What does a positive Hepatitis C (HCV) antibody test but a negative Hepatitis C polymerase chain reaction (PCR) quantitative test indicate?

Interpreting a Positive HCV Antibody with Negative HCV PCR Quantitative Test

A positive hepatitis C antibody test with a negative HCV PCR quantitative test most likely indicates a past resolved HCV infection that has been cleared either spontaneously or through treatment, and the patient should be informed they do not have active HCV infection. 1

Diagnostic Interpretation

When evaluating these test results, consider the following interpretation algorithm:

1. Positive HCV antibody/Negative HCV RNA (PCR):

   • This pattern typically indicates:
     • Past infection that has resolved spontaneously (15-25% of cases)
     • Successful treatment with viral clearance
     • Rarely, a false-positive antibody test 2

2. Confirmatory testing:

   • For patients with positive antibody but negative PCR, a recombinant immunoblot assay (RIBA) can be performed to confirm antibody status 1
   • A positive RIBA with negative PCR confirms past resolved infection
   • A negative RIBA suggests a false-positive antibody test 2

Clinical Management

• Patient counseling: Inform patients with this pattern that they do not have current HCV infection and do not need follow-up testing for HCV 1

• No further HCV monitoring needed: Unlike patients with active infection, those with resolved infection do not require:

  • Liver function monitoring
  • HCV viral load monitoring
  • Hepatology referral for treatment evaluation 1

• Risk of reinfection: Patients should understand that prior infection does not confer immunity, and they can be reinfected if re-exposed to HCV 1

Special Considerations

• Immunocompromised patients: In severely immunocompromised individuals (e.g., HIV/AIDS, hemodialysis), consider repeat HCV RNA testing as antibody formation may be impaired 1

• Recent exposure: For patients with known exposure within the past 6 months, consider repeat testing as they may be in the window period before seroconversion 1

• Ongoing risk factors: For patients with ongoing risk behaviors (e.g., injection drug use), periodic retesting with HCV RNA may be warranted 1

Common Pitfalls to Avoid

1. Misinterpreting as active infection: A common error is assuming any positive antibody test indicates current infection, leading to unnecessary referrals and patient anxiety

2. Missing false positives: In low-prevalence populations, false-positive antibody results are more common, making confirmatory testing important 2

3. Overlooking recent infection: Very early infection may present with negative antibody but positive PCR, so consider direct PCR testing in patients with recent exposure 2

4. Failing to document resolved status: Clearly document in the patient's record that they had past exposure but no current infection to prevent future confusion

By following this approach, you can accurately interpret these test results and provide appropriate guidance to patients with a history of HCV exposure but no current infection.