What are the next steps for a patient who is Hepatitis C (HCV) antibody positive and Hepatitis B (HBV) quantification negative?

Next Steps for HCV Antibody Positive, HBV Quantification Negative Patient

The immediate next step is to order HCV RNA testing (PCR) to determine if there is active hepatitis C infection, as a positive HCV antibody alone cannot distinguish between current infection, resolved infection, or a false-positive result. 1, 2

Immediate Testing Algorithm

HCV RNA Testing (Priority Action)

• Order quantitative HCV RNA testing with a detection limit ≤15 IU/mL (or at minimum <1,000 IU/mL) to confirm active viremia 1, 2
• This test differentiates between:
  • Active infection (HCV RNA positive) - requires hepatology referral and treatment evaluation 2
  • Resolved infection or false-positive (HCV RNA negative) - requires confirmatory antibody testing 3, 4

If HCV RNA is Positive (Active Infection)

• Obtain baseline laboratory evaluation: 1
  • Quantitative HCV RNA viral load
  • HCV genotype (essential for treatment planning)
  • Liver function tests: ALT, AST, bilirubin, albumin, prothrombin time
  • Complete blood count with platelets
• Refer to hepatology or infectious disease specialist for treatment evaluation 1, 2
• Screen for coinfections with overlapping risk factors: 1
  • HIV antibody/antigen testing
  • Hepatitis B surface antigen (HBsAg) and anti-HBc (hepatitis B core antibody) - critical before starting HCV treatment
  • Syphilis, gonorrhea, chlamydia testing
  • Hepatitis A antibody (IgG) to assess immunity
• Vaccinate against hepatitis A and B if non-immune (safe and recommended for all HCV-positive patients) 1

If HCV RNA is Negative (Resolved or False-Positive)

• Perform confirmatory HCV antibody testing using a different assay platform (e.g., recombinant immunoblot assay/RIBA or alternative EIA) 1, 3, 4
  • If second antibody test is negative: Initial test was false-positive; patient does not have HCV infection 4
  • If second antibody test is positive: Indicates cleared/resolved HCV infection (occurs in ~20% of infections); patient is not infectious 3, 4

Critical Timing Considerations

Recent Exposure Window (Within 6 Months)

• If potential HCV exposure occurred within the past 6 months, repeat HCV RNA testing is essential even if initially negative 2, 3
• During acute infection, HCV RNA may be transiently negative or intermittently detectable 1
• HCV RNA becomes detectable 1-2 weeks after exposure, while antibodies may take 2-6 months to develop 1, 4

Immunocompromised Patients

• HCV antibody tests may be falsely negative in immunocompromised individuals (including hemodialysis patients, HIV-positive patients, transplant recipients) 2
• If clinical suspicion remains high despite negative antibody, proceed directly to HCV RNA testing 1, 2

Hepatitis B Status Clarification

Your question states "HBV quantification negative" - this requires clarification:

Complete HBV Testing Panel Needed

• HBsAg (hepatitis B surface antigen) - indicates active HBV infection 5
• Anti-HBc (hepatitis B core antibody) - indicates past or current HBV exposure 5
• Anti-HBs (hepatitis B surface antibody) - indicates immunity from vaccination or resolved infection

This is critically important because: If HCV treatment is initiated, all patients must be tested for HBsAg and anti-HBc before starting direct-acting antivirals, as HBV reactivation can occur during HCV treatment and has resulted in fulminant hepatitis, hepatic failure, and death 6, 5

Common Pitfalls to Avoid

• Never rely on a single positive HCV antibody test alone to diagnose active HCV infection - approximately 35% of positive antibody results in low-prevalence populations are false-positives 1, 4
• Do not assume HCV RNA negative definitively rules out infection without confirmatory antibody testing - this could represent false-positive antibody, resolved infection, or intermittent viremia 1, 3
• Never initiate HCV treatment without complete HBV serologic testing (HBsAg and anti-HBc) - HBV reactivation during HCV treatment is a boxed warning for all direct-acting antivirals 6, 5
• Ensure proper specimen handling for HCV RNA testing - serum/plasma must be separated within 2-6 hours and stored appropriately to avoid false-negative results 2
• Do not repeat HCV antibody testing after confirmed positive result - antibodies persist for life in most cases and repeat testing adds no clinical value 1

Patient Counseling (If Active Infection Confirmed)

Liver protection measures: 1

• Avoid alcohol completely
• Review all medications (prescription, over-the-counter, herbal) with physician before use
• Vaccinate against hepatitis A if liver disease present

Transmission prevention: 1

• Do not donate blood, organs, tissue, or semen
• Do not share personal items that may have blood (toothbrushes, razors, nail clippers)
• Cover cuts and wounds
• Sexual transmission risk is low with long-term monogamous partners but not zero; discuss barrier precautions 1