How to manage a patient with negative HBsAg and HBsAb but positive HBcAb?

Management of Patients with HBsAg Negative, HBsAb Negative, and HBcAb Positive Status

Patients who are HBsAg negative and HBcAb positive but HBsAb negative should undergo HBV DNA testing to rule out occult HBV infection, with management determined by HBV DNA results and immunosuppression risk. 1

Initial Assessment

1. HBV DNA Testing

   • Perform HBV DNA testing immediately to determine if there is occult HBV infection 2, 1
   • This serological pattern (HBsAg-, HBcAb+, HBsAb-) suggests:
     • Previous HBV infection with loss of HBsAb over time
     • Occult HBV infection (low-level viral replication with undetectable HBsAg)
     • False positive anti-HBc result (rare)

2. Risk Stratification

   • Determine if the patient requires immunosuppressive therapy
   • Assess for other liver diseases (hepatitis C, alcohol use, fatty liver disease)
   • Check liver function tests (ALT, AST, bilirubin)

Management Algorithm Based on HBV DNA Results

If HBV DNA is Negative:

1. Consider HBV vaccination 2

   • Patients who are negative for HBsAg and HBsAb but positive for anti-HBc should consider vaccination after confirming absence of chronic infection 2
   • Monitor HBsAb levels 1-2 months after completing vaccination series

2. Regular Monitoring

   • If not receiving immunosuppression: routine liver function test monitoring
   • If planning to receive immunosuppression: follow risk-based approach below

If HBV DNA is Positive:

1. Refer to hepatology for management of occult HBV infection
2. Consider antiviral therapy with entecavir or tenofovir if:
   • Evidence of active liver disease
   • Planning to receive immunosuppressive therapy

Management During Immunosuppressive Therapy

Risk-Based Approach to Prophylaxis 2, 1

1. High Risk (>10% reactivation risk)

   • Anti-CD20 agents (rituximab, ofatumumab)
   • Stem cell transplantation
   • Recommendation: Antiviral prophylaxis (strong recommendation) 2
   • Continue for at least 12 months after completing immunosuppression

2. Moderate Risk (1-10% reactivation risk)

   • TNF inhibitors (adalimumab, infliximab, etc.)
   • Anthracycline derivatives (doxorubicin, epirubicin)
   • High-dose corticosteroids (>20mg prednisone daily for ≥4 weeks)
   • Recommendation: Consider antiviral prophylaxis (weak recommendation) 2
   • Continue for at least 6 months after completing immunosuppression

3. Low Risk (<1% reactivation risk)

   • Traditional immunosuppressants (methotrexate, azathioprine)
   • Low-dose corticosteroids (<10mg prednisone daily)
   • Recommendation: Monitoring without prophylaxis 2

Monitoring During Immunosuppression

If prophylaxis is not given:

• Monitor HBsAg, ALT, and HBV DNA every 1-3 months during therapy 2, 1
• Continue monitoring for at least 6 months after completing immunosuppression (12 months for anti-CD20 therapy) 2
• Initiate antiviral therapy immediately if HBsAg or HBV DNA becomes positive 2, 1

Important Considerations and Pitfalls

• Risk of fatal reactivation: Cases of fatal HBV reactivation have been reported in HBsAg-negative, HBcAb-positive patients receiving rituximab, even when HBsAb was positive 3, 4

• Preferred antiviral agents: Entecavir or tenofovir are preferred due to high barrier to resistance 2, 1

• Duration of prophylaxis:

  • Standard immunosuppression: at least 6 months after completing therapy
  • Anti-CD20 therapy: at least 12 months after completing therapy 2

• Monitoring without prophylaxis: If choosing monitoring over prophylaxis, be prepared to initiate antiviral therapy immediately if signs of reactivation occur

This approach balances the risk of HBV reactivation against unnecessary antiviral treatment while prioritizing patient safety and preventing potentially fatal outcomes from HBV reactivation.