title: Incidence of hepatitis B virus reactivation in patients with resolved infection on immunosuppressive therapy for rheumatic disease: a multicentre, prospective, observational study in Japan.
abstract: BACKGROUND
  Although the reactivation of hepatitis B virus (HBV) is recognised as a serious complication in patients with rheumatic disease (RD) receiving immunosuppressive drugs (ISDs), the incidence and risk factors for reactivation remain controversial.
  
  
  OBJECTIVE
  To investigate the incidence and risk factors for HBV reactivation in patients with RD.
  
  
  METHODS
  We performed a multicentre, observational, prospective study over 2 years in patients with resolved HBV infection. Patients with RD treated with a dose of ≥5 mg/day prednisolone and/or synthetic or biological ISDs with negative HB virus surface antigen and positive anti-HB virus surface antibody (HBsAb) and/or anti-HB virus core antibody (HBcAb) were enrolled. Quantitative HBV DNA results and related data were regularly recorded.
  
  
  RESULTS
  Among 1042 patients, including 959 with rheumatoid arthritis, HBV DNA was detected in 35 (1.93/100 person-years), with >2.1 log copies/mL observed in 10 patients (0.55/100 person-years). None of the reactivated patients, including seven treated with a nucleic acid analogue, showed overt hepatitis. Low HBsAb titres and advanced age seemed to be risk factors for HBV reactivation; however, reactivation was observed in three patients with positive HBsAb and negative HBcAb test results. The risk of reactivation was lower with methotrexate but higher with prednisolone among the different types of ISDs. The intervals from the start of ISD to reactivation were relatively long (3-182 months; median, 66 months).
  
  
  CONCLUSIONS
  The incidence of HBV reactivation with ISD use was 1.93/100 person-years in patients with RD with resolved HBV infection. No overt hepatitis was observed in the reactivated patients.
authors.affiliation: Center for Rheumatic Disease, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Fukuda
authors.affiliation: Department of Rheumatology, Nagaoka Red Cross Hospital, Niigata, Japan.
authors.forename: Tadamasa
authors.initials: T
authors.lastname: Hanyu
authors.affiliation: Department of Rheumatology, Osaka Red Cross Hospital, Osaka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Katayama
authors.affiliation: Department of Rheumatology, Matsuyama Red Cross Hospital, Ehime, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Mizuki
authors.affiliation: Department of Rheumatology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan.
authors.forename: Akitomo
authors.initials: A
authors.lastname: Okada
authors.affiliation: Department of Internal Medicine, Japanese Red Cross Fukushima Hospital, Fukushima, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyata
authors.affiliation: Department of Rheumatology, Saitama Red Cross Hospital, Saitama, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Handa
authors.affiliation: Department of Orthopedic Surgery and Rheumatology, Nagano Red Cross Hospital, Nagano, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Rheumatology, Japanese Red Cross Okayama Hospital, Okayama, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Koyama
authors.affiliation: Department of Internal Medicine, Japanese Red Cross Kochi Hospital, Kochi, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Arii
authors.affiliation: Department of Orthopedics, Japanese Red Cross Fukui Hospital, Fukui, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kitaori
authors.affiliation: Yokohama City Minato Red Cross Hospital, Kanagawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hagiyama
authors.affiliation: Department of Rheumatology, Matsue Red Cross Hospital, Shimane, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Urushidani
authors.affiliation: Department of Rehabilitation, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: Department of Rheumatology, Nasu Red Cross Hospital, Tochigi, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ikeno
authors.affiliation: Division of Allergy and Rheumatology, Japanese Red Cross Medical Center, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Center for Rheumatic Disease, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Omoto
authors.affiliation: Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Sugitani
authors.affiliation: Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Allergy and Rheumatology, Chiba Central Medical Center, Chiba, Japan.
authors.forename: Shigeko
authors.initials: S
authors.lastname: Inokuma
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000453:epidemiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects; D008875:Middle Aged; D011239:Prednisolone / Q000009:adverse effects; D011446:Prospective Studies; D012216:Rheumatic Diseases / Q000188:drug therapy*; D012307:Risk Factors; D013997:Time Factors; D014775:Virus Activation; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D007166:Immunosuppressive Agents; D011239:Prednisolone; D008727:Methotrexate
keywords: Epidemiology; Infections; Rheumatoid Arthritis; Treatment