What to Do When HCV Antibody Test is Reactive
Order HCV RNA testing immediately on the same blood sample to determine if the patient has current active infection. 1, 2
Immediate Next Step: Reflex HCV RNA Testing
The reactive HCV antibody result must be followed by nucleic acid testing (NAT) for HCV RNA to distinguish between three possibilities: current active infection, past resolved infection, or false-positive antibody result 1, 2, 3
Use the same venipuncture blood sample for HCV RNA testing without requiring the patient to return for another blood draw (reflex testing) 1, 2, 3
The HCV RNA assay should have a detection level of ≤25 IU/mL 3
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 2, 3
Before initiating antiviral therapy, retest HCV RNA on a subsequent blood sample to confirm persistent viremia 2
Provide counseling about transmission prevention, alcohol avoidance, and vaccination against hepatitis A and B 2
Test for hepatitis B virus (HBV) coinfection by measuring HBsAg and anti-HBc before starting any HCV treatment, as HBV reactivation can occur during HCV therapy and may result in fulminant hepatitis, hepatic failure, and death 4
Obtain quantitative HCV RNA (viral load) and HCV genotype testing to guide treatment decisions 3, 5
Assess degree of liver fibrosis with either liver biopsy or noninvasive testing to determine treatment urgency 5
If HCV RNA is Not Detected (Negative):
This indicates either past resolved HCV infection or a false-positive antibody result—no treatment is needed 1, 2, 3
No further action is required in most cases 2
If you need to distinguish between true past infection versus false-positive antibody, test with a different FDA-approved HCV antibody assay using different antigens/platform, as biologic false positivity is unlikely to occur on multiple different assays 1, 2, 3
Special Circumstances Requiring Modified Testing
Recent Exposure (Within Past 6 Months):
Repeat HCV RNA testing even if the initial RNA is negative, as the patient may be in the window period where antibodies are present but viremia is not yet detectable 1, 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 test even if antibody is negative, as antibody response may be blunted or absent in immunocompromised individuals 1, 2, 3
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) 2, 3
Consider concerns about specimen handling or storage that might have affected the initial RNA test 1
Critical Pitfalls to Avoid
Never report a reactive HCV antibody alone as "positive for hepatitis C" without RNA confirmation—this represents only presumptive infection, not confirmed current infection 2
Do not rely solely on antibody testing without confirmatory RNA testing, as this leads to misdiagnosis 3
Do not assume a positive antibody with negative RNA means no infection if the patient had recent exposure within 6 months or is immunocompromised 1, 2