What to order next for a patient with a reactive Hepatitis C Virus (HCV) antibody test but a negative viral load?

Next Steps for Reactive HCV Antibody with Negative Viral Load

Inform the patient they do not have current HCV infection and typically require no further testing or treatment. 1, 2

Interpretation of Results

A reactive HCV antibody with negative (undetectable) HCV RNA indicates one of two scenarios:

• Past resolved infection (most common) - the patient was previously infected with HCV but spontaneously cleared the virus or cleared it with treatment 1, 2
• Biologic false positive antibody test (rare) - the antibody test was falsely reactive 1

The patient is NOT currently infected and is NOT infectious to others. 2

Standard Management (No Additional Testing Needed)

For most patients with this test pattern, no further action is required:

• No antiviral therapy indicated - HCV RNA negativity definitively rules out current infection requiring treatment 2
• No routine monitoring needed - the patient does not have active disease 2
• Antibody will remain positive lifelong - repeat antibody testing is unnecessary and will remain reactive even after viral clearance 1

When to Consider Additional Testing

Repeat HCV RNA Testing

Consider repeating HCV RNA in specific high-risk scenarios:

• Recent exposure within past 6 months - patient may be in the window period before viremia becomes detectable 1, 3
• Ongoing HCV risk factors (active injection drug use, high-risk sexual practices, occupational exposure) - to detect potential reinfection 1, 2
• Immunocompromised patients (HIV, organ transplant, hemodialysis) - may have delayed seroconversion or intermittent viremia 1, 3
• Clinical evidence of liver disease - unexplained elevated ALT/AST or other signs of hepatitis 1, 3

Confirmatory RIBA Testing (Optional)

If either the clinician or patient wishes to distinguish between past resolved infection versus false positive antibody:

• Order recombinant immunoblot assay (RIBA) - a second antibody test using different methodology 1
• RIBA positive = confirms true past HCV infection 1
• RIBA negative = confirms false positive screening test 1
• Clinical significance is minimal - this distinction rarely changes management since the patient has no active infection regardless 2

Common Pitfalls to Avoid

• Do NOT treat with antivirals - negative HCV RNA definitively excludes current infection requiring therapy 2
• Do NOT repeat antibody testing - antibody remains positive after viral clearance and provides no additional information 1
• Do NOT assume the patient was never infected - positive antibody most likely represents past resolved infection rather than false positivity 2
• Do NOT order unnecessary liver imaging or biopsy - no active disease is present 2

Patient Counseling

Provide clear communication to prevent confusion:

• Explain they had HCV infection in the past that resolved (or rarely, a false positive test) 2
• Reassure they are not currently infected and cannot transmit HCV to others 2
• If ongoing risk factors exist, counsel on HCV transmission prevention and consider periodic HCV RNA retesting for reinfection 2