What precautions should be taken for a hepatitis B core positive patient starting rituximab (Rituxan) treatment?

Management of Hepatitis B Core Positive Patients Starting Rituximab Therapy

Patients who are hepatitis B core antibody positive (anti-HBc+) should receive prophylactic antiviral therapy with entecavir or tenofovir before starting rituximab, regardless of hepatitis B surface antigen (HBsAg) status. 1

Initial Assessment and Screening

Before starting rituximab therapy, complete the following hepatitis B screening:

• HBsAg (hepatitis B surface antigen)
• Anti-HBc (hepatitis B core antibody)
• Anti-HBs (hepatitis B surface antibody)
• HBV DNA level

Management Algorithm Based on Screening Results

For HBsAg-positive AND anti-HBc-positive patients:

1. Start antiviral prophylaxis with entecavir or tenofovir (preferred over lamivudine due to high genetic barrier to resistance) 1
2. Begin prophylaxis at least 1-2 weeks before rituximab when possible, or at the latest, simultaneously with rituximab initiation 1
3. Continue antiviral therapy during rituximab treatment and for at least 12 months after the last rituximab dose 1
4. Monitor liver enzymes (ALT, AST) and HBV DNA every 3-6 months during treatment 1

For HBsAg-negative BUT anti-HBc-positive patients:

1. Prophylactic antiviral therapy is strongly recommended with entecavir or tenofovir 1
2. Begin prophylaxis at least 1-2 weeks before rituximab when possible 1
3. Continue antiviral therapy during rituximab treatment and for at least 12 months after the last rituximab dose 1
4. Monitor for HBV reactivation with HBsAg, HBV DNA, and liver enzymes every 3 months during and after treatment 1

Choice of Antiviral Agent

• First-line agents: Entecavir or tenofovir 1

  • Higher genetic barrier to resistance
  • Recommended for both active carriers and those with resolved infection
  • Particularly important if baseline HBV DNA is detectable or long-term therapy is anticipated

• Alternative agent: Lamivudine

  • May be considered in patients with resolved infection (HBsAg-negative, anti-HBc-positive) with undetectable HBV DNA 1
  • However, entecavir and tenofovir are still preferred due to risk of resistance 1

Duration of Prophylaxis

• Continue antiviral therapy during rituximab treatment and for at least 12 months after the last dose of rituximab 1
• Some guidelines recommend up to 18-24 months of prophylaxis after rituximab 1
• The extended duration is necessary because immune recovery may be delayed and risk of reactivation with rituximab has been observed up to 1-2 years after the last dose 1

Post-Treatment Monitoring

• After completing antiviral prophylaxis, continue monitoring:
  • HBV DNA and liver enzymes (ALT, AST) every 3-6 months for at least 12 months 1
  • Monitor for delayed HBV reactivation for up to 2 years after the last dose of rituximab 1

Common Pitfalls to Avoid

1. Inadequate screening: Failure to screen for HBV before starting rituximab is common and dangerous 2
2. Underestimating risk in anti-HBc-positive patients: HBV reactivation can occur in up to 55% of patients with resolved HBV infection receiving rituximab 3
3. Using lamivudine for long-term prophylaxis: Higher resistance rates make entecavir or tenofovir preferred options 1
4. Stopping antiviral therapy too early: Reactivation risk persists for up to 2 years after rituximab therapy 1
5. Inadequate monitoring: Failure to monitor HBV DNA and liver enzymes during and after prophylaxis 1

Special Considerations

• Consult with a hepatologist for patients with positive HBsAg or anti-HBc before starting rituximab 4
• Higher baseline HBV DNA levels (≥20 IU/mL) significantly increase reactivation risk (adjusted HR: 10.9) 3
• Fatal outcomes including fulminant hepatitis and liver failure can occur with HBV reactivation 4, 5

By following this comprehensive approach, you can significantly reduce the risk of HBV reactivation, which carries substantial morbidity and mortality in patients receiving rituximab therapy.