What test confirms a positive diagnosis for hepatitis C?

Diagnostic Testing for Hepatitis C

The definitive test for confirming hepatitis C infection is a positive HCV RNA PCR test, which directly detects the virus in the blood and confirms current infection. 1

Diagnostic Algorithm for Hepatitis C

Initial Screening

• Start with a third-generation enzyme immunoassay (ELISA-3) test for anti-HCV antibodies
  • Current ELISA-3 tests have a sensitivity of 97% 1
  • This is the recommended first-line screening test for suspected HCV infection 1

Confirmation Testing

1. If ELISA is positive:

   • Proceed to HCV RNA PCR testing to confirm active infection 1
   • A positive PCR result confirms current HCV infection and viraemia 1
   • A negative PCR suggests:
     • Resolved infection
     • Transient absence of viraemia
     • False-positive antibody test 1

2. If ELISA is positive but PCR is negative:

   • Perform a recombinant immunoblot assay (RIBA) to confirm antibody status 1
   • RIBA-positive/PCR-negative indicates past resolved infection 1
   • RIBA-negative indicates a false-positive ELISA result 1

3. For indeterminate RIBA results:

   • Evaluate for viral replication and liver disease 1
   • HCV RNA is detected in 58% of indeterminate RIBA-3 cases 1

Special Considerations

Immunocompromised Patients

• Direct HCV RNA PCR testing is recommended without antibody testing first 1
• Immunodeficient patients may be antibody-negative despite active infection 1

Patients with Chronic Liver Disease

• A positive ELISA test may be sufficient to diagnose HCV infection 1
• Confirmatory PCR testing is still suggested for these patients 1

Low Prevalence Settings

• False-positive rates with ELISA can be high (15-60%) in populations with <10% prevalence 1
• Confirmatory testing is critical in these settings 1

Interpretation of Results

Test Combination	Interpretation
ELISA+/PCR+	Current HCV infection [1]
ELISA+/PCR-/RIBA+	Past resolved infection [1]
ELISA+/PCR-/RIBA-	False-positive antibody test [1]
ELISA+/PCR-/RIBA indeterminate	Requires clinical evaluation [1]

Common Pitfalls

1. Relying solely on antibody testing

   • Antibody tests cannot distinguish between current and past infection 1
   • False-positive results are common in low-prevalence populations 1

2. Misinterpreting PCR results

   • PCR sensitivity varies between laboratories 2
   • Only 16% of laboratories performed perfectly in quality control testing 2
   • Use laboratories with established facilities for HCV RNA testing 1

3. Testing during the window period

   • Antibodies may not be detectable in early infection
   • Direct PCR testing is necessary for recently infected patients 1

4. Inadequate sample handling

   • Serum or plasma must be collected and handled properly for accurate PCR results 1

By following this diagnostic algorithm, clinicians can accurately diagnose hepatitis C infection, distinguish between current and past infection, and avoid false-positive results that could lead to unnecessary anxiety and medical interventions.