What is the next step for a patient with a reactive Hepatitis C Virus (HCV) antibody test?

Next Step for Reactive HCV Antibody Test

Order HCV RNA testing immediately on the same blood sample to distinguish current infection from past resolved infection or false positivity. 1, 2

Immediate Action Required

Reflex to HCV RNA nucleic acid testing (NAT) without requiring a second venipuncture. 1, 2 The CDC explicitly recommends collecting specimens during a single patient visit to ensure complete testing and prevent patients from being lost to follow-up. 3

Two Operational Approaches:

• Preferred: Collect two tubes at initial venipuncture—one for HCV antibody testing and a second for automatic HCV RNA testing if antibody is reactive 1
• Alternative: Submit blood from subsequent venipuncture for HCV RNA if initial sample tests antibody-reactive 1

Interpretation Based on HCV RNA Results

If HCV RNA is Detected (Positive):

• This confirms current chronic HCV infection requiring immediate linkage to specialist care for antiviral therapy evaluation. 1, 2
• Provide counseling on transmission prevention, alcohol avoidance, and hepatitis A/B vaccination 1, 2
• Before initiating treatment, retest HCV RNA on a subsequent blood sample to confirm persistent viremia 2
• Report as a nationally notifiable condition to local/state health departments 2

If HCV RNA is Not Detected (Negative):

• This indicates either past resolved HCV infection or false-positive antibody result—no further action required in most cases. 1, 2
• If distinguishing between true past infection versus false positivity is clinically important, test with a different FDA-approved HCV antibody assay using different platform/antigens 2

Critical Special Circumstances

Recent Exposure (Within 6 Months):

Repeat HCV RNA testing even if initial RNA is negative, as antibodies may be present before detectable viremia develops 1, 2

• Alternatively, perform follow-up HCV antibody testing to demonstrate seroconversion 1, 2

Immunocompromised Patients:

Consider HCV RNA testing as the primary diagnostic modality even with negative antibody, as antibody response may be blunted in immunosuppressed individuals 2, 4

Persistent Clinical Suspicion:

Repeat HCV RNA testing if initial RNA is negative but elevated transaminases or liver disease symptoms persist, as false-negative RNA results can occur 2

Common 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 disease 2
• Avoid strategies requiring multiple patient visits for sample collection—incomplete testing occurs in approximately one-third of patients when follow-up visits are needed 5, 3
• Do not use the discontinued RIBA supplemental antibody test—this assay is no longer available and has been replaced by HCV RNA testing as the only FDA-approved supplemental test 1

Laboratory Implementation

Laboratories should implement automatic reflexive HCV RNA testing of all HCV antibody-reactive specimens to ensure complete diagnostic workup. 5, 3 Only 54% of US public health laboratories consistently perform this automatic reflex testing, representing a significant gap in diagnostic practice. 5