What does a hepatitis C antibody reactive result indicate?

What Does a Hepatitis C Antibody Reactive Result Mean?

A reactive hepatitis C antibody test indicates one of three possibilities: current HCV infection, past resolved HCV infection, or false positivity—and you must immediately proceed to HCV RNA testing to determine which. 1

The Three Possible Interpretations

A reactive anti-HCV result does not confirm active infection. According to CDC guidelines, it means: 1

• Current HCV infection (most common in high-risk populations)
• Past, resolved infection (antibodies persist after viral clearance)
• False-positive result (particularly in low-prevalence populations)

Critical Next Step: HCV RNA Testing

You cannot stop at a reactive antibody test—reflex HCV RNA testing is mandatory. 1

The Testing Algorithm:

• If HCV RNA is detected → Current HCV infection confirmed; patient needs treatment evaluation 1
• If HCV RNA is not detected → Either past resolved infection OR false-positive antibody result 1

The distinction between current and past infection is crucial because only patients with detectable HCV RNA require antiviral therapy and are infectious to others. 1

Understanding False-Positive Results

False-positive antibody results are surprisingly common, especially in low-risk populations. Even with test specificity >99%, the positive predictive value drops significantly in populations with HCV prevalence <10%. 1

False-Positive Rates by Population:

• Low-risk populations (blood donors, general population, healthcare workers): approximately 35% false-positive rate (range 15-60%) 1
• Immunocompromised populations (hemodialysis patients): approximately 15% false-positive rate 1

This is why you should never rely exclusively on a reactive antibody screening test to determine HCV infection status. 1

Practical Implementation

The recommended approach is reflex testing—automatically performing HCV RNA testing on the same specimen when antibody is reactive, without requiring a second blood draw. 1, 2

Operational Options:

• Reflex testing from same specimen: The initial blood sample is automatically tested for HCV RNA if antibody is reactive (preferred method) 1
• Second venipuncture: New blood draw for HCV RNA if initial sample was antibody-reactive 1

Only 54% of U.S. public health laboratories consistently perform automatic reflex RNA testing, representing a significant gap in practice that can lead to patients being lost to follow-up. 2

Important Caveats

Early Infection Window Period:

Antibody tests can be falsely negative in the first weeks after infection (during the "window period" before antibody develops), though HCV RNA becomes detectable within 1-2 weeks of exposure. 1 If recent exposure is suspected (within past 6 months) and antibody is negative, HCV RNA testing should still be performed. 1

Immunocompromised Patients:

Occasionally, immunocompromised patients with chronic HCV infection remain persistently antibody-negative, and HCV RNA detection may be the only evidence of infection. 1 Consider direct RNA testing in immunocompromised individuals even with negative antibody results if clinical suspicion exists. 1

Resolved Infection:

In some patients whose HCV infection has spontaneously resolved, anti-HCV antibodies may decline below detectable levels over time, though this is uncommon. 1

What NOT to Do

Do not report a reactive antibody result as "HCV positive" without confirmatory RNA testing. 1 This causes unnecessary psychological harm and inappropriate medical interventions in patients with false-positive results. 1

Do not assume antibody presence means current infection—antibodies do not distinguish between current and past infection. 1