What is the management approach for a patient with a serological profile indicating past hepatitis B (HBV) infection, as evidenced by hepatitis B surface antigen (HBsAg) negativity, hepatitis B surface antibody (HBsAb) reactivity, and hepatitis B core antibody (HBcAb) positivity?

Management of Past Hepatitis B Infection

Patients with HBsAg negative, anti-HBs positive, and anti-HBc positive serological profile have resolved past HBV infection with natural immunity and generally require no specific treatment, but should be monitored for potential reactivation if immunosuppressive therapy is planned. 1

Interpretation of Serological Profile

This serological pattern (HBsAg negative, anti-HBs positive, anti-HBc positive) indicates:

• Resolved past HBV infection with natural immunity 2
• The patient has successfully cleared the acute infection and developed protective antibodies
• Despite clearance of HBsAg, covalently closed circular DNA (cccDNA) remains in the liver hepatocytes 2

Risk Assessment for HBV Reactivation

The risk of HBV reactivation depends on several factors:

1. Immunosuppression status:

   • High risk: Patients receiving anti-CD20 monoclonal antibodies (e.g., rituximab) or hematopoietic stem cell transplantation 2
   • Moderate risk: Patients receiving TNF inhibitors, other cytokine inhibitors, or high-dose corticosteroids
   • Low risk: Patients receiving conventional immunosuppressive drugs or low-dose corticosteroids

2. Anti-HBs titer level:

   • Higher anti-HBs titers (>100 IU/mL) are associated with lower reactivation risk 2
   • Lower anti-HBs titers correlate with increased reactivation risk

Management Recommendations

For Immunocompetent Patients:

• No specific antiviral treatment is required
• Routine monitoring of liver function tests annually
• Counseling regarding prevention of transmission to others
• Hepatitis A vaccination if not immune 2

For Patients Requiring Immunosuppressive Therapy:

• High-risk immunosuppression (anti-CD20 therapy, stem cell transplantation):

  • Prophylactic antiviral therapy (entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide) 2
  • Start before immunosuppression and continue for at least 12 months after completion of immunosuppression 2
  • Monitor HBV DNA and liver function tests every 3-6 months during and after prophylaxis

• Moderate-risk immunosuppression:

  • Consider prophylactic antiviral therapy or
  • Close monitoring with HBV DNA and ALT every 1-3 months
  • Initiate antiviral therapy if HBV DNA becomes detectable

• Low-risk immunosuppression:

  • Monitor HBV DNA and ALT every 3 months
  • Initiate antiviral therapy if HBV DNA becomes detectable

Antiviral Options for Prophylaxis or Treatment

When prophylaxis is indicated, preferred medications include 2:

• Entecavir
• Tenofovir disoproxil fumarate
• Tenofovir alafenamide

These agents have higher potency and high viral resistance barriers compared to older agents like lamivudine.

Important Considerations and Pitfalls

1. Do not rely solely on anti-HBs status: Despite having protective antibodies, patients can still experience HBV reactivation during immunosuppression 3

2. Test for HBV DNA before immunosuppression: Consider baseline HBV DNA testing in patients with resolved HBV infection who will undergo immunosuppressive therapy 2

3. HIV testing: Test for HIV before starting antiviral therapy, as some HBV antivirals have anti-HIV properties and HIV monotherapy is not recommended 2

4. Duration of monitoring: For high-risk immunosuppression, continue monitoring for up to 2 years after cessation of immunosuppressive therapy, as delayed reactivation can occur 2

5. Alternative monitoring approach: If prophylaxis is not used, implement rigorous monitoring (HBV DNA every 4 weeks) during immunosuppression, with immediate antiviral initiation if reactivation is detected 2

By following these guidelines, the risk of HBV reactivation and its potentially severe consequences, including fulminant hepatitis and death, can be significantly reduced in patients with resolved HBV infection.