What is the risk of Hepatitis B reactivation in patients taking CellCept (mycophenolate mofetil) and Ourania, and how can it be managed?

Hepatitis B Reactivation Risk with CellCept (Mycophenolate Mofetil) and Ourania

Patients taking CellCept (mycophenolate mofetil) have a low risk (<1%) of hepatitis B reactivation, but this risk increases substantially when combined with other immunosuppressive agents, particularly B-cell depleting therapies like rituximab. 1

Risk Stratification for HBV Reactivation

High Risk (≥10% reactivation rate)

• B-cell depleting therapies (rituximab, ofatumumab)
• High-dose corticosteroids (>20mg prednisone daily for ≥4 weeks)
• Anthracycline derivatives
• Bone marrow/stem cell transplantation

Moderate Risk (1-10% reactivation rate)

• TNF-alpha inhibitors
• Tyrosine kinase inhibitors
• Moderate-dose corticosteroids (10-20mg prednisone daily for ≥4 weeks)

Low Risk (<1% reactivation rate)

• Mycophenolate mofetil (CellCept) 1
• Azathioprine
• Methotrexate
• Low-dose corticosteroids (<10mg prednisone daily)

Management Algorithm Based on HBV Status

For HBsAg-Positive Patients

1. Screen all patients before starting immunosuppressive therapy with HBsAg, anti-HBc, and HBV DNA 1
2. Initiate prophylactic antiviral therapy regardless of HBV DNA level before starting CellCept 1
   • Preferred agents: entecavir or tenofovir (higher barrier to resistance)
   • Start 2-4 weeks before immunosuppression when possible
3. Continue antiviral therapy for at least 6 months after discontinuation of immunosuppression 1
   • For rituximab-containing regimens, continue for at least 12 months after last dose

For HBsAg-Negative/Anti-HBc-Positive Patients

1. High-risk immunosuppression (rituximab, etc.): Provide prophylactic antiviral therapy 1, 2
2. Moderate/low-risk immunosuppression (CellCept alone): Monitor HBV DNA and ALT every 1-3 months 1
   • Initiate antivirals immediately if HBV DNA becomes detectable or HBsAg seroconversion occurs

Important Considerations

CellCept-Specific Information

• The FDA label for CellCept specifically mentions the risk of reactivation of viral infections, including hepatitis B 3
• CellCept alone is classified as a low-risk agent for HBV reactivation 1
• When combined with other immunosuppressants (especially corticosteroids), the risk increases 3, 4

Evidence on CellCept and HBV

• A study in renal transplant recipients with chronic HBV infection showed that prophylactic lamivudine with MMF was well-tolerated, though HBV DNA became positive in some patients despite prophylaxis 5
• Another study showed that adding MMF did not provide beneficial effects in suppressing HBV replication in liver transplant recipients with lamivudine resistance 6
• In patients with nephrotic syndrome who were HBsAg carriers, MMF combined with lower-dose prednisone resulted in significantly lower rates of HBV reactivation compared to standard-dose prednisone alone (36.8% vs 63.6%) 4

Monitoring Recommendations

1. Before starting therapy:

   • Screen all patients for HBsAg and anti-HBc
   • If positive, check HBV DNA levels and liver function tests
   • Consider hepatology consultation

2. During therapy:

   • For patients on prophylaxis: Monitor ALT every 1-3 months
   • For patients being monitored: Check HBV DNA and ALT every 1-3 months

3. After therapy:

   • Continue monitoring for at least 6-12 months after discontinuation of immunosuppression

Common Pitfalls to Avoid

1. Failure to screen for HBV before starting immunosuppression
2. Delayed initiation of antiviral prophylaxis
3. Premature discontinuation of antiviral therapy
4. Inadequate monitoring during and after immunosuppression
5. Overlooking the additive risk when multiple immunosuppressive agents are used together

By following this algorithm, the risk of HBV reactivation in patients taking CellCept can be effectively managed, reducing morbidity and mortality associated with this potentially serious complication.