What are the implications and next steps for a patient with a reactive Hepatitis C (HCV) antibody test but undetectable HCV RNA by real-time PCR, indicating a potentially cleared infection?

Interpretation: Resolved HCV Infection

This patient has either a past, resolved HCV infection or a false-positive antibody test—they do NOT have active hepatitis C and do NOT require antiviral treatment. 1

Diagnostic Interpretation

Your test results indicate:

• Reactive HCV antibody: Indicates prior exposure to hepatitis C virus
• Undetectable HCV RNA (<15 IU/mL): Confirms absence of active viral replication 1

According to CDC and EASL guidelines, when HCV RNA is undetectable in an anti-HCV positive patient, this indicates either past resolved infection or false antibody positivity. 1

Mandatory Next Step: Confirmatory Testing

You must repeat HCV RNA testing in 3 months (12 weeks) to definitively confirm viral clearance. 1

This is critical because:

• Brief periods of undetectable HCV RNA can occur during active infection, particularly in acute hepatitis C 1, 2
• Spontaneous viral clearance typically occurs within 4-6 months of initial infection, so testing beyond this window confirms true resolution 1
• A single negative RNA test is insufficient to rule out active infection in certain contexts 3

Clinical Implications During the 3-Month Window

The patient is NOT infectious and does NOT require treatment at this time. 1

However, you should:

• Counsel the patient that they likely cleared the infection either spontaneously or after previous treatment (if applicable) 1
• Advise risk reduction to prevent reinfection if ongoing risk factors exist (injection drug use, high-risk sexual practices) 1
• Check liver enzymes (ALT) to assess for any residual liver inflammation 4, 2

After Confirmatory Testing at 3 Months

If HCV RNA remains undetectable:

• Diagnosis confirmed: Past, resolved HCV infection 1
• No antiviral therapy needed 1
• Counsel on reinfection risk if ongoing exposure risk exists 1
• Consider hepatitis A and B vaccination if not immune 1
• No further HCV RNA monitoring needed unless new risk exposure occurs 1

If HCV RNA becomes detectable:

• This would indicate either:
  • Acute infection that was in an early fluctuating phase 2
  • New reinfection (requires genotype comparison if prior infection documented) 1
• Proceed with full HCV workup: quantitative HCV RNA, genotyping, liver disease staging 3
• Initiate antiviral therapy per current treatment guidelines 1

Critical Pitfall to Avoid

Do NOT assume this is a false-positive antibody without confirmatory RNA testing at 3 months. While false-positive HCV antibodies can occur (particularly in low-risk populations with autoimmune conditions), the majority of reactive antibody tests in patients without detectable RNA represent true past infection that has cleared. 1, 4 The 3-month retest distinguishes between these scenarios and catches any cases of fluctuating viremia. 1