What are the management and treatment options for a patient with hepatitis B core antibodies (HBcAb) and a negative hepatitis B surface antigen (HBsAg)?

Management of Patients with Positive Hepatitis B Core Antibody and Negative Surface Antigen

Patients with positive hepatitis B core antibody (anti-HBc) and negative hepatitis B surface antigen (HBsAg) should be monitored for potential HBV reactivation based on their risk level, with antiviral prophylaxis recommended for high-risk patients receiving immunosuppressive therapy.

Clinical Interpretation of Serology

The serological pattern of HBsAg negative with anti-HBc positive indicates one of the following scenarios:

1. Resolved HBV infection: Most common interpretation, especially if anti-HBs is also positive
2. Occult HBV infection: Low-level HBV replication with undetectable HBsAg
3. False positive anti-HBc: Rare but possible
4. Window period during acute infection: Uncommon, would typically show IgM anti-HBc positivity

Risk Assessment for HBV Reactivation

The risk of HBV reactivation in HBsAg-negative/anti-HBc-positive patients varies based on:

High Risk (>10% reactivation risk)

• B-cell depleting agents (e.g., rituximab, ofatumumab)
• Stem cell transplantation
• Anti-CD20 monoclonal antibodies

Moderate Risk (1-10% reactivation risk)

• TNF-alpha inhibitors
• Cytokine/integrin inhibitors
• Tyrosine kinase inhibitors
• Moderate-to-high dose corticosteroids (≥10 mg prednisone daily) for ≥4 weeks
• Anthracycline derivatives in HBsAg-negative/anti-HBc-positive patients

Low Risk (<1% reactivation risk)

• Traditional immunosuppressants (azathioprine, methotrexate)
• Low-dose corticosteroids (<10 mg prednisone daily) for ≤4 weeks

Management Algorithm

1. Initial Evaluation

• Complete HBV serology panel: HBsAg, anti-HBc, anti-HBs
• HBV DNA testing if anti-HBc positive
• Liver function tests (ALT, AST)

2. Management Based on Risk Level

For High-Risk Patients:

• Initiate antiviral prophylaxis before starting immunosuppressive therapy 1
• Continue for at least 12 months after completing immunosuppressive therapy
• Use antivirals with high barrier to resistance (entecavir or tenofovir) rather than lamivudine 1

For Moderate-Risk Patients:

• Antiviral prophylaxis is suggested over monitoring alone 1
• Continue for at least 6 months after completing immunosuppressive therapy
• Alternative approach: Close monitoring with ALT and HBV DNA every 1-3 months if patient values avoiding long-term antiviral therapy 1

For Low-Risk Patients:

• Monitoring alone is suggested without routine antiviral prophylaxis 1
• Monitor ALT and HBV DNA every 3 months

3. Monitoring During and After Treatment

• For patients on prophylaxis: Monitor HBV DNA every 6 months during therapy
• For patients being monitored: Check ALT and HBV DNA every 1-3 months
• If reactivation occurs (detectable HBV DNA or HBsAg seroconversion), initiate antiviral therapy immediately

Special Considerations

Presence of Anti-HBs

• The presence of anti-HBs may provide some protection against reactivation but does not eliminate the risk 1, 2
• Higher anti-HBs titers (>100 IU/mL) may offer better protection, but this should not alter management decisions 2

Patients with Cancer

• All cancer patients should be screened for HBV (HBsAg and anti-HBc) prior to initiating systemic anticancer therapy 1
• For hematologic malignancies, especially those receiving anti-CD20 therapy, prophylaxis is strongly recommended for anti-HBc positive patients regardless of anti-HBs status 1

Occult HBV Infection

• Patients with anti-HBc positivity may have occult HBV infection with HBV DNA integrated into hepatocytes 3
• This poses a risk for reactivation during immunosuppression and potential progression of liver disease over time

Clinical Pitfalls to Avoid

1. Do not rely solely on anti-HBs status to determine prophylaxis needs
2. Do not use lamivudine for prophylaxis due to high resistance rates
3. Do not delay immunosuppressive therapy while waiting for HBV test results
4. Do not discontinue monitoring too early after completing immunosuppressive therapy
5. Do not miss coordinating care with a clinician experienced in HBV management for complex cases

By following this evidence-based approach, clinicians can effectively manage patients with positive hepatitis B core antibody and negative surface antigen, minimizing the risk of HBV reactivation and associated complications.