Updates on management strategies of hepatitis B virus reactivation in patients with resolved hepatitis virus B infection undergoing immunosuppressive therapy in rheumatology and the current situation in Niigata Rheumatic Center

Abstract

With the introduction of methotrexate, biological disease-modifying antirheumatic drugs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs), the disease activity of patients with rheumatoid arthritis has been dramatically ameliorated. However, these drugs have strong immunosuppressive effects and can cause reactivation of hepatitis B virus (HBV) in patients with resolved HBV infection. Corticosteroids or immunosuppressants used for other connective tissue diseases or vasculitis also carry a risk of inducing reactivation of HBV. Therefore, every rheumatologist should know how to detect the resolved infection of HBV in patients with rheumatic diseases receiving immunosuppressive therapy and how to monitor it when resolved infection is revealed. Of note, the cut-off index was changed from 2.1 log copies/ml to 20 IU/ml (1.3 Log IU/ml) in 2017. Rheumatologists should start nucleic acid analog administration at reactivation of HBV while performing ongoing immunosuppressive therapy in order to prevent severe or fulminant hepatitis. A low titer of HBs antibody (Ab) or lack of HBs Ab is a risk factor of reactivation of HBV. However, the reactivation of HBV cannot be prevented by HBs Ab titers at baseline or changes overtime. Rheumatologists should recognize that every immunosuppressive therapy, regardless of the mode of action, has a potential risk of reactivation. To facilitate proper management of patients with HBV infection, collaboration between rheumatologists and hepatologists is strongly encouraged. Patients’ education, systems for checking electronic medical charts, and multidisciplinary efforts are considered important for detecting HBV reactivation.

Keywords:

• Hepatitis B virus
• resolved infection
• immunosuppressive therapy
• reactivation
• nucleic acid analog

Acknowledgments

I want to thank Dr. Daisuke Kobayashi of the Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, for evaluating resolved infections of hepatitis B in our rheumatic center while working there. I also want to thank Dr. Masashi Watanabe, Department of Internal medicine, Niigata Prefectural Shibata hospital, who helped me treat a patient with reactivation of HBV. Furthermore, I wish to thank Dr. Hideshi Yamazaki, Orthopedic Department of Marunouchi Hospital, for providing the explanatory sheet concerning reactivation of HBV that we give to patients.

Conflict of interest

S. Ito has received a speaking fee (approximately US $5000) from Eisai Co., Ltd.; Mitsubishi Tanabe Pharma Corporation; Janssen Pharmaceutical K. K.