Rituximab carries high risks of hepatitis B virus reactivation in hematologic and rheumatic patients with chronic or resolved hepatitis B

J Gastroenterol Hepatol. 2024 Nov;39(11):2447-2455. doi: 10.1111/jgh.16725. Epub 2024 Aug 24.

Abstract

Background and aim: Rituximab therapy is associated with a high risk of hepatitis B virus (HBV) reactivation. We aimed to assess whether the risk of reactivation differed among various underlying diseases and between hepatitis B surface antigen (HBsAg) carriers and patients with resolved HBV infection.

Methods: We retrospectively analyzed patients with chronic or resolved HBV infection who received rituximab without prophylactic anti-HBV therapy at a tertiary medical center. The risks of HBV reactivation, hepatitis, and hepatic decompensation were compared between the patients with hematologic and rheumatic diseases.

Results: There were 78 patients with hematologic diseases and 39 patients with rheumatic diseases included. Among them, 43 (59%) HBsAg-positive patients and 24 (55%) patients with resolved HBV infection experienced HBV reactivation at a median of 14.6 months after rituximab therapy. After rituximab treatment, the 1-year HBV reactivation rate among patients with hematologic and rheumatic diseases was 29% and 45% in HBsAg-positive patients, respectively, while the rates were 38% and 17% in patients with resolved HBV infection. The reactivation risk continued to increase even 2 years after rituximab therapy and was comparable between hematologic and rheumatic patients. A higher baseline HBV DNA level (≥20 IU/mL vs <20 IU/mL) was an independent predictor for HBV reactivation (adjusted hazard ratio [aHR]: 10.9, 95% confidence interval [CI]: 1.1-107) and HBV-associated hepatitis (aHR: 14.8, 95% CI: 1.4-158).

Conclusions: Rituximab therapy is associated with a 50-64% risk of HBV reactivation regardless of underlying diseases and HBsAg status. HBV DNA levels should be assessed before initiating rituximab.

Keywords: hematology; hepatitis B; rheumatology; risk factor; rituximab.

MeSH terms

  • Adult
  • Aged
  • DNA, Viral / blood
  • Female
  • Hematologic Diseases*
  • Hepatitis B Surface Antigens* / blood
  • Hepatitis B virus* / genetics
  • Hepatitis B virus* / physiology
  • Hepatitis B, Chronic* / complications
  • Hepatitis B, Chronic* / drug therapy
  • Hepatitis B, Chronic* / virology
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Rheumatic Diseases* / complications
  • Rheumatic Diseases* / drug therapy
  • Risk
  • Risk Factors
  • Rituximab* / adverse effects
  • Rituximab* / therapeutic use
  • Virus Activation* / drug effects

Substances

  • Rituximab
  • Hepatitis B Surface Antigens
  • DNA, Viral