What is the recommended screening test for Hepatitis C (HCV) infection?

Recommended Screening Test for Hepatitis C Infection

The recommended screening test for Hepatitis C (HCV) infection is a two-step process starting with HCV-antibody testing using an FDA-approved assay, followed by reflex HCV RNA polymerase chain reaction (PCR) testing to confirm active infection. 1

Initial Screening Approach

• HCV screening should follow a two-step process that begins with HCV-antibody testing and automatically proceeds to reflex HCV RNA PCR testing when antibody results are positive 1
• The reflex testing approach requires only a single blood collection, eliminating the need for patients to return for confirmatory testing, which addresses a major barrier in the HCV care continuum 1
• This approach is endorsed by the American Association for the Study of Liver Diseases as the standard initial screening strategy for hepatitis C infection in adults 1

Special Testing Considerations

• For individuals with recent exposure (within 6 months), HCV RNA testing or follow-up HCV-antibody testing at least 6 months after exposure is recommended if initial antibody tests are negative 1
• Direct HCV RNA testing should be considered for immunocompromised patients, as antibody production may be delayed or inadequate in these individuals 1
• For patients at risk for reinfection, HCV RNA testing is recommended since antibody tests will remain positive after prior clearance of infection 1
• In rural or difficult-to-access populations, dried blood spot collection can be used for sequential antibody and reflex RNA testing, requiring only a fingerstick rather than venipuncture 1

Test Interpretation

• A positive antibody test with positive RNA indicates current (active) HCV infection, requiring evaluation for treatment 1
• A positive antibody test with negative RNA suggests past resolved infection or false positive; these patients should be informed they do not have current infection but are not protected from reinfection 1
• A negative antibody test indicates no evidence of current or past infection, unless there was recent exposure or the patient is immunocompromised 1

Common Pitfalls to Avoid

• Relying solely on antibody testing without reflex RNA testing can miss active infection or incorrectly classify resolved infections as current 1
• Failure to implement reflex RNA testing can lead to patients being lost to follow-up between antibody and confirmatory testing 1
• Using only antibody testing in previously infected patients will miss reinfection, as antibodies persist after viral clearance 1
• Missing the diagnosis in high-risk groups, especially in people who inject drugs or immunocompromised patients, can have significant consequences 1

Who Should Be Screened

• Universal screening with one-time HCV testing is recommended for all adults aged 18-79 years 1, 2
• Risk-based screening is recommended for persons under 18 years with risk factors, such as those with a history of injection drug use 1
• Periodic testing is recommended for those with ongoing risk factors, with frequency determined by individual risk assessment 1
• Annual testing is specifically recommended for people who inject drugs and men with HIV who have unprotected sex with men 1

The two-step HCV antibody testing with reflex HCV RNA PCR approach has become the standard of care, replacing older screening methods that required separate confirmatory testing visits, which often resulted in patients being lost to follow-up 1, 2. This approach provides the most efficient and accurate method for identifying both past exposure and current active infection.