Challenges and Controversies

Rituximab is a high risk immunosuppressive regimen. Essentially, it shuts down the B cell response and patients can have a severe hepatitis flare, sometimes going into fulminant liver failure. For this reason, I start my patients in similar situations on antivirals and watch them carefully with laboratory surveillance during the first six months of rituximab. I would check HBV DNA before starting therapy and include this test in regular lab monitoring, in conjunction with LFTs or a chem 20. Then one can monitor labs q 3-6 months. In addition, I continue prophylaxis for one year after stopping rituximab.

Hepatitis B can reactivate because there is a stable form of hepatitis B that remains in the nucleus in the majority of people even after spontaneous recovery. This form is called covalently closed circular DNA or cccDNA and is the template for transcribing all viral RNAs to complete the replication cycle. Antibodies are important for control of HBV replication and rituximab depletes B cells. The guidelines for prophylaxis for HBV reactivation with immunosuppression state that people who receive rituximab are at high risk for reactivation. Thus, prophylaxis with either tenofovir (Disoproxil fumarate or Alafenamide) or entecavir is recommended while on rituximab and for at least a year after rituximab is stopped.