Hepatitis B virus reactivation in rheumatoid arthritis and ankylosing spondylitis patients treated with anti-TNFα agents: a retrospective analysis of 49 cases

Clin Rheumatol. 2012 Jun;31(6):931-6. doi: 10.1007/s10067-012-1960-1. Epub 2012 Feb 17.


Clinical guidelines regarding anti-viral prophylaxis for HBV surface antigen (HBsAg) carriers starting anti-TNFα agents are not yet fully established, even in endemic regions of HBV infection. We retrospectively collected the clinical data of 52 HBsAg carriers with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) that had been administered anti-TNFα treatment at seven medical centers in South Korea. Periodic data of liver function tests and serum HBV DNA were both utilized to assess HBV reactivation. The YMDD motif mutation of HBV DNA polymerase was tested in lamivudine-treated patients with elevated HBV DNA. Three of the 52 patients were excluded from the analysis. Of the 49 analyzed patients, 20 patients received anti-viral prophylaxis (15 lamivudine, five entecavir) with anti-TNFα treatment. The remaining 29 patients were treated with anti-viral agents if needed at the discretion of the clinician and did not receive prophylaxis. Of the 29 patients who did not receive primary prophylaxis, two (6.9%) developed viral reactivation within a year of anti-TNFα treatment. In the prophylaxis group, one patient developed viral reactivation at week 64 of anti-TNFα therapy attributed to YMDD mutation caused by lamivudine. Patients with HBV reactivation all responded well to anti-viral therapy. In summary, anti-viral prophylaxis helped preventing HBV reactivation in HBsAg carriers with RA or AS starting anti-TNFα, yet mutation in the YMDD motif of HBV DNA polymerase could be detrimental to some patients under long-term lamivudine prophylaxis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Motifs
  • Antiviral Agents / pharmacology
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / virology*
  • DNA-Directed DNA Polymerase / metabolism
  • Female
  • Hepatitis B / complications
  • Hepatitis B / virology*
  • Hepatitis B virus / metabolism*
  • Humans
  • Lamivudine / pharmacology
  • Male
  • Middle Aged
  • Mutation
  • Retrospective Studies
  • Spondylitis, Ankylosing / complications
  • Spondylitis, Ankylosing / virology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Virus Activation


  • Antiviral Agents
  • Tumor Necrosis Factor-alpha
  • Lamivudine
  • DNA-Directed DNA Polymerase