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

HCV Antibody Reactive: Next Steps

A reactive HCV antibody test must be followed immediately by HCV RNA testing to distinguish current infection from past resolved infection or false positivity. 1

Immediate Action: Reflex to HCV RNA Testing

• Order HCV RNA testing (nucleic acid test/NAT) on the same blood sample used for the initial antibody test whenever possible, without requiring a second venipuncture 1
• This "reflex testing" approach is critical because approximately one-third of patients historically have incomplete testing when a second visit is required 2
• Single-visit sample collection is now the standard of care to prevent patients from being lost to follow-up 2

Interpretation Based on HCV RNA Results

If HCV RNA is Detected (Positive):

• This confirms current HCV infection requiring linkage to care and treatment 1
• Provide appropriate counseling about transmission prevention, alcohol avoidance, and vaccination against hepatitis A and B 1
• Link patient to specialist care for antiviral therapy evaluation 1
• Before initiating antiviral therapy, retest HCV RNA on a subsequent blood sample to confirm viremia 1

If HCV RNA is Not Detected (Negative):

• This indicates either past resolved HCV infection or false-positive antibody result 1
• No further action required in most cases 1
• If distinction between true past infection and false positivity is desired, test with a different FDA-approved HCV antibody assay (different platform/antigens reduce likelihood of repeated false positivity) 1

Special Circumstances Requiring Modified Approach

Recent Exposure (Within Past 6 Months):

• Repeat HCV RNA testing is recommended even if initial RNA is negative, as antibodies may be present before viremia is detectable 1
• Alternatively, perform follow-up HCV antibody testing to demonstrate seroconversion 1

Immunocompromised Patients:

• Consider HCV RNA testing even with negative antibody, as antibody response may be blunted 1
• HCV RNA testing should be considered the primary diagnostic modality in this population 1

Clinical Evidence of HCV Disease:

• Repeat HCV RNA testing if initial RNA is negative but clinical suspicion remains high (elevated transaminases, liver disease symptoms) 1

Critical Pitfalls to Avoid

• Never report a reactive HCV antibody as "positive for hepatitis C" without RNA confirmation - this represents only presumptive infection 1
• Do not require patients to return for a second blood draw for RNA testing - this leads to 30%+ incomplete testing rates 2
• Do not skip RNA testing in patients with chronic liver disease who are antibody-positive - confirmatory testing is unnecessary in this setting as the pretest probability is very high 3
• Always test for HBV coinfection (HBsAg and anti-HBc) before initiating HCV treatment, as HBV reactivation can cause fulminant hepatitis, liver failure, and death 4, 5

Laboratory Reporting Requirements

• Reactive HCV antibody and positive HCV RNA results are nationally notifiable conditions requiring reporting to health departments per local/state regulations 1
• Reports should specify whether testing indicates acute hepatitis C or past/present infection 1