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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2015; 21(36): 10274-10289
Published online Sep 28, 2015. doi: 10.3748/wjg.v21.i36.10274
Hepatitis B virus reactivation associated with antirheumatic therapy: Risk and prophylaxis recommendations
Shunsuke Mori, Shigetoshi Fujiyama
Shunsuke Mori, Department of Rheumatology, Clinical Research Center for Rheumatic Diseases, NHO Kumamoto Saishunsou National Hospital, Kumamoto 861-1196, Japan
Shigetoshi Fujiyama, Department of Hepatology and Gastroenterology, Kumamoto Shinto General Hospital, Kumamoto 862-8655, Japan
Author contributions: All authors contributed to the study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript and making critical revisions with regard to important intellectual content, and final approval of the manuscript.
Supported by Research funds from the National Hospital Organization, Japan.
Conflict-of-interest statement: Dr. Shunsuke Mori has received research grants from Chugai Pharmaceutical Co., Bristol-Myers Squibb, Eisai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., and Astellas Pharma Inc. Dr. Shigetoshi Fujiyama has no financial relationships that could lead to a conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Shunsuke Mori, MD, PhD, Department of Rheumatology, Clinical Research Center for Rheumatic Diseases, NHO Kumamoto Saishunsou National Hospital, 2659 Suya, Kohshi, Kumamoto 861-1196, Japan. moris@saisyunsou1.hosp.go.jp
Telephone: +81-96-2421000 Fax: +81-96-2422619
Received: April 1, 2015
Peer-review started: April 2, 2015
First decision: June 2, 2015
Revised: June 20, 2015
Accepted: August 25, 2015
Article in press: August 25, 2015
Published online: September 28, 2015
Abstract

Accompanying the increased use of biological and non-biological antirheumatic drugs, a greater number of cases of hepatitis B virus (HBV) reactivation have been reported in inactive hepatitis B surface antigen (HBsAg) carriers and also in HBsAg-negative patients who have resolved HBV infection. The prevalence of resolved infection varies in rheumatic disease patients, ranging from 7.3% to 66%. Through an electronic search of the PubMed database, we found that among 712 patients with resolved infection in 17 observational cohort studies, 12 experienced HBV reactivation (1.7%) during biological antirheumatic therapy. Reactivation rates were 2.4% for etanercept therapy, 0.6% for adalimumab, 0% for infliximab, 8.6% for tocilizumab, and 3.3% for rituximab. Regarding non-biological antirheumatic drugs, HBV reactivation was observed in 10 out of 327 patients with resolved infection from five cohort studies (3.2%). Most of these patients received steroids concomitantly. Outcomes were favorable in rheumatic disease patients. A number of recommendations have been established, but most of the supporting evidence was derived from the oncology and transplantation fields. Compared with patients in these fields, rheumatic disease patients continue treatment with multiple immunosuppressants for longer periods. Optimal frequency and duration of HBV-DNA monitoring and reliable markers for discontinuation of nucleoside analogues should be clarified for rheumatic disease patients with resolved HBV infection.

Keywords: Hepatitis B virus, Antirheumatic therapy, Resolved hepatitis B virus infection, Occult hepatitis B virus carrier, Reactivation

Core tip: In the literature, the prevalence of resolved hepatitis B virus (HBV) infection varied in rheumatic disease patients, ranging from 7.3% to 66%, which seems to be related directly to the general prevalence of HBV infection in the respective geographic areas. When calculated using data from observational cohort studies, the incidence rate was 1.7% in rheumatic disease patients receiving biological therapy and 3.2% in those treated with non-biological drugs. In antirheumatic therapy, multiple immunosuppressants are administered during long periods. Optimal frequency and duration of HBV-DNA monitoring and reliable markers for discontinuation of nucleoside analogues remain unclear for rheumatic disease patients with resolved HBV infection.