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 (NAT) to confirm active infection. 1

Understanding HCV Antibody Results

A positive HCV antibody test can indicate three possible scenarios:

• Current active HCV infection
• Past resolved HCV infection
• False positive result 1

This is why RNA testing is essential to determine the current infection status.

Recommended Testing Algorithm

1. HCV RNA Testing (Quantitative NAT)

   • Should ideally be performed as a reflex test from the same blood sample
   • Use an FDA-approved assay with detection level ≤25 IU/mL 1
   • This test directly confirms the presence of the virus

2. Interpretation of Results:

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

Additional Testing for Confirmed Active Infection

For patients with confirmed active HCV infection (RNA positive), the following assessments should be performed:

• Liver fibrosis assessment
• Screening for coinfections:
  • Test for HBV (HBsAg and anti-HBc)
  • Test for HIV
• Liver function tests: ALT, AST, bilirubin, albumin, INR
• Complete blood count
• Creatinine (to evaluate kidney function) 1

Special Considerations

• Recent exposure: For individuals with exposure within the past 6 months and negative HCV RNA, repeat testing is recommended 6 months after exposure 1

• Immunocompromised patients: May require HCV RNA testing even with negative antibody results, as their antibody response may be diminished 1

• HBV coinfection risk: Test all patients for evidence of current or prior HBV infection (HBsAg and anti-HBc) before initiating HCV treatment, as HBV reactivation can occur during HCV treatment 2, 3

Patient Counseling

• Patients with resolved infection or false positive results should be informed they do not have evidence of current infection but are not protected from future infection 1

• For confirmed active infection, counsel on:

  • Alcohol abstinence
  • Preventing transmission
  • Treatment options with direct-acting antivirals (DAAs) 1

Common Pitfalls to Avoid

• Incomplete testing: Studies show up to 33% of antibody-positive patients do not receive RNA testing to confirm diagnosis 4

• Loss to follow-up: Consider reflex RNA testing from the initial sample to prevent patients not returning for confirmatory testing 1

• False positives: False-positive antibodies are more common during acute viral hepatitis (29% in one study) and are associated with higher IgM levels 5

• Misinterpreting antibody positivity: Antibody positivity alone cannot distinguish between current infection, past infection, or false positive results 6