Next Step After Positive HCV Antibody Test
Immediately order HCV RNA testing (nucleic acid test/NAT) on the same blood sample to distinguish current infection from past resolved infection or false positivity. 1, 2
Immediate Action: Reflex HCV RNA Testing
A reactive HCV antibody result alone indicates only presumptive HCV infection and requires confirmatory HCV RNA testing to determine if active infection is present. 1, 2
The HCV RNA test should ideally be performed on the same venipuncture blood sample used for the initial antibody test, without requiring a second blood draw (reflex testing). 1, 2
A positive HCV antibody can represent three distinct scenarios: current active infection, past resolved infection, or false positivity—only HCV RNA testing can differentiate these. 1, 2
Interpretation Based on HCV RNA Results
If HCV RNA is Detected (Positive):
This confirms current active HCV infection requiring immediate linkage to specialist care for treatment evaluation. 1, 2
Before initiating antiviral therapy, retest HCV RNA on a subsequent blood sample to confirm persistent viremia. 1, 2
Provide counseling on transmission prevention, alcohol avoidance, and vaccination against hepatitis A and B. 2
Test all patients for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before starting HCV treatment, as HBV reactivation during HCV therapy can cause fulminant hepatitis, hepatic failure, and death. 3, 4, 5
If HCV RNA is Not Detected (Negative):
This indicates either past resolved HCV infection or false-positive antibody result—no further action is required in most cases. 1, 2
If distinction between true past infection and false positivity is clinically important, test with a different FDA-approved HCV antibody assay using different antigens/platforms, as biologic false positivity is unlikely to occur on multiple different assays. 1, 2
Special Circumstances Requiring Modified Approach
Recent Exposure (Within Past 6 Months):
Repeat HCV RNA testing even if initial RNA is negative, as the patient may be in the window period where antibodies are present but viremia is not yet detectable or is intermittent. 1, 2
Alternatively, perform follow-up HCV antibody testing to demonstrate seroconversion. 1
Immunocompromised Patients:
Consider HCV RNA testing as the primary diagnostic modality, as antibody response may be blunted or absent despite active infection. 1, 2
HCV RNA testing should be performed even if antibody testing is negative when clinical suspicion exists. 1, 2
Clinical Evidence of Liver Disease:
Repeat HCV RNA testing if initial RNA is negative but clinical suspicion remains high (elevated transaminases, symptoms of liver disease). 1, 2
Consider specimen handling issues that may have caused false-negative RNA results. 1
Critical Pitfalls to Avoid
Never report a reactive HCV antibody as "positive for hepatitis C" or "HCV infection" without RNA confirmation—this represents only presumptive infection requiring further testing. 2
Do not assume a negative HCV RNA definitively rules out infection without considering timing of exposure, immunocompromised status, or specimen handling issues. 1, 2
Avoid ordering supplemental antibody testing (RIBA) as the next step—this older approach has been replaced by direct HCV RNA testing as the preferred confirmatory method. 1, 2