Hepatitis B virus reactivation in HBsAg-positive patients with rheumatic diseases undergoing anti-tumor necrosis factor therapy or DMARDs

Int J Rheum Dis. 2013 Oct;16(5):527-31. doi: 10.1111/1756-185X.12154.


Objective: The aim of this study was to assess the effects of anti-tumor necrosis factor (TNF) agents or disease-modifying antirheumatic drugs (DMARDs) on hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-positive patients with rheumatic diseases.

Methods: Evidence of HBV reactivation after anti-TNF therapy or DMARDs in HBsAg-positive patients with rheumatic disease was summarized by performing a systematic review.

Results: A total of 122 HBsAg-positive rheumatic disease-positive patients undergoing treatment with an anti-TNF agent or with DMARDs were identified in nine studies. In eight of the studies, the anti-TNF agents used were etanercept in 56 cases, adalimumab in 25 cases and infliximab in 14 cases. Follow-up periods ranged from 6 to 52 months. Antiviral prophylaxis was administrated in 48 of the 122 patients (39.3%). HBV reactivation in HBsAg-positive patients taking an anti-TNF agent or DMARD was reported in 15 cases (15/122 = 12.3%). Ten of the 15 patients provided individual data on HBV reactivation: four patients had rheumatoid arthritis, four had ankylosing spondylitis and two had psoriatic arthritis; four received etanercept, and two received infliximab. In one of the four etanercept-treated cases in which the patient had elevated HBV-DNA levels, antiviral prophylaxis was also administered. Antiviral treatment was also administered in seven patients receiving other treatments: lamivudine in one, adefovir in one and entecavir in five. Clinical outcomes were satisfactory in all 10 cases of HBV reactivation.

Conclusions: Hepatitis B virus reactivation was found in 15 (12.3%) patients among the 122 HBsAg-positive patients with rheumatic diseases treated with anti-TNF agents or DMARDs.

Keywords: DMARD; anti-tumor necrosis factor therapy; hepatitis B virus reactivation; rheumatic diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antirheumatic Agents / adverse effects*
  • Antiviral Agents / therapeutic use
  • Biological Products / adverse effects*
  • Biomarkers / blood
  • Hepatitis B / blood
  • Hepatitis B / diagnosis
  • Hepatitis B / drug therapy
  • Hepatitis B / immunology
  • Hepatitis B / virology*
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / immunology
  • Humans
  • Rheumatic Diseases / drug therapy*
  • Rheumatic Diseases / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Virus Activation / drug effects*


  • Antirheumatic Agents
  • Antiviral Agents
  • Biological Products
  • Biomarkers
  • Hepatitis B Surface Antigens
  • Tumor Necrosis Factor-alpha