Risk of Hepatitis B Virus Reactivation in Patients With Inflammatory Arthritis Receiving Disease-Modifying Antirheumatic Drugs: A Systematic Review and Meta-Analysis

Arthritis Care Res (Hoboken). 2018 May;70(5):724-731. doi: 10.1002/acr.23346. Epub 2018 Apr 12.


Objective: To assess hepatitis B virus (HBV) reactivation rates in patients with resolved or chronic HBV infection, receiving disease-modifying antirheumatic drugs (DMARDs) and with or without antiviral prophylaxis.

Methods: We conducted a systematic review and meta-analysis. Electronic searches were conducted in PubMed, Medline, and Embase using Ovid through December 31, 2015. A search strategy was developed for each database using the following inclusion criteria: for participants, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and resolved or chronic HBV infection; for intervention, tumor necrosis factor (TNF) inhibitors or non-TNF biologic or nonbiologic DMARDs; and for outcome, HBV reactivation. Four reviewers independently extracted study data and assessed study quality using the Newcastle-Ottawa Scale. To determine the pooled HBV reactivation rate, the variances of the raw proportions were stabilized using a Freeman-Tukey-type arcsine square root transformation, using a random-effects model.

Results: Twenty-five studies met the inclusion criteria. The overall pooled rate of HBV reactivation was 1.6% (95% confidence interval [95% CI] 0.8-2.6) in patients with resolved HBV. Similar rates were observed in resolved patients taking TNF inhibitors (1.4% [95% CI 0.5-2.6]), non-TNF biologics (6.1% [95% CI 0.0-16.6]), and nonbiologic DMARDs (1.7% [95% CI 0.2-4.2]). We also found that the reactivation rate was lower in patients with chronic HBV infection who received antiviral prophylaxis (9.0% [95% CI 4.1-15.5]) than in those who did not (14.6% [95% CI 4.3-29.0]).

Conclusion: We found that the HBV reactivation rate in inflammatory arthritis patients receiving DMARDs was low in resolved patients and moderate in patients with chronic HBV infection. Further, lower rates were observed in patients with chronic HBV infection who were using antiviral prophylaxis.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Systematic Review

MeSH terms

  • Antirheumatic Agents / therapeutic use
  • Antiviral Agents / therapeutic use
  • Arthritis / complications*
  • Arthritis / drug therapy
  • Hepatitis B, Chronic / prevention & control
  • Hepatitis B, Chronic / virology*
  • Humans


  • Antirheumatic Agents
  • Antiviral Agents