Journal of Gastroenterology

, Volume 46, Issue 4, pp 556–564 | Cite as

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

  • Akihiro TamoriEmail author
  • Tatsuya Koike
  • Hitoshi Goto
  • Shigeyuki Wakitani
  • Masahiro Tada
  • Hiroyasu Morikawa
  • Masaru Enomoto
  • Masaaki Inaba
  • Tatsuya Nakatani
  • Masayuki Hino
  • Norifumi Kawada
Original Article—Liver, Pancreas, and Biliary Tract



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.


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.


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.


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.


Anti-tumor necrosis factor-α Anti-HBs Entecavir HBV reactivation Rheumatoid arthritis 



Alanine aminotransferase


Antibodies against hepatitis B core antigen


Antibodies against HBsAg


Anti-tumor necrosis factor-α


Disease-modifying anti-rheumatic drugs


Hepatitis B virus


HBV surface antigen




Rheumatoid arthritis



We thank Ms. Rie Yasuda and Ms. Sanae Deguchi for their assistance in data/sample collection. This work was supported by the Liver Disease Research Fund in Osaka City University Graduate School of Medicine.

Conflict of interest

All authors declare that we have no conflict of interest in relation to the submission of this manuscript.


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Copyright information

© Springer 2011

Authors and Affiliations

  • Akihiro Tamori
    • 1
    Email author
  • Tatsuya Koike
    • 2
  • Hitoshi Goto
    • 3
  • Shigeyuki Wakitani
    • 4
  • Masahiro Tada
    • 4
  • Hiroyasu Morikawa
    • 1
  • Masaru Enomoto
    • 1
  • Masaaki Inaba
    • 3
  • Tatsuya Nakatani
    • 5
  • Masayuki Hino
    • 6
  • Norifumi Kawada
    • 1
  1. 1.Department of HepatologyOsaka City University Graduate School of MedicineOsakaJapan
  2. 2.Department of RheumatosurgeryOsaka City University Graduate School of MedicineOsakaJapan
  3. 3.Department of Metabolism, Endocrinology and Molecular MedicineOsaka City University Graduate School of MedicineOsakaJapan
  4. 4.Department of Orthopaedic SurgeryOsaka City University Graduate School of MedicineOsakaJapan
  5. 5.Department of UrologyOsaka City University Graduate School of MedicineOsakaJapan
  6. 6.Department of HematologyOsaka City University Graduate School of MedicineOsakaJapan

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