Clinical characteristics and molecular analysis of hepatitis B virus reactivation in hepatitis B surface antigen-negative patients during or after immunosuppressive or cytotoxic chemotherapy

Kazuhiko Hayashi, Masatoshi Ishigami, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Yoshihiko Tachi, Tetsuya Ishikawa, Yoshiaki Katano, Kentaro Yoshioka, Hidenori Toyoda, Takashi Kumada, Hidemi Goto, Yoshiki Hirooka

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1081-1089
Number of pages9
JournalJournal of Gastroenterology
Volume51
Issue number11
DOIs
Publication statusPublished - 01-11-2016

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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