Clinical Significance of a Reactive Hepatitis C Antibody Test
A reactive hepatitis C antibody test indicates one of three possibilities: current HCV infection, past resolved HCV infection, or false positive result, and requires follow-up HCV RNA testing to determine current infection status. 1
Interpretation Algorithm for Reactive HCV Antibody Results
Step 1: Understand the Initial Reactive Result
A reactive (positive) HCV antibody test alone cannot distinguish between:
- Current active HCV infection
- Past resolved HCV infection
- False positive result 1
Step 2: Mandatory Follow-up Testing
- HCV RNA testing is required for all patients with reactive HCV antibody results 1
- This should ideally be performed as reflex testing on the same blood sample to prevent loss to follow-up 2
- Testing sequence: HCV antibody → if reactive → HCV RNA test
Step 3: Interpret HCV RNA Results
If HCV RNA is Positive:
- Confirms current HCV infection requiring medical evaluation and potential treatment 1
- Approximately 98.9% of patients with confirmed HCV antibodies have detectable HCV RNA, indicating chronic infection 3
- Patient needs referral for:
- Medical evaluation of liver disease
- Treatment options assessment
- Liver health monitoring 1
If HCV RNA is Negative:
- Indicates either:
- Past resolved HCV infection (most common)
- False positive antibody result 1
- No further testing or follow-up needed for HCV infection 1
- No risk of HCV transmission to others
Special Considerations
Recent Exposure
- For persons with possible HCV exposure within the past 6 months:
- HCV RNA testing is recommended even with negative antibody results
- Antibody may not have developed yet during acute infection 1
Immunocompromised Patients
- Consider direct HCV RNA testing or HCV antigen testing
- Antibody production may be impaired in immunocompromised hosts 1, 4
- HCV antigen testing shows high sensitivity (98.4%) and specificity (100%) in immunocompromised patients 4
Common Pitfalls to Avoid
Failing to order HCV RNA after reactive antibody test
- Only 54% of laboratories automatically reflex HCV RNA testing 2
- This leads to incomplete diagnosis and potential loss to follow-up
Misinterpreting antibody positivity as current infection
- Approximately half of reported cases have antibody testing only without RNA confirmation 5
- This prevents proper identification of those needing treatment
Assuming negative RNA means no infection in acute phase
- During acute infection, HCV RNA may temporarily decline as antibody increases 1
- Serial testing may be needed if acute infection is suspected
Public Health Implications
- Hepatitis C is reportable to public health authorities 1
- Proper diagnosis through complete testing algorithm is essential for:
- Accurate surveillance
- Appropriate treatment referrals
- Prevention of transmission 5
The key clinical significance is that a reactive HCV antibody test is just the first step in diagnosis and must be followed by HCV RNA testing to determine if the patient has current infection requiring treatment or past resolved infection requiring no further action.