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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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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.

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Acknowledgments

We thank Ms. Yasue Hasegawa and Mr. Nobuhiro Yasuda for assistance of serological assays.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Kazuhiko Hayashi, Masatoshi Ishigami, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Tetsuya Ishikawa, Hidemi Goto & Yoshiki Hirooka

  2. Department of Gastroenterology, Komaki City Hospital, 1-20 Joubushi, Komaki, 485-8520, Japan

    Yoshihiko Tachi

  3. Department of Internal Medicine, Banbuntane Hotokukai Hospital, Fujita Health University School of Medicine, 3-6-10 Otobashi, Nakagawa-ku, Nagoya, 454-8509, Japan

    Yoshiaki Katano

  4. Division of Liver and Biliary Diseases, Department of Internal Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan

    Kentaro Yoshioka

  5. Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, 503-8502, Japan

    Hidenori Toyoda & Takashi Kumada

Authors
  1. Kazuhiko Hayashi
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  2. Masatoshi Ishigami
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Corresponding author

Correspondence to Masatoshi Ishigami.

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Conflict of interest

Hidemi Goto received a research grant from AstraZeneca, Astellas Pharma, Ajinomoto Pharmaceutical Co, Bristol-Myers Squibb, Chugai Pharmaceutical Co, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eisai, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical Co and Takeda Pharmaceutical Co.

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Hayashi, K., Ishigami, M., Ishizu, Y. et al. Clinical characteristics and molecular analysis of hepatitis B virus reactivation in hepatitis B surface antigen-negative patients during or after immunosuppressive or cytotoxic chemotherapy. J Gastroenterol 51, 1081–1089 (2016). https://doi.org/10.1007/s00535-016-1187-z

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  • DOI: https://doi.org/10.1007/s00535-016-1187-z

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