Kazuhiko Hayashi1, Masatoshi Ishigami2, Yoji Ishizu1, Teiji Kuzuya1, Takashi Honda1, Yoshihiko Tachi3, Tetsuya Ishikawa1, Yoshiaki Katano4, Kentaro Yoshioka5, Hidenori Toyoda6, Takashi Kumada6, Hidemi Goto1, Yoshiki Hirooka1. 1. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. 2. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. masaishi@med.nagoya-u.ac.jp. 3. Department of Gastroenterology, Komaki City Hospital, 1-20 Joubushi, Komaki, 485-8520, Japan. 4. Department of Internal Medicine, Banbuntane Hotokukai Hospital, Fujita Health University School of Medicine, 3-6-10 Otobashi, Nakagawa-ku, Nagoya, 454-8509, Japan. 5. Division of Liver and Biliary Diseases, Department of Internal Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan. 6. Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, 503-8502, Japan.
Abstract
BACKGROUND AND AIM: Reactivation of hepatitis B virus (HBV) in hepatitis B surface antigen (HBsAg)-positive patients treated with immunosuppressive or cytotoxic chemotherapy is well known and has emerged as an important clinical issue. The risk is low, but reactivation of HBV in HBsAg-negative patients after resolution of HBV infection also occurs; however, the clinical and virological characteristics remain somewhat unclear. We investigated HBsAg-negative patients who developed HBV reactivation during or after immunosuppressive or cytotoxic chemotherapy to clarify the clinical and virological features. METHODS: Reactivation of HBV in 30 previously infected that is HBsAg-negative patients during or after immunosuppressive or cytotoxic chemotherapy was examined. Direct sequencing at the time of reactivation was used to evaluate 11 patients. RESULTS: The majority of patients had diffuse large B cell lymphoma treated by rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone. Fulminant hepatic failure developed in three patients, who did not survive. HBV subgenotypes A2/Ae (n = 1), B1/Bj (n = 2), and C2/Ce (n = 8) were detected. There were no significant differences in the prevalence of BCP/PC variants between HBV reactivation and acute self-limited hepatitis patient groups. BCP and PC variants were not associated with development of fulminant hepatic failure from HBV reactivation. The prevalence of HBV S region variants, including immune-escape mutants, among reactivation patients was significantly higher than that in acute self-limited hepatitis patients. CONCLUSIONS: Reactivation risk factors included male sex, advanced age, and hematological malignancy. HBV S gene immune-escape mutants were frequently found in the HBsAg-negative reactivation patients during or after immunosuppressive or cytotoxic chemotherapy.
BACKGROUND AND AIM: Reactivation of hepatitis B virus (HBV) in hepatitis B surface antigen (HBsAg)-positive patients treated with immunosuppressive or cytotoxic chemotherapy is well known and has emerged as an important clinical issue. The risk is low, but reactivation of HBV in HBsAg-negative patients after resolution of HBV infection also occurs; however, the clinical and virological characteristics remain somewhat unclear. We investigated HBsAg-negative patients who developed HBV reactivation during or after immunosuppressive or cytotoxic chemotherapy to clarify the clinical and virological features. METHODS: Reactivation of HBV in 30 previously infected that is HBsAg-negative patients during or after immunosuppressive or cytotoxic chemotherapy was examined. Direct sequencing at the time of reactivation was used to evaluate 11 patients. RESULTS: The majority of patients had diffuse large B cell lymphoma treated by rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone. Fulminant hepatic failure developed in three patients, who did not survive. HBV subgenotypes A2/Ae (n = 1), B1/Bj (n = 2), and C2/Ce (n = 8) were detected. There were no significant differences in the prevalence of BCP/PC variants between HBV reactivation and acute self-limited hepatitispatient groups. BCP and PC variants were not associated with development of fulminant hepatic failure from HBV reactivation. The prevalence of HBV S region variants, including immune-escape mutants, among reactivation patients was significantly higher than that in acute self-limited hepatitispatients. CONCLUSIONS: Reactivation risk factors included male sex, advanced age, and hematological malignancy. HBV S gene immune-escape mutants were frequently found in the HBsAg-negative reactivation patients during or after immunosuppressive or cytotoxic chemotherapy.
Entities:
Keywords:
Genotype; Hepatitis B virus; Phylogenetic analysis; Reactivation
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