Next Step After Reactive HCV Antibody Screen
Order HCV RNA testing (nucleic acid test/NAT) immediately on the same blood sample to confirm current infection. 1, 2, 3
Why HCV RNA Testing is Essential
A reactive HCV antibody result does not confirm active infection—it indicates one of three possibilities: current HCV infection, past resolved infection, or false positivity. 1, 2 HCV RNA testing is the only way to distinguish between these scenarios and identify patients who need treatment. 1, 3
The CDC explicitly states that persons with reactive HCV antibody results should be evaluated for the presence of HCV RNA in their blood, as antiviral treatment is intended only for persons with current infection. 1
Optimal Testing Approach
Use reflex testing protocols to avoid losing patients to follow-up: 2, 3, 4
Option 1 (Preferred): The same blood sample used for initial HCV antibody testing is automatically reflexed to HCV RNA testing if reactive—no second venipuncture needed. 1, 2, 3
Option 2: Collect two tubes at the initial venipuncture: one for antibody testing and a second held for HCV RNA testing if the antibody is reactive. 1, 2
Only 54% of U.S. public health laboratories consistently perform automatic reflex HCV RNA testing, representing a significant gap in diagnostic practice that leads to patients being lost to follow-up. 4
Interpreting HCV RNA Results
If HCV RNA is Detected (Positive):
- This confirms current HCV infection requiring immediate linkage to specialist care for treatment evaluation. 2, 3
- Provide counseling on transmission prevention, alcohol avoidance, and vaccination against hepatitis A and B. 3
- Before initiating antiviral therapy, retest HCV RNA on a subsequent blood sample to confirm persistent viremia. 3
- Report as a nationally notifiable condition per local/state regulations. 3
If HCV RNA is Not Detected (Negative):
- This indicates either past resolved HCV infection or false-positive antibody result—no current infection exists. 1, 2, 3
- No further action required in most cases. 3
- If distinguishing between true past infection and false positivity is clinically important, test with a different FDA-approved HCV antibody assay using different antigens/platform to reduce likelihood of repeated false positivity. 2, 3
Special Populations Requiring Modified Approach
Recent Exposure (Within 6 Months):
- Repeat HCV RNA testing even if initial RNA is negative, as antibodies may be present before viremia is detectable. 2, 3
- Alternatively, perform follow-up HCV antibody testing 6 months after exposure to demonstrate seroconversion. 2, 3
Immunocompromised Patients:
- Consider HCV RNA testing as the primary diagnostic modality even with negative antibody, as antibody response may be blunted or absent. 2, 3
Clinical Suspicion Despite Negative RNA:
- Repeat HCV RNA testing if initial RNA is negative but clinical suspicion remains high (elevated transaminases, liver disease symptoms). 3
Technical Specifications
Use an FDA-approved NAT assay with detection sensitivity ≤25 IU/mL for HCV RNA testing. 2 The gold standard for diagnosis of HCV infection is detection of HCV RNA in serum by PCR assay. 5, 6
Critical Pitfalls to Avoid
- Never report a reactive HCV antibody as "positive for hepatitis C" without RNA confirmation—this represents only presumptive infection, not confirmed current infection. 3
- Do not assume positive antibody equals active infection requiring treatment—approximately 15-25% of HCV infections resolve spontaneously, leaving persistent antibodies without viremia. 1
- Avoid ordering a second venipuncture for RNA testing when reflex testing from the original sample is possible—this creates unnecessary barriers and patient loss to follow-up. 4