What is the next step for a patient with a reactive Hepatitis C Antibody (HCV Ab) test result?

Management of Reactive Hepatitis C Antibody Test Results

The next step for a patient with a reactive Hepatitis C Antibody (HCV Ab) test result is to perform HCV RNA testing (nucleic acid test/NAT) to determine if there is current HCV infection. 1

Understanding HCV Antibody Results

A reactive HCV antibody result indicates one of three possibilities:

1. Current HCV infection
2. Past HCV infection that has resolved
3. False positive result

HCV RNA testing is essential because:

• It detects HCV viremia, which is only present in currently infected individuals
• It distinguishes between active infection requiring treatment and resolved infection
• It confirms true infection versus false positive antibody results

Testing Algorithm

Step 1: HCV RNA Testing

• For patients with reactive HCV antibody results, perform HCV RNA testing using an FDA-approved nucleic acid test (NAT) 1
• This can be done through several operational approaches:
  • Reflex testing using the same blood sample (preferred)
  • Collection of a second specimen during the same visit
  • Scheduling a follow-up visit for RNA testing

Step 2: Interpretation of HCV RNA Results

• If HCV RNA is detected:

  • Confirms current HCV infection
  • Patient requires evaluation for treatment
  • Report to health department as required by local regulations 1

• If HCV RNA is not detected:

  • Indicates either past, resolved HCV infection or false antibody positivity
  • Consider repeat HCV RNA testing if:
    • Recent exposure (within past 6 months)
    • Clinical evidence of HCV disease
    • Concerns about specimen handling/storage 1

Special Considerations

Recent Exposure

• For persons potentially exposed to HCV within the past 6 months, consider:
  • Direct HCV RNA testing even with negative antibody
  • Follow-up HCV antibody testing 1

Immunocompromised Patients

• Consider direct HCV RNA testing as antibody tests may be falsely negative 1, 2

Distinguishing False Positivity from Resolved Infection

• If clinically important to differentiate between past resolved infection and false positive:
  • Consider testing with a second, different HCV antibody assay 1
  • HCV antibody assays vary in antigens, platforms, and performance characteristics, making biologic false positivity unlikely across multiple tests 1

Additional Testing for HBV Co-infection

• Test all patients with HCV for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc before initiating HCV treatment 3
• HBV reactivation has been reported in HCV/HBV coinfected patients undergoing HCV treatment with direct-acting antivirals 3
• Monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during and after HCV treatment in patients with serologic evidence of HBV infection 3

Benefits of Complete Testing

Accurate identification of current HCV infection enables:

1. Appropriate care and treatment to be offered
2. Patients to make informed decisions about medical care and treatment options
3. Implementation of measures to limit disease progression (e.g., alcohol reduction, hepatitis A/B vaccination)
4. Reduction of transmission risk 1

Common Pitfalls to Avoid

• Loss to follow-up: Only 54% of public health laboratories automatically reflex HCV antibody-reactive specimens to HCV RNA testing, potentially leading to incomplete diagnosis 4
• Delayed diagnosis: Separate appointments for RNA testing increase the risk of patients being lost to follow-up 5
• Incomplete testing: Failing to test for HBV co-infection before initiating HCV treatment 3
• Misinterpretation: Assuming antibody positivity always indicates current infection 6, 7

Reflex HCV RNA testing has been shown to increase HCV viral load test uptake (RR: 1.35; 95% CI: 1.16-1.58) and may improve linkage to care among people with positive HCV RNA tests 5.