How do I interpret Hepatitis C (HCV) lab results and guide treatment decisions?

Interpretation of Hepatitis C Lab Results and Treatment Decision Guide

For accurate diagnosis and optimal patient outcomes, HCV testing should follow a sequential algorithm starting with antibody testing followed by HCV RNA testing to confirm active infection and guide treatment decisions. 1

Initial Testing and Interpretation

HCV Antibody Testing

• HCV antibody nonreactive: No HCV antibody detected, indicating no infection

  • No further action required in most cases
  • Exception: If recent exposure is suspected, test for HCV RNA 1

• HCV antibody reactive: Indicates presumptive HCV infection

  • Could represent:
    • Current HCV infection
    • Past HCV infection that has resolved
    • Biologic false positivity
  • Always requires follow-up testing with HCV RNA to identify current infection 1

HCV RNA Testing (Confirmatory)

• HCV antibody reactive + HCV RNA detected: Confirms current HCV infection

  • Requires patient counseling and linkage to medical care and treatment
  • Important: Before initiating antiviral therapy, retest for HCV RNA in a subsequent blood sample to confirm HCV RNA positivity 1

• HCV antibody reactive + HCV RNA not detected: No current HCV infection

  • May represent:
    • Resolved infection
    • False-positive antibody result
  • If distinction between true positivity and biologic false positivity is desired, test with another HCV antibody assay 1

Special Testing Considerations

When to Perform Additional Testing

• For suspected recent exposure (within past 6 months):

  • HCV RNA testing is recommended even with negative antibody results
  • HCV RNA can be detected 1-2 weeks after exposure, while antibodies may take longer to develop 1

• For immunocompromised patients:

  • Consider direct HCV RNA testing regardless of antibody results
  • These patients may have false-negative antibody results despite active infection 1

• For indeterminate antibody results:

  • Collect another sample for repeat anti-HCV testing (>1 month later)
  • Or proceed directly to HCV RNA testing 1

Clinical Management Based on Test Results

For Confirmed Active HCV Infection

1. Evaluate for liver disease:

   • Check alanine aminotransferase (ALT) levels
   • Consider assessment for cirrhosis

2. Prepare for treatment:

   • Determine HCV genotype to guide treatment selection
   • Confirm HCV RNA positivity in a second sample before starting treatment 1

3. Link to care:

   • Provide appropriate counseling
   • Connect patient to medical care for treatment evaluation 1

Common Pitfalls to Avoid

• Failing to confirm active infection: Never initiate treatment based solely on antibody results without HCV RNA confirmation
• Missing acute infections: In early infection, antibody tests may be negative while HCV RNA is positive
• Misinterpreting intermittent viremia: A single negative HCV RNA result may not rule out infection in all cases - consider clinical context 1
• Neglecting reporting requirements: HCV infection is a notifiable condition in most jurisdictions 1

Reporting Considerations

• All positive results from HCV antibody and HCV RNA testing that indicate acute or past/present HCV infection are reportable to health departments in most jurisdictions 1
• Laboratory reports should include:
  • Antibody level (signal-to-cutoff ratio)
  • Type of immunoassay used
  • Clear interpretation guidelines 2

By following this systematic approach to HCV testing and interpretation, clinicians can accurately diagnose HCV infection, distinguish between current and past infection, and make appropriate treatment decisions to improve patient outcomes and reduce disease transmission.