What labs are recommended for Hepatitis C screening in high-risk individuals?

Laboratory Testing for Hepatitis C Screening

All persons being screened for hepatitis C should first undergo HCV antibody testing with reflex HCV RNA PCR testing using a single blood draw. 1, 2, 3

Initial Screening Test

• The two-step reflex testing approach is the standard of care: Start with an FDA-approved anti-HCV antibody assay (enzyme immunoassay or rapid test), followed by automatic reflex to HCV RNA PCR testing if the antibody is positive. 1, 2, 3
• This reflex approach requires only a single blood collection, eliminating the need for patients to return for confirmatory testing and preventing loss to follow-up—a major barrier in the HCV care continuum. 2, 3
• A nonreactive (negative) antibody result indicates no HCV infection and no further testing is needed in immunocompetent persons without recent exposure. 2

Test Interpretation After Initial Screening

• HCV antibody positive + HCV RNA positive = Current active infection requiring treatment evaluation. 2, 3
• HCV antibody positive + HCV RNA negative = Prior resolved infection (or false positive); the patient does not have current infection but is not protected from reinfection. 2, 3
• HCV antibody negative = No evidence of infection unless recent exposure or immunocompromised status applies. 3

Special Testing Scenarios

Recent Exposure (Within 6 Months)

• If the initial antibody test is negative but exposure occurred within the past 6 months, perform direct HCV RNA testing or repeat antibody testing ≥6 months after exposure. 1, 2, 3
• Antibody production may be delayed 8-9 weeks after exposure, so RNA testing is superior for detecting acute infection. 2

Immunocompromised Patients

• Consider direct HCV RNA testing for immunocompromised patients (including those with HIV, on dialysis, or receiving immunosuppressive therapy), as antibody production may be delayed or inadequate. 2, 3
• This is a critical pitfall to avoid—relying solely on antibody testing in immunocompromised patients can miss active infection. 2, 3

Suspected Reinfection

• For patients at risk for reinfection (e.g., ongoing injection drug use), use HCV RNA testing rather than antibody testing, since antibodies remain positive after prior clearance. 2, 3

Pre-Treatment Laboratory Evaluation (Once Active Infection Confirmed)

After confirming active HCV infection with positive HCV RNA, obtain the following baseline tests before initiating therapy:

• Quantitative HCV RNA viral load to establish baseline. 2, 3
• HCV genotype determination (though less critical now with pangenotypic direct-acting antivirals). 2
• Complete blood count (CBC) 2
• Comprehensive metabolic panel 2
• Hepatic function panel 2
• International normalized ratio (INR) 2
• Hepatitis B surface antigen and HIV antibody testing due to overlapping risk factors and impact on prognosis and treatment. 1, 2

Who Should Be Screened

Universal Screening

• All adults aged 18-79 years should receive one-time screening regardless of risk factors. 3
• The American Association for the Study of Liver Diseases recommends universal screening for all adults aged 18 years and older without an upper age limit. 3
• All pregnant women should be screened during each pregnancy. 3

Risk-Based Screening (Key High-Risk Groups)

• Current or past injection drug users (even if only once). 1
• Persons on long-term hemodialysis (ever). 1
• Recipients of blood transfusions or organ transplants before July 1992. 1
• Recipients of clotting factor concentrates produced before 1987. 1
• HIV-infected individuals. 1
• Persons with unexplained chronic liver disease or persistently elevated ALT levels. 1
• Healthcare workers after needlestick or mucosal exposure to HCV-infected blood. 1
• Children born to HCV-infected mothers. 1
• Persons who were ever incarcerated. 1
• Men who have sex with men (especially HIV-positive men engaging in unprotected sex). 1
• Persons with intranasal illicit drug use. 1
• Persons who received tattoos in unregulated settings. 1

Periodic Screening for Ongoing Risk

• Annual HCV testing is recommended for persons who inject drugs and HIV-seropositive men who have unprotected sex with men. 1, 3
• Periodic testing should be offered to other persons at ongoing risk of HCV exposure, with frequency determined by individual risk assessment. 1, 3

Common Pitfalls to Avoid

• Never rely solely on antibody testing to determine active infection—this misses the critical distinction between current and resolved infection. 2, 3
• Do not use antibody testing to detect reinfection in previously infected patients, as antibodies remain positive after clearance; always use HCV RNA testing. 2, 3
• Ensure reflex RNA testing is implemented to avoid loss to follow-up between antibody and confirmatory testing. 2, 3
• Do not use ALT levels alone to screen or stage disease—ALT fluctuates and does not correlate with fibrosis stage, and 20-30% of infected persons have persistently normal ALT. 1, 2
• Remember that immunocompromised patients may have false-negative antibody tests—consider direct RNA testing in these populations. 2, 3
• Do not assume elevated ALT is required for diagnosis—if all persons with a single elevated ALT were tested, approximately 50% of chronic cases would remain unidentified. 1