What lab tests should be run after a patient tests positive for Hepatitis C (HCV) antibodies?

Follow-up Testing After Positive Hepatitis C Antibody Result

After a positive hepatitis C antibody test, the next laboratory test to run is HCV RNA testing (PCR) to determine if active infection is present. 1

Testing Algorithm

• HCV RNA testing (PCR) should be performed on all patients with positive HCV antibody tests to determine if they have active infection 1
• A positive HCV RNA result confirms current viremia and active HCV infection, requiring further medical evaluation 1, 2
• A negative HCV RNA result in an antibody-positive patient requires additional testing with recombinant immunoblot assay (RIBA) to confirm the antibody status 1

Interpretation of Results

Positive HCV RNA

• Indicates active HCV infection requiring further evaluation and potential treatment 1
• These patients should undergo additional testing including:
  • Liver function tests (ALT/AST) to assess liver damage 1
  • Consideration of liver biopsy to determine disease severity in patients being considered for treatment 1

Negative HCV RNA

• Does not definitively rule out HCV infection without additional testing 1
• Possible interpretations include:
  • Resolved infection (15-25% of older adults and 40-45% of younger adults spontaneously clear the virus) 1, 2
  • False-positive antibody result 1, 2
  • Intermittent viremia (rare) 1
  • Very early acute infection 1

Special Considerations

• For immunocompromised patients with suspected HCV infection, qualitative PCR testing is particularly important as antibody tests may be falsely negative 1
• If the initial HCV RNA test is negative but clinical suspicion remains high, consider repeating the HCV RNA test, especially if the patient might have been exposed within the past 6 months 2, 1
• Proper specimen handling is crucial for accurate HCV RNA testing:
  • Blood should be collected in sterile tubes with no additives or EDTA tubes 1
  • Serum or plasma must be separated from cellular components within 2-6 hours 1
  • Samples can be stored at 2-5°C for up to 72 hours; longer storage requires freezing at -20°C or -70°C 1

Common Pitfalls to Avoid

• Relying solely on antibody testing without confirming active infection status with HCV RNA testing 3, 4
• Misinterpreting a negative HCV RNA result as definitively ruling out infection without confirmatory RIBA testing 1
• Inadequate specimen handling leading to false-negative HCV RNA results 1
• Failing to consider the possibility of intermittent viremia, which may require repeat testing 1

By following this testing algorithm, clinicians can accurately diagnose active HCV infection, identify false-positive antibody results, and ensure appropriate patient management and treatment decisions.