Risk of hepatitis B virus (HBV) reactivation in non-Hodgkin lymphoma patients receiving rituximab-chemotherapy: a meta-analysis

J Clin Virol. 2013 Jul;57(3):209-14. doi: 10.1016/j.jcv.2013.03.010. Epub 2013 Apr 4.


Background: The addition of Rituximab to standard chemotherapy (C) has been reported to improve the end of treatment outcome in non-Hodgkin lymphoma (NHL) patients. Nevertheless, rituximab has been associated with hepatitis B virus reactivation (HBV-R).

Objectives: The aim of this systematic review and meta-analysis is to research the relationship between rituximab and HBV-R.

Study design: We searched the commonly used databases both in English and Chinese from November 1997 to June 30, 2012. Meta-analysis was performed in fixed/random-effects models using Review Manager 5.1 and STATA 10.0. Publication bias was examined through Egger's test and Begg's funnel plot.

Results: Nine eligible articles were selected in this review (8 studies in English and 1 studies in Chinese), which included 971 adult patients and met all inclusion and exclusion criteria. Of rituximab-associated HBV-R cases reported through case series (n=387), 304 were HBcAb (+)/HBsAg (-) and 83 HBsAg (+). The pooled effect of rituximab-based therapy on HBV-R significantly increased under fixed-effects model [Relative risk (RR) 2.14, 95%CI 1.42-3.22, P=0.0003]. In subgroup analysis, rituximab-associated HBV-R in isolated HBcAb (+) patients remained high, and the RR was 5.52 (95%CI 2.05-14.85, P=0.0007). The RR of HBV-R in NHL patients with HBsAg (+) treated with R-based therapy when compared with the control population was 1.63 by the random-effects model.

Conclusions: Rituximab therapy may increase the risk of developing HBV-R in NHL patients with HBcAb(+).

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / administration & dosage*
  • Antibodies, Monoclonal, Murine-Derived / adverse effects*
  • Hepatitis B virus / drug effects*
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / adverse effects*
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Risk Assessment
  • Rituximab
  • Virus Activation / drug effects*


  • Antibodies, Monoclonal, Murine-Derived
  • Immunologic Factors
  • Rituximab