What is the next step in evaluation for a patient who is Hepatitis C Virus (HCV) antibody positive?

Next Step in Evaluation for HCV Antibody Positive Patient

The next step in evaluation for a patient with a positive HCV antibody test is to perform HCV RNA testing to confirm current infection and distinguish it from resolved infection or false positivity. 1

Diagnostic Algorithm for HCV Antibody Positive Patients

1. Confirm Active Infection

• Perform HCV RNA testing immediately after receiving a positive HCV antibody result 2, 1
• RNA testing should ideally be performed reflexively on the same blood sample when possible 1
• This step is critical as a positive antibody test alone cannot distinguish between:
  • Current active infection
  • Past, resolved infection
  • False positive antibody result 2

2. Interpret HCV RNA Results

• If HCV RNA is positive:

  • Confirms current HCV infection
  • Patient requires appropriate counseling and linkage to medical care and treatment 2
  • Before initiating antiviral therapy, retest for HCV RNA in a subsequent blood sample to confirm HCV RNA positivity 2

• If HCV RNA is negative:

  • Indicates no current HCV infection
  • May represent either resolved infection or false positive antibody result 2
  • In most cases, no further action is required 2
  • Consider additional testing in specific situations (see below)

3. Special Situations Requiring Additional Testing

• If HCV RNA is negative but distinction between resolved infection and false positivity is desired:

  • Test with a second FDA-approved HCV antibody assay that differs from the initial test 2, 1
  • HCV antibody assays vary in antigens and test platforms, making biological false positivity unlikely across multiple tests 2

• Repeat HCV RNA testing if:

  • Patient had suspected HCV exposure within past 6 months (may be in "window period")
  • Patient has clinical evidence of HCV disease
  • Concerns exist about specimen handling or storage 2, 1

Additional Laboratory Testing

After confirming active HCV infection (HCV RNA positive), additional testing should include:

• Liver function tests (AST, ALT, alkaline phosphatase, GGT, bilirubin, albumin) 1
• Complete blood count 1
• Prothrombin time 1
• Creatinine to evaluate kidney function 1
• Testing for coinfections (HBV, HIV) 1, 3
  • Important: Test all patients for evidence of current or prior HBV infection (HBsAg and anti-HBc) before initiating HCV treatment to prevent HBV reactivation 3

Clinical Considerations

Interpretation of Test Results

• Up to 30% of HCV-antibody-positive patients have negative HCV RNA, indicating resolution of infection 4
• False positive rates for HCV antibody can be significant, particularly in low-prevalence populations:
  • In NHANES data (2007-2012), among antibody-positive individuals, 22% were confirmed false positives and 10% had indeterminate results 5
  • Only 51% of antibody-positive individuals had chronic infection 5

Common Pitfalls to Avoid

1. Relying solely on antibody testing: An antibody-positive result alone cannot distinguish between current infection, resolved infection, or false positivity 2, 1

2. Assuming normal liver enzymes rule out infection: About 50% of HCV-infected (antibody and PCR positive) patients have normal transaminase values 2

3. Missing HCV infection in immunocompromised patients: Immunocompromised individuals may have false-negative antibody results, so consider direct HCV RNA testing in these patients 2, 1

4. Failing to test for HBV coinfection: All patients should be tested for HBV before initiating HCV treatment due to risk of HBV reactivation 3

5. Inadequate follow-up: Ensure appropriate linkage to care for all patients with confirmed active HCV infection 2

By following this evidence-based approach to HCV diagnosis, you can accurately identify patients with active infection who require treatment, while avoiding unnecessary interventions for those with resolved infection or false positive antibody results.