Is ordering Hepatitis C Virus (HCV) viral RNA, quantitative, Polymerase Chain Reaction (PCR) the correct next step after a positive HCV antibody test?

Follow-up Testing After Positive HCV Antibody Test

Yes, ordering HCV viral RNA, quantitative, PCR is the correct next step after a positive HCV antibody test. 1, 2

Rationale for HCV RNA Testing

• HCV RNA testing via PCR is the recommended follow-up test for all patients with positive HCV antibody tests to determine if they have active infection 2
• A positive HCV antibody test alone cannot distinguish between current active infection, past resolved infection, or a false positive result 1
• HCV RNA testing is necessary to confirm active HCV infection and guide further management decisions 1

Interpretation of HCV RNA Test Results

• Positive HCV RNA result:

  • Confirms current (active) HCV infection requiring further evaluation and potential treatment 2
  • Indicates the need for additional testing including liver function tests to assess liver damage 1
  • Necessitates referral to a specialist experienced in hepatitis management 1

• Negative HCV RNA result:

  • May indicate a resolved infection or a false positive antibody test 1
  • Requires additional testing with a different antibody assay platform to distinguish between these possibilities 1, 2
  • Does not completely rule out infection if exposure was recent (within 6 months) 1

Benefits of Quantitative PCR Testing

• Modern quantitative HCV RNA PCR assays provide both detection and viral load measurement in a single test 1, 3
• Quantitative testing establishes baseline viral load, which may affect treatment decisions 1
• Real-time PCR assays have high sensitivity (detection limit of 12-15 IU/mL) and broad measuring range (up to 7-8 log IU/mL) 1
• These assays have 98-99% diagnostic specificity independent of HCV genotype 1

Additional Recommended Testing

If HCV RNA is positive, the following additional tests should be performed:

• Basic laboratory testing to evaluate liver disease: bilirubin, ALT, AST, albumin, platelet count, and prothrombin time 1
• HCV genotype testing to help plan future treatment 1
• Screening for other infections with overlapping risk factors: HIV, hepatitis B, and potentially other STIs 1
• Assessment of hepatitis A and B immunity status for vaccination purposes 1

Common Pitfalls to Avoid

• Misinterpreting a negative HCV RNA result as definitively ruling out infection without confirmatory testing, especially if exposure was recent 2, 1
• Inadequate specimen handling leading to false-negative HCV RNA results 2
• Failing to consider the possibility of intermittent viremia, which may require repeat testing in some cases 2
• Not ordering HCV genotype testing, which is important for treatment planning 1

Special Considerations

• For immunocompromised patients, HCV RNA testing is particularly important as antibody tests may be falsely negative 1, 2
• If clinical suspicion remains high despite negative HCV RNA, consider repeating the test, especially with recent exposure 2
• Proper specimen handling is crucial for accurate HCV RNA testing, with appropriate collection and storage procedures 2