What is the next step after testing positive for Hepatitis C Virus (HCV) antibodies?

Next Steps After Positive HCV Antibody Test

After testing positive for Hepatitis C Virus (HCV) antibodies, the next step should be HCV RNA testing with a quantitative nucleic acid test to confirm active infection. 1, 2

Testing Algorithm Following Positive HCV Antibody

A positive HCV antibody test can indicate three possibilities:

• Current active HCV infection (acute or chronic)
• Past resolved HCV infection
• False positive result 1

Confirmatory Testing

1. HCV RNA Testing:

   • Perform quantitative nucleic acid test (NAT) for HCV RNA
   • Ideally, this should be done as a reflex test from the same blood sample 1
   • Use an FDA-approved assay with detection level ≤25 IU/mL 1

2. Interpretation of Results:

   • If HCV RNA is detected: Confirms current HCV infection
   • If HCV RNA is not detected: Indicates either resolved infection or false positive antibody 1

Management Based on HCV RNA Results

If HCV RNA is Positive (Active Infection):

• Obtain baseline laboratory tests:
  • Liver function tests (ALT, AST, bilirubin, albumin)
  • Complete blood count
  • Prothrombin time/INR
  • Renal function tests 2
• Consider HCV genotype testing if it may alter treatment recommendations 1
• Evaluate for liver fibrosis severity using non-invasive markers or liver biopsy 2
• Screen for coinfections (HBV, HIV) 2
• Refer to a hepatologist or infectious disease specialist for treatment evaluation 1, 2
• Counsel patient about preventing transmission 2

If HCV RNA is Negative:

• To distinguish between false positive antibody and resolved infection:
  • Consider retesting with an alternative HCV antibody assay platform 1
  • If alternative antibody test is negative: Initial test was likely false positive
  • If alternative antibody test is positive: Indicates cleared infection 1
• Inform patient they do not have evidence of current infection but are not protected from reinfection 1

Special Considerations

• Recent Exposure: If exposure to HCV occurred within the past 6 months and HCV RNA is negative, repeat HCV RNA or antibody testing 6 months after exposure 1
• Immunocompromised Patients: Consider HCV RNA testing even with negative antibody results, as antibody response may be diminished 1
• High-Risk Individuals: For persons at risk for reinfection (e.g., PWID, HIV-positive MSM), annual HCV testing is recommended 1

Common Pitfalls to Avoid

• Incomplete Testing: Approximately one-third of antibody-positive patients do not receive RNA testing, leading to incomplete diagnosis 3
• False Reassurance: Don't assume a negative HCV RNA test excludes infection if tested during the acute phase, as viral load may fluctuate 1
• Delayed Follow-up: Ensure RNA testing is completed promptly; reflex testing from the initial sample is ideal to prevent loss to follow-up 1, 3
• Misinterpretation: Don't assume normal ALT excludes viral hepatitis, as levels may fluctuate or be normal in chronic infection 2

By following this algorithm, you can accurately determine whether a patient with positive HCV antibodies has active infection requiring treatment or has resolved infection/false positive result, ensuring appropriate clinical management and counseling.