What are the next steps after a positive Hepatitis C (HCV) antibody test?

Follow-Up Testing After a Positive Hepatitis C Antibody Test

After a positive hepatitis C antibody test, the next essential step is to order HCV RNA testing (nucleic acid test) to confirm current infection status, as antibody testing alone cannot distinguish between active infection and resolved past infection.

Diagnostic Algorithm for Positive HCV Antibody

1. Confirm active infection with HCV RNA testing

   • HCV RNA testing is mandatory following a positive antibody test 1, 2
   • This distinguishes between:
     • Current active infection (HCV RNA positive)
     • Resolved past infection or false-positive result (HCV RNA negative)

2. Interpret results based on HCV RNA findings:

   HCV Antibody	HCV RNA	Interpretation	Next Steps
   Positive	Positive	Current HCV infection	Medical evaluation and treatment
   Positive	Negative	Resolved infection OR false positive	Consider testing with alternative antibody assay

For Patients with Confirmed Active HCV Infection (RNA Positive)

1. Initial laboratory assessment:

   • Baseline viral load (quantitative HCV RNA)
   • Liver function tests: ALT, AST, bilirubin, albumin
   • Complete blood count and platelet count
   • Prothrombin time
   • HCV genotype testing 1, 2

2. Additional testing:

   • Screen for coinfections (HIV, HBV, HAV) 1, 2
   • Consider vaccination against HAV and HBV if not immune 1

3. Referral:

   • Refer to a specialist experienced in managing HCV infection 1

For Patients with Positive Antibody but Negative RNA

If HCV RNA is negative with a positive antibody test, consider:

1. Testing with an alternative antibody assay platform to distinguish between:

   • False-positive initial antibody test (alternative assay negative)
   • Cleared infection (alternative assay positive) 1

2. Repeat HCV RNA testing if:

   • Recent exposure is suspected (within past 6 months)
   • Clinical evidence of liver disease exists
   • Concerns about specimen handling or storage 1

Important Considerations

• HBV reactivation risk: Test all patients for HBsAg and anti-HBc before initiating HCV treatment, as HBV reactivation can occur during or after HCV treatment 3, 4

• False negatives: HCV RNA may be intermittently detectable in chronic infection, so a single negative result should be interpreted with caution in the appropriate clinical context 1

• Testing gaps: Studies show approximately one-third of antibody-positive patients do not receive follow-up RNA testing, leading to incomplete diagnosis 5

• Reflex testing: Consider implementing reflex HCV RNA testing for all positive antibody tests to improve diagnostic completion rates 5

Common Pitfalls to Avoid

1. Stopping at antibody testing alone - This provides incomplete diagnostic information and can miss active infections requiring treatment

2. Misinterpreting a positive antibody test as definitive evidence of current infection - Remember that 15-45% of infected individuals spontaneously clear the virus while remaining antibody-positive 2

3. Failing to test for HBV coinfection - HBV reactivation during HCV treatment can lead to severe hepatitis, liver failure, and death in some cases 3, 4

4. Missing intermittent viremia - A single negative HCV RNA test may not definitively rule out infection in all cases, particularly early in infection 1

By following this systematic approach to follow-up testing after a positive HCV antibody result, you can accurately diagnose patients and ensure they receive appropriate evaluation and treatment when needed.