Follow-Up Testing After Positive HCV Antibody
A positive HCV antibody test must be immediately followed by HCV RNA testing (quantitative nucleic acid test) to determine if active infection is present. 1
Immediate Next Step: HCV RNA Testing
- Order quantitative HCV RNA (PCR) testing on the same serum sample or as soon as possible to distinguish between current infection, resolved infection, or false-positive antibody result 1
- HCV RNA is the gold standard for confirming active HCV infection and can detect viremia at levels <15 IU/mL with modern assays 1
- The recombinant immunoblot assay (RIBA) is no longer available or recommended as a confirmatory test 1
Interpretation of Results
If HCV RNA is Positive (Viremia Detected):
- This confirms current, active HCV infection requiring hepatology referral and treatment evaluation 1, 2
- Obtain baseline laboratory tests including:
- Refer to hepatology for treatment consideration - modern direct-acting antivirals achieve >95% cure rates 1
If HCV RNA is Negative (No Viremia):
Do not stop here - additional testing is required to interpret the positive antibody result 1, 2, 3
Perform repeat anti-HCV testing using a different antibody assay platform (alternative manufacturer/methodology) to distinguish false-positive from cleared infection 2, 3
If alternative assay is negative:
- The initial test was a false-positive - no HCV infection present 2, 3
- No further HCV evaluation needed unless new risk exposures occur 3
If alternative assay is positive:
Special Circumstances Requiring Repeat HCV RNA Testing
Even with negative HCV RNA, repeat testing is indicated in the following situations 2, 3:
- Recent exposure within past 6 months - antibodies may not yet be detectable, but RNA can be positive in acute infection 1, 2
- Clinical evidence of liver disease (elevated ALT/AST, hepatomegaly, jaundice) despite negative RNA 2, 3
- Immunocompromised patients (HIV coinfection, transplant recipients, chemotherapy) - may have intermittent viremia or delayed antibody response 1
- Concerns about specimen handling or storage - improper handling can lead to RNA degradation and false-negative results 2, 3
- Retest at 12 and 24 weeks if acute HCV infection is suspected 1
Additional Hepatitis Screening in HCV-Positive Patients
Mandatory Hepatitis B Testing:
All patients with positive HCV antibody must be tested for current or prior HBV infection before initiating any HCV treatment 4
This is critical because HBV reactivation has been reported during HCV treatment with direct-acting antivirals, resulting in fulminant hepatitis, liver failure, and death 4
Consider Hepatitis A Testing:
- Check hepatitis A antibody (total or IgG) to determine immunity status 1
- Vaccinate if non-immune, as HAV superinfection in chronic HCV can cause severe acute hepatitis 1
HIV Testing:
- Recommend HIV testing given overlapping transmission routes 1
- HCV/HIV coinfection affects treatment decisions and monitoring 1, 4
Common Pitfalls to Avoid
- Never assume a single negative HCV RNA definitively rules out infection without performing alternative antibody assay testing or considering timing of exposure 2, 3, 5
- Do not rely solely on antibody results - up to 35% of positive anti-HCV tests in low-prevalence populations are false-positives 1, 5, 6
- Do not forget mandatory HBV testing before initiating HCV treatment - this is an FDA boxed warning requirement 4
- Recognize intermittent viremia - HCV RNA can fluctuate in chronic infection, so a single negative result doesn't exclude active disease if clinical suspicion is high 2, 3
- Avoid inadequate specimen handling - HCV RNA degrades rapidly; serum/plasma should be separated within 2-6 hours and stored properly 2