor race, cause of donor death, ABDRMM (definition of this acronym not provided) NR Percentage estimated by ECRI Institute from Figure 1 in the publication

Patient survival 36 90% (N = NR) 88% (N = NR) Adjusted for previous
trans plant, recipient age, recipient race, peak panel reactive antibody, recipient HCV, duration of dialysis, donor age, cold ischemia time, donor race, cause of donor death, ABDRMM (definition of this acronym not provided) NR Percentage

e stimated by ECRI Insti tute from Figure 1 in the publication457 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Madayag et al. (1997) 56 Graft survival 12 93.4% (N = 32) 100% (N = 37) Adjusted for sex, pre

transplant HBsAg,
pre

- transplant anti

- HBs,
pre

- transplant anti

- HBc, organ type, and date of transplant n.s. Recipients of positive organs were significantly older (Mean: 49 vs. 44; p = 0.03).

Graft survival 36 86.1% (N = 8) 100% (N = 11) Adjusted for sex, pre

transplant HBsAg,
pre

- transplant anti

- HBs,
pre

- tran splant anti

- HBc, organ type, and date of transplant n.s. Recipients of positive organs were significantly older (Mean: 49 vs. 44; p = 0.03).

Graft survival, cumulative graft loss risk Mean: 24 (R ange : 2

- 64) 11% (5/45) 2% (1/45) Adjusted for sex,
pre

- tran splant HBsAg,
pre

- transplant anti

- HBs,
pre

- transplant anti

- HBc, organ type, and date of transplant n.s.; Relative risk was 5.7 in favor (but not statistically significant) of the recipients of negative organs (95% CI : 0.52 to 52.17 Recipients of positive o rgans were significantly older (Mean: 49 vs. 44; p = 0.03).

Lai et al. (1996) 95

- 97 Patient survival, living donor 12 100% (N = N R) 91.7% (N = NR) None p = 0.334 for the comparison of patient survival curves for D+ vs. D

- when the donor was a living donor

Patient survival, deceased donor 12 76.5% (N = NR) 100% (N = NR) None p = 0.063 for the comparison of patient survival

curves for D+ vs. D

- when the donor was deceased458 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Patient survival, living donor 60 100% (N = NR) 72.4% (N = NR) None p = 0.334 for the comparison of patient survival curves for D+ vs. D

- when the donor was a living donor

Patient survival, deceased donor 60 58.8% (N = NR) 96.6% (N = NR) None p = 0.063 for the comparison of patient survival curves for D+ vs. D

- when the donor was deceased

Graft survival, living donor 12 100% (N = NR) 91.6% (N = NR) None p = 0.0013 for the comparison of graft survival

curv es for D+ vs. D

- when the donor was a living donor

Graft survival, deceased donor 12 76.5% (N = NR) 100% (N = NR) None p = 0.0035 for the comparison of graft survival curves for D+ vs. D

- when the donor was deceased

Graft survival, living donor 60 100% (N = NR) 53.9% (N = NR) None p = 0.0013 for the comparison of graft survival curves for D+ vs. D

- when the donor was a living donor459 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Graft survival, deceased donor 60 58.8% (N = NR) 92.4% (N = NR) None p = 0.0035 for the comparison of graft surviva l curves for D+ vs. D

- when the donor was deceased

Saab et al. (2003) 91 Patient survival 12 94% (N = N R) 91% (N = NR) None p = 0.65 comparing the survival curves

Patient survival 36 73% (N = NR) 81% (N = NR) None p = 0.65 comparing the survival curves

Patient survival 60 73% (N = NR) 81% (N = NR) None p = 0.65 comparing the survival curves

Graft

s urvival 12 87% (N = NR) 84% (N = NR) None p = 0.94 comparing the survival curves

Graft survival 36 71% (N = NR) 75% (N = NR) None p = 0.94 comparing the survival curves

Graft survival 60 71% (N = NR) 75% (N = NR) None p = 0.94 comparing the survival curves460 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Recipients Positive Before Transplant; Comparison of Clinical Outcomes After HCV+ Donor vs. HCV

- Donor

Kasprzyk et al. (2007) 98 Graft survival Range : 12

- 156 78% (47/60) 70% (140/199) None n.s.; this statistical test result included reci pients who were negative before transplant, but the percentages themselves in this table are restricted to those who were positive before transplant

Patient survival Range : 12

- 156 95% (57/60) 85% (169/199) None n.s.; this statistical test result include d recipients who were negative before transplant, but the percentages themselves in this table are restricted to those who were positive before transplant461 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Abbott et al. (2003) 83,84 Patient survival NR; see
comments Una djusted hazard ratio of death was 1.43 (95% CI : 1.02 to 2.02) in favor of recipients of negative organs. None Significant This comparison was restricted to the ~90% of
p atients who survived at least 2 years after transplant, because of the violation of the proportional hazards assumption. There was no difference between groups up to 2 years post

transplant.

Patient survival NR; see
comments Adjusted hazard ratio of death was 2.04 (95% CI : 1.20 to 3.45) in favor of recipients of negative
organs. Donor age, recipient age, HLA mis match, elevated creatinine at 1 year post

- transplantation,
years of dialysis before transplantation, and albumin level. Significant This comparison was restricted to the ~90% of patients w ho survived at least 2 years after transplant

, because of the violation of the proportional hazards assumption. There was no difference between groups up to 2 years post

transplant.

Graft survival NR 91.7% (542/593) 90.9% (769/846) None NR Denominator fo r D

calculated by ECRI Institute based on re ported percentage and number of events462 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Woodside et al. (2003) 85 Graft survival 12 89% (N = 19) 89% (N = 19) None NR

Patient survival 12 89% (N = 17) 89% (N = 17) None NR

Mandal et al. (2000) 86 Graft survival Median : 16,

M ean : 15 (standard error of the

mean : 2),

R ange : 3

- 33 56% (11/19) 50% (5/10) None NR In the D+ group, there were 19 operations in the 18 patients.

Diabetes was

more common in D+ recipients (5/18) than D

- recipients (1/10).
D+ recipients were significantly older (46 vs. 35).
D+ recipients rate of antiCMV was higher (87% vs. 50%)

. Mismatching of HLA

- A and HLA

- B was h igher in the D+ recipients (3.2 vs. 2.3).463 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Patient survival Median : 16,

M ean : 15 (standard error of the

mean : 2),

R ange : 3

- 33 94% (17/18) 90% (9/10) None NR In the D+ group, there were 19 operations in the 18 patients.

Diabetes was more common in D+ recipients (5/18) than D

- recipients (1/10).
D+ recipients were

s ignificantly older (46 vs. 35).
D+ recipients rate of antiCMV was higher (87% vs. 50%).
Mismatching of HLA

- A and HLA

- B was higher in the D+ recipients (3.2 vs. 2.3).

Ali et al. (1998) 99 Graft survival Mean 36,

R ange : 12

- 60 50% (14/28) 31% (5/16) None p

- value was reported as
p >0.3. However the chi

- squared test yields
p = 0.23.464 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Morales et al. (1995) 87 Graft survival 26 months (SD : 8) for those who received a positive
organ, and 30 months (SD : 10) for those who received a negative
organ 96% (23/24) 93% (37/40) None n.s. Number of blood transfusions less in D+ recipients (7 vs. 21); p <0.05.

Patient survival 26 months (SD : 8) for those who received a positive
organ, and 30 months (SD : 10) for those who received a negative
organ 100% (24/24) 98% (39/40) None n.s. Number of blood transfusions less in D+ recipients (7 vs. 21); p <0.05.

Saab et al. (2003) 91 Patient survival 12 89% (N = NR) 87% (N = NR) None p = 0.22 comparing the survival curves

Patient survival 36 89% (N = NR) 79% (N = NR) None p = 0.22 comparing the survival curves

Patient survival 60 89% (N = NR) 69% (N = NR) None p = 0.22 comparing the survival curves465 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Graft survival 12 73% (N = NR) 78% (N = NR) None p = 0.7 7 comparing the survival curves

Graft survival 36 73% (N = NR) 70% (N = NR) None p = 0.77 comparing the survival curves

Graft survival 60 73% (N = NR) 59% (N = NR) None p = 0.77 comparing the survival curves

Velidedeoglu et al. (2002) 93,94 Penn data Graft survival 12 69.2% (N = 13) 79.6% (N = 103) None p

- value comparing graft survival curves
was p = 0.6778 These data refer to patients seen at Penn

Graft survival 36 69.2% (N = NR) 71.6% (N = NR ) None p

- value comparing graft survival curves
was p = 0.6778 These data refer to patients seen at Penn

Graft survival 60 69.2% (N = NR) 61.2% (N = NR) None p

- value comparing graft survival curves
was p = 0.6778 These data refer to patients seen at Penn

Patient survival Mean : 23.4 77% (10/13) 78.7% (81/103) None NR These data refer to patients seen at Penn466 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Velidedeoglu et al. (2002) 93,94 UNOS data Graft survival 12 76.9% (N = 190) 80.6% (N = 5

, 053) None p

- value comparing graft survival curves
was p = 0.965 These data refer to patients from UNOS

Graft survival 36 72.6% (N = NR) 69.1% (N = NR) None p

- value comparing graft survival curves
was p = 0.965 These data refer to patients from UNOS

Graft

s urvival 60 69.3% (N = NR) 62.2% (N = NR) None p

- value comparing graft survival curves
was p = 0.965 These data refer to patients from UNOS

Marroquin et al. (2001) 90 Patient survival 6 95% (N = NR) 85% (N = NR) None p = 0.01 for the comparison of patient survival

curves Recipients of positive organs were more likely to have liv er cancer (8.3% vs. 3.1%;
p = 0.01),

more likely to have ABO incompatibility (4.2% vs. 1.3%;
p = 0.04), and they had poorer waitlist status (see Table 5 in the publication).

Patient survival 12 90% (N = NR) 82% (N = NR) None p = 0.01 for the comparison o f patient survival

curves Recipients of positive organs were more likely to have liver cancer (8.3% vs. 3.1%;
p = 0.01),

mor e likely to have ABO incompatibility (4.2% vs. 1.3%;
p = 0.04), and they had poorer waitlist status (see Table 5 in the publication)

.467 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Patient survival 18 90% (N = NR) 79% (N = NR) None p = 0.01 for the comparison of patient survival

curves Recipients of positive organs were more likely to have liver cancer (8.3% vs. 3.1%;
p = 0.01), more likely to have ABO incompatibility (4.2% vs. 1 .3%;
p = 0.04), and they had poorer waitlist status (see Table 5 in the publication).

Patient survival 24 90% (N = NR) 77% (N = NR) None p = 0.01 for the comparison of patient survival

curves Recipients of positive organs were more likely to have liver c ancer (8.3% vs. 3.1%;
p = 0.01), more likely to have ABO incompatibility (4.2% vs. 1.3%;
p = 0.04), and they had poorer waitlist status (see Table 5 in the publication).468 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Patient survival, overall Median

was 34 months for those who received a positive
org an, and 37 months for those who received a negative
organ 90% (86/96) 77% (2194/2827) None NR Recipients of positive organs were more likely to have liver cancer (8.3% vs. 3.1%;
p = 0.01), more likely to have ABO incompatibility (4.2% vs. 1.3%;
p = 0.04), and they had poorer waitlist status (see Table 5 in the publication).

Graft survival 6 88% (N = NR) 81% (N = NR) None NR Data estimated by ECRI Institute from Figure 3 in the publication. Recipients of positive organs were more likely to have liver canc er (8.3% vs. 3.1%;
p = 0.01), more likely to have ABO incompatibility (4.2% vs. 1.3%;
p = 0.04), and they had poorer waitlist status (see Table 5 in the publication).469 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Graft survival 12 76% (N = NR) 76% (N = NR) None NR Data estimated by ECRI Institute fr om Figure 3 in the publication. Recipients of positive organs were more likely to have liver cancer (8.3% vs. 3.1%;
p = 0.01), more likely to have ABO incompatibility (4.2% vs. 1.3%;
p = 0.04), and they had poorer waitlist status (see Table 5 in the public ation).

Graft survival 18 76% (N = NR) 72% (N = NR) None NR Data estimated by ECRI Institute from Figure 3 in the publication. Recipients of positive organs were more likely to have liver cancer (8.3% vs. 3.1%;
p = 0.01), more likely to have ABO incompat ibility (4.2% vs. 1.3%;
p = 0.04), and they had poorer waitlist status (see Table 5 in the publication).470 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Graft survival 24 76% (N = NR) 70% (N = NR) None NR Data estimated by ECRI Institute from Figure 3 in the publication. Recipients of positive organs were more likely to have liver cancer (8.3% vs. 3.1%;
p = 0.01), more likely to have ABO incompatibility (4.2% vs. 1.3%;
p = 0.04), and they had poorer waitlist status (see Table 5 in the publication).

Graft survival, adjusted odds 3 0.7 See previous col umn Adju sted for sex/age/weight of both donor and recipient, ABO incompatibility, coexisting diseases, change in liver function tests, immunosuppressive regimens , causes of graft failure, UNOS status at time of transplant, ICU length of stay, hospital leng th of stay n.s.471 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Graft survival, adjusted odds 6 0.66 See previous column Adjusted for sex/age/weight of both donor and recipient, ABO incompatibility, coexisting diseases, change in liver function tests, immunosuppressive regimens, causes of graft failu re, UNOS status at time of transplant, ICU length of stay, hospital length of stay n.s.

Graft survival, adjusted odds 12 1 See previous column Adju sted for sex/age/weight of both donor and recipient, ABO incompatibility, coexisting diseases, change in l iver function tests, immuno

- suppressive regimens, causes of graft failure, UNOS status at time of transplant, ICU length of stay, hospital length of stay n.s.

Graft survival, adjusted odds 24 0.88 See previous column Adju sted for sex/age/weight of both donor and recipient, ABO incompatibility, coexisting diseases, change in liver function tests, immuno

- suppressive regimens, causes of graft failure, UNOS status at time of transplant, ICU length of stay, hospital length of stay n.s.472 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Patient survival, ad justed odds 3 0.37 See previous column Adju sted for sex/age/weight of both donor and recipient, ABO incompatibility, coexisting diseases, change in liver function tests, immuno

- suppressive regimens, causes of graft failure, UNOS status at time of transplan t, ICU length of stay, hospital length of stay n.s.

Patient survival, adjusted odds 6 0.39 See previous column Adju sted for sex/age/weight of both donor and recipient, ABO incompatibility, coexisting diseases, change in liver function tests, immuno

- supp ressive regimens, causes of graft failure, UNOS status at time of transplant, ICU length of stay, hospital length of stay n.s.

Patient survival, adjusted odds 12 0.56 See previous column Adju sted for sex/age/weight of both donor and recipient, ABO incom patibility, coexisting diseases, change in liver function tests, immuno

- suppressive regimens, causes of graft failure, UNOS status at time of transplant, ICU length of stay, hospital length of stay n.s.473 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Patient survival, adjusted odds 24 0.51 See previo us column Adju sted for sex/age/weight of both donor and recipient, ABO incompatibility, coexisting diseases, change in liver function tests, immuno

suppressive regimens, causes of graft failure, UNOS status at time of transplant, ICU length of stay, hospit al length of stay n.s.

Salizzoni et al. (2001) 88 Patient survival 12 83.3% (N = NR) 82.4% (N = NR) None n.s.

Graft survival 12 83.3% (N = NR) 79.8% (N = NR) None n.s.

Vargas et al. (1999) 92 Graft survival NR 87% (20/23) 91% (154/169) None n.s.

Patient survival 12 89% (N = NR) 88% (N = NR) None n.s.

Patient survival 60 72% (N = NR) 73% (N = NR) None n.s.

Testa et al. (1998) 89 Graft survival 48 71.9% (N = NR) 76.2% (N = NR) None n.s.

Patient survival 48 83.9% (N = NR) 79.1% (N = NR) None n.s.474 Study Outcome Timepoint D+ Outcome D

- Ou tcome Adjustment for Comorbidities Statistical Test Result Comments

Patient survival 40 months (R ange : 12

- 58) for those who received a positive
organ, and 36 months (R ange : 17

- 135) for those who received a negative
organ 82% (18/22) 81% (93/115) None n.s.

Shah et al. (1993) 12 Graft survival 24 80% (4/5) 70% (N = NR) None n.s.

Patient survival 24 100% (N = NR) 80% (N = NR) None n.s.

NR

– Not reported

n.s.

– Not statistically significant475 

# Evidence Reviews: V **. Potential risks and benefits of transplanting, or not transplanting,**  **solid organs from d onors**  **with risk factors for HIV, HBV, or HCV**

**Question 8.**  **How do the clinical outcomes of transplant recipients who receive organs from donors with behavioral or**  **nonbehavioral risk**  **factors compare to those who remain on the transplant list?**

This question is similar to Question 7

, however

, Question 7 involved the use of an organ known to be infected, whereas Question 8 involves an organ from a donor at increased risk of infection

. S ome individuals may test negative for HIV/HBV/HCV and yet have the virus ( poss ibly due to the window period for virus detection , or because of test insensitivity ).

Two studies met the inclusion criteria ( Schweitzer et al. [ 2007 ] 203 

### and Freeman and Cohen [ 2009 ] 204 

### )

. Both performed simulations on the key dilemma of whether to use organs from serologically negative
donors who have behavioral risks of infection . The two studies, howe ver, made different comparisons, and so they we re considered separate ly

. Schweitzer et al. (2007 ) 203 

### estimated mortality after transplanting
the kidneys vs. keeping patients on the waitlist. Freeman and Cohen (2009) 204 

### estimated waitlist mortality

rates, however they did not estimate mortality of all who received organs from at

- risk donors . Instead

, they reported the overall prevalence of infection among recipients of organs from at

- risk donors ( which

was exceedingly low) , and then estimated mortality just for infected recipients

. Both studies are described
in more detail in the sections below.

Due to the small amount of evidence, we also looked for studies com paring the clinical outcomes of two

t ypes of recipients: recipients of organs from at

- risk donors , and recipients of organs from not

- at

- risk donors (these donors may or may not have been infected). We defin ed “ at risk ” for this question as having

a potential behavioral risk factor, or having a clinical symptom /physical finding associated with infection, or having a medical comorbidity associated with infection. N o such comparative studies were identified.

Schweitzer et al. (2007) 203



### T h i s simulation addressed the question: Should the kidneys of negative

- serology donors who are at
increased risk of infection based on 1994 CDC criteria be transplanted or discarded ? Authors constructed a complicated Markov model of these two alternatives. Th ey considered four types of increased

- risk donors ( IRDs ) : intravenous drug users (IDU), men who have sex with men (MSM), commercial sex
work er s (CSW), and priso n inmates. The authors ’ methods, our quality assessment, and study results are
detailed in the t ext below, as well as in Table 69 through Table 75

.476 

### The model considered a 20

- year interval, with one

- year cycles. During each year, each simulated patient
was in one of ni ne states:

Recipient HIV status Recipient HCV status

1) On the waitlist HIV

- H CV

2) Received a kidney HIV

- HCV

3) On the waitlist HIV + HCV

4) On the waitlist HIV

- HCV +

5) On the waitlist HIV + HCV +
6) Received a kidney HIV + HCV

7) Received a kidney HIV

- HCV +
8) Received a kidney HIV + HCV +

9) Dead

Each of the first eight health states was associated with a different death rate, a different quality

- of

- life, and a different cost of care. For simplicity, authors assumed that all recipients were immune to acute HBV infection, which explains why none of the nine states involve HBV status . Transition probabilities between states were based on various assumptions using the published literature (see Table 69 through
Table 71 below).

The epidemiology assumptions listed in Table 70 and Table 71 can be compared informally with the

cor responding estimates in Question 1 of this evidence review. For HIV, the incidence estimates matched closely (Schweitzer assumed 0.02 per 100 person

- years, and the estimate in Question 1 was 0.019 per
100 person years). However, the prevalence of HIV was a bout one

- third of the estimate from Question 1 (0.128% vs 0.37%). Also, for HCV, the incidence rates were very dif ferent (Schweitzer assumed
0.11 cases per 100 person

- years but in Question 1 the estimate was 0.057 per 100 person

- years). For HCV prevalence, the assumed 1.8% was within the range of estimates from Question 1 (1.3% to 1.9%).

The base case simulation assumed that the CDC

- IRD donors were all seronegative injection drug users, and the results appear in Tabl e 72 . The t ransplant strategy resulted in lower mortality, more quality

adjusted life

- years (QALYs) , and also lower cost. There were more HIV infections using the t ransplant strategy, but the number of them was too small (and the resulting health problems not severe enough) to overcome the advantages of transplantation. Interestingly, with HCV, there were act ually more infections
with the d iscard strategy. This was because the d iscard strategy led to more time on hemodialysis than the

t ransplant strategy; the assumed incidence of HCV when on hemodialysis (0.34 per 100 patient

- years) was 30 times higher than the assumed incidence of HCV after kidney transplant (0.011 per 100 patient

years; see the bottom two rows of T able 71 ).

Authors performed separate analyses for three other types of increased

- risk donors (MSM, C SW, and inmates); results were very similar to the base case for outcomes such as the number of transplants,477 

### survival, QALYs, and costs. There were some di fferences, however, regarding HIV and HCV infections ( Table 73 ). Infection counts due to the use of kidneys from MSM or inmates were low for both HIV and HCV. The counts for CSW were somewhat higher, but even for t his subgroup the total number of
infections using the t ransplant strategy (13.7, comprised of 3.4 H IV and 9.3 HCV) was still lower than the
total number of infection s using the d iscard strategy (14.8, comprised of 1.9 HIV and 12.9 HCV).

Authors conducted n umerous one

- way sensitivity analyses (in which a singl e assumption is altered and
all others left unchanged) , and they stated that in most cases the conclusions of the base case “ were not substantially changed ” . They did note that the number of HCV infecti ons was strongly influenced by assumptions about incidence rates, but concluded that “ the ‘ Discard ’ policy would yield fewer HCV infections only in a setting where a recipient ’ s risk of in fection on dialysis is very low , while the probability of CDC

- IRD in fection in a donor is high ”

. 203



### Authors also conducted a “ worse

- case scenario ” analysis that used the following alternate assumptions:

- That CDC

- IRD donors have much higher HIV incidence ( 25 per 100 person

- years) and HIV

prevalence ( 50%) than assumed in the base case analysis (2 per 100 person

- years, and 18%, respectively)

- That CDC

- IRD donors have higher HCV incidence (25 per 100 person

- years) and HCV prevalence

(50%) than assumed in the base case ana lysis (21 per 100 person

- years, and 38%, respectively)

- While on the waitlist, the risk of HCV is much lower (0.1 infections per 100 person

- years instead of

the 0.34 assumed in the base case)

- Lower chance of an individual receiving an offer of a CDC

- IRD kid ney because of increased number

of eligible individuals for those kidneys (30% instead of the base case 5%)

- Lower percentage of CDC

- IRD kidneys (2% of donors instead of 5%)

- Higher cost associated with HIV or HCV infection ($30,000/year instead of $21,000)

- Lower utility associated with HIV or HCV infection (0.45 instead of 0.78 for HIV and 0.82 for HCV)

Interestingly, even though these assumptions were slanted against the Transplant strategy

, it still was preferable to the d iscard strategy, resulting in more transplants, less time on the waitlist, more time with a functioning transplant, lower mortality, more QALYs, and lower cost.

Finally, because NAT testing may not be widely available, authors also modeled a scenario where only antibody testing was availab le, lengthening the window period for HIV to 22 days from 11; lengthening the window period for HCV to 70 days from 10). Results still favored the transplant strategy for all outcomes except the number of infections, which rose to 2.6 HIV infections per 1

, 000 patients and

27.7 HCV infections per 1000 patients. These additional infections were not sufficient to overcome the overall advantag es of the t ransplant strategy.

The GRADE evidence profile appears in Table 76

. The evidence was rated as Very Low, because this was a simulation and not an empirical study. The GRADE system does not consider simulations as informative as empirical studies.478 

### Table 69

. Assumptions in the Sc hweitzer et al. (2007 ) M odel

Key Assumptions about D onors

**•** Deceased donors only

**•** All donors tested negative on antibody and nucleic amplification tests (NAT) for both HIV and HCV. NAT has a relatively short window period (i.e., the duration when it cannot detect the virus), so it would be relatively unlikely to miss a virus for this reason.

**•** 5% of donors are classified as “ CDC

- IRD ” (IRD = increased risk donor; sensitivity analyses ranging 2%

- 8%), defined as being in one of the seven categories in the 1994 CDC guideline on HIV.

Key Assumptions about R ecipients

**•** 50

- year old hemodialysis patients (sensitivity analyses ranging from 18

- 65)

**•** All recipients were willing to accept kidneys from CDC

- IRDs.

**•** All recipients were immune to “ acute HBV infection ” . Thus if any donor were HBV+, thi s had no impact on the analysis.

**•** In any given year, a recipient could acquire either HIV or HCV, but not both. They could acquire the other one in subsequent years.

**•** 5% of patients on waitlist would be candidates for CDC

- IRD kidney (sensitivity analyses ran ging from 1%

- 30%)

**•** Number of patients on the waitlist at the end of 2002 was 50,535

**•** Annual number of standard deceased donor kidney transplants in 2002 was 8,288

**•** Median time to transplant for new waiting list registrants was 3.5 years

**•** Annual standard donor kidney transplant rate was 20% (sensitivity analyses ranging 2%

- 53%

**•** Median waiting time for CDC

- IRD kidney transplants was 3.5 years

Key Assumptions about Death R ates

**•** Annual death rate among all patients on the U.S. kidney waitlist was 3.7% for those 18

- 34; 5.4% for those aged 35

- 49; 9.2% for those aged 50

- 64; and 12.9% for those aged 65+

**•** Annual death rate in the first year after kidney transplant was 2.3% for those 18

- 34; 3.9% for those aged 35

- 49; 8.0% for those aged 50

- 64; and 11.6% for those aged 65+

**•** Annual death rate in all subsequent years after kidney transplant was 2.1% for those 18

- 34; 2.3% for those aged 35

- 49; 4.0% for those aged 50

- 64; and 7.2% for those aged 65+

**•** Relative risk of death due to HIV infection was 1.5

**•** Relative risk of death due to HCV infection was 1.7479 Key Assumptions about C osts and Quality

- Adjusted

- Life

- Years (QALYs)

**•** Costs in 2002 dollars, adjusted using the medical care component of the consumer price index

**•** Cost of “ Stat HIV ” and HCV nucleic acid testing (NAT) were estimated at $500/donor or $250/kidney was added to the cost when the donor was CDC

- IRD

**•** Cost of hemodialysis $61,000/year (sensitivity analyses ranging from) (sensitivity analyses ranging from $49,000

- $71,000)

**•** Cost of care of kidney recipient in the first year after t ransplant $97,000/year (sensitivity analyses ranging from $76,000

- $177,000)

**•** Cost of care kidney recipient in all subsequent years $21,000/year (sensitivity analyses ranging from $17,000

- $38,000)

**•** Cost of care for HIV infection was $21,000/year (sensitivity analyses ranging from $19,000

- $23,000)

**•** Cost of care for HCV infection was $2,000/year (sensitivity analyses ranging from $1,000

- $30,000)

**•** Utility of being on hemodialysis was 0.57 (0 denotes death, 1 denotes perfect) (sensitivity analyses ranging from 0.41

- 0.64)

**•** Utility of post

- transplant quality

- of

- life was 0.70 (0 denotes death, 1 denotes perfect) (sensitivity analyses ranging from 0.62

- 0.82)

**•** Utility of HIV was 0.82 (0 denotes death, 1 denotes perfect) (sensitivity analyses ranging from 0.45

- 1.00)

**•** Utility of HCV was 0.78 (0 denotes death, 1 denotes perfect) (sensitivity analyses ranging from 0.60

- 0.86)

**•** Discounting of both costs and QALYs at 3%

Other A ssumptions

**•** Overall risk of graft failure after kidney transplant was 6% in the first year (sensitivity ana lyses ranging fr om 4%

- 7%), and 4% in subsequent years (sensitivity analyses ranging from 2%

- 6%). After graft failure, the patient returned to one of the waitlist health states.

**•** Relative risk of graft failure specifically due to HIV infection was 1.0 (sensi tivity analyses ranging from 1.0 to 1.3)

**•** Relative risk of graft failure specifically due to HCV infection was 1.6 (sensitivity analyses ranging from 1.4 to 1.8)

**•** The window period for HIV antibody testing alone was 22 days; for HIV antibody plus NAT was 11 days ; for HCV antibody alone was 70 days; for HCV antibody plus NAT was 10 days

**•** The false

- negative rate for pre

- transplant serological testing of CDC

- IRDs donors was 5%. Together with the window period, this incorporated the possibility of missed viruses.480 

### Table 70

. HIV E pidemiology A ssumptions in the Schweitzer et al. (2007) M odel

HIV Incidence a Prevalence

Population Base Case Sensitivity Range Base Case Sensitivity Range

General population 0.02 N.A. 0.128% N.A.

Potential D ono rs
Intravenous drug users 2 1

- 3 18% 1

- 49

Men who have sex with men 3 1

- 12 25% 0

- 40

Commercial sex workers 10 3

- 30 24% 0

- 60

Inmates 0.2 0

- 0.4 2% 1

- 17

Potential R ecipients

Hemodialysis patients 0.02 N.A. N.E. N.E.

Kidney transplant patients 0.02 N.A. N.E. N.E.

a Incidence is the number of new cases per 100 patient

- years

. N.A.

– Not applicable because no sensitivity analysis of this parameter was performed

. N.E.

– Not estimated, because the model did not require estimates of the prevalence of HIV or HC V among recipients

.



### Table 71

. HCV E pidemiology A ssumptions in the Schweitzer et al. (2007) M odel

HIV Incidence a Prevalence

Population Base Case Sensitivity Range Base Case Sensitivity Range

General population 0.011 N.A. 1.8% N.A.

Potential D onors
Intravenous drug users 21 10

- 45 38% 10

- 90

Men who have sex with men 0.2 0

- 1 4% 2

- 18

Commercial sex workers 10 5

- 23 12% 6

- 45

Inmates 1 0.3

- 6 23% 16

- 41

Potential R ecipients

Hemodialysis patients 0.34 0.1

- 3 N.E. N.E.

Kidney transplant patients 0.011 N.A. N.E. N.E.

a Incidence is the number of new cases per 100 patient

- years

. N.A.

– Not applicable because no sensitivity analysis of this parameter was performed

. N.E.

– Not estimated, because the model did not require estimates of the pr evalence of HIV or HCV among recipients

.481 

### Table 72

. Base Case R esults of the Schweitzer et al. (2007) M odel

Outcome Transplant Discard

Number of kidney transplants per 1 ,000 patients Total: 990

Standard donors: 495

CDC

- IRD donors: 4 95 Total: 740, all standard donors

Survival 1

- year: 91%

5

- year: 68%

10

- year: 49%

20

- year: 23% 1

- year: 91%

5

- year: 65%

10

- year: 45%

20

- year: 20%

Quality

- adjusted life

- years 5.6 5.1

Cost of care over 20 years for a typical patient $338,000 $363,000

HIV i nfections per 1 ,000 patients over 20 years 2.3, comprising 1.9 infections when on the waitlist or community acquired, and 0.3 from window

- period CDC

- IRD donations (these do not add to 2.3 due to rounding) 1.9, all while on the waitlist or community

- acquire d

HCV infections per 1 ,000 patients over 20 years 10.8*, comprising 7.9 infections when on the waitlist or community acquired, and 2.9 from window

- period CDC

- IRD donations 12.9*, all while on the waitlist or community

- acquired

CDC

- IRD

– CDC increased

- ri sk donor

* The reason that there were actually more HCV infections using the d iscard strategy is that the d iscard strategy led to

more time on hemodialysis than the t ransplant strategy; the assumed incidence of HCV when on hemodialysis (0.34 per 100 patien t

- years) was 30 times higher than the assumed incidence of HCV afte r kidney transplant (0.011;

see the bottom two rows of Table 71 ).482 

### Table 73

. HIV and HCV Infection R esults in Recipients of K idn eys from CDC

- IRD D onors

Outcome HIV HCV

Total Waitlist or Community

A cquired Transplant

A cquired Total Waitlist or Community

A cquired Transplant

A cquired

Injection drug users (base case) 2.3 * 1.9 0.3 10.8 7.9 2.9

Men who have sex with men 2.4 1.9 0 .5 8.0 7.9 0.1

Commercial sex workers 3.4 1.9 1.5 9.3 7.9 1.4

Prison inmates 2.0 1.9 0.1 8.1 7.9 0.2

* All numbers are the number of infections per 1

, 000 patients, all in the Transplant group willing to receive kidneys

from CDC increased

- risk donors . Du e to rounding, numbers in the two columns “ Waitlist or community acquired ” and

“ Transplant

- acquired ” may not add up exactly to the numbers in the Total column.483 

### Freeman and Cohen (2009) 204



### This study was a comprehensive risk analysis of numerous considerations pertaining to solid organ donation. Authors emphasized that the risk of transmitting an infection to a recipient is only one among a set of competing risks, including the risk of dying while on the wai tlist, the risk of dying after the transplant (regardless of the donor’s status), and risks of dying from medications, employment, transportation, and recreation. Taking this broad perspective, the authors provided real

- world context to
critical decisions about organ donation.

Most of the data reported in the article did not address this particular research question. These include data on the transmission of other pathogens or conditions (e.g., CMV), mortality risks after receiving an organ from an extended

- criteria kidney or a standard criteria kidney , and everyday mortality risks. This question specifically involves the comparison of the clinical outcomes (e.g., mortality rates) of two types of potential recipients: 1) those who remained on the waitlist, a nd 2) those who received organs from at

risk donors. For at

- risk donors, the study only addressed mortality after HIV (see Table 3 of the article;

a row for “High risk donors” appears in the HIV section).

The waitlist mortality estimates are reproduced in Table 74 below. These were based on the authors ’
Markov model that utilized 90

- day waitlist mortality and transplantation probabilities from the OPTN/SRTR 2007 Annual Report. Authors reported rates separately for 1 2 different types of recipients (see table). Three

- year estimates were also provided for kidney recipients. For confirmation, ECRI
Institute replicated the reported results using the reported probabilities using TreeAge Pro (TreeAge
So ftware Inc., Williams town, MA).

The GRADE evidence profile appears in Table 76 ; the evidence was rated as Very Low, because it was a simulation; the GRADE rating system provides higher ratings to empirical studies.484 

### Table 74

. Waitlist M ortality E stimates by Freeman and Cohen (2009)

Type of R ecipient 1

- year E stimated Waitlist Mortality 3

- year E stimated W aitlist Mortality

Kidney recipient, age 18

- 34 2.7% 9.8%

Kidney recipient, age 35

- 49 4.6% 17.2%

Kidney recipien t, age 50

- 64 7.5% 28.0%

Kidney recipient, age 65+ 10.5% 40.3%

Liver recipient, Model for End

- Stage Liver Disease (MELD) score 10 or less 4.1% NR

Liver recipient, MELD score 11

- 14 7.1% NR

Liver recipient, MELD score 15

- 20 11.4% NR

Liver recipient, MELD score 21

- 30 18.5% NR

Liver recipient, MELD score 31+ 37.1% NR

Heart recipient, status 2 5.9% NR

Heart recipient, status 1B 13.6% NR

Heart recipient, status 1A 21.8% NR

NR

– Not reported

. Note : These data are from Table 3 of the Freeman and Co hen article. 204 Other data in that table (such as one

- year mortality after receiving an immediate extended

- criteria kidney, and one

- year mortality after receiving an immediate standard

- criteria kidney, liv er or heart ) do not address Que stion 8 of this evidence review, and therefore are not included in this table.



### For consideration of at

- risk donors, authors stated that “The 2,189 CDC ‘high

- risk’ donors since 2004 have resulted in 1 HIV positive donor, corre sponding to an infection risk of 46 per 100,000.”(footnote b
of Table 3 of the article) 204 

### In a conservative analysis, they assumed that HIV is 100% fatal, and therefore
estimated that the HIV

- related mort ality per 100,000 recipients of organs from at

- risk donors was 46 in 100,000. This corresponds to 0.046%, which is much lower than all of the waitlist mortality rates in
Table 74 (the lowest in the entire table is 2.7%, which is 59 times higher than HIV

- related mortality after receiving organs from at

- risk donors). The authors concluded that the waitlist mortality risk far outweighs
the risk of HIV

- related mortality associated with receiving an organ from a serologi cally negative donor with a behavioral risk factor. They did not attempt to make mortality estimates for either HBV or HCV due to insufficient documentation in the literature regarding the mortality rate for infected recipients.485 

### Table 75

. Questions 8/9: Quality A ssessment

Study 8a or 9a 8b or 9b 8c or 9c 8d or 9d 8e or 9e 8f or 9f 8g or 9g 8h o r 9h

Schweitzer et al. (2007) 203 Simulation

Freeman and Cohen (2009) 204    

The Schweitzer et al. (2007) 203 article was not assessed with these items because it was a simulation rather than a study enrolling patients. Ex tensive details about this simulation appear in the text for Question 8. A checkmark (  ) means that the study met the quality criterion for this Question; the lack of a checkmark means that the study either did not meet the criterion, or it was unclear whe ther the study met the criterion. The criteria specific to this Question were:

8a. Were the patients randomly assigned to treatments?

8b. Was the study planned prospectively (i.e., before any data were collected)

8c. Were all consecutive patients enrolled (or a rando m sample of eligible patients)?

8d. Were the two groups comparable at baseline? (age, sex, comorbidities, indication for transplant, previous duration on waitlist)

8e. If not, were statistical adjustments performed to control for baseline differences?

8f. Were the tw o groups treated concurrently? 8g. Did at least 85% of the study enrollees provide data?

8h. Was the between

- group difference in study completion rates less than 15%?486 

### Table 76

. GRADE T able for Question 8 ( Clinical Outcomes of At

- risk Orga ns vs. Waitlist or Not

- at

- risk O rgans )

Comparison Outcome Quantity and T ype of E vidence FindingsStarting Grade Decrease GRADE Increase GRADE

GRADE of Evidence for Outcome Overall GRADE of Evidence BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseConfounders wouldreduce the effect

Transplant vs. discard kidneys from at

- risk donors who test negative Recipient survival One simulation 203 91% s urvival in both groups at

one year.
At five years, survival was 68% for the transplant
group an d 65% for the discard group.

At 10 years, survival was 49% for the transplant group and 45% for the discard group.

At 20 years, survival was 23% for the transpla nt group and 20% for the discard group

. Very Low 0

- 1 0 0 0 0 0 0 Very Low

Very Low

Quality of life One simulation 203 5.6 QALYs for the
trans plant strategy, compared to 5.1 QALYs for the discard s trategy Very Low 0

- 1 0 0 0 0 0 0 Very Low487 Comparison Outcome Quantity and T ype of E vidence FindingsStarting Grade Decrease GRADE Increase GRADE

GRADE of Evidence for Outcome Overall GRADE of Evidence BaseStudy QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose ResponseConfounders wouldreduce the effect

Waitlist survival vs. survival of infected recipients of at

- risk organs Recipient survival One simulation 204 One

- year w aitlist mortality for kidneys was 3% to 1 1% (increasing with age); for livers it was 4% to 37% (increasing with MELD score ) ; for hearts it was 6% to 22% (increasing with criticality status) . No mortality estimates provided for all those who received
at

- risk organs

. Of
2

, 189 ‘high

- risk’ donors, th ere was only one confirmed cases of HIV infection. Very Low 0

- 1 0 0 0 0 0 0 Very Low Very Low488 

## Question **9. What is the impact of excluding potential solid organ donors**
**with behavioral or nonbehavioral**  **risk factors on the organ donor pool?**

T he exclusion of any potential donors , if employed, would reduce the size of the organ donor pool. This question is intended to quantify the size of that potential reduction if exclusion were based on the presense of a risk factor for HIV, HBV, or HCV

. O ne study was in cluded for this question ( Schweitzer et
al

. (2007)

. 203 

### This simulation study was described in great detail under Question 8.

Over a 20

- year period, the simulation estimated that if at

- risk kidneys w ere excluded from transplantation, there would only be 740 transplanted kidneys per 1

, 000 patients, instead of 990 if at

- risk donors were included in the pool. Thus 250 fewer kidneys would have been transplanted. This is a reduction of 25.3% (250/990). Not e that the study only considered four types of behavioral exclusions ( IDU

, MSM

, CSW

, and prison inmates), and furthermore the study considered only HIV and HCV. Exclusions for other reasons (e.g., HBV risk, or nonbehavioral risk factors for HIV or HCV ) wou ld mean a larger reduction in the organ donor pool.489 

## Question **10. What is the impact of false positive tests on the organ donor pool?** 

No studies were identified that met the inclusion criteria

.490 

# Gaps **in the Current L iterature** 

This systematic review uncovere d numerous gaps in the literature about the possible transmission of HIV, HBV, or HCV through solid organ transplantation. This section describes the most prominent gaps.

In Question 1, we sought to identify literature on the prevalence and incidence of HI V, HBV, and HCV among people whose organs are being considered for donation. Only four small studies of this population were identified, and two involved living relatives wishing to donate solid organs to children , which comprise only a small proportion of potential organ donors . None of the studies reported incidence, and only two of the four studies reported rates of HIV.

In Question 2, the major gap was the lack of studies of the rate of HIV transmission . This is likely
because federal regulations prohi bit the use of organs from donors testing positive for HIV for transplant

. .
Several important gaps affect the usefulness of the current evidence for Questions 3 and 4 . Very little literature on potential organ donors exists, and the applicability of data from other populations is unclear. In addition, almost no information on children was found, and there is very little information on HBV

. Nearly all of the studies focused on risk factors for prevalent infection; little information on factors for
incident infection, including signs and symptoms, has been published. Differentiating dependent from independent risk factors was inconsistent. Most of the information on identification of factors came from
self

- report, and the reliability of next

- of

- kin interviews on highly private and personal behavioral factors is brought into question by the sole stu dy of potential tissue donors.

Data on performance of diagnostic tests in potential organ donors is lacking for Question 5 . For some of the tests, there is no data a t all. For many tests, some or most of the data is from analytic validation studies and may not be applicable to real

- world use. Study of the test in relevant clinical applications, or at least reasonably similar applications or populations, is needed to d raw strong conclusions regarding the
‘real

- world’ use of these tests in this context. This is also needed to enable the calculation of useful statistics including predictive values, likelihood ratios, and post

- test probabilities of diseases.

Question 6

, o n inactivation

, only yielded a single uncontrolled study that had been published in 1994; no additional studies of the inactivation of solid organs have appeared since then. The last three questions (8 through 10) all contained low amounts of evidence, and are all potential targets for future research.

In Question 7, only one included study had a waitlist control group. Numerous studies used a control group of recipients who received organs from negative donors, however, those studies had various quality

p roblems (e.g., differing pre

- transplant characteristics, without statistical adjustment) that limit the interpretability of their results. More comprehensive analyses of competing risks (of both transplanting and discarding organs from infected donors) wou ld help inform critical decision making.

Question 8 included only two studies, both of which estimated survival on the waitlist using Markov
models. One of them also provided data for Question 9 on the size of red uction in the organ donor pool,
and no stud ies addressed Question 10.491 

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# Appendix A

**Details of Litera ture Search** 

Electronic Database Searches
The following databases have been searched for relevant information:



### Table 77

. Electronic Databases Searched

Database Date Limits Platform/Provider

The Cochrane Central Register of Controlle d Trials (CENTRAL) Through 2009, Issue 3 www.thecochranelibrary.com

The Cochrane Database of Methodology Reviews (Methodology Reviews) Through 2009, Issue 3 www.thecochranelibrary.com

The Cochrane Database of Systematic Reviews (Cochrane Reviews) Through 2009, Issue 3 www.thecochranelibrary.com

Database of Abstracts of Reviews of Effects (DARE) Through 2009

, Issue 3 www.thecochranelibrary.com

E MBASE (Excerpta Medica) 1990

– July 13, 2009 OVID

Health Technology Assessment Database (HTA) Through 2009

, Issue 3 ww w.thecochranelibrary.com

Healthcare Standards Searched February 10, 2009 ECRI Institute

MEDLINE 1990

– July 13, 2009 Searches for some key questions not limited by date OVID

Pre MEDLINE Searched July 13, 2009 OVID

U.K. National Health Service Economic Evaluation Database (NHS EED) Through 2009

, Issue 3 www.thecochranelibrary.com

U.S. National Guideline Clearinghouse TM (NGC) Searched February 10, 2009 www.ngc.gov



### Hand Searches of Journal and Nonjournal Literature
Journals and supplements maintained in ECRI ’ s collections were routinely reviewed. Nonjournal publications and conference proceedings from professional organizations, private agencies, and government agencies were also screened. Other mechanisms used to retrieve additional relevant information included review of bibliographies/reference lists from peer

- reviewed and gray lite rature. (Gray literature consists of reports, studies, articles, and monographs produced by federal and local government agencies, private organizations, educational facilities, consulting firms, and corporations. These documents do not appear in the peer

- reviewed journal literature.)504 

### Grey Literature Searches
The following resources have been searched for information relevant to specific diagnostic tests:

Resource Date Limits Platform/Provider

Google (“CE Mark” OR “CE marked” OR registered) (test name) Sea rched August 8, 2009 www.google.com

Health Protection Agency Microbiological Diagnostics Ass essment Service Evaluations Searched August 7, 2009 www.hpa

- midas.org.uk

HealthC anada Searched August 8, 2009 http://www.hc

- sc.gc.ca/dhp

mps/index

- eng.php

Manufacturer W eb sites Searched August 8, 2009 www.abbottdiagnostics.co m

www.abbott.com
www.abbottdiagnostics.com.au

www.beckman.com

www.bio

- rad.com

www.biomerieux.com

www.biomerieux

- diagnostics.com

www.chiron.com

www.gen

- probe.com
www.innogenetics.be

www.orthoclinical.com

www.roche.com

www.roche

- diagnostics.com

www.siemens.com
www.diagnostics.siemens.com

National Serology Reference Laboratory Searched August 7, 2009 www.nrl.gov.au

U.S. Food and Drug Adm inistration (FDA) Web site Searched August 6, 2009 www.fda.gov

World Health Organization W eb site Searched August 7, 2009 www.who.int/en/505 

### Search Strategies
The search strategies e mployed combinations of free text keywords as well as controlled vocabulary terms including (but not limit ed to) the following concepts. The strategy below is presented in OVID syntax; the search was simultaneously conducted across EMBASE, MEDLINE , and Psy cINFO.

A parallel strategy was used to search the databases comprising the Cochrane Library.

Medical Subject Headings (MeSH), E MTREE and Keywords

Conventions:

OVID

$ = truncation character (wildcard)

exp = “explodes” controlled vocabulary term (e .g. , expa nds search to all more specific related terms in the vocabulary’s hierarchy)

/ = limit controlled vocabulary heading

.fs. = floating subheading

.hw. = limit to heading word

.md. = type of methodology (PsycINFO)

.mp. = combined search fields (default if no fields are specified)

.pt. = publication type

.ti. = limit to title

.tw. = lim it to title and abstract fields

Dialog

? = truncation character (wildcard)

! = “explodes” controlled vocabulary term (e. g. , expands search to all more specific related terms in the vocabulary’s hierarchy)

/de = limit controlled vocabulary heading

pt = publication type

/ti = limit to title

/ti,ab = lim it to title and abstract fields506 

### Topic

- specific Search Terms

Concept Controlled Vocabulary Keywords

Analytic validity Accuracy
Dia gnostic accuracy Exp diagnostic error/ Exp diagnostic errors/
Likelihood Observer variation
Precision Exp Prediction and forecasting/
Predictive value of tests Receiver operating characteristic ROC curve Sensitivity and specificity Accurate Accuracy
Anal ytic adj2 valid$
Borderline Concordance False negative False positive
Intraobserver
Intra

- observer
Interobserver
Inter

- observer Interpret$ Kappa
Likelihood Observer bias Observer variability Observer variation
Precision Predict$ Reader$
Reader concorda nce Receiver operating characteristic Reliab$ Repeatab$ Replicabil$
ROC True negative True positive Valid$ Window$ WPRT$

Diagnosis Exp diagnosis/ di.fs. (diagnosis) Diagnos$

Disease transmission Disease transmission/pc Disease transmission, horizontal/ pc Transmission.fs.507 Concept Controlled Vocabulary Keywords

Donors Cadaver Cadaver donor
Donor Kidney donor Living donor Living donors Organ donor Exp tissue/ Exp Tissue donors/ Exp Tissue and organ procurement/ Exp Transplantation

Classification.fs. Supply & distribution.fs. Donor$ Donat$

Epidemiology eh.fs. (ethnology) ep.fs. (epidemiology) prevalence exp United States/ Epidemiol$
Incidence Prevalen$
US.ti. United States USA.tw.

Risk Exp Anamnesis/ Behavioral risk factor surveillance system High risk behavior High risk patient High risk population Exp Medical history taking/
Medical record review
Medical records Exp Physical examination/ Population characteristics Risk factor Risk factors
Risk reduction behavior
Risk

- taking Sexual behavior Substance abuse, intravenous
Unsafe sex Behavio r Chart review Gaol Haemophilia$ Hemophilia$ High adj2 risk$ Intravenous drug$ IV drug$ Incarcerat$ Inmate$ Injectable drug$ Jail$
MSM Medical history Multiple adj2 partner$ Needle adj shar$ Patient history Penitentiary Prison$ Risk (in the title) Sex

S creening Exp Mass screening/ Exp screening/ Screen$508 Concept Controlled Vocabulary Keywords

Solid organ & tis sue transplantation Allotransplantation Exp organ transplantation/

Transplantation, homologous Tr.fs. (transplantation) Allograft$ Bone$ Bowel$ Composite vascular Cornea$ Face$ Hand$
H eart Homograft$ Intestin$ Kidney
Liver Lung$ Ovar$
Pancreas Solid organ
Testes Testicl$ Tissue$ Transplant$

Specific infections Communicable diseases Hepatitis antigens Hepatitis b Hepatitis c Exp hepatitis b antigen/ Exp hepatitis b antigens/ Exp hepat itis c antigens/ Exp HIV Infections/
HTLV

- 1 infections Exp human immunodeficiency virus Human immunodeficiency virus antigen Exp human immunodeficiency virus infections/ hepatitis Hepatitis B Hepatitis C HIV$
HBV HCV

Specific publications MMWR morbidity & mortality weekly report.jn.509 Concept Controlled Vocabulary Keywords

Testing DNA microarray Exp gene amplification/ Exp hybridization/ Exp in situ hybridization/ Microarray analysis Exp Microarray analysis/ Molecular diagnostic techniques Exp molecular probe/ Exp molecular probe techniques/
E xp nucleic acid amplification techniques/ Exp nucleic acid hybridization/ Serological tests ADVIA Centaur
AMRAD
anti

- p22 antibody test
Architect Assay$
AxSYM
Blot
Borderline Centaur COBAS Amplicor COBAS AmpliScreen Core Corecell haemagglutination
assay C ORZYME Coulter antigen Coulter p24 Elecsys Enzygnost Genetic$ adj System$
Genscreen HBsAG
HIVAB INNOTEST MATRIX HCV
Monolisa
Murex
NAT Nucleic acid amplification NucliSens

- AmpliScreen Occult Ortho ELISA PCR$
PRISM ProCleix Qiagen QIAmp
Roche combo
Roche m odular TaqMan Test$
Uni

- Form VERSANT HCV VIDAS DUO
Vironostika
Virus BioRobot
Vitros Window$ WPRT$510 Concept Controlled Vocabulary Keywords

Virus inactivation Exp *antiviral agents/ Exp*antivirus agent/
Virus inactivation

Organ perfusion Organ preservation exp Organ preservation/
Perfusion Tissue perfusion Tissue preservation Deactivat$ Inactivat$ Irrigat$511 

### Searches
Unless otherwise specified, all searches were limited to human popu lation and by date range 1990

– 2009.

Donor 1966

– 2009

Set Number Concept Search S tatement

1 Transplantat ion exp organ transplantation/

2 (((transplantation, homologous or allotransplantation).de. or tr.fs.) and (solid organ or heart or lung$ or kidney$ or liver or intestin$ or bowel$ or pancreas or face or hand$ or (composite adj vascular) or ovar$ or test es or testicl$))

3 Exp tissue transplantation/

4 Combine sets or/1

- 3

5 Donors exp tissue donors/ or exp tissue/ or living donors/ or donor/ or kidney donor/ or living donor/ or organ donor/ or cadaver donor/ or cadaver/

6 donor$.ti.

7 6 and (soli d organ or heart or lung$ or kidney$ or liver or intestin$ or bowel$ or pancreas or face or hand$ or (composite adj vascular) or ovar$ or testes or testicl$)

8 Combine sets or/5

- 7

9 Combine sets (tissue donors) 4 and 8

10 Specific infections exp HIV in fections/ or exp human immunodeficiency virus infections/ or exp hepatitis b antigens/ or exp hepatitis c antigens/ or exp hepatitis b antigen/ or (hepatitis b or hepatitis c or hepatitis c antigen).de. or (hepatitis adj (b or c) or HIV$)

11 Combine sets (Infections and tissue transplantation) 9 and 10

13 Limit by publication type 12 not (letter/ or editorial/ or news/ or comment/ or note/ or conference paper/ or (letter or editorial or news or comment).pt.)

14 Eliminate overlap Remove duplicates from 13512 

### Epidemiology (Q1) (2004

- 2009)

Set Number Concept Search S tatement

1 Specific infections exp HIV infections/ or exp human immunodeficiency virus infections/ or exp hepatitis b antigens/ or exp hepatitis c antigens/ or exp hepatitis b antigen/ or (hepati tis b or hepatitis c or hepatitis c antigen).de. or (hepatitis adj (b or c))

2 Epidemiology 1 and ep.fs.

3 1 and eh.fs.

4 1 and prevalence.de.

5 1 and (prevalen$ or incidence or epidemiol$).ti.

6 Combine sets or/2

- 5

7 Reviews 6 and review$.ti,de,p t.

8 RCTs

Narrow filter 6 and (random$.ti. or randomized controlled trial.pt.)

9 Limit by publication type 6 not (letter/ or editorial/ or news/ or comment/ or note/ or conference paper/ or case reports/ or (letter or editorial or news
or comment or case reports).pt.))

10 Systematic reviews

Broad filter 9 and ((research synthesis or pooled).mp. or review.ti,pt. or (systematic review or meta analysis or meta

- analysis).de. or ((evidence base$ or methodol$ or systematic or quantitative$ or studies).mp. and (review.de. or review.pt.)))

11 Eliminate overlap Remove duplicates from 10

The retrieval was still too large so we used another approach

12 5 and 11

13 Limit by region 12 and (exp United States/ or United States.tw. or us.ti. or usa.ti.)

14 HIV in fections as major topic Exp *HIV infections/ep,eh

15 Exp *human immunodeficiency virus infection/ep

16 Hepatitis infection as major topic *hepatitis b/ep or *hepatitis c/ep

17 Combine sets or/15

- 17

18 Systematic reviews

Broad filter 17 and ((research synthesis or pooled).mp. or review.ti,pt. or (systematic review or meta analysis or meta

- analysis).de. or ((evidence base$ or methodol$ or systematic or quantitative$ or studies).mp. and (review.de. or review.pt.)))

19 Limit by region 18 and (exp United S tates/ or United States.tw. or us.ti. or usa.ti.)513 Set Number Concept Search S tatement

20 Limit by concept 18 and prevalence.ti.

One more another approach

21 Limit by concept 17 and prevalence.ti.

22 21 and (hepatitis or HIV$ or HBV$ or HCV$).ti.

23 Limit by publication type 22 not (( letter or editorial or news or comment or case reports or note or conference paper).de. or (letter or editorial or news or comment or case reports).pt.)

24 Limit by region 23 and (exp United States/ or United States.tw. or us.ti. or usa.tw.)

25 Limit by publication 23 and mmwr morbidity & mortality weekly report.jn.

25 Author search (Armstrong$ and Wasley$ and Simard$).au.

26 Related articles search Find articles related to The prevalence of hepatitis C virus infection in the United States, 1999 throug h 2002514 

### Inactivation (Q 6 )

– includes animal population

Set Number Concept Search S tatement

1 Transplantation exp organ transplantation/

2 (((transplantation, homologous or allotransplantation).de. or tr.fs.) and (solid organ or heart or lung$ or kidney $ or liver or intestin$ or bowel$ or pancreas or face or hand$ or (composite adj vascular) or ovar$ or testes or testicl$))

3 Exp tissue transplantation/

4 (((transplantation, homologous or allotransplantation).de. or tr.fs.) and (tissue$ or bone$ or a llograft$ or homograft$))

5 Combine sets or/1

- 4

6 Organ donors ((exp tissue donors/ or exp tissue/) and organ procurement/) or (living donors or donor or kidney donor or living donor or organ donor).de.

7 donor$.ti.

8 7 and (solid organ or heart or l ung$ or kidney$ or liver or intestin$ or bowel$ or pancreas or face or hand$ or (composite adj vascular) or ovar$ or testes or testicl$ or tissue or bone or allograft$ or homograft$)

9 Combine sets 6 or 8

10 Combine sets 5 or 9

11 Specific infections e xp HIV infections/ or exp human immunodeficiency virus infections/ or exp hepatitis b antigens/ or exp hepatitis c antigens/ or exp hepatitis b antigen/ or (hepatitis b or hepatitis c or hepatitis c antigen).de. or (hepatitis adj (b or c)) or HIV$

12 Infe ctions and transplantation

Combine sets 10 and 11

13 Limit by publication type 12 not ((letter or editorial or news or comment or case reports or note or conference paper).de. or (letter or editorial or news or comment or case reports).pt.)

14 Virus inac tivation 13 and (Virus inactivation.de. or (inactivat$ or deactivat$).tw.)

15 13 and (Exp *antiviral agents/ or exp *antivirus agent/)

16 13 and irrigat$

17 Combine sets or/14

- 16

18 Eliminate overlap Remove duplicates from515 

### Hepatitis B (1966

– 200 9)

Set Number Concept Search S tatement

1 Hepatitis B Exp hepatitis b antigens/ or exp hepatitis b antigen/ or hepatitis b/ or hepatitis b or HBV

2 Diagnosis 1 and (exp diagnosis/ or di.fs. or receiver operating characteristic/ or ROC curve/ or sensitivit y and specificity/ or accuracy/ or diagnostic accuracy/ or precision or exp prediction and forecasting/ or likelihood or ((false or true) adj (positive or negative)) or predictive value of tests/)

3 Molecular testing (EMTREE) 2 and (exp molecular probe/ o r exp hybridization/ or exp molecular probe/ or exp gene amplification/ or Microarray analysis/ or DNA microarray/)

4 Molecular testing (MeSH) 2 and (molecular diagnostic techniques/ or exp molecular probe techniques/ or exp nucleic acid amplification tec hniques/ or exp nucleic acid hybridization/ or exp in situ hybridization/ or exp microarray analysis/)

5 Specific tests ((HBsAg adj2 (Elecsys or AxSYM or Architect or Centaur or Enzygnost or Vitros)) or AMRAD or NucliSens

- AmpliScreen or VERSANT HCV PRISM HCV or anti

- p22 antibody test or NAT or nucleic acid amplification technology or Cobas Amplicor or Qiagen QIAamp or Virus BioRobot or PCR or TaqMan or MATRIX HCV or western blot or corecell haemagglutination assay).mp,df, dm.

6 Combine sets or/3

- 5

7 Elim inate overlap Remove duplicates from 6

8 Limit by publication type 12 not ((letter or editorial or news or comment or case reports or note or conference paper).de. or (letter or editorial or news or comment or case reports).pt.)516 

### Risk (Q 3 and Q4 ) 7/2/09

Set Number Concept Search S tatement

1 Specific infections exp HIV infections/ or exp human immunodeficiency virus infections/ or exp hepatitis b antigens/ or exp hepatitis c antigens/ or exp hepatitis b antigen/ or (hepatitis b or hepatitis c or hepatitis c antigen).de. or (hepatitis adj (b or c) or HIV)

2 Donors ((exp tissue donors/ or exp tissue/) and organ procurement/) or (living donors or donor or kidney donor or living donor or organ donor or cadaver donor or cadaver).de. or donor$ or donat$

3 Risk (risk

- taking or risk reduction behavior or behavioral risk factor surveillance system or risk factors or population characteristics or sexual behavior or unsafe sex or substance abuse, intravenous).de.

4 (high risk behavior or risk factor or high risk p opulation or high risk patient).de.

5 (high adj2 risk$).ti. or (multiple adj2 partner$) or ((intravenous or iv or injectable) adj drug$) or (needle adj shar$) or hemophilia$ or haemophilia$ or incarcerat$ or prison$ or gaol or jail$ or inmate$ or MSM.tw.

6 Donor history (exp Medical history taking/ or exp Physical examination/ or exp Anamnesis/ or exp Physical examination/ or (medical records or medical record review ).de. or ((Medical or patient) adj history) or chart review)

7 Combine sets or/3

- 6

8 C ombine sets 1 and 2 and 6

9 Eliminate overlap Remove duplicates from 7

10 Limit by publication type 8 not ((letter or editorial or news or comment or case reports or note or conference paper).de. or (letter or editorial or news or comment or case reports ).pt.)

11 Limit by major concept 10 and (*risk factor/ or *risk factors/ or *risk

- taking/ or *high risk behavior/)

12 Limit by concept 10 and risk$.ti.

14 Limit by concept 10 and (behavio?r$ or sex$)

15 Combine sets 6 and 10

16 Combine sets or/11

- 15517 

### Screening

Set Number Concept Search S tatement

1 Specific infections exp HIV infections/ or exp human immunodeficiency virus infections/ or exp hepatitis b antigens/ or exp hepatitis c antigens/ or exp hepatitis b antigen/ or (hepatitis b or hepatitis c

o r hepatitis c antigen).de. or (hepatitis adj (b or c))

2 Screening 1 and (screen$.ti. or exp screening/ or exp mass screening/)

3 Limit by publication type 2 not ((letter or editorial or news or comment or note or conference paper).de. or (letter or edi torial or news or comment).pt.)

6 Eliminate overlap Remove duplicates from 5

7 Analytic validity of
tests 6 and (Analytic adj2 valid$)

8 Exp “prediction and forecasting”/

9 6 and 8

10 6 and ((predictive value of tests or receiver operating characte ristic or ROC curve or sensitivity and specificity or accuracy or diagnostic accuracy or precision or likelihood).de. or ((false or true) adj (positive or negative)))

11 6 and Valid$.ti,ab.

12 6 and ((intraobserver or intra

- observer or interobserver or inter

observer or interpret$ or kappa or observer bias or observer variability or reader$ or reader concordance or reliab$ or repeatab$ or replicat$).tw. or observer variation.de.)

13 Combine sets or/7,9

- 12

14 Donors 13 and ((Living donor or cadaver d onor).de. or exp Tissue donors/ or exp transplantation/ or donor$ or donat$)

15 exp “Tissue and organ procurement”/

16 Combine sets 13 and 15

17 Combine sets 14 or 16

18 Combine sets 13 not 17518 

### Specific Tests (Q5 )

Set Number Concept Search Statement

1 Genetics System (GS) HIV 1

- 1/HIV

- 2 Plus 0 EIA ((genetic$ adj system$) and ((HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$) or Bio

- Rad or Biorad).mp.) or (genetic$ adj system$).dv.

2 HIVAB HIV

- 1/HIV

- 2 (rDNA) EIA HIVAB$.mp,dv.

3 AxSYM (AxSYM and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

HB$ or anti

- HC$ or HBc$)).mp,dv.

4 ADVIA Centaur (ADVIA Centaur and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

5 PRISM (PRISM and (core$ or HIV$ or HBV$ or H CV$ or HbsAg or anti

HB$ or anti

- HC$ or HBc$)).mp,dv.

6 CORZYME (CORZYME and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

7 COBAS AmpliScreen ((COBAS and (core or AmpliScreen )) and (core$ or HIV$ or HBV$ or HCV$ or Hbs Ag or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

8 ProCleix HIV

- 1/HCV (ProCleix and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

9 VIDAS DUO ((VIDAS and DUO) and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

10 ARCHITECT (ARCHITECT and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

11 Genscreen (Genscreen and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

12 Murex (Mure x and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

HB$ or anti

- HC$ or HBc$)).mp,dv.

13 Enzygnost (Enzygnost and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

14 Vironostika ((Vironostika or Uni

- Form) and (core$ or HI V$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

15 INNOTEST (INNOTEST and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

16 Monolisa (Monolisa and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

17 Ortho ELISA v 3 (Ortho and ELISA and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

18 Coulter HIV

- 1 p24 Antigen Assay (Coulter and (antigen$ or p24) and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.519 Set Number Concept Search Statement

19 Modular HIV Combo (Roche and (modular or combo) and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

20 HCV EIA 2.0 (Abbot and EIA and 2$ and (core$ or HIV$ or HBV$ or HCV$ or HbsAg or anti

- HB$ or anti

- HC$ or HBc$)).mp,dv.

21 Combine sets or/1

- 20

22 Eliminate overlap Remove duplicates from 21

23 Limit by publication type 22 not ((letter or editorial or news or comment or case reports or note or conference paper).de. or (l etter or editorial or news or comment or case reports).pt.)

24 Limit to diagnosis & screening 23 and (screen$ or diagnos$.tw. or exp diagnosis/ or di.fs. or receiver operating characteristic.de. or ROC curve.de. or sensitivity and specificity/ or accuracy .de. or diagnostic accuracy.de. or precision or exp prediction and forecasting/ or exp diagnostic errors/ or exp diagnostic error/ or likelihood or ((false or true) adj (positive or negative)) or predictive value of tests.de.)

25 Window 23 and (window$ or WPRT$).tw.

26 Combine sets 24 or 25

27 23 and borderline$

28 Combine sets 26 or 27

29 23 and occult$

30 Combine sets 28 or 29