1. HCV Diagnosis

2. Features of Hepatitis C Virus Infection Incubation periodAverage 6-7 weeks Range 2-26 weeks Acute illness (jaundice)Mild (<20%) Case fatality rateLow Chronic infection75%-85% Chronic hepatitis70% (most asx) Cirrhosis10%-20% Mortality from CLD1%-5%

3. Chronic Hepatitis C Factors Promoting Progression or Severity Increased alcohol intake Age > 40 years at time of infection HIV co-infection ?Other –Male gender –Other co-infections (e.g., HBV)

4. Serologic Pattern of Acute HCV Infection with Recovery Symptoms +/- Time after Exposure Titer anti- HCV ALT Normal 012345 61234 Years Months HCV RNA

5. Serologic Pattern of Acute HCV Infection with Progression to Chronic Infection Symptoms +/- Time after Exposure Titer anti- HCV ALT Normal 012345 61234 Years Months HCV RNA

6. Estimated Incidence of Acute HCV Infection United States, 1960-1999 Decline in transfusion recipients Decline in injection drug users Source: Hepatology 2000;31:777-82; Hepatology 1997;26:62S-65S

7. Transmission of HCV Percutaneous –Injecting drug use –Clotting factors before viral inactivation –Transfusion, transplant from infected donor –Therapeutic (contaminated equipment, unsafe injection practices) –Occupational (needlestick) Permucosal –Perinatal –Sexual

8. Sources of Infection for Persons with Hepatitis C Sexual 15% Other* 5% Unknown 10% Injecting drug use 60% Transfusion 10% (before screening) *Nosocomial; Health-care work; Perinatal Source: Centers for Disease Control and Prevention

9. Posttransfusion Hepatitis C All volunteer donors HBsAg Donor Screening for HIV Risk Factors Anti-HIV ALT/Anti-HBc Anti-HCV Improved HCV Tests Adapted from HJ Alter and Tobler and Busch, Clin Chem 1997

10. HCV Testing Routinely Recommended Ever injected illegal drugs Received clotting factors made before 1987 Received blood/organs before July 1992 Ever on chronic hemodialysis Evidence of liver disease Healthcare, emergency, public safety workers after needle stick/mucosal exposures to HCV- positive blood Children born to HCV-positive women Based on increased risk for infection Based on need for exposure management

11. Routine HCV Testing Not Recommended (Unless Risk Factor Identified) Health-care, emergency medical, and public safety workers Pregnant women Household (non-sexual) contacts of HCV-positive persons General population

12. HCV Counseling Prevent transmission to others –Direct exposure to blood –Perinatal exposure –Sexual exposure Refer to support group

13. Preventing HCV Transmission to Others Do not donate blood, body organs, other tissue or semen Do not share items that might have blood on them –personal care (e.g., razor, toothbrush) –home therapy (e.g., needles) Cover cuts and sores on the skin Avoid Direct Exposure to Blood HCV Counseling

14. Mother-to-Infant Transmission of HCV Postexposure prophylaxis not available No need to avoid pregnancy or breastfeeding –Consider bottle feeding if nipples cracked/bleeding No need to determine mode of delivery based on HCV infection status Test infants born to HCV-positive women –Consider testing any children born since woman became infected –Evaluate infected children for CLD HCV Counseling

15. History of HCV Testing First tests licensed by the Food and Drug Administration in 1990 Since 1990 new versions of these and other FDA- approved anti HCV tests have been used for –Clinical Diagnosis of HCV –Screening of asymptomatic persons

16. Testing Rationale Testing for HCV infection by using anti-HCV is performed for 1)Clinical diagnosis of patients with signs or symptoms of liver disease 2)Management of occupational and perinatal exposures 3)Screening asymptomatic persons to identify HCV- infected persons who should receive counseling and related to the persons tested is often lacking, and even persons with risk factors for HCV infection might be at sufficiently low enough risk for infection that there screening tests could be falsely positive (e.g. health care professionals-risk but low prevalence)

17. HCV Infection Testing Algorithm for Diagnosis of Asymptomatic Persons EIA for Anti-HCV Negative (non-reactive) STOP Positive (repeat reactive) OR RIBA for Anti-HCV RT-PCR for HCV RNA Negative STOP Additional Laboratory Evaluation (e.g. PCR, ALT) Negative Positive Indeterminat e Medical Evaluation Positive Negative PCR, Normal ALT Positive PCR, Abnormal ALT Source: MMWR 1998;47 (No. RR 19)

18. Approved Testing Kits Comprised of –Two enzyme immunoassays (EIA) Abbot HCV EIA 2.0 ORTHO HCV Version 3.0 ELISA –One enhanced chemiluminescence immunoassay (CIA) VITROS All of the above immunoassays use HCV- encoded recombinant antigens

19. Available Supplemental Tests Tests include –Serologic anti-HCV assay Nucleic acid test (NAT) –Qualitative detection of HCV-RNA »AMPLICOR Version 2 »COBAS AMPLICOR Version 2 Recombinant immunoblot assay (RIBA) The Laboratory used determines the type of test performed

20. Interpreting Antibody to Hepatitis C Virus (anti-HCV) Test Results

21. Anti-HCV -Positive Defined as 1) Anti-HCV screening test positive* AND Recombinant immunoblot assay (RIBA)-positive OR Nucleic acid test (NAT) – positive *Interpretation of screening immunoassasy test results based on criteria provided by the manufacturer

22. Anti-HCV -Positive 2) anti-HCV screening test positive, NAT- negative, RIBA- positive –An anti-HCV positive result indicates past or current HCV infection. An HCV RNA-positive result indicates current (active) infection BUT the significance of a single HCV RNA-negative result is unknown; it does not differentiate intermittent viremia from resolved infection

23. Anti-HCV-Positive All anti-HCV positive persons should receive –Counseling –Undergo medical evaluating, including additional testing for the presence of virus and liver disease Anti-HCV testing usually does not need to be repeated after a positive anti-HCV result has been confirmed

24. Anti-HCV -Negative Defined as: 1)Anti-HCV screening test negative* OR 2) Anti-HCV screening test positive, RIBA- negative OR 3) Anti-HCV screening test positive, NAT- negative, RIBA-negative *Interpretation of screening immunoassasy test results based on criteria provided by the manufacturer

25. Anti-HCV- Negative An anti-HCV person is considered uninfected No further evaluation or follow-up for HCV is required, unless recent infection is suspected or other evidence exists to indicate HCV infection Abnormal liver enzyme levels in an immuno- compromised person A person with no other etiology for their liver disease

26. Anti-HCV- Indeterminate Defined as: Anti-HCV screening test positive, RIBA- indeterminate

27. Anti-HCV- Indeterminate An indeterminate anti-HCV result indicates that the HCV antibody status cannot be determined –Can indicate a false positive anti HCV screening test result, the most likely interpretation among those at low risk for HCV infection; such persons are HCV RNA- negative –Can occur as a transient finding in a recently infected person who is in the process of seroconversion: such persons usually are HCV RNA -positive

28. Anti-HCV- Indeterminate –Can be persistent finding among persons chronically infected with HCV; such persons usually are HCV RNA -positive If NAT is not performed, another sample should be collected for repeat anti-HCV testing (> 1 month later)

29. Signal to Cutoff Ratios Analysis of enzyme immunoassay and chemiluminescence assay data indicates that s/co ratios can be used to predict supplemental test-positive results A specific s/co ratio can be identified for each test that would predict a true antibody-positive result (as defined by the results of supplemental testing) ≥95% of the time, regardless of the anti- HCV prevalence or characteristics of the population being tested.

30. Screening test kit nameManufacturerAssay Format Signal-to-cut—off ratio predictive of a true positive ≥ 95% of the time Ortho HCV Version 3.0 ELISA Test System Ortho EIA (Enzyme Immunoassay) ≥ 3.8 Abbott HCV EIA 2.0Abbott EIA (Enzyme Immunoassay) ≥ 3.8 VITROS Anti-HCVOrtho CIA (Chemiluminescennt Immunoassay) ≥ 8.0 AxSYM Anti-HCVAbbott MEIA (Microparticle Immunoassay) ≥ 10.0 Architect Anti-HCVAbbott CMIA (Chemiluminescent Microparticle Immunoassay) ≥ 5.0 Advia Centaur HCVBayer CIA (Chemiluminescennt Immunoassay) ≥ 11.0