35 © Springer Nature Singapore Pte Ltd. 2019 H. Ohira, K. Migita (eds.), Gastrointestinal and Hepatic Manifestations of Rheumatic Diseases, https://doi.org/10.1007/978-981-13-6524-9_3 Chapter 3 De Novo Hepatitis B Virus Infection Ken Okai, Kazumichi Abe, Atsushi Takahashi, and Hiromasa Ohira Abstract Hepatitis B virus (HBV) reactivation is defned as HBV reproliferation under specifc conditions, such as immunosuppression. A state of reactivation coun- teracts a state of immunosuppression. Thus, hepatitis that occurs due to an attack on HBV-infected hepatocytes by a recovered immune system is known as de novo hepatitis B infection. HBV reactivation is induced by various agents that are used for chemotherapy and immunosuppressive therapy, and the risk of reactivation determines the severity of both HBV infection and immunosuppression. Several reports have described HBV reactivation due to antirheumatic agents used to treat rheumatic and connective tissue disorders. However, HBV reactivation does not occur frequently, and immunosuppressive treatment is usually long term; thus, the risk of hepatitis onset due to an immune response is low. However, de novo hepatitis B infection tends to be severe, and if the patient becomes ill, the mortality risk is not only high, but treatment of the underlying disease is also complicated by hepatitis onset. Therefore, preventing onset itself is of primary importance. Currently, accord- ing to the “Guidelines for the Management of Hepatitis B Virus Reactivation Caused by Immunosuppression/Chemotherapy”, it is imperative to perform monitoring and administer preventive treatment with nucleic acid analogues to all patients with rheumatic and connective tissue disorders who are likely to develop hepatitis B reactivation. In addition, future research should consider clarifying viral and host factors related to HBV reactivation and severity to defne high-risk patients. Keywords HBV reactivation · Immunosuppressive therapy · Rheumatoid arthritis · Nucleic acid analogue · Hepatitis B Treatment Guidelines K. Okai (*) · K. Abe · A. Takahashi · H. Ohira Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan e-mail: okaken@fmu.ac.jp; k-abe@fmu.ac.jp; junior@fmu.ac.jp; h-ohira@fmu.ac.jp