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April 23, 2012 

Recommendations for the Identification of Hepatitis C Virus (HCV) Chronic Infection

Among Persons Born during 1945 through 1965 

Disclaimer:

This information is distributed solely for the purpose of pre-dissemination public comment under 

applicable information quality guidelines. It has not been formally disseminated by the Centers 

for Disease Control and Prevention. It does not represent and should not be construed to 

represent any agency determination or policy." 
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Contents 

SUMMARY .................................................................................................................................... 4

INTRODUCTION .......................................................................................................................... 4

BACKGROUND ............................................................................................................................ 5

RATIONALE FOR AUGMENTING HCV TESTING .................................................................. 6

METHODS ................................................................................................................................... 12

Research Questions ................................................................................................................... 15

Prevalence Data ..................................................................................................................... 16

Patient-important Outcomes .................................................................................................. 16

RESULTS ..................................................................................................................................... 17

Review of HCV Infection Prevalence Data .............................................................................. 17

Patient-Important Outcomes ..................................................................................................... 17

All-Cause Mortality ............................................................................................................... 18

Hepatocellular Carcinoma .................................................................................................... 18

Failure to Achieve Sustained Virologic Response ................................................................. 18

Treatment-Related Serious Adverse Events ........................................................................... 19

Quality of Life ........................................................................................................................ 19

HCV Transmission ................................................................................................................. 19

Alcohol Use............................................................................................................................ 20

Determination of the Recommendations ...................................................................................... 20

Resource Implications ................................................................................................................... 21

RECOMMENDATIONS .......................................................................................................... 23

PUBLIC HEALTH TESTING CRITERIA .................................................................................. 23

TESTING METHODS.................................................................................................................. 24

PREVENTION MESSAGES........................................................................................................ 26

LINKAGE TO CARE AND TREATMENT ................................................................................ 26

FUTURE DIRECTIONS .............................................................................................................. 27

REFERENCES ............................................................................................................................. 28

APPENDICES .............................................................................................................................. 36

Appendix A. Acronyms Used in this Document .......................................................................... 37

Appendix B. Conflicts of Interest ................................................................................................. 39
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Appendix C. Analytic Framework ................................................................................................ 45

Appendix D. Search Strategy for HCV Prevalence ...................................................................... 46

Appendix E. Flow Chart for HCV Prevalence .............................................................................. 47

Appendix F. Search Strategy for Patient-Important Outcomes .................................................... 48 

Appendix G. Flow Chart for All-Cause Mortality ........................................................................ 50

Appendix H. Flow Chart for Hepatocellular Carcinoma .............................................................. 51

Appendix I. Meta-Analysis of the Effects of Treatment Response on Incidents of Hepatocellular 

Carcinoma ..................................................................................................................................... 52

Appendix J. Summary of Findings Tables .................................................................................... 53

Authors .......................................................................................................................................... 58
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Recommendations for the Identification of Hepatitis C Virus (HCV) Chronic Infection

Among Persons Born from 1945 through 1965 

SUMMARY 

Hepatitis C virus (HCV) causes substantial morbidity and mortality in the United States. Many 

of the 2.7-3.9 million persons living with HCV are unaware they are infected and do not receive 

care or potentially lifesaving treatment. To ensure that persons at greatest risk for 

hepatocellular carcinoma and other HCV-related liver disease are tested for HCV and linked to 

needed care and treatment if infected, the Centers for Disease Control and Prevention (CDC) is 

expanding its 1998 guidelines(1) to recommend testing of persons born during 1945 through 

1965, a population with a disproportionately high prevalence of HCV infection and related 

disease. Persons in this birth cohort account for three-fourths of all HCV infections in the United 

States(2) and 73% of HCV-associated mortality(3). With the advent of new therapies that can 

halt disease progression and provide a virologic cure (sustained viral clearance 24 weeks 

following completion of treatment) for many patients living with hepatitis C, testing and linkage 

to care of infected persons born 1945-1965 is expected to reduce HCV-related morbidity and 

mortality. CDC developed these recommendations with the assistance of a work group 

representing diverse perspectives. The recommendations are informed by the Grading of 

Recommendations Assessment, Development, and Evaluation (GRADE) methodology (4), an 

approach that provides guidance and tools to define the research questions, conduct the 

systematic review, assess the overall quality of the evidence, and determine the direction and 

strength of the recommendations. This report, which is intended to augment CDC’s 1998 

Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCVRelated Chronic Disease, will serve as a resource for health-care professionals, public health 

officials, and organizations involved in the development, implementation, and evaluation of 

prevention and clinical services.

INTRODUCTION

In the United States, an estimated 2.7-3.9 million persons (1.0%-1.5%) are living with 

hepatitis C infection (5), and approximately 20,000 persons are newly infected each year. 

Although effective treatments are available to eradicate hepatitis C virus (HCV) infection, most 

persons with HCV do not know they are infected therefore they do not receive needed care and

cannot be evaluated for treatment. HCV testing is a critical first step toward improving health 

outcomes for persons infected with HCV. 

Since 1998, routine HCV testing has been recommended for persons most likely to be 

infected with HCV. This determination is made on the basis of a known epidemiologic 

relationship between a risk factor and acquiring HCV infection, the prevalence of a risk behavior 

or characteristic in the population, the prevalence of infection among those with a risk behavior 

or characteristic, and the presence of a recognized exposure to HCV. 

These recommendations were developed by the Hepatitis C Virus (HCV) Birth Cohort 

Testing Work Group, which included experts from CDC and other federal agencies, professional 
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associations, community and advocacy groups, and medical associations. The Work Group 

employed the Grading of Recommendations Assessment, Development, and Evaluation 

(GRADE) methodology (4, 6-13) to inform recommendation development. The GRADE 

approach provides guidance and tools to define the research questions, conduct the systematic 

review, assess the overall quality of the evidence, and determine the direction and strength of the 

recommendations. Following this evidence review, CDC’s Division of Viral Hepatitis (DVH) 

developed this report, which was then peer-reviewed by external experts and was posted for 

public comment. 

These birth-year-based recommendations are intended to augment the 1998 HCV testing 

guidelines. CDC currently is conducting systematic reviews of risk-based and medical 

indication-based screening and testing guidelines and will publish updated, comprehensive 

recommendations for the identification and prevention of HCV infection when this process is 

completed. Moving forward, these comprehensive recommendations will be reviewed every 5 

years and updated to include advances in the published evidence. 

BACKGROUND

HCV causes acute infection, which may be characterized by mild to severe illness but is 

usually asymptomatic. In approximately 75%-85% of persons, HCV persists as a chronic 

infection, placing infected persons at risk for hepatocellular carcinoma (HCC), cirrhosis, and

extrahepatic complications that develop over the decades following onset of infection (14). 

Because HCV is a bloodborne infection, risks for HCV transmission primarily are 

associated with exposures to contaminated blood or blood products (1). In 1998, the highest 

prevalence of antibody to HCV (anti-HCV) was found among persons with substantial or 

repeated direct percutaneous exposures, such as persons who inject drugs, persons who received 

blood from infected donors, and persons with hemophilia (60%-90%); moderate rates were

found among those with repeated direct or unapparent percutaneous exposures involving smaller 

amounts of blood, such as hemodialysis patients (10%-30%). Persons with unapparent 

percutaneous or mucosal exposures, including those with high-risk sexual behaviors, sexual and 

household contacts of persons with chronic HCV infection (1%-10%), and persons with sporadic 

percutaneous exposures (e.g., health-care workers [1%-2%]) had lower rates. The lowest rates of 

anti-HCV occurred among persons reporting no high-risk characteristics (e.g., volunteer blood 

donors [0.3%]). 

 Prior to 1965, the estimated annual incidence of HCV infection (then known as Non ANon B hepatitis) was low (18 cases per 100,000 persons). However, due to increasing injection 

drug use (IDU) and increased use of blood and blood products for transfusion, the incidence of 

HCV infection increased steadily into the 1980s and remained high (130 cases per 100,000 

population), representing an average of 230,000 infections per year during that decade (15). In 

1988, HCV was identified, and by 1992, sensitive multiantigen serologic assays for testing the 

blood supply had been developed and licensed. From 1992 – 2004, the number of reported cases 

of new HCV infection decreased 78.4% (16), a decline attributed largely to a decrease in cases 

among persons who inject drugs (PWID).(17) Safer injection practices among PWID 

contributed to some of this decline, but the downward trend was most likely related to HCV 

infection saturation of the injection drug-using population.(17) A smaller proportion of the 
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overall decline in HCV infection incidence was attributed to effective screening of blood donors 

to prevent HCV transmission. Most of the declines in HCV incidence occurred in the 1990s. 

Since 2004, HCV incidence has remained stable (17). In 2009, the estimated number of newly 

acquired (i.e., acute) infections in the United States was 16,000 (16, 18). Among American Red 

Cross Blood Service systems in the United States, prevalence among first time blood donors has 

decreased by 53% from 0.35% in 1999 to 0.16% in 2008.(19)

The overall prevalence of anti-HCV in the general population of the United States can be 

estimated by analyzing the National Health and Nutrition Examination Survey (NHANES) data, 

a representative sample of the civilian non-institutionalized population. NHANES data indicate 

that HCV infection prevalence did not change from 1988 through 2002 (1.6%-1.8%), consistent 

with the finding that the incidence of infection declined and then remained stable during this 

time period (5, 15, 17, 20). The anti-HCV prevalence estimate has been lower in recent years, at 

1.3%1 during 2005-2008 (21), representing an estimated 3.61 million anti-HCV positive persons 

(95% CI= xx-xx

1

); of these persons, 2.81 million (95% CI=xx-xx

1

) are chronically infected. 

NHANES data underestimate the actual national prevalence, because these surveys do not 

include samples of incarcerated or homeless persons, populations known to have high prevalence 

of HCV infection. Although there are no systematic surveys comparable to NHANES that 

sample these populations, their inclusion would likely increase the estimated number of infected 

persons by about 500,000(22). 

RATIONALE FOR AUGMENTING HCV TESTING RECOMMENDATIONS

In 1998, recommendations for identifying HCV-infected persons were issued as part of a 

comprehensive strategy for the prevention and control of HCV infection and HCV-related 

chronic disease (1). HCV testing was recommended for patients at high risk of HCV infection, 

including persons who 1) had ever injected drugs, 2) were ever on chronic hemodialysis, 3) 

received blood transfusions or organ transplants prior to July 1992, or 4) received clotting factor 

concentrates produced prior to 1987. Screening also was recommended for persons who had a 

recognized exposure (healthcare, emergency medical, and public safety workers after needle 

sticks, sharps, or mucosal exposures and children born to HCV-infected mothers) and persons 

with laboratory evidence of liver disease (persistently elevated alanine aminotransferase levels). 

In 1999, HCV testing was recommended additionally for persons infected with human 

immunodeficiency virus (HIV). (23) 

Limited Effectiveness of Current Testing Strategies

Current risk-based testing strategies have met limited success, as evidenced by the 

substantial number of HCV-infected persons who remain unaware of their infection (24). 

Estimates of the proportion of U.S. adults who are chronically infected yet unaware of their HCV 

infection status range from 45%-85% (25-28) depending on setting, risk level in the population, 

and site-specific testing practices. Even among high-risk populations for whom routine testing is 

recommended, testing for HCV seromarkers is variable (25, 26), and a sizeable percentage of 

these persons remain unaware of their infection status (29). Inadequate health insurance 

coverage and limited access to regular health care pose barriers to HCV testing and 

 

1 These estimates will be revised when updated surveillance data become available.
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diagnosis(28); however, even among the well insured, risk-based testing practices have not been 

successful in identifying most HCV-infected persons (27). 

A more significant barrier to the success of the risk-based approach to HCV testing 

occurs at the provider level. Many providers lack knowledge about hepatitis serology and

treatment; studies have shown that providers’ level of knowledge regarding HCV infection 

prevalence, natural history, available tests, and testing procedures is low (30-33). Although upto-date professional guidelines on HCV testing are available from the American Academy of 

Family Physicians (AAFP) (34) and the American Association for the Study of Liver Disease 

(AASLD)(14, 35), 41.7% of primary care physicians reported they were unfamiliar with them 

(36). Physicians’ reluctance to assess risk factors also contributes to low testing rates; fewer than 

half of all U.S. physicians ask their patients sensitive questions related to high-risk behaviors 

(e.g., IDU) (31). In addition, accuracy of patient recall of risk behaviors, including drug use and 

sexual encounters, decreases over time (37). 

Increasing Morbidity and Mortality

HCV-associated disease is the leading indication for liver transplantation and a leading 

cause of HCC in the United States (24, 38-40). HCC and cirrhosis have been increasing among 

persons infected with HCV (41, 42), and these outcomes are projected to rise substantially in the 

coming decades (43, 44). Annual HCV-related mortality in the United States now outpaces that 

of HIV. A CDC review of death certificate data found that the hepatitis C mortality rate 

increased significantly from 1999-2007 (annual mortality rate change: +0.18 deaths/100,000 per 

year). In 2007, HCV caused 15,106 deaths, whereas the number of deaths from HIV declined to 

12,734 (3). Of the HCV-related deaths, 73.4% occurred among persons aged 45-64 years.

Incidence of HCC is increasing significantly in the United States representing the fastest growing 

cause of cancer-related mortality, and infection with HCV accounts for more than 50% of 

incident HCC (45). 

Data for observed HCV disease progression over a 20-year period indicate that 20% of 

infected persons will progress from fibrosis to cirrhosis and as many as 5% will die from HCVrelated liver disease. (46) Modeling studies have forecasted substantial increases in morbidity 

and mortality among HCV-infected persons as they progress into their third, fourth, and fifth 

decades living with the disease (47, 48). Over the next 40-50 years, these models project that 

1.76 million (60.7%) persons with untreated HCV infection (44) will develop cirrhosis, with a 

peak prevalence of 1 million cases occurring from the mid-2020s through the mid-2030s (44); 

approximately 400,000 will develop HCC (44). Of persons with hepatitis C who do not receive 

needed care and treatment, approximately 1 million will die from related complications (44, 49). 

Benefits of HCV Diagnosis and Care

Clinical preventive services, regular medical monitoring, and behavioral changes can 

improve health outcomes for persons with HCV infection. Because co-infection with HIV and 

consumption of alcohol (51) hasten the progression of HCV (50), professional practice 

guidelines for hepatitis C management issued by AASLD (14) include counseling to decrease or 

eliminate alcohol consumption and hepatitis A virus (HAV) and hepatitis B virus (HBV)

vaccination for susceptible persons (14). Additional guidance from AASLD includes: 1) 
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counseling and education to reduce interactions between herbal supplements, over-the-counter, 

and prescription medications (14, 50) and 2) counseling to encourage weight loss for persons who 

are overweight to reduce the likelihood of insulin resistance and disease progression (14, 52). 

Excess weight has been linked to increased disease progression among HCV-infected persons 

(51). As HCV-associated liver disease progresses, the likelihood of sustaining a treatment 

response decreases (52, 53); therefore, early clinical evaluation and linkage to care are critical

interventions. 

Benefits of HCV Treatment 

AASLD recommendations, endorsed by the Infectious Disease Society of America 

(IDSA) and American Gastroenterological Association (AGA), propose antiviral treatment for 

persons with histological signs of bridging fibrosis, septal fibrosis, or cirrhosis. In May 2011, the 

first generation of new direct-acting antiviral agents (DAAs), the HCV NS3/4A protease 

inhibitors telaprevir and boceprevir, were licensed for clinical use in the United States. 

Compared with conventional pegylated interferon and weight-based ribavirin therapy alone, the 

addition of one of these two protease inhibitors to the standard treatment regimen in clinical 

trials increased sustained virologic response (SVR) rates from 44% to 75% and 38% to 63%, 

respectively, in persons with HCV genotype 1(the most common genotype in the United States) 

(54, 55). Persons who achieve an SVR after treatment have a substantial reduction in risk for allcause mortality (54%) (56) and substantially lower rates of liver-related death and 

decompensated cirrhosis (57, 58). Given the recent introduction of these new treatment 

regimens, the long-term effects of treatment in every day clinical practice remain to be 

established, and the benefits may be different in community settings. In addition to the new 

FDA-approved medications, there are currently 22 new HCV treatments (protease and 

polymerase inhibitors) in Phase II or Phase III clinical trials, (59) and treatment 

recommendations are expected to change as new medications are available for use in the United 

States. 

CONSIDERATION OF A NEW HCV TESTING STRATEGY

Given the limited effectiveness of the current risk-based HCV testing recommendations, 

CDC has evaluated alternative public health strategies for increasing the proportion of infected 

persons who know their HCV infection status. Several analyses of nationally representative data 

have found a disproportionately high prevalence of HCV infection among persons who were 

born between the mid-1940s and the mid-1960s. In an analysis of 1988-1994 National Health 

and Nutrition Examination Survey (NHANES) data, 65% of persons with HCV infection were 

30-49 years of age (20), roughly corresponding to this birth cohort. In an analysis of NHANES 

data from 1999-2002, a similarly high proportion of all persons with HCV antibody had been 

born from 1945 through 1964 (Figure 1) (5). A recent analysis of 1999-2008 NHANES data 

found that the prevalence of HCV among persons in the 1945-1965 birth cohort was 3.25% 

(95%CI, 2.80 to 3.76); persons born during these years accounted for over three fourths (76.5%) 

of the total anti-HCV prevalence in the United States (2). Given the disproportionately higher 

prevalence among persons born during these years, CDC evaluated multiple birth cohorts within 

these years for targeted HCV testing. 
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Selection of a Target Birth Cohort

To select a target birth cohort for an expanded testing strategy, CDC examined the 

prevalence, proportion of burden, race/ethnicity and sex stratifications for seven birth cohorts of 

differing intervals (Figure 1). The 1945-1965, 1950-1970, and 1945-1970 cohorts captured the 

population with the most anti-HCV prevalence, whereas the 1950-1965 and 1950-1960 cohorts 

included persons born in years with the highest HCV prevalence. The 1945-1949 and 1966-1970 

birth cohorts represent the tails of the prevalence curve and were examined separately to consider 

how wide the birth cohort should extend. The weighted, unadjusted anti-HCV prevalence and 

estimates of the size of the chronically infected population within each proposed birth cohort 

were determined (Table 1). 

Figure 1. Prevalence of hepatitis C virus antibodies by age group (A) and year of birth (B). 
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Table 1. Prevalence rates and burden of hepatitis C virus (HCV) infection, by seven birth cohorts 

Proposed 

birth 

cohort 

Anti-HCV 

prevalence* 

(weighted, 

unadjusted)

Current U.S. 

population 

(in millions)†

Number of 

anti-HCV 

positive 

persons (in 

millions)

Number of 

chronically 

infected 

persons (in 

millions)§

Proportion of 

infected 

population 

identified

1945-1965 3.27% 78.8 2.58 1.94 75.9%

1950-1970 3.22% 86.1 2.77 2.08 78.4%

1945-1970 2.98% 98.8 2.94 2.21 84.7%

1950-1965 3.65% 66.1 2.41 1.81 67.9%

1950-1960 4.04% 44.2 1.79 1.34 52.3%

1945-1949 1.65% 12.7 0.21 0.16 7.1%

1966-1970 1.77% 20.0 0.35 0.26 9.7%

*Unpublished data from National Health and Nutrition Examination Survey (NHANES) 1999-2008 data. Prevalence not 

adjusted by age or other covariates. 

†

Source: U.S. Census Bureau. Current Population Reports: Population Projections of the U.S. by Age, Sex, Race, and Hispanic

Origin: 1995 to 2050, P25-1130.

§

75% of anti-HCV positive persons are estimated to be chronically infected.

 

On the basis of prevalence rates and burden, the 1945-1965 birth cohort was selected as 

the target population. Because this cohort included the 1950-1965 and the 1950-1960 cohorts, 

these were eliminated from further consideration. The three remaining cohorts (1945-1965, 

1950-1970, and 1945-1970) each represented a substantial proportion of the population and a 

substantial proportion of the infected population. Further, only minimal differences in the antiHCV prevalence, number of anti-HCV positive persons, and number of chronically infected 

persons were observed. The three cohorts were additionally stratified by race/ethnicity and 

gender (Table 2). The differences in the male to female ratio were insignificant and do not drive 

the selection decision. However, the difference in prevalence by race/ethnicity between the birth 

cohorts is substantial. Both the 1950-1970 and 1945-1970 cohorts have a lower prevalence of 

HCV-infected non-Hispanic black populations than the 1945-1965 cohort. Because non-Hispanic 

black populations have a greater prevalence of HCV infection than their white counterparts, a 

testing strategy based on the 1945-1965 cohort was selected to enable this health disparity to be 

addressed. Of the 210,000 anti-HCV positive persons in the 1945-1949 cohort, approximately 

71,000 (35%) are African American.
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When examining testing strategies using the 1945-1970 birth cohort versus the 1945-

1965 birth cohort, the health impact (identifying ~260,000 chronic cases) did not justify the 

increased costs ($800 million) associated with the 1945-1970 birth cohort. Also, the cost per 

chronic case identified for the 1945-1965 compared with the 1945-1970 birth cohort ($2,874 vs. 

$3,161) and the number needed to screen to avert a single HCV-related death in the 1945-1965 

birth cohort compared with the 1945-1970 birth cohort (607 vs. 679) were lower in both 

instances. Data collected through CDC consumer testing also supported use of the 1945-1965 

birth cohort. Such testing demonstrated that the 1945-1965 birth cohort is a recognized subpopulation understood as the “baby boomers;” familiarity with this sub-population and the term 

used to describe it likely will facilitate adoption of the recommendation. Based on these 

assessments, CDC selected the 1945-1965 birth cohort as the target population. 

The confluence of the high incidence of HCV infection in the relatively remote past, the 

high prevalence of chronic infection, and a long period of subclinical infection (2, 60) contribute 

to a large proportion of persons who remain unaware of their HCV infection status. Taken 

together, these factors create a unique and challenging public health situation: an age wave of 

persons progressing through time who are at increasing risk for severe liver disease that is 

preventable by appropriate testing, care and treatment. 

HCV Infection Prevalence in the 1945-1965 Birth Cohort 

Although the prevalence of anti-HCV in the U.S. population is an estimated 1.6% (5), it 

is about two times higher among persons born from 1945 through 1965 (3.25%). Among persons 

born outside the cohort, prevalence is substantially lower (0.88%). The high prevalence among 
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persons in this birth cohort reflects the substantial number of new infections that occurred 

throughout the 1970s and 1980s and the high likelihood of HCV persisting chronically. Males in 

this cohort had almost twice the prevalence as their female counterparts; HCV infection 

prevalence was highest among non-Hispanic black males (8.12%), followed by non-Hispanic 

white males (4.05%) and Mexican-American males (3.41%). 

Complicating health outcomes among HCV-infected persons born during 1945-1965 are 

a lack of health insurance (31.5%) and use of alcohol. Of all anti-HCV positive persons in the 

1945-1965 birth cohort who self-reported alcohol use, 57.8% reported drinking an average of 

two or more alcoholic drinks per day. 

METHODS

In April 2011, the HCV Birth Cohort Testing Work Group convened to explore the 

practicality of developing a recommendation for one-time HCV testing for persons unaware of 

their infection status. While the epidemiologic data exist to support the consideration of a birth 

year testing strategy, a formal review of the literature was needed to examine the effect that this 

testing would have on diagnosing persons unaware of their HCV infection status, as well as the 

potential benefits and harms that this strategy would have on persons tested. The HCV Birth 

Cohort Testing Work Group consisted of 1) a steering committee in the CDC Division of Viral 

Hepatitis (DVH), which led and conducted the evidence reviews; 2) an internal (to DVH) work 

group (consisting of representatives from DVH’s Laboratory Branch and from the DVH

Prevention and Epidemiology and Surveillance Branches), which was tasked with reviewing and 

providing input on the evidence compiled by the steering committee through biweekly meetings; 

and 3) an external (to CDC) work group that provided input on materials compiled by the 

steering committee through regular teleconferences, an evidence grading methodology training 

workshop, and a consultation. The external work group members were identified by their

involvement in hepatitis- and recommendation-specific activities (e.g., publications, hepatitis C 

advocacy group representation, self-identified HCV infection, and relevant federal agency 

appointments) and included members from a wide range of disciplines, organizations, and 

geographic regions, including 

• federal organizations (Agency for Healthcare Research and Quality, National 

Cancer Institute, Food and Drug Administration, Veteran’s Affairs, Health 

Resources and Services Administration, Substance Abuse and Mental Health 

Services Administration, and National Institute of Diabetes Digestive and Kidney 

Diseases), 

• professional associations (e.g., the American Medical Association and the 

American Academy of Family Physicians),

• community and advocacy groups (e.g., the Adult Viral Hepatitis Prevention 

Coordinator program and the National Viral Hepatitis Roundtable), and 

• medical specialty associations (e.g., AASLD and AGA).

Several subject matter experts (e.g., hepatologists, economists, and guideline 

methodologists) also served as members of the external group. All HCV Birth Cohort Testing 

Work Group participants were required to disclose conflicts of interest (if any) and were notified 
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of the restrictions regarding lobbying during the recommendation development process 

(Appendix B: Conflicts of Interest). No members’ activities were restricted based on the 

information disclosed. 

Comprehensive systematic reviews of the literature were conducted, analyzed, and 

assessed in two stages to examine the availability and quality of the evidence regarding HCV 

infection prevalence and the effects of one-time HCV testing for persons unaware of their status.

HCV Birth Cohort Testing Work Group members communicated through regular 

teleconferences, an in-persons GRADE methodology workshop, and a consultation. Initial 

evidence from the systematic review of the prevalence data was shared during the 

teleconferences and the birth years, 1945-1965, were selected. Following that selection, the 

systematic review focused on the effects of testing persons born during 1945 through 1965 for 

HCV infection, which were presented at the consultation. 

In August 2011, CDC convened a 2-day consultation with HCV Birth Cohort Testing 

Work Group members to review and evaluate the quality of the evidence of effectiveness of the 

proposed strategy of one-time testing of all members of the 1945-1965 birth cohort, consider 

benefits versus harms of patient-important outcomes (Appendix J: Summary of Findings Tables), 

weigh the variability between the values and preferences of HCV testing among potential 

patients, and consider resource implications. During the consultation, presentations were given to 

review the rationale for these recommendations, population-level data on the prevalence of HCV 

infection among persons born from 1945 through 1965, and the results of the systematic reviews 

conducted to determine the benefits and harms of the patient-important outcomes. For each 

patient-important outcome, a summary of findings table with an analysis of the quality of the 

evidence was presented to consultation attendees for discussion (Appendix J: Summary of 

Findings Tables). At the conclusion of the consultation, work group members provided input on 

the quality of the evidence and strength of the recommendations. Following the consultation, the 

DVH Steering Committee and Internal CDC Work Group reviewed all of the information and 

reached a decision regarding the strength of the recommendations. At that time, a

recommendations statement and qualifying remarks were developed in accordance with GRADE 

methodology. 

External feedback from the public was solicited through conference presentations, 

meetings with national stakeholders, peer review, and public comment2

. External HCV Birth 

Cohort Testing Work Group members were asked to comment on the recommendations 

statement and remarks during the public comment process. Feedback was reviewed by the CDC 

Steering Committee and the draft was modified accordingly. Throughout the development 

process, CDC also sought input from participants at national conferences, including AASLD’s 

2011 Single Topic Conference, the 2010 Annual Meeting of the American Public Health 

Association, the 2010 AASLD Conference, and the 2011 Guidelines International Network 

Conference. 

GRADE Methodology 

 

2 This document will be made available for public comment after clearance and this section will be revised to 

include specific dates of that process. 
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These recommendations were developed using GRADE methodology (4, 6-13). The GRADE 

methodology has been adopted by over 60 organizations, including CDC federal advisory 

committees (i.e., the Advisory Committee on Immunization Practices [ACIP] [63] and 

Healthcare Infection Control Practices Advisory Committee [HICPAC]), the World Health 

Organization (WHO), the Infectious Disease Society of America (IDSA), AGA, and the 

Cochrane Collaboration (www.gradeworkinggroup.org). GRADE provides guidance and tools to 

define research questions, develop an analytic framework, conduct systematic reviews, assess the 

overall quality of the evidence, and determine the direction and strength of the recommendations. 

Research questions were formulated to guide the development of the recommendation using 

a population, intervention, comparator, and outcome (PICO) format. The research questions 

were developed to support a two-stage approach to the evidence review: 1) to determine the 

baseline risk of HCV infection and 2) to measure the effects of an intervention (i.e., patientassociated benefits and harms). 

Per the GRADE process, the HCV Birth Cohort Testing Work Group designed an analytic 

framework (Appendix C: Analytic Framework), which was used to examine patient-important 

outcomes associated with each step of the testing effort, from the identification of the target 

population to the treatment of persons found to be infected with HCV. 

To measure the benefits and harms of HCV screening and treatment, patient-important 

outcomes were compiled. These outcomes were ranked, each according to its relevance to the 

recommendation (a rating of 1-3 being of low importance; 4-6 being important but not critical to 

decision making; and 7-9 as critical to decision making). Literature reviews were conducted on 

outcomes identified as important or critical to decision making. Work group members had three 

opportunities to rank the outcomes: 1) when the outcomes were first identified, 2) after the 

evidence was presented, and 3) during the discussion of the benefits and harms, allowing the 

work group to weigh the relative importance of the outcomes based on the evidence presented 

and the benefits and harms. 

The quality of the evidence for each patient-important outcome was assessed collectively

by individual outcome, not by individual studies, in the GRADE profiler software (GRADEpro 

3.6). The quality of the evidence was categorized as being “high,” “moderate,” “low,” or “very 

low” depending on the established criteria for downgrading or upgrading the quality. Studies 

were downgraded if they met at least one of the following five criteria: 1) risk of bias; 2) 

inconsistency or heterogeneity; 3) indirectness; 4) imprecision; or 5) publication bias. 

Conversely, studies were upgraded if they met any of three criteria: 1) large effect size; 2) doseresponse; or 3) plausible confounders (i.e., when biases from a study may be working to 

underestimate an apparent intervention effect) (Appendix J: Summary of Findings Tables). 

Outcomes were re-ranked for importance after consideration of evidence by the work group 

members. 

The following four factors were considered when determining the relevance and strength 

of a GRADE-based recommendation: 1) quality of evidence, 2) balance between benefits and 

harms, 3) values and preferences, and 4) resource implications. During the consultation, the 

HCV Birth Cohort Testing Work Group considered each of these factors in light of the evidence 

presented. A statement based on the direction and strength of the recommendation was 
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developed using the GRADE criteria; statements were either “for” or “against” an intervention 

and were either strong (designated by a “should” statement) or conditional (designated by a “may 

consider” statement). 

Research Questions

 To facilitate a succinct, systematic review of the evidence, the HCV Birth Cohort Testing 

Work Group developed several review questions (Box 1) to be considered when examining 

prevalence data and patient-important outcomes (Appendix C: Analytic Framework); review 

questions were aligned with the analytic framework and were formed in accordance with PICO. 

The division of these questions into two topics, prevalence data and patient-important outcomes, 

reflects the two-stage approach that was used to 1) define the testing strategy and birth years of 

interest, and 2) to examine the effects of testing persons born during 1945 through 1965 for HCV 

infection. Because the patient-important outcomes questions encompass a multitude of 

outcomes, they are formed without listing one specific outcome; they present only the 

population, intervention, and comparator. 

Box 1. Research questions 

Literature Review

The DVH steering committee evaluated current HCV testing guidelines (1, 14, 61-65), 

reviewed existing scientific evidence, and conducted systematic-reviews and meta-analyses to 

synthesize the evidence available on the review questions. This evidence was compiled and 

presented to the Hepatitis C Virus Birth Cohort Testing Work Group throughout the development 

process. 

The systematic review process for these recommendations was separated into two stages: 

1) a review of HCV infection prevalence to determine the effect of a birth-year testing strategy, 

and 2) a review of the patient-important outcomes to understand the effect of a testing

intervention for persons born from 1945-1965. Search strategies varied for each stage; however, 

following the initial collection of results from the search, titles and abstracts were reviewed by 

two persons. If disagreement on the inclusion of an article occurred, an independent third 

Prevalence Data

1. What is the effect of a birth-year based testing strategy versus the standard of care (i.e., 

risk-based testing) among persons for HCV infection?

Patient-Important Outcomes

1. Should HCV testing followed by antiviral treatment versus no testing (or failed treatment) 

be conducted among persons born from 1945 through 1965?

2. Should HCV testing versus no testing be used in average risk adults born from 1945 

through 1965?

 

 
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reviewer decided whether the article would be included. For the titles and abstracts that met the 

inclusion criteria, the full article was retrieved and reviewed. Information from the full articles 

was extracted for the GRADE profiles to conduct the meta-analyses. 

Prevalence Data

During the first stage of the review, the effect of a birth-year-based screening strategy for 

persons infected with HCV was considered. The goal of the review was to determine if prior 

literature addressed a birth-year-based strategy or provided additional support for the prevalence 

estimates (see Selection of a Target Birth Cohort). The DVH steering committee reviewed all 

literature regarding the effect of a birth-year-based testing strategy for HCV infection that had 

been published after CDC’s 1998 recommendation. To be selected for review, articles had to 

have been published from 1995 through 2011, describe results of U.S.-based studies, and include 

participants within the birth cohort. Case studies were excluded, as well as studies of persons coinfected with HBV or HIV. Seven databases were searched for primary research, including grey 

literature and conference abstracts: Pubmed/Medline, Embase, Sociological Abstracts, Cochrane 

(e.g., Database of Systematic Reviews, Central Register of Controlled Trials, and Economic 

Evaluation Database), CINAHL, Database of Abstracts of Reviews of Effects, and the New York 

Academy of Medicine (Appendix D: Search Strategy for HCV Prevalence Review). 

Patient-important Outcomes

A literature search for the effect of patient-important outcomes on persons tested and 

treated for HCV was conducted in PubMed. A search of previously published systematic reviews 

and meta-analyses was conducted initially and used to address the patient-important outcomes 

when available and of high quality. When systematic reviews or meta-analyses were

unavailable, primary studies were sought and added to the results (Appendix F: Search Strategy 

for Review of Patient-Important Outcomes). When possible, data from primary studies were 

entered into systematic review software (Review Manager, 2008) to produce meta-analyses for 

estimation of effect sizes. Otherwise, effect size data were extracted directly from published 

meta-analyses. 

 The selection criteria for the primary literature search included intervention studies (i.e., 

controlled trials, cohort studies, and case-control studies) conducted world-wide, published 

during 1995 through 2011 in English. Case studies were excluded, along with studies of 

transplant recipients and persons co-infected with HBV or HIV. To be selected, studies needed to 

present data inclusive of persons born during 1945 through 1965. Because protease inhibitors 

(PIs) have only recently been licensed, evidence was insufficient on their long-term effect on the 

patient-important outcomes. Therefore, only studies providing treatment regimens with 

Pegylated Interferon (with and without Ribavirin) or Interferon (with or without Ribavirin) were 

examined.

Separate, targeted literature reviews were conducted for those outcomes given ratings of 

4 or higher by the group; these outcomes included 

• all-cause mortality;

• HCC; 

• sustained viral response (SVR) (a marker of virologic cure); 
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• serious adverse events (i.e., treatment-related side effects); and

• quality of life;

• HCV transmission; and

• brief alcohol interventions. 

A systematic, targeted review was conducted to examine potential harmful and beneficial 

patient-important outcomes associated with HCV testing and treatment. A similar review also 

was conducted to examine reduction or cessation of alcohol use associated with strategic brief 

interventions provided to persons identified as HCV-infected. Only those outcomes considered 

critical to decision making (i.e., all-cause mortality, HCC, SVR, treatment-related serious 

adverse effects, quality of life, HCV transmission, and alcohol use) were graded on their quality 

and used to inform the strength of the recommendations. 

RESULTS

Review of HCV Infection Prevalence Data

Of the 10,619 articles that met the search criteria for the HCV infection prevalence 

review, 31 papers provided data on HCV infection prevalence by birth year (Appendix E: Flow 

Chart for HCV Prevalence). Three of those papers (5, 20, 66) examined nationally 

representative data from NHANES. Compared with the other 28 articles, the quality of the 

nationally representative, population-based NHANES data was much higher; for this reason, 

NHANES data from 1999 through 2008 were used to determine the most efficacious birth years 

to target when testing persons for HCV infection. The NHANES analysis revealed a 3.25% 

prevalence of anti-HCV among persons born during 1945 through 1965 (95%CI, 2.80-3.76). 

Persons in the birth cohort are five times more likely than persons outside of the birth cohort to 

be anti-HCV positive (2). Infected persons in the 1945-1965 birth cohort represent 76.5% of all 

adults living with HCV infection in the United States.

Prevalence data for the 1945-1965 birth cohort were presented to the HCV Birth Cohort 

Testing Work Group early in the development process. The results were reviewed again during a 

discussion of patient-important outcomes at the consultation.

Patient-Important Outcomes

Of the patient-important outcomes determined to be either important or critical for 

decision making (see GRADE Methodology), evidence was found in the literature on all-cause 

mortality, HCC, SVR, serious adverse events, quality of life, and alcohol use. However, for 

several other important or critical outcomes (i.e., HCV transmission, insurability, reassurance of 

testing negative, false reassurance of testing negative, and worry or anxiety caused by testing 

true positive), no studies examining their importance and relevance to a birth cohort 

recommendation could be identified. 

At the consultation, the Hepatitis C Virus Birth Cohort Testing Work Group re-ranked the 

patient-important outcomes based on the findings from the literature and determined that while 

evidence about HCV transmission was not available, it remained critical to decision-making and 
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would still be considered as evidence. The relative importance of the outcomes associated with 

insurability, reassurance of testing negative, false reassurance of testing negative, and worry or 

anxiety caused by testing true positive were re-ranked based on the evidence and the benefits and 

harms (Appendix J: Summary of Findings Tables). While these outcomes were not presented in 

the evidence table, they were considered when determining the balance of benefits and harms. 

All-Cause Mortality 

Previously published systematic reviews and meta-analyses did not provide all-cause 

mortality information relevant to this population, so a systematic review was carried out 

(Appendix F. Search Strategy for Patient-Important Outcomes). A total of 22 published articles 

examined all-cause mortality among persons tested and treated for HCV infection (Appendix G: 

Flow Chart for All-Cause Mortality). However, a review of the full articles and meta-analysis of 

the extracted data revealed weaknesses in most of these studies resulting from insufficient 

sample sizes, unrepresentative study populations, and other sources of confounding. However,

one study was found to be both directly applicable to the target population and of high quality on 

the basis of representation of the U.S.-based study population, sample size, and rigor (57). These 

factors improved the Work Group’s confidence in the estimate of the effect. This study, which 

included a sample size of 16,868 HCV-infected persons identified through the U.S. Department 

of Veterans Affairs (VA), found that treatment-related SVR reduced the risk of mortality among 

persons diagnosed with HCV infection (RR=0.46; 95% CI=0.41-0.51). However, this study only 

compares persons who responded to therapy with persons who did not respond to therapy and 

does not address a screened population or an untreated population. Therefore, the confidence in 

the estimate of effect was deemed to be low, and no upgrading of the quality of evidence was 

performed despite a large estimated treatment effect. (Appendix J: Summary of Findings Tables) 

Hepatocellular Carcinoma 

A systematic review was conducted to examine HCC as a patient-important outcome. A 

total of 37 observational studies (n=29,575) examined the incidence of HCC among persons 

achieving an SVR versus those who did not respond to treatment (Appendix H: Flow Chart for 

HCC; Appendix I: Meta-Analysis of the Effects of Treatment Response on Incidents of HCC) 

(67-103). Data from these studies revealed that treatment-related SVR reduced the risk of HCC 

(0.29; 95% CI=0.24, 0.35). Minimal heterogeneity was reported (I2

=25%), mainly attributed to

the few occurrences of HCC and small sample sizes in the studies. No other criteria were fully 

met to justify downgrading the quality of the evidence for this outcome. Instead, the quality of 

the evidence was upgraded to Moderate because of the substantial risk-ratio effect (Appendix J: 

Summary of Findings Tables).

Failure to Achieve Sustained Virologic Response 

A previously published Cochrane systematic review, which included randomized, 

controlled trials conducted from 1995 through March 2009, examined the outcome of SVR 

among persons randomized to receive either interferon monotherapy or interferon plus ribavirin 

(104). An additional systematic review of the evidence was not conducted because of the high 

quality of the initial review. For the Cochrane review, SVR failure was defined as detectable 

HCV RNA at least 6 months after treatment. Sixty randomized, controlled trials (n=9,146) 

featuring treatment-naïve patients, patients who had received treatment but relapsed, and nonresponders to therapy were analyzed. Treatment consisting of interferon without ribavirin 

significantly increased the failure of SVR among patients (risk ratio=0.75; 95% CI=0.71, 0.79); 
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treatment with both interferon and ribavirin is more likely to result in SVR, and therefore is 

considered more protective. Although SVR was initially judged by the HCV Birth Cohort 

Testing Work Group to be directly associated with patient-important outcomes (e.g., reduced 

viral transmission), further deliberation resulted in SVR being defined as an intermediary 

outcome that is predictive of reduced morbidity and mortality, particularly from HCC. Thus, 

downgrading SVR from high to moderate quality evidence was justified given the indirectness of 

the outcome (Appendix J: Summary of Findings Tables). 

Treatment-Related Serious Adverse Events

Treatment for HCV infection can result in serious adverse events (SAEs), including 

nausea, anemia, and suicidal thoughts. The Cochrane systematic review, which examined the 

effect of treatment for HCV infection on development of SVR, also examined 11 RCTs to 

determine the association between SAEs and the course of HCV treatment (104). This review 

found that compared with monotherapy, combination therapy did not increase risk of SAEs.

Because the treatment-related SAEs are derived from high quality, randomized controlled trials 

and the estimates of those effects are precisely quantifiable, the quality of evidence was judged 

to be high (Appendix J: Summary of Findings Tables).

Since the standard of care changed to include the new direct acting antivirals when they 

were approved for use in the United States market in June, 2011 there has not been sufficient 

time to collect data for a systematic review of their SAEs since the clinical trials. In the 

Telaprevir phase III clinical trial the most common adverse events included gastrointestinal 

disorders, pruritus, rash and anemia, and 11% of those receiving Telaprevir discontinued therapy 

due to the adverse events compared with 1% of those receiving pegylated interferon and ribavirin 

alone(54). In the Boceprevir phase III clinical trial the most common adverse events included 

fatigue, headache, nausea and anemia. There were no differences in discontinuation rates 

between study arms (55 – Poordad, unlinked). The harms of these new treatments may be 

different in community settings.

Quality of Life

One systematic review was identified that examined the effect of HCV testing and 

treatment on patients’ quality of life (QoL) (105). This study included seven observational 

studies. While analysis of these studies did not yield an effect size, the mean QoL associated 

with the SVR in the intervention group was 6.6 points higher than the control group. On the basis 

of study design and the limited evidence available regarding QoL, the quality of the evidence for 

this outcome was rated as low (Appendix J: Summary of Findings Tables). 

HCV Transmission

Searches were conducted for previously published systematic reviews, meta-analyses, 

and individual articles that addressed HCV transmission. No intervention studies examining the 

effect of HCV testing on the patient-important outcome of HCV transmission were identified. 

However, HCV transmission was found to be of relatively high importance when determining 

the strength of the recommendations, despite the absence of related intervention studies 

(Appendix J: Summary of Findings Tables). Future research is needed to address this critical gap 

in knowledge. 
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Alcohol Use 

A search was conducted for systematic reviews, meta-analyses, and individual articles on 

the effect of an alcohol-use-reduction intervention among persons found to be infected with 

HCV. Due to a paucity of available evidence, the search was broadened to include reviews 

focused on alcohol interventions for persons tested for HCV, not just those found positive. 

Recently, a meta-analysis of 22 randomized, controlled trials (n=7,619) examined the effects of 

HCV testing followed by a brief alcohol intervention (i.e., an assessment of the drinking 

behaviors of patients and provision of brief, one-on-one counseling to those patients determined 

to drink alcohol excessively) on drinking behaviors versus testing alone (106). The mean 

reduction of drinking (grams/week) in the intervention groups was 38.42% lower (95% CI = 

30.91, 65.44) than in the control groups after follow-up at ≥1 year. The quality of this evidence 

was initially rated as high, because it was derived from RCTs without major risk of bias. 

However, because the body of evidence was not specifically derived from persons with HCV 

infection, the quality of evidence was downgraded to moderate due to indirectness (Appendix J: 

Summary of Findings Tables). 

Determination of the Recommendations

Four factors must be considered when determining the relevance and strength of a 

GRADE-based recommendation: quality of evidence, balance between benefits and harms, 

values and preferences, and resource implications. During the consultation, the Hepatitis C Virus 

Birth Cohort Testing Work Group considered each of these factors in light of the evidence 

presented. 

Determining the Quality of the Evidence across Outcomes Critical for Decision Making

The GRADE methodology follows the principle that the overall quality of evidence 

should be determined based on the lowest quality of evidence of any outcome deemed critical for 

decision making. For the proposed HCV testing recommendation, critical factors included allcause mortality, HCC, SVR, and SAEs (107). However, rating the overall quality of evidence 

must take two factors into consideration: 1) the desirable effects of testing and treatment (the low 

quality evidence of mortality reduction and the moderate quality evidence of reducing HCC) and 

2) the harms of testing and treatment (the high quality evidence of adverse events associated with 

HCV eradication) (Table 3. Quality of the Evidence across Outcomes Critical for Decision 

Making). Thus, if the reduction in HCC alone is a sufficiently significant desirable outcome to 

support testing and treatment (moderate quality evidence), and no uncertainty exists regarding 

the effect of the undesirable consequences (i.e., high quality evidence of SAEs), then the overall 

quality of evidence supporting testing and treatment in this cohort is determined to be moderate. 

Table 3. Quality of the evidence critical for decision making, by outcome 

Outcome Ranking Quality of Evidence

Undesirable Outcome

SAEs Critical for decision making High

Failure to Achieve SVR Critical for decision making Moderate
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Desirable Outcome

HCC Critical for decision making Moderate

All-cause Mortality Critical for decision making Low

Benefits versus Harms

Upon review of both published and anecdotal evidence, the benefits of testing and 

treating persons with HCV infection were determined to be greater than the harms. Published 

evidence was predominantly drawn from the summary of findings tables, as well as additional 

literature shared by the HCV Birth Cohort Testing Work Group. To supplement that 

information, anecdotal evidence on the benefits and harms associated with several factors was

considered, including the receipt of a false positive test result, the need to wait or return for test 

results, access to treatment, and the effect of HCV-infection notification for insurance and 

employment.

While certain harms (i.e., worry or anxiety while waiting for test results, complications 

due to insurability, and occurrence of SAEs during treatment) can be uncomfortable for patients, 

the benefits associated with effective treatment include SVR which is associated with reductions 

in liver-related morbidity and all-cause mortality. Based on this understanding, the benefits 

associated with HCV treatment were judged to be greater than the harms. Additional factors 

support this judgment. For instance, concerns about receipt of inaccurate HCV test results can be 

assuaged by the accuracy of HCV RNA testing, and the time and resources needed to screen, 

provide a brief alcohol intervention, and refer patients to care is outweighed by the efficacy of 

these interventions in reducing alcohol use. 

Values and Preferences 

HCV testing is widely accepted among various populations (108, 109). No evidence 

exists to support the assumption that persons born during 1945-1965 would have different 

attitudes about HCV testing. 

Resource Implications

Only two U.S.-based studies specifically examined the cost effectiveness and resource 

implications of birth-year-based HCV testing linked to HCV care and treatment; both studies 

found the interventions to be cost effective.(49, 110) These studies, which evaluated slightly 

different definitions of “birth cohort,” compared birth-cohort testing and treatment with the 

status quo of risk- and medical-indication based testing recommendations; both studies 

demonstrated nearly identical cost-effectiveness results. The first study, which defined the birth 

cohort as persons born from 1945 through 1965, estimated a cost per quality-adjusted life year 

(QALY) gained of $35,700 based on a 12-week response-guided course of Telaprevir added to 

the standard treatment regimen (i.e., pegylated interferon with ribavirin); cost per QALY was an 

estimated $15,700 when assuming treatment with the standard regimen alone (49). The second 

study defined the birth cohort as persons born from 1946 through 1970 and estimated a cost per 

QALY gained of $39,963 for patients treated with Telaprevir in addition to pegylated interferon 

with ribavirin (110). 
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These cost-effectiveness studies had different assumptions about the timing of HCV 

testing and treatment. The study that examined the 1945-1965 birth cohort included all possible 

costs and benefits in a single year (49), whereas the study that examined the 1946-1970 birth 

cohort assumed 20% of the eligible population would be screened and treated each year for 5 

years. (2, 49) Per person testing costs would be approximately $54 including antibody testing, 

nucleic acid testing of antibody positives, and post-test counseling (44). 

In addition to reductions in morbidity and mortality (Table 4), the increase in testing and 

treatment of persons born from 1945 through 1965 would increase testing and treatment costs 

compared with current risk-based testing and treatment strategies. Costs can be determined using 

three different scenarios: risk-based testing with pegylated interferon and ribavirin (PR) therapy; 

birth cohort testing with PR therapy; and birth cohort testing with PR therapy and a new direct 

acting antiviral (DAA), the current standard of care. Testing the 1945-1965 birth cohort and 

treating with PR+DAA is expected to cost $15.2 billion more than risk-based testing followed by 

PR alone, but this approach averts an estimated $2.5 billion in medical costs (49)(Table 5). 

Table 4. Testing and clinical outcomes, by hepatitis C virus (HCV) testing strategy 

Outcome Risk-based

testing + 

pegylated 

interferon 

with 

ribavirin 

(PR)

Birth cohort testing 

+ PR with a direct 

acting agent (DAA) 

Differential

Antibody tests 

administered 

14,793,816 60,404,514 45,610,698 more tests 

conducted

Positive results 

delivered to patient

262,260 1,070,840 808,580 more cases 

identified

Patients treated 135,089 551,800 416,711 more patients 

treated

Patients who 

achieved a sustained 

viral response 

53,160 310,855 257,695 more patients 

achieved SVRs

Ever developed 

compensated 

cirrhosis

994,291 791,053 203,238 cirrhosis cases 

averted

Ever developed 

decompensated 

cirrhosis (DCC)

360,388 286,699 73,689 DCC cases averted

Ever developed 

hepatocellular 

carcinoma (HCC)

230,784 183,595 47,189 HCC cases averted

Ever received a 

transplant 

75,752 60,268 15,484 transplants averted

HCV-related deaths 591,172 470,293 120,879 deaths averted
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Table 5. Cost of hepatitis C virus (HCV) testing and treatment (in millions)* 

Risk-based testing

+ PR

Birth cohort testing

+ PR

Birth cohort testing

+ PR+DAA

Testing costs $754 $3,078 $3,078

Treatment costs $1,508 $6,162 $20,662

Total medical costs $2,262 $9,240 $23,740

*Rein D, Smith, B.D., Wittenborn, J.S., Lesesne, S.B. The Cost-Effectiveness of Birth Cohort Hepatitis C Antibody Screening in 

U.S. Primary Care Settings. Annals of Internal Medicine. 2012;156(4):263-70.

Colorectal screening rates were reviewed to estimate the testing costs associated with

one-time HCV testing for persons in the 1945-1965 birth cohort. Both interventions focus on 

screening at a single time point in time (i.e., at age 50 for colorectal screening); therefore, data 

from colorectal screening programs are useful for estimating the rate of adoption of a 

recommendation for one-time prevention services. In an analysis of 2005 National Health 

Interview Survey data (a nationally representative household survey), 19.8% of women and 

23.7% of men reported receiving colorectal screening in the previous 3 years (the time since 

implementation of the United States Preventive Services Task Force [USPSTF] screening

recommendation).(111) These percentages were obtained after years of updated colorectal 

screening recommendations and implementation of extensive educational campaigns, so they 

likely are higher than those expected to follow adoption of HCV testing recommendations. 

However, if the birth cohort recommendation was adopted at the same level, approximately 5.6 

million women and 6.7 million men would be tested for HCV within the first 3 years of 

implementation at a cost of $664 million; more than 400,000 HCV infected persons would be 

identified. 

RECOMMENDATIONS

The following recommendations for HCV testing are intended to augment the 

Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCVRelated Chronic Disease issued by CDC in 1998 (1). 

In addition to testing adults of all ages at risk for HCV infection, CDC recommends that: 

• Adults born from 1945 through 1965 should receive one-time testing for HCV without 

prior ascertainment of HCV risk factor status (Strong Recommendation, Moderate 

Quality of Evidence), and

• All persons with identified HCV infection should receive a brief alcohol screening and 

intervention as appropriate, followed by referral to appropriate care and treatment 

services for HCV infection and related conditions as indicated (Strong Recommendation, 

Moderate Quality of Evidence). 

PUBLIC HEALTH TESTING CRITERIA
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A strategy for testing persons in the 1945-1965 birth cohort for HCV infection is 

consistent with established general public health screening criteria (112) as evidenced by the 

following factors: 1) HCV infection is a serious health problem affecting a large number of 

people with significant negative health outcomes that can be diagnosed before symptoms appear; 

2) testing for HCV infection is readily available, minimally invasive, and reliable; 3) benefits 

include limiting disease progression and facilitating early access to treatments that can save 

significant life years; and 4) testing is cost effective. Such testing would help identify 

unrecognized infections and help HCV-infected persons receive beneficial care and therapy prior 

to onset of severe HCV-related disease (112). 

TESTING METHODS

Hepatitis C Antibody Testing

Laboratory testing methods for HCV included in these recommendations were 

established by CDC’s Guidelines for laboratory testing and result reporting of antibody to 

hepatitis C virus in 2003 (113). No new methods are introduced in these recommendations. HCV 

testing should be initiated with an FDA-approved serologic test for antibody to HCV (antiHCV). These assays are highly sensitive. A person who tests anti-HCV negative does not have 

HCV infection and has not been infected in the past. Except for persons who have ongoing or 

recent risks for HCV exposure (e.g., IDU), no further testing is needed (1). Positive or 

indeterminate test results should be followed by supplemental testing to confirm anti-HCV (e.g., 

an immumoblot assay) or presence of HCV RNA by nucleic acid test (NAT). 

FDA-approved HCV antibody tests also have a high level of specificity, and a person 

whose anti-HCV test is confirmed positive should be presumed to either 1) have active (i.e., 

current) HCV infection or 2) have had HCV infection in the past that has subsequently resolved 

(i.e., cleared). Anti-HCV testing cannot distinguish between active HCV infection and past, 

cleared HCV infection; this distinction requires that persons who initially test anti-HCV positive 

be tested by an HCV NAT. 

Hepatitis C Nucleic Acid Testing

One of the following FDA-approved HCV NATs, commonly known as “HCV RNA 

tests,” should be used to identify active HCV infection among persons who have tested antiHCV positive: 1) quantitative NATs (i.e., for viral load) or 2) qualitative NATs. Persons who test

anti-HCV positive and are also positive by HCV NAT should be considered to have active HCV 

infection; these persons need further medical evaluation and care. A person who is anti-HCV 

positive but who tests negative by HCV NAT is considered to have past, cleared HCV infection 

(114). In the absence of ongoing risk, these persons do not require further testing. 

All specimens with an anti-HCV antibody test result of “indeterminate” also should be 

tested by NAT (113). Persons with a positive NAT after an indeterminate anti-HCV test result 

should be considered actively infected; these persons require further medical evaluation and care

(113). 

Provision of HCV Test Results 

Negative Test Results

Persons with negative anti-HCV test results should be informed of their test results and 

reassured that they are not infected unless they were recently at risk for infection. Repeat testing 
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can be considered for persons with ongoing risk behaviors. If persons reveal other health-related 

concerns, they should be evaluated or medically referred as indicated.

Indeterminate Test Results

Persons whose HCV test results are indeterminate should be advised that the result is 

inconclusive. These persons should be provided appropriate follow-up testing or referral for 

further testing and should be instructed about how to reduce the risk of possible transmission 

until they are retested and their infection status is known (see Prevention Messages). 

Positive Test Results

Persons who test positive for both HCV antibody and HCV RNA should be told that they 

are infected and need further medical evaluation for liver disease, ongoing monitoring, and 

possible treatment. At the time positive test results are communicated to patients, providers 

should evaluate their level of alcohol use and provide a brief alcohol intervention to those found 

to use alcohol excessively or engage in binge drinking. Persons with HCV infection also should 

be provided information (either through face-to-face sessions, video, or written materials) about 

1) HCV infection, 2) risk factors for disease progression, and 3) preventive self-care and 

treatment options, also addressing how to prevent transmission of HCV to others. HCV-infected 

patients also should know about the resources available to them within their communities, 

including providers of medical evaluation and social support. 

Post-test Counseling Messages

Persons found to be infected with HCV also can benefit from the following types of 

counseling messages. 

• Contact a health care provider or specialist (hepatologist, gastroenterologist, infectious 

disease) for

o medical evaluation of the presence or development of chronic liver disease;

o advice on possible treatment decisions and strategies; and

o advice on how to monitor the health of your liver, even if treatment is not 

recommended . 

• To protect the liver from further harm, 

o consider vaccination against hepatitis A and B if liver disease is present; 

o reduce or discontinue alcohol consumption; 

o avoid taking new medicines, including over-the-counter and herbal agents (14), 

without checking with your health care provider; and 

o obtain HIV risk assessment and testing. 

• For persons who are overweight and/or obese (BMI> 30kg/m2) (51), 

o consider weight management or losing weight and

o follow a healthy diet and stay physically active. 

• To minimize the risk of transmission to others, 

o do not donate blood, body organs, tissue, or semen and
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o do not share appliances that may come into contact with blood, such as 

toothbrushes, dental appliances, razors, and nail clippers. 

PREVENTION MESSAGES

HCV-specific information and secondary prevention messages (e.g., alcohol reduction 

messages) should be provided to patients infected with, and at risk for acquiring HCV. 

Prevention messages can help reduce the risk for HCV transmission to others (for specific 

prevention messages, refer to CDC’s Recommendations for Prevention and Control of Hepatitis 

C Virus (HCV) Infection and HCV-Related Chronic Disease [1]). This information may be 

provided at time of testing or when results are delivered. For persons who access testing for 

HCV infection, general information should be available regarding HCV, along with information 

about the antibody test for HCV and NAT. Persons also should be informed of how they will be 

receiving their HCV test result.

LINKAGE TO CARE AND TREATMENT

Many persons identified as HCV-infected do not receive recommended medical 

evaluation and care after the diagnosis of HCV infection (33); this gap in linkage to care can be 

attributed to several factors, including being uninsured or underinsured, failure to provide a 

referral or failure to follow up on a referral, drug or alcohol use issues, and other barriers,. The 

lack of such care, or significant delays before care is received, has a negative impact on the 

health outcomes of infected persons. Although routine testing of persons born 1945-1965 is 

expected to lead to more HCV-infected persons being identified earlier in the course of disease,

to improve health outcomes, persons testing positive for HCV must be provided with appropriate 

care and treatment. Linking patients to care and treatment is a critical component of the strategy 

to reduce the burden of disease.

Alternative strategies are needed for HCV-infected persons who are experiencing barriers 

to care. These persons may benefit from the replication of effective linkage-to-care models and 

from the development of other evidence-based interventions. Active linkage-to-care programs 

provided in a culturally sensitive manner (115-117) (e.g., the use of case managers to schedule 

appointments, bring infected patients to doctors’ appointments, and follow-up with patients) 

have been found to be more effective (115) than passive referral methods (e.g., providing 

patients with information about the disease and a list of resources or referrals to medical care). 

Such linkage creates opportunities for patients to receive information, vaccinations, prevention 

counseling messages, and to more fully engage in care (118). Once patients receive care, case 

management can provide active linkage (119-121) to social services (116, 122), referral to 

substance abuse services (123-126), and assistance with transportation and housing (117, 120). 

Recommendations for the medical management of HCV infection and disease are updated 

regularly by AASLD. As noted above, significant advances are being made in the care, 

management, and treatment of HCV infection at the time of publication of this recommendation. 

Although primary care clinicians can readily provide much of the care necessary for initial 

evaluation and management of persons with HCV infection, antiviral treatment is complex, and 

collaboration between primary providers and specialists is critical for optimal care. CDC is 
DRAFT FOR PUBLIC COMMENT

27

working with academic and clinical partners and with other federal and state agencies to replicate 

best practices and develop new models for collaborative care (127). 

FUTURE DIRECTIONS

CDC is planning a national education campaign called Know More Hepatitis, which

targets primary care providers as well as persons born within the birth cohort. For this campaign, 

CDC will employ various communication and social media strategies to raise awareness among 

health-care professionals about high rates of chronic viral hepatitis infection among their 

patients, the need for testing, and the benefits of early identification and appropriate medical 

management. These communication strategies are designed to complement the more targeted 

technical training and education being undertaken by CDC and its academic and medical 

partners. Reaching out directly to health-care professionals helps build the knowledge and 

capacity of the provider community to respond to patients who will be reached by the public 

education campaign, which encourages patients to be aware of their risk and to get tested. CDC 

also plans to work with national, regional and local medical societies and health-care 

organizations to educate their members about chronic viral hepatitis infection, as well as to 

promote CDC resources, including professional clinical tools, training modules, guidelines, and 

patient education materials. The Know More Hepatitis campaign also includes a multi-media 

public education component designed to encourage testing for hepatitis C among the age cohort 

as called for within these guidelines. 

CDC will conduct demonstration studies to guide implementation efforts for these 

recommendations; conduct surveillance to monitor implementation, adoption, and impact; and 

evaluate and grade new evidence as it becomes available. CDC will soon begin conducting 

systematic reviews of other testing and prevention recommendations that were included in the 

1998 HCV testing recommendations (1). Additionally, CDC will be reviewing evidence related 

to the potential benefits and harms of testing persons who were determined to be of “uncertain 

need” in the 1998 recommendations (i.e., those with risks that have not been well defined, such 

as intranasal drug use or a history of multiple sex partners). Upon completion of these reviews, 

recommendations will be revised as necessary. The revised guidelines, which will incorporate 

the present birth-cohort-based recommendations as well as risk-based strategies, will provide 

updated, comprehensive recommendations for the identification and management of HCV 

infection in the United States. 
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in early hepatitis C virus infection. Transfusion. 2005 Jun;45(6):994-1002.

115. Gardner LI, Metsch LR, Anderson-Mahoney P, Loughlin AM, del Rio C, Strathdee S, et al. Efficacy 

of a brief case management intervention to link recently diagnosed HIV-infected persons to care. AIDS. 

2005 Mar 4;19(4):423-31.

116. Horstmann E, Brown J, Islam F, Buck J, Agins BD. Retaining HIV-infected patients in care: Where 

are we? Where do we go from here? Clin Infect Dis. 2010 Mar 1;50(5):752-61.

117. Molitor F, Waltermeyer J, Mendoza M, Kuenneth C, Aguirre A, Brockmann K, et al. Locating and 

linking to medical care HIV-positive persons without a history of care: findings from the California Bridge 

Project. AIDS Care. 2006 Jul;18(5):456-9.

118. Mayer KH. Introduction: Linkage, engagement, and retention in HIV care: essential for optimal 

individual- and community-level outcomes in the era of highly active antiretroviral therapy. Clin Infect 

Dis. 2011 Jan 15;52 Suppl 2:S205-7.

119. Cunningham CO, Sanchez JP, Li X, Heller D, Sohler NL. Medical and support service utilization in a 

medical program targeting marginalized HIV-infected individuals. J Health Care Poor Underserved. 2008 

Aug;19(3):981-90.

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treating HIV-infected drug users. AIDS. 2010 Jan 28;24(3):331-40.

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APPENDICES
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Appendix A. Acronyms Used in this Document

AAFP American Academy of Family Physicians

AASLD American Association for the Study of Liver Disease

AGA American Gastroenterological Association

BAI Brief alcohol intervention

CDC Centers for Disease Control and Prevention 

DAA Direct acting antivirals

DVH Division of Viral Hepatitis

GRADE Grading of Recommendations Assessment, Development, and Evaluation 

HAV Hepatitis A virus

HBV Hepatitis B virus

HCC Hepatocellular carcinoma

HCV Hepatitis C virus

HIV Human immunodeficiency virus 

HRQOL Health-Related Quality of Life 

ICER Incremental Cost Effectiveness Ratio

IDSA Infectious Diseases Society of America

IDU Injection drug use 

NAT Nucleic acid test

NHANES National Health and Nutrition Evaluation Survey 

NIH National Institutes of Health

NVHR National Viral Hepatitis Roundtable 

OMB Office of Management and Budget

PCI Positive case identification

PICO Population, Intervention, Comparator, Outcome 
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PWID Persons who inject drugs 

QALY Quality-adjusted life year

RNA Ribonucleic acid

SAE Serious adverse events

STI Sexually transmitted infection

SVR Sustained virologic response 

WHO World Health Organization
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Appendix B. Conflicts of Interest

External Work Group Members

Miriam Alter, PhD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Sanjeev Arora, MD, FACP, FACG

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: Consultancy:

Served on Advisory Board of Vertex Pharmaceuticals in 2009

Grants/Grants Pending:

Grants from Vertex Pharmaceuticals, Roche/ Genentech, 

Gilead, Zyrnogenetics, Bristol Myers, Pharmasett, and Abbott 

paid to institution for clinical trials

Lectures/ Speakers Bureaus:

Scherring Corp., served on September Bureau for Roche 

Pharmaceuticals until mid-2009

Bruce Bacon, MD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Doug Campos-Outcalt, MD, MPA

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Alfred DeMaria, Jr., MD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Janet Durfee, MSN, RN, APRN

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Yngve Falck-Ytter, MD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Colleen Flanigan

For the Work Under Consideration: Support for Travel:

CDC Foundation

Other Relevant Financial Activities: No financial conflict of interest reported

Marc Ghany, MD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Robert Gish, MD
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For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: Board Membership:

Hepahope 

Consultancy:

Performed as a consultant to Abbott, Anadys Pharmaceuticals, 

Inc., Bayer AG, Bristol-Myers Squibb Company, Durect, 

Hepahope, Hoffman-LaRoche Ltd., Genentech, Gilead 

Sciences, GlaxoSmithKline, GlobeImmune, Human Genome 

Sciences, Merck, Metabasis Therapeutics, OSI/Astellas 

Parmasset, Schering-Plough Corporation, Three Rivers 

Pharma, VitalTherapies, and ZymoGenetics; payments directed 

to an SPF fund for research and education 

Lectures/ Speakers Bureaus:

Speakers bureau activities for Bayer, Bristol-Myers Squibb 

Company, F. Hoffman-LaRoche Ltd., Gilead Sciences, Inc., 

GlaxoSmithKline, Onyx, Merck/Schering-Plough Corporation, 

Three Rivers, Salix, SciClone Pharmaceuticals focused on 

HBV, HCV, and liver cancer, specifically epidemiology, 

diagnosis, and treatment, with additional program presentations 

for HBV and management of complications of cirrhosis; has a 

speakers contract to do promotional talks for BMS, Roche, 

Schering-Plough, Gilead Sciences, Bayer and Onyx; payments 

are directed to an SPF fund for research and education

Grants/ Grants Pending:

Support from Bayer-Onyx, Bristol-Myers Squibb Company, 

Genentech/ F. Hoffman-LaRoche, Ltd., Gilead Sciences, 

Genentech, Pharmasset, Zymogenetics; payments directed to an 

institutional fund under contract to CPMC

Stock/ Stock Options: 

Major Stock Shareholder for Hepahope

Fasiha Kanwal, MD, MSHS

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Emmett Keeffe, MD, MACP

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: Consultancy:

Vertex

Travel/ Accommodations:

Vertex

Kathleen Koechlin, PhD, MPH, BSN, RN

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Cameron Lewis

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Jake Liang, MD
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For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Robert Lubran, MPA, MS

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Iris Mabry-Hernandez, MD, MPH

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Katherine McGlynn, PhD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Barbara McGovern, MD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: Employment:

Editor at UpToDate

Other:

Editor at Infectious Diseases Society of America

Rachel McLean, MPH

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Michael Ninburg

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: Consultancy:

Vertex, Abbott, Genentech, GlaxoSmithKline, Merck, Hoffman 

LaRoche, Tibotec, Beoringer Ingelheim 

Grants/ Grants Pending: 

Grants from Vertex, Merck, Genentech, Hoffman La Roche, 

Schering Plough, Gilead, Novartis, and Human Genome 

Sciences paid to institution

Payment for the Development of Educational Presentations:

Vertex, Hoffmann La Roche, and Schering Plough, paid to 

institution

Phillip Reichert, MPH

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Vinod Rustgi, MD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: Consultancy:

Merck, Vertex

Grants/ Grants Pending:

Grants from BMS, Gilead, Anadys, Boehringer-IngelheimAbbott paid to institution

Lectures/ Speakers Bureaus:
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Merck, Vertex, Genentech, Gilead, Onyx

Lorren Sandt

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: Consultancy:

Abbott, for community advisory board and paid to institution 

Grants/ Grants Pending: 

Unrestricted educational grants from Vertex, Merck, and 

Genentech paid to institution; Conference grant from Gilead 

paid to institution

Travel/ Accommodations:

Money for travel from BMS, Vertex, Boehringer Ingelheim, 

Merck, Genentech/Roche and Tibotec for community advisory 

boards and paid to institution

Gloria Searson

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Anne Spaulding, PhD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: Consultancy:

Georgia Correctional Healthcare; clinical consultant for 

hepatitis and HIV care

Grants/ Grants Pending: 

Grant support from DHHS, CDC, HRSA, and indirectly from 

NIH paid to institution 

Lectures/ Speakers Bureaus:

Hepatitis Foundation International, Albany Medical College

Donna Sweet, MD, AAHIVS, MACP

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: Grants/ Grants Pending:

Pfizer, BMS Pharmaceuticals

Lectures/ Speakers Bureaus:

Abbott, BMS, Boehringer Ingelheim, Tibotec, Gilead

Andrew Talal, MD, MPH

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: Board Membership:

Merck & Co., Genentech/Roche, Boehringer Ingelheim, Pfizer, 

Bayer/ Onyx, Vertex 

Consultancy:

Merck & Co., Genentech

Grants/ Grants Pending:

Merck & Co., Vertex, Boehringer-Ingelheim, and 

Genentech/Roche, Pfizer, Bayer/Onyx paid to institution 

Lectures/ Speakers Bureaus:

Vertex and Genentech/ Roche 

Payment for Development of Educational Presentations:

Merck & Co., Medscape
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Litjen Tan, PhD, MS

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Chris Taylor

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: Grants/ Grants Pending:

Vertex, Gilead, OraSure, Merck & Co., Janssen, BMS paid to 

institution

Travel/ Accommodations: 

Vertex, OraSure

Lisa Townshend-Bulson, MSN, FNP

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: Expert Testimony:

CDC Cooperative Agreement with ANTHC, paid to institution

Tam Van

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Kathleen Whitaker, PhD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Richard Wild, MD, JD, MBA, FACEP

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

John Wong, MD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

CDC Work Group Members

Geoff Beckett, PA, MPH

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Scott Holmberg, MD, MPH

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Deborah Holtzman, PhD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Rebecca Morgan, MPH

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported
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Dan Riedford, JD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Bryce Smith, PhD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Philip Spradling, MD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

Chong-Gee Teo, MD, PhD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported

John Ward, MD

For the Work Under Consideration: No financial conflict of interest reported

Other Relevant Financial Activities: No financial conflict of interest reported
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Appendix C. Analytic Framework
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Appendix D. Search Strategy for HCV Prevalence
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Appendix E. Flow Chart for HCV Prevalence
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Appendix F. Search Strategy for Patient-Important Outcomes 
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Appendix G. Flow Chart for All-Cause Mortality
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Appendix H. Flow Chart for Hepatocellular Carcinoma
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Appendix I. Meta-Analysis of the Effects of Treatment Response on 

Incidents of Hepatocellular Carcinoma
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Appendix J. Summary of Findings Tables
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1

 Intervention with goal to achieve SVR 

2

 Over 70% relative risk reduction 

3

 Comparison of mortality in patients achieving SVR vs. no SVR 

4

 Although adjustment for cirrhosis severity (e.g., CP or MELD score) would be ideal, Backus et al. adjusted for presence of cirrhosis 

in general and albumin, bilirubin, and platelet count which are valid substitutes for severity of underlying liver disease. Not 

downgraded. 

5

 The results are for genotype 1 (72% of cohort). Genotype 2: HR 0.64 (CI 0.46, 0.88); genotype 3: 0.51 (CI 0.35, 0.73) 

6

 Study included the years from 2001 to 2009. The median follow-up period was 3.8 years after final outcome (SVR/NVR) was 

established. The interquartile range was 2.5 to 5.2 years. 

7

 Total number of participants: 5,978; distribution between participants and controls not given 

8

 CI not provided. Effect was reported as significant. Minimally clinically important difference estimated to be 4.2 (range, 3-5). Effect 

size results: 0.3; no CI given; according to Cohen, small effect sizes are in the 0.2 and less range; moderate 0.5; large 0.8 and larger 

range.

9

 SVR considered as viral cure (eliminating infection). Not downgraded for indirectness. 

10 From meta-analysis of RCTs of PEG-interferon alpha 2a vs. 2b 

11 Severe adverse effects that lead to treatment discontinuations include (but are not limited to): 99% will experience at least one of the 

following: cytopenias (anemia, neutropenia, thrombocytopenia); flu-like symptoms, neuro-psychiatric disturbances (depression, 

irritability, insomnia, anxiety, psychosis etc.), teratogenicity, rash, etc. 

12 Assumption: almost no patients with chronic, established HCV will spontaneously clear the virus without treatment.
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Authors

Bryce D. Smith, PhD, Division of Viral Hepatitis, CDC, Atlanta, GA; Rebecca L. Morgan, 

MPH, Division of Viral Hepatitis, CDC, Atlanta, GA; Geoff Beckett, PA-C, MPH, Division of 

Viral Hepatitis, CDC, Atlanta, GA; Yngve Falck-Ytter, MD, Case Western Reserve University, 

Cleveland Heights, OH; Chong-Gee Teo, MD, PhD, Division of Viral Hepatitis, CDC, Atlanta, 

GA; Amy Jewett, MPH, Division of Viral Hepatitis, CDC, Atlanta, GA; Brittney Baack, MPH, 

Division of Viral Hepatitis, CDC, Atlanta, GA; Deborah Holtzman, PhD, Division of Viral 

Hepatitis, CDC, Atlanta, GA; David B. Rein, PhD, NORC at the University of Chicago, Atlanta, 

GA; Nita Patel, PhD, Division of Viral Hepatitis, CDC, Atlanta, GA; John W. Ward, MD, 

Division of Viral Hepatitis, CDC, Atlanta, GA; Miriam Alter, PhD, University of Texas Medical 

Branch, Galveston, TX.

Contributors

DVH Steering Committee

Geoff A. Beckett, PA-C, MPH, Division of Viral Hepatitis, CDC, Atlanta, GA; Rebecca L. 

Morgan, MPH, Division of Viral Hepatitis, CDC, Atlanta, GA; Bryce D. Smith, PhD, Division 

of Viral Hepatitis, CDC, Atlanta, GA; John W. Ward, MD, Division of Viral Hepatitis, CDC, 

Atlanta, GA.

DVH Internal Work Group 

Geoff Beckett, PA, MPH, Division of Viral Hepatitis, CDC, Atlanta, GA; Scott Holmberg, MD, 

MPH, Division of Viral Hepatitis, CDC, Atlanta, GA; Deborah Holtzman, PhD, Division of 

Viral Hepatitis, CDC, Atlanta, GA; Rebecca L. Morgan, MPH, Division of Viral Hepatitis, CDC, 

Atlanta, GA; Dan Riedford, JD, Division of Viral Hepatitis, CDC, Atlanta, GA; Bryce Smith, 

PhD, Division of Viral Hepatitis, CDC, Atlanta, GA; Phil Spradling, MD, Division of Viral 

Hepatitis, CDC, Atlanta, GA; Chong-Gee Teo, MD, PhD, Division of Viral Hepatitis, CDC, 

Atlanta, GA; John Ward, MD, Division of Viral Hepatitis, CDC, Atlanta, GA. 

Hepatitis C Virus Birth Cohort Testing Work Group 

Miriam Alter, PhD, University of Texas Medical Branch, Galveston, TX; Sanjeev Arora, MD, 

FACP, FACG, University of New Mexico, Albuquerque, NM; Bruce Bacon, MD, Saint Louis 

University School of Medicine, St. Louis, MO; Doug Campos-Outcalt, MD, MPA, University of 

Arizona College of Medicine, Phoenix, AZ; Alfred DeMaria, Jr., MD, Council of State and 

Territorial Epidemiologists and Massachusetts Department of Public Health, Jamaica Plain, MA; 

Janet Durfee, MSN, RN, APRN, Veterans Health Administration, Washington, D.C.; Colleen 

Flanigan, New York State Department of Health, Albany, NY; Marc Ghany, MD, National 

Institutes of Health, Bethesda, MD; Robert Gish, MD, University of California, San Diego, La 

Jolla, California; Fasiha Kanwal, MD, MSHS, St. Louis VA Medical Center, St. Louis, MO; 
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Emmett Keeffe, MD, MACP, Stanford University Medical Center, Stanford, CA; Kathleen 

Koechlin, PhD, MPH, BSN, RN, Ohio Department of Health, Columbus, OH; Cameron Lewis,

Arizona Department of Health Services, Phoenix, AZ; Jake Liang, MD, National Institute of 

Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD; Robert Lubran, MPA, MS, 

Substance Abuse and Mental Health Services Administration, Rockville, MD; Iris MabryHernandez, MD, MPH, U.S. Department of Health and Human Services, Rockville, MD; 

Katherine McGlynn, PhD, National Cancer Institute, NIH, Bethesda, MD; Barbara McGovern, 

MD, Lemuel Shattuck Hospital, Jamaica Plain, MA; Rachel McLean, MPH, California 

Department of Public Health, Sacramento, CA; Michael Ninburg, Hepatitis Education Project, 

Seattle, WA; Monica Parker, PhD, Association of Public Health Laboratories, Silver Spring, 

MD; Phillip Reichert, MPH, Florida Department of Health, Tallahassee, FL; Vinod Rustgi, MD, 

American Gastroenterological Association, Fairfax, VA; Lorren Sandt, Caring Ambassadors 

Program, Oregon City, OR; Gloria Searson, ICSW, COPE, Inc., New York, NY; Averell 

Sherker, MD, FRCP(C), National Institutes of Health, Bethesda, MD; Anne Spaulding, PhD, 

Emory University School of Public Health, Atlanta, GA; Donna Sweet, MD, AAHIVS, MACP, 

University of Kansas School of Medicine, Wichita, Wichita, KS; Andrew Talal, MD, MPH, 

Weill Cornell Medical College, New York, NY; Litjen Tan, PhD, MS, American Medical 

Association, Chicago, IL; Chris Taylor, National Alliance of State and Territorial AIDS 

Directors, Washington, D.C.; Lisa Townshend-Bulson, MSN, FNP, Alaska Native Tribal Health 

Consortium, Anchorage, AK; Tam Van, Association of Public Health Laboratories, Silver 

Spring, MD; Kathleen Whitaker, PhD, Food and Drug Administration, Silver Spring, MD; 

Richard Wild, MD, JD, MBA, FACEP, Centers for Medicare and Medicaid Services, Atlanta, 

GA; John Wong, MD, Tufts Medical Center, Boston, MA. 

Additional Consultation Attendees

Faruque Ahmed, CDC, Atlanta, GA; Brittney Baack, Division of Viral Hepatitis, CDC; John 

Douglas, MD, CDC, Atlanta, GA; Alycia Downs, Division of Viral Hepatitis, CDC, Atlanta, 

GA; Jeff Efird, MPA, Division of Viral Hepatitis, CDC, Atlanta, GA; Amy Jewett, CDC, 

Atlanta, GA; Cynthia Jorgensen, DrPH, Division of Viral Hepatitis, CDC, Atlanta, GA; Amanda 

Lewis, MPH, CHES, Division of Viral Hepatitis, CDC, Atlanta, GA; Nita Patel, DrPH, Division 

of Viral Hepatitis, CDC, Atlanta, GA; Meredith Reilly, Department of Health and Human 

Services Office of the Assistant Secretary for Health, Washington, D.C.; Rachel Wilson, 

Division of Viral Hepatitis, CDC, Atlanta, GA.

Senior Methodologist 

Yngve Falck-Ytter, MD, Case Western Reserve University, Cleveland Heights, OH. 

Peer Reviewers
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Holly Hagan, PhD, New York University College of Nursing, New York, NY; Ray Kim, MD, 

Mayo Clinic, Rochester, MN; Linda Kinsinger, MD, MPH, Veterans Health Administration, 

Washington, D.C.; Anna Lok, MD, FRCP, University of Michigan, Ann Arbor, MI. 

Acknowledgements

Ashia Boyce, Georgetown University, Washington, D.C.; Thein Lwin, MPH, Georgia State 

University, Atlanta, GA; Marc Pitasi, MPH Candidate, Emory University, Atlanta, GA; Aida 

Risman, Emory University, Atlanta, GA; Becky Satterthwaite, Public Health Library and 

Information Center, CDC, Atlanta, GA; Rachel Wilson, Division of Viral Hepatitis, CDC, 

Atlanta, GA