Meta-analysis: hepatitis B reactivation in patients receiving biological therapy

Aliment Pharmacol Ther. 2022 Oct;56(7):1104-1118. doi: 10.1111/apt.17155. Epub 2022 Aug 17.


Background: The use of biologics poses a moderate to high risk for hepatitis B virus reactivation (HBVr) in chronic carriers.

Aim: To determine the prevalence of HBVr with TNF alpha inhibitors, ustekinumab and vedolizumab METHOD: We followed the MOOSE guidelines and conducted a comprehensive literature search. We conducted a systematic search of EMBASE (Ovid), MEDLINE (Ovid) and PubMed. The studies included patients who were chronic and occult HBV carriers with various rheumatological, dermatological or gastroenterological conditions. We used a random effects model using pooled estimates (prevalence of HBVr with 95% confidence intervals (CI)).

Results: We included 29 studies with 1409 patients infected with HBV. The prevalence of HBVr in chronic carriers of HBV was 17.1% (95% CI: 7.0-35.9, n = 5), 16.6% (95% CI: 9.5-27.5%, n = 6), 40.5% (95% CI: 20.3-64.5%, n = 4) and 19.1% (95% CI: 7.3-41.2%, n = 2), respectively, for adalimumab, etanercept, infliximab and ustekinumab. The respective prevalence for reactivation in patients with occult HBV infection was 5.0% (95% CI: 2.8-8.7%, number of studies: n = 18), 2.6% (95% CI: 1.4-4.7%, n = 18), 4.4% (95% CI: 2.2-8.7%, n = 12) and 6.4% (95% CI: 2.2-16.8, n = 5). There were 39 HBVr (26 in chronic HBV and 13 in the occult group) without any hepatic failure or death. In the chronic HBVr group, only three of 24 patients received antiviral prophylaxis.

Conclusions: HBVr prevalence rates differ between the chronic carrier state and the occult carrier state. The uptake of prophylactic antiviral therapy in high-risk groups was low, contrary to clinical practice guidelines.

Keywords: adalimumab; hepatitis B; inflammatory bowel disease; infliximab; ustekinumab.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antiviral Agents / adverse effects
  • Biological Therapy* / adverse effects
  • Hepatitis B virus
  • Hepatitis B* / drug therapy
  • Hepatitis B* / epidemiology
  • Humans
  • Ustekinumab / adverse effects
  • Virus Activation


  • Antiviral Agents
  • Ustekinumab