Does a reactive Hepatitis C (Hep C) antibody test result in an adult with a history of high-risk behaviors indicate active Hepatitis C infection?

Does a Reactive Hepatitis C Antibody Mean Active Infection?

No, a reactive Hepatitis C antibody test does NOT necessarily mean active infection—it only indicates exposure to HCV at some point, which could represent current infection, past resolved infection, or a false-positive result. 1, 2

Critical Next Step: HCV RNA Testing Required

You must immediately proceed to HCV RNA testing to determine if active infection is present. 1, 2 The antibody test alone cannot distinguish between these three scenarios and therefore cannot guide clinical management. 1

Interpretation Algorithm

If HCV RNA is Detected (Positive):

• This confirms current, active HCV infection requiring medical evaluation and antiviral treatment consideration. 2, 3
• The patient is infectious to others and needs transmission prevention counseling. 2
• Most individuals with detectable HCV RNA have chronic infection. 2

If HCV RNA is Not Detected (Negative):

• This definitively indicates NO current HCV infection. 2, 4, 3
• The reactive antibody represents one of three possibilities:
  • Past resolved infection (most common—occurs in 15-25% of older adults, 40-45% of those infected when younger) 1
  • Successful past antiviral treatment 4, 3
  • False-positive antibody test (approximately 35% of reactive results in low-prevalence populations) 2, 4
• The patient is NOT infectious and does NOT require treatment. 2, 3
• No further testing is typically needed. 2, 4

Important Clinical Caveats

When to Repeat HCV RNA Testing Despite Initial Negative Result:

• Recent exposure within the past 6 months (window period consideration) 2, 4, 3
• Immunocompromised patients (may have delayed or intermittent viremia) 2, 4
• Clinical evidence of active liver disease (elevated ALT, hepatic symptoms) 2, 4
• Concerns about specimen handling or storage 2, 4

Critical Pitfall to Avoid:

Do NOT treat patients based on antibody results alone without confirming active infection with HCV RNA. 3 Many clinicians mistakenly assume a reactive antibody means active disease, leading to unnecessary treatment or conversely, failure to confirm active infection in those who need therapy. 1

Additional Considerations:

• HCV RNA can be transiently negative during acute infection as antibody titers rise. 1
• Intermittent HCV RNA positivity has been observed in chronic infection. 1
• HCV antibodies do NOT provide protective immunity—patients can be reinfected if exposed again. 2, 4
• In high-risk populations with ongoing exposure risk, periodic retesting may be warranted even after negative RNA results. 3

The bottom line: Reactive antibody = exposure history. Only HCV RNA = active infection requiring treatment. 2, 4