Prospective study of HBV reactivation risk in rheumatoid arthritis patients who received conventional disease-modifying antirheumatic drugs

Clin Rheumatol. 2012 Aug;31(8):1169-75. doi: 10.1007/s10067-012-1988-2. Epub 2012 Apr 28.


Studies that reported hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients have caused attention of disease-modifying antirheumatic drug (DMARD)-related HBV reactivation. Most of the studies were focused on HBV reactivation risk of biologic DMARDs; insufficient data are available to identify the exact risk of conventional DMARD (c-DMARD)-related HBV reactivation. This prospective study aimed to investigate the risk of HBV reactivation in HBV-infected RA patients who received c-DMARDs. A total of 476 RA patients were screened in this prospective non-randomized, non-controlled study. HBV-infected patients characterized by hepatitis B surface antigen (HBsAg) positive or HBsAg negative/anti-hepatitis B core antigen (anti-HBc) positive were analyzed for HBV DNA, followed with HBV DNA monitoring scheduled every 3 months, serum alanine aminotransferase test at 2-month intervals, or more frequently. Prevalence of HBsAg positive and HBsAg negative/anti-HBc positive was 6.51 and 51.1 %, respectively, among the 476 RA patients. Among 211 patients (23 patients were HBsAg positive and 188 patients were HBsAg negative/anti-HBc positive) who received c-DMARDs without antiviral prophylactic treatment, 4 patients developed HBV reactivation. Both HBsAg positive and HBsAg negative/anti-HBc positive patients have the possibility of developing HBV reactivation. There was no correlation between HBV reactivation and any specific c-DMARD. Glucocorticoid coadministration and negative anti-hepatitis B surface antigen (anti-HBs) at baseline showed correlation with reactivation. In conclusion, it would be rational to initiate antiviral prophylaxis according to risk stratification rather than universal prophylaxis for HBV-infected RA patients. Conventional DMARDs are relatively safe to HBV-infected patients with low reactivation risk (low HBV DNA level, no GCs administration, and anti-HB positive).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • DNA, Viral / blood
  • Female
  • Follow-Up Studies
  • Hepatitis B / epidemiology
  • Hepatitis B / immunology
  • Hepatitis B / prevention & control
  • Hepatitis B / virology*
  • Hepatitis B Antibodies / blood
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B virus / immunology
  • Hepatitis B virus / physiology*
  • Humans
  • Male
  • Middle Aged
  • Prevalence
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction
  • Risk Factors
  • Virus Activation / immunology
  • Virus Activation / physiology*


  • Antirheumatic Agents
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens