Prospective study of reactivation of hepatitis B virus in patients with rheumatoid arthritis who received immunosuppressive therapy: evaluation of both HBsAg-positive and HBsAg-negative cohorts

J Gastroenterol. 2011 Apr;46(4):556-64. doi: 10.1007/s00535-010-0367-5. Epub 2011 Jan 19.


Background: Screening and prophylactic treatment for hepatitis B virus (HBV) reactivation is recommended for patients who receive immunosuppressive or cytotoxic therapy. The aim of this study was to clarify the prevalence of HBV reactivation in rheumatoid arthritis (RA) patients who had received more than 1 year of immunosuppressive therapy. This study also evaluated guidelines for determining HBV reactivation in patients with RA.

Methods: This was a prospective non-randomized, non-controlled study. We enrolled 50 patients with RA who had antibodies against hepatitis B core antigen (anti-HBc) and who had started treatment with disease-modifying anti-rheumatic drugs, including those who had additionally received anti-tumor necrosis factor-α (anti-TNF-α). HBV DNA levels were measured every 2-3 months by a real-time, polymerase chain reaction-based method. Entecavir was administered to patients with HBV DNA levels >2.1 log/ml.

Results: The mean observation period was 23 months (range 12-32 months). HBV reactivation occurred in 2 of 5 patients with HBV surface antigen (HBsAg) and in 1 of 45 patients without HBsAg. In patients who received anti-TNF-α therapy, antibodies against HBsAg decreased significantly. Entecavir therapy inhibited HBV amplification and prevented HBV-associated flares of hepatitis.

Conclusions: The incidence of HBV reactivation was low in RA patients in whom HBV infection had been resolved. Screening for HBV reactivation and prophylactic therapy with entecavir were effective means of preventing HBV-associated hepatic failure in patients with HBsAg, as well as in those with only anti-HBc who received immunosuppressive therapy for RA.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Antiviral Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • DNA, Viral / analysis
  • Female
  • Follow-Up Studies
  • Guanine / analogs & derivatives
  • Guanine / therapeutic use
  • Hepatitis B / drug therapy
  • Hepatitis B / virology*
  • Hepatitis B Core Antigens / immunology
  • Hepatitis B virus / drug effects
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Liver Failure / prevention & control
  • Liver Failure / virology
  • Male
  • Mass Screening / methods
  • Middle Aged
  • Polymerase Chain Reaction
  • Practice Guidelines as Topic
  • Prospective Studies
  • Time Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Virus Activation / drug effects*


  • Antirheumatic Agents
  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Core Antigens
  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • entecavir
  • Guanine