Risk of Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Undergoing Tocilizumab-Containing Treatment

Dig Dis Sci. 2021 Nov;66(11):4026-4034. doi: 10.1007/s10620-020-06725-1. Epub 2021 Jan 2.


Background and aim: To investigate the risk of hepatitis B virus reactivation in patients undergoing long-term tocilizumab therapy for rheumatoid arthritis.

Method: From January 2011 through August 2019, a total of 97 patients were enrolled in this retrospective study. Clinical data, comedications, and the occurrence of HBV reactivation were recorded.

Results: Seven patients were HBsAg+ (7.2%), 64 were HBsAg-/HBcAb+ (65.9%), and 26 were HBsAg-/HBcAb- (26.8%). The median disease follow-up time was 9 years. TCZ was administered for a median of 29 months. Four patients (4.1%) experienced HBV reactivation after tocilizumab therapy. Of the 7 HBsAg+ patients, 4 received antiviral prophylaxis and had no HBV reactivation; the remaining 3 patients did not receive antiviral prophylaxis, and all 3 (100%) experienced HBV reactivation and hepatitis flare-up. Hyperbilirubinemia occurred in 2 of these 3 patients, with mild prothrombin time prolongation in one. After salvage entecavir treatment, all patients had a favorable outcome. Of the 64 HBsAg-/HBcAb+ patients, only one became positive for serum HBV DNA (2.5 × 107 IU/mL) after 18 months of tocilizumab treatment (1.6%; 1/64). This patient was immediately treated with entecavir, which prevented hepatitis flare-up.

Conclusions: Tocilizumab is widely used in treating rheumatoid arthritis and has the potential to reduce the mortality rate among severe COVID-19 patients. However, HBV reactivation needs to be considered. HBsAg+ patients have a high risk of HBV reactivation, which could be prevented by antiviral prophylaxis. Although the risk of reactivation is low in HBsAg-/HBcAb+ patients, strict monitoring is necessary.

Keywords: HBV reactivation; Hepatitis flare-up; Rheumatoid arthritis; Tocilizumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Antiviral Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Guanine / analogs & derivatives
  • Guanine / therapeutic use
  • Hepatitis B Antibodies / blood
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B virus / physiology
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Retrospective Studies
  • Risk Factors
  • Virus Activation / drug effects*
  • Virus Latency / drug effects


  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Antiviral Agents
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • entecavir
  • Guanine
  • tocilizumab