What is the appropriate workup for a patient with a positive anti-Hepatitis C Virus (HCV) test?

Workup of Anti-HCV Positive Patient

A positive anti-HCV antibody test must be immediately followed by quantitative HCV RNA testing to distinguish current active infection from past resolved infection or false positivity. 1, 2

Initial Confirmatory Testing

• Order quantitative HCV RNA testing (nucleic acid test) on all anti-HCV positive patients using an FDA-approved assay with detection sensitivity ≤25 IU/mL 2
• The most efficient approach is reflex testing: use the same blood sample for automatic HCV RNA testing when anti-HCV is reactive, avoiding the need for patient recall 2, 3
• HCV RNA is detectable as early as 1-3 weeks after exposure, while antibodies develop 2-6 months post-exposure 1

Interpretation of Results

If HCV RNA is Detected (Positive):

• This confirms current active HCV infection requiring immediate linkage to hepatology care and treatment 1, 2
• Obtain baseline laboratory evaluation including:
  • Liver function tests (ALT, AST, bilirubin, albumin) 1
  • Complete blood count 1
  • Quantitative HCV RNA viral load (if not already done) 2
  • HCV genotype testing (may influence treatment selection) 2
  • Hepatitis B testing (HBsAg and anti-HBc) to screen for coinfection before initiating HCV treatment 4
• Refer to hepatologist for treatment planning 1

If HCV RNA is Not Detected (Negative):

• This indicates either past resolved infection or false-positive antibody result - no current infection present 1, 2
• To distinguish between these two possibilities, test with a second different HCV antibody assay platform 1, 2
• If the alternative antibody assay is negative, the initial test was false-positive 1
• If the alternative antibody assay is positive, this indicates cleared/resolved infection 1

Special Populations Requiring Modified Approach

Recent Exposure (Within 6 Months):

• If anti-HCV is positive but HCV RNA is negative, repeat HCV RNA testing in 2-4 weeks as this may represent acute infection during the window period 1, 2
• Alternatively, repeat anti-HCV antibody testing 6 months after exposure to document seroconversion 1, 2

Immunocompromised Patients:

• Consider direct HCV RNA testing even if anti-HCV is negative, as antibody development may be delayed or absent in immunosuppressed individuals 1, 2
• This includes patients on hemodialysis, HIV-positive patients, transplant recipients, and those on immunosuppressive therapy 1

Patients with Prior HCV Clearance at Risk of Reinfection:

• HCV RNA testing is essential because anti-HCV antibodies persist after clearance, making antibody testing unreliable for detecting reinfection 2

Common Pitfalls to Avoid

• Never rely solely on anti-HCV antibody results without confirmatory RNA testing - a positive antibody can represent current infection, past infection, or false positivity 1
• Do not assume anti-HCV positive with negative RNA means no infection in recently exposed patients - repeat RNA testing is required 1, 2
• In low-prevalence populations (blood donors, general population screening), false-positive anti-HCV rates average 35% (range 15-60%), making confirmatory testing absolutely essential 1
• Avoid patient loss to follow-up by implementing automatic reflex HCV RNA testing rather than requiring separate visits 2, 3
• Do not forget hepatitis B screening (HBsAg and anti-HBc) before initiating HCV treatment, as HBV reactivation can cause fulminant hepatitis and death in coinfected patients 4

Additional Laboratory Monitoring

• If HCV RNA is positive and treatment is planned, retest HCV RNA in a subsequent blood sample before initiating antiviral therapy to confirm persistent viremia 1
• Baseline liver disease assessment through liver function tests is essential for all RNA-positive patients 1