# Presentation: 825495

## Guidelines for Laboratory Testing and Result Reporting for Antibody to Hepatitis C Virus

**Miriam J. Alter, Ph.D.**
**Division of Viral Hepatitis**
**Centers for Disease Control and Prevention**

**BPAC September 18, 2003**

## Guidelines Development

**Working group**
**Federal agencies**
**CDC, FDA (CDRH, CBER)**
**Professional associations**
**APHL**
**ASCP**
**CAP**
**NACB**
**AACC**
**ACLA**
**Other experts**
**University and VA hospital laboratories**

**Other collaborators**
**Blood collection establishments**
**Manufacturers**

## These Guidelines Are NOT Intended

**For screening or notification of blood, plasma or other donors, as provided for under FDA guidance or regulations**
**To change manufacturers labeling for performing a specific test**
**To dictate medical practice, i.e., what tests physicians are able to order**

## Testing for Anti-HCV

**Recommended for initially identifying persons with HCV infection**
**Antibody screening assay followed by more specific assay for screening-test-positives**
**As is done for HBsAg and anti-HIV**
**Verifying presence of anti-HCV**
**Minimizes unnecessary medical visits and psychological harm for persons who test falsely positive**
**Ensures counseling, medical referral and evaluation targeted for persons serologically confirmed as having been HCV infected**

## Performance of Screening Tests

**Positive Predictive Value (PPV)**
**Probability that a person with a positive test is a true positive**
**Varies depending on prevalence of infection in population being screened**

## How Anti-HCV Test Results Are Used

**Clinical diagnosis of etiology of liver disease**
**Postexposure management**
**Screening asymptomatic persons**
**Most being tested for the first time**
**Risk for infection highly variable**
**High-risk (e.g., injection drug users)**
**Low-risk (e.g., health-care workers)**
**Lower-risk (e.g., worried well)**
**Public health surveillance**
**Monitor incidence and prevalence to target and evaluate prevention efforts **

## Testing Practices

**In 1998, CDC published recommendations that all screening-test positives undergo more specific testing**
**Broad educational programs targeted to physicians and other health care providers**
**Little impact on test ordering practices**
**Substantial variation among laboratories in routine testing algorithms**
**Many report screening test positive results only**
**Those that confirm use different methods (RIBA, NAT)**
**Without additional information, may not be able to determine true antibody or HCV infection status**

## Anti-HCV Testing Practices of State and Territorial Public Health and VA Medical Center Laboratories, 2002

**Tests offered****	****	**** ****	****	****	**_**n=43**_**	****	**_**n=67**_
**	****Screening test****	****	****	****	****	****65%****	****	****100%**
**	****RIBA****	****	****	****	****	****38%****	**** ****	****21%**
**	****Qualitative NAT****	****	****	****	****29%****	**** ****	****75%**
**	****Quantitative NAT****	****	****	****	****13%****	**** ****	****98%**
**Supplemental testing performed****	****	****	**_**n=29**_**	****	**_**n=67**_
**	****All screening-test-positive results****	****	****35%****	**** ****	****22%**
**	****Low-positive screening-test results*****	****	****10%****	**** ****	**** 3%**
**	****Only by physician request****	****	****	****17%****	**** ****	****75%**
**	****None offered****	****	****	****	****	****38%****	**** ****	**** 0%**

*** Signal to cut-off ratio below a specified value**

**Source: Werner B, APHL, 2002; Dufour R, VA, 2002**

_**Testing Practices**_**	****	****	**_** Public health**_**	****     **_**VAMC**_

## Purpose of Laboratory Guidelines

**Adoption of standard algorithm by all laboratories that perform in vitro diagnostic testing***
**Ensure results reflect true antibody status**
**Independent of clinical information or origin of sample**
**Educate**
**Importance of more specific testing**
**Accurate interpretation of screening and supplemental results**
**When more specific testing should be performed**
**Which tests to use **
**Eliminate cost as barrier to more specific testing **

*** Not intended for screening or notification of donors**

## Options for More Specific Testing When Anti-HCV Test Requested 

**Perform more specific testing on all screening-test positives; or**
**Use screening test positive signal to cutoff ratios to determine need for more specific testing **
**Cutoff performs the same regardless of the population being tested**

## Evaluation of Anti-HCV S/CO Ratios

**Screening tests**
**Ortho 3.0 enzyme immunoassay (EIA) (n=25,532)**
**Abbott 2.0 EIA (N=8,754)**
**Ortho VITROS enhanced chemiluminescent assay  (CIA) (n=1326)**
**More specific testing of screening-test positives**
**RIBA 3.0**
**NAT (Amplicor, Procleix, Nested RT-PCR)**

## Study Groups for Evaluating EIA and CIA S/Co Ratios by Prevalence of HCV Infection

**1187***

**2066**

**6606**

**388**

**6340**

*** Number tested**

**>9000**

- 12

## Proportion of Anti-HCV RR EIA Results Testing RIBA Positive by S/CO Ratio

**Source: MMWR 2003;52(No. RR-3):1-15.**

**(N=231)**

**(N=18)**

**(N=21)**

**(N=765)**

**EIA S/CO Ratio**

_** **__**_**_

- 13

## Proportion of Anti-HCV EIA* Screening-Test Positives Testing RIBA or NAT Positive by Average S/Co Ratio

**Source: MMWR 2003;52(No. RR-3):1-15.**

*** EIA 2.0 or EIA 3.0**

_**_**_

- 14

## Proportion of Anti-HCV CIA* Screening Test Positives Testing RIBA Positive by S/Co Ratio

**Source: MMWR 2003;52(No. RR-3):1-15**

*** VITROS Anti-HCV assay**

**Prevalence**

_**>**_

- 15

## Proportion of Anti-HCV Screening Test Positives Requiring RIBA Based on Low S/Co Ratiosby HCV Prevalence

**Source: MMWR 2003;52(No. RR-3):1-15**

- 16

## Using Screening Test Positive S/Co Ratio to Determine Need For Additional Testing* 

**Positives with high s/co ratios can be reported based on screening test results alone**
_**>**_**95% will be RIBA positive**
**Only positives with low s/co ratios require additional testing (most falsely positive)**
**<20% will confirm positive**
**Limits cost while improving accuracy of reported results**
**<5% of high risk persons require additional testing **

***Applies only to HCV EIA 2.0, HCV version 3.0 ELISA, and VITROS Anti-HCV**

## Implementation

**Determine reflex testing option to be used**
**Revise SOP**
**Algorithm chosen**
**Procedure for reporting results**
**Provide interpretation of results with report**
**Educate staff and customers**
**Modify requisition form**

## Implications

**Patients and physicians can reliably interpret results**
**Further clinical evaluation limited to true positives**
**Limit unnecessary medical visits and psychological stress on patients who test falsely positive**
**Substantially improve ability to establish public health surveillance systems to monitor effect of prevention and intervention activities**

## Slide 20

## Interpretation of HCV Test Results

**Screening ****	****RIBA for****	**** NAT for****	****Anti-HCV****	****HCV Infection**
**	**_**Test**_** ****	**_**Anti-HCV**_**	**_**HCV RNA**_**	****	**_**Status**_**	****	**_**Status**_

**	****+****	****-****	****	****	****NA****	****	****-****	****	****None**

**	****+****	****	****+****	****Not done****	****+****	****Past/current**

**	****+****	****+/****	****not done ****	****	****+****	****	****+****	****Current**
**	**

**	****+****	****Not done****	****Not done****	****Unknown****	****Unknown****	**