What does a reactive Hepatitis C Virus (HCV) Antibody (Ab) result mean?

What Does a Reactive HCV Antibody Mean?

A reactive HCV antibody result means that antibodies to hepatitis C virus have been detected in your blood, indicating one of three possibilities: current HCV infection, past resolved infection, or a false-positive result. 1

Immediate Next Step Required

You must obtain HCV RNA testing to determine if there is active infection. 1, 2 The antibody test alone cannot distinguish between these three scenarios, making RNA testing essential for proper diagnosis and management. 1

Three Possible Interpretations

1. Current Active Infection

• If HCV RNA is detected, this confirms current HCV infection requiring medical evaluation and potential antiviral treatment 1, 2
• Most persons with detectable HCV RNA have chronic infection 1
• These patients need counseling, preventive services, and evaluation for treatment 1

2. Past Resolved Infection

• If HCV RNA is not detected, this indicates either past infection that has resolved (spontaneously in 15-25% of acute cases or through successful treatment) 2
• These patients are not infectious and require no treatment 2
• Important caveat: They can be reinfected if exposed again, as HCV antibodies do not provide protective immunity 2, 3

3. False-Positive Result

• If HCV RNA is not detected, this may also represent a false-positive antibody test 1, 2
• False-positive rates are substantial: approximately 35% (range 15-60%) in low-prevalence populations such as general population, healthcare workers, and blood donors 1
• In immunocompromised populations (e.g., hemodialysis patients), false-positive rates average 15% 1

Testing Algorithm

For most patients with reactive HCV antibody:

• Proceed directly to HCV RNA testing on the same or subsequent blood sample 1
• No additional antibody testing is needed 1

Special circumstances requiring consideration:

• Recent exposure (within 6 months): May need repeat HCV RNA or follow-up antibody testing, as antibodies may not yet be detectable 1
• Immunocompromised patients: Consider HCV RNA testing even if initial antibody is negative, as these patients may be persistently antibody-negative despite chronic infection 1

Clinical Management Based on Results

If HCV RNA is detected (active infection):

• Refer for hepatitis specialist evaluation 1
• Assess liver disease with ALT and other liver function tests 1
• Counsel on transmission prevention 1
• Consider hepatitis A and B vaccination 1
• Advise alcohol avoidance or reduction 1

If HCV RNA is not detected (no active infection):

• No further action required in most cases 2
• Patient is not infectious and needs no isolation precautions 2
• Repeat RNA testing only if: suspected recent exposure, clinical evidence of liver disease, or immunocompromised status 1, 2

Common Pitfalls to Avoid

• Never rely solely on antibody results to diagnose active HCV infection—this leads to unnecessary treatment considerations or missed diagnoses 1
• Do not assume immunity: A reactive antibody does not mean protection from future infection 2, 3
• Consider timing: In acute infection, antibodies may not appear for weeks, while HCV RNA can be detected as early as 1-2 weeks after exposure 1
• Signal-to-cutoff ratios matter: Very low antibody levels (low S/CO ratios) are more likely false-positives, though current CDC guidelines recommend RNA testing regardless rather than using supplemental antibody tests like RIBA 1, 4