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

Management of a Reactive Hepatitis C Antibody Test Result

For a patient with a reactive Hepatitis C Antibody (HCV Ab) test, the next step must be HCV RNA testing (nucleic acid testing/NAT) to confirm current infection and distinguish it from resolved infection or false positivity. 1

Interpretation of Initial Reactive HCV Antibody Result

A reactive HCV antibody test indicates one of three possibilities:

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

The CDC guidelines clearly outline that all reactive HCV antibody tests should be followed by HCV RNA testing to determine infection status 1, 2.

Testing Algorithm

1. HCV RNA Testing (NAT):

   • This should be performed reflexively on the same blood sample when possible 1
   • If the initial test was performed using a fingerstick rapid test (like OraQuick), a separate venipuncture sample is required for RNA testing 1

2. Interpretation of Results:

   • HCV RNA positive → Current HCV infection
   • HCV RNA negative → Either past, resolved infection or false antibody positivity 1

Special Considerations

• Recent Exposure: For patients with suspected exposure within the past 6 months, direct HCV RNA testing is recommended as antibodies may not be detectable for up to 12 weeks after infection 2
• Immunocompromised Patients: Consider direct HCV RNA testing as antibody development may be impaired 2

If HCV RNA is Positive (Current Infection)

1. Additional Testing:

   • Complete blood count
   • Liver function tests (AST/ALT, alkaline phosphatase, bilirubin, albumin)
   • Prothrombin time
   • Creatinine
   • Abdominal ultrasound to assess liver disease severity 2

2. HBV Testing:

   • Test for HBV coinfection (HBsAg and anti-HBc) before initiating HCV treatment 3
   • This is critical as HBV reactivation can occur during HCV treatment, potentially resulting in fulminant hepatitis, hepatic failure, and death 3

3. Treatment Evaluation:

   • Direct-acting antiviral (DAA) therapy is the standard of care
   • Treatment selection based on HCV genotype, presence/absence of cirrhosis, prior treatment history, and comorbidities 2

If HCV RNA is Negative

1. Consider Supplemental Antibody Testing:

   • If distinguishing between resolved infection and false positivity is desired, a second FDA-approved HCV antibody assay (different from the initial test) can be used 1
   • Biologic false positivity is unlikely to be exhibited by more than one test 1

2. Repeat RNA Testing If:

   • Patient had suspected HCV exposure within past 6 months
   • Patient has clinical evidence of HCV disease
   • Concerns exist about specimen handling or storage 1

Preventive Measures

For all patients with history of HCV infection (even resolved):

• Counsel on alcohol abstinence 2
• Vaccinate against hepatitis A and B if not immune 2
• For those with advanced fibrosis/cirrhosis, implement hepatocellular carcinoma surveillance with ultrasound every 6 months 2

Public Health Considerations

• HCV test results are subject to mandatory reporting to health departments in most jurisdictions 1
• Accurate diagnosis is essential for proper clinical management, patient counseling, and prevention of transmission 2

Common Pitfalls to Avoid

1. Failing to order HCV RNA testing after a reactive antibody test - this is the most critical step and should be done reflexively when possible 1, 4

2. Misinterpreting a reactive antibody test as definitive evidence of current infection - only HCV RNA testing can confirm current infection 1

3. Not testing for HBV before HCV treatment - HBV reactivation is a serious risk during HCV treatment 3

4. Losing patients to follow-up between antibody and RNA testing - ideally, the entire testing algorithm should be completed with samples collected during a single patient visit 4