Wataru Fukuda1, Tadamasa Hanyu2, Masaki Katayama3, Shinichi Mizuki4, Akitomo Okada5, Masayuki Miyata6, Yuichi Handa7, Masatoshi Hayashi8, Yoshinobu Koyama9, Kaoru Arii10, Toshiyuki Kitaori11, Hiroyuki Hagiyama12, Yoshinori Urushidani13, Takahito Yamasaki14, Yoshihiko Ikeno15, Tsuyoshi Suzuki16, Atsushi Omoto1, Toshifumi Sugitani17, Satoshi Morita17, Shigeko Inokuma18. 1. Center for Rheumatic Disease, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan. 2. Department of Rheumatology, Nagaoka Red Cross Hospital, Niigata, Japan. 3. Department of Rheumatology, Osaka Red Cross Hospital, Osaka, Japan. 4. Department of Rheumatology, Matsuyama Red Cross Hospital, Ehime, Japan. 5. Department of Rheumatology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan. 6. Department of Internal Medicine, Japanese Red Cross Fukushima Hospital, Fukushima, Japan. 7. Department of Rheumatology, Saitama Red Cross Hospital, Saitama, Japan. 8. Department of Orthopedic Surgery and Rheumatology, Nagano Red Cross Hospital, Nagano, Japan. 9. Department of Rheumatology, Japanese Red Cross Okayama Hospital, Okayama, Japan. 10. Department of Internal Medicine, Japanese Red Cross Kochi Hospital, Kochi, Japan. 11. Department of Orthopedics, Japanese Red Cross Fukui Hospital, Fukui, Japan. 12. Yokohama City Minato Red Cross Hospital, Kanagawa, Japan. 13. Department of Rheumatology, Matsue Red Cross Hospital, Shimane, Japan. 14. Department of Rehabilitation, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan. 15. Department of Rheumatology, Nasu Red Cross Hospital, Tochigi, Japan. 16. Division of Allergy and Rheumatology, Japanese Red Cross Medical Center, Tokyo, Japan. 17. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan. 18. Department of Allergy and Rheumatology, Chiba Central Medical Center, Chiba, 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. OBJECTIVES: 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
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. OBJECTIVES: 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.