What is the next step in management for a patient with a positive Hepatitis C (HCV) antibody test?

Next Step After Positive Hepatitis C Antibody Test

The next step is to immediately order HCV RNA testing (PCR) to determine if the patient has active viral infection. 1, 2

Confirmatory Testing Algorithm

Order quantitative or qualitative HCV RNA testing with a detection level ≤25 IU/mL to confirm active infection. 2 This single test distinguishes current infection requiring treatment from past resolved infection or false-positive antibody results. 1, 2

Interpretation of HCV RNA Results

If HCV RNA is positive:

• This confirms active viral replication and current HCV infection requiring further evaluation 1, 2
• Proceed to additional testing including:
  • Liver function tests (ALT/AST) to assess hepatic injury 1
  • HCV genotyping (essential for treatment planning) 3
  • Assessment of liver disease severity through noninvasive fibrosis testing or liver biopsy 3

If HCV RNA is negative:

• Most commonly indicates past resolved infection (15-45% of infected individuals spontaneously clear the virus) 4
• Alternative explanations include false-positive antibody test or very rarely intermittent viremia 1, 4
• No further testing is required in most cases 4
• Reassure the patient they are not infectious and antibodies may persist for life 4

Special Circumstances Requiring Modified Approach

Recent exposure (within 6 months):

• If exposure occurred recently, repeat HCV RNA testing is recommended as RNA may be transiently negative during early acute infection 1, 4
• Average time to seroconversion is 8-9 weeks, but HCV RNA becomes detectable as early as 2 weeks post-infection 3

Immunocompromised patients:

• HCV RNA testing is particularly critical as antibody tests may be falsely negative in hemodialysis patients, HIV coinfection, solid organ transplant recipients, or hypogammaglobulinemia 3, 1
• Consider HCV RNA testing even with negative antibody if clinical suspicion exists 3

Low signal-to-cutoff (S/CO) ratios:

• If the initial antibody test has a low S/CO ratio (particularly <3.8), consider repeat antibody testing with a different assay platform to exclude false positivity 2, 5
• High S/CO ratios (>3.8) have 95% probability of being true positive 3

Critical Pitfalls to Avoid

• Never rely on antibody testing alone to diagnose active infection—antibodies persist indefinitely after viral clearance and cannot distinguish current from past infection 2
• Do not use ALT levels to confirm or exclude HCV infection—liver enzymes can be normal despite active viremia 2
• Avoid misinterpreting negative HCV RNA as definitively ruling out infection without considering timing of exposure and immune status 1
• Ensure proper specimen handling: serum/plasma must be separated within 2-6 hours and stored appropriately to prevent false-negative RNA results 1

Concurrent Clinical Assessment

While awaiting HCV RNA results, obtain:

• Complete medical history focusing on transmission risk factors (injection drug use, blood transfusions pre-1992, hemodialysis, occupational exposure) 3
• Physical examination for signs of chronic liver disease 3
• Baseline ALT/AST levels 3

3, 1, 2