What does a positive Hepatitis C (HCV) antibody test result indicate?

What Does a Positive Hepatitis C Antibody Test Mean?

A positive HCV antibody test indicates either current HCV infection or past infection that has cleared—it does NOT distinguish between active and resolved infection, so you must immediately order HCV RNA testing to determine if the patient has active viremia requiring treatment. 1

Critical First Step: Confirm with HCV RNA Testing

• All patients with a positive HCV antibody must undergo HCV RNA (nucleic acid) testing to differentiate active infection from cleared infection 1, 2
• HCV RNA testing should ideally be performed reflexively or as soon as possible after the positive antibody result 1, 3
• The HCV RNA test is the definitive marker for active, current infection 1, 4

Interpreting the Results

If HCV Antibody Positive AND HCV RNA Positive:

• This confirms active HCV infection requiring immediate medical evaluation, liver disease assessment, and consideration for antiviral treatment 1, 2
• These patients need referral for further evaluation including liver function tests (ALT/AST), assessment of liver fibrosis, and HCV genotyping 2, 4
• Counsel patients about preventing transmission, alcohol avoidance, and hepatitis A/B vaccination if susceptible 1

If HCV Antibody Positive BUT HCV RNA Negative:

• This result has two possible interpretations that require additional testing to distinguish 5, 2:

  • Cleared/resolved infection (15-45% of infections spontaneously clear, with higher rates in younger patients) 1, 5
  • False-positive antibody test (particularly common in low-prevalence populations where 15-60% of positive antibody tests are false-positives) 1

• The CDC recommends performing repeat HCV antibody testing using a different antibody assay platform to distinguish these two scenarios 5

• If the second antibody test is negative, the initial test was false-positive and no infection occurred 5

• If the second antibody test is positive, the infection has cleared and the patient does not need treatment 5

Important Clinical Caveats

False-Positive Antibody Results Are Common:

• In low-prevalence populations (general population, healthcare workers, blood donors), approximately 35% of positive antibody tests are false-positives (range 15-60%) 1
• This is why you cannot rely on antibody testing alone—supplemental testing is mandatory 1

False-Negative Scenarios to Consider:

• Early acute infection: Antibodies may not be detectable for the first few weeks after exposure, though HCV RNA can be detected as early as 1-2 weeks post-exposure 1
• Immunocompromised patients: May have persistently negative antibodies despite active infection; HCV RNA may be the only evidence of infection 1
• Resolved infection with antibody waning: Rarely, antibodies decline below detectable levels in persons whose infection has cleared 1

Intermittent Viremia:

• A single negative HCV RNA does not definitively exclude active infection in all cases 1, 2
• Intermittent HCV RNA positivity can occur in chronic infection 1, 2
• Consider repeat HCV RNA testing if clinical suspicion remains high, especially with recent exposure within 6 months, clinical evidence of liver disease, or immunocompromised status 5, 2

Common Pitfalls to Avoid

• Never assume a positive antibody alone means active infection—you must confirm with HCV RNA 1
• Never assume a single negative HCV RNA definitively rules out infection without confirmatory antibody testing on an alternative platform when the initial antibody was positive 5, 2
• Do not order unnecessary repeat testing in patients with confirmed cleared infections (antibody positive, RNA negative on multiple occasions) 5
• Ensure proper specimen handling for HCV RNA testing—improper handling can lead to false-negative results 2