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Reactivation of hepatitis B virus following systemic chemotherapy for malignant lymphoma

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Abstract

Reactivation of hepatitis B virus (HBV) has been reported not only in HBsAg-positive patients undergoing systemic chemotherapy, but also in a proportion of HBsAg-negative patients with HBc antibody and/or HBs antibody. Recently, rituximab-plus-steroid combination chemotherapy (R-CHOP, etc.) has been identified as a risk factor for HBV reactivation in HBsAg-negative patients with malignant lymphoma. Prophylaxis with antiviral drugs is essential for preventing HBV reactivation in HBsAg-positive patients, but there is little evidence on which to base the choice of drug or appropriate duration of prophylaxis. There are also few clinical data on HBsAg-negative patients and no established standard of care for such patients with HBV reactivation. Based on the limited number of previous reports, preemptive therapy, guided by serial HBV-DNA monitoring, is a reasonable strategy to prevent HBV reactivation in HBsAg-negative patients. However, clinical evidence alone is insufficient for determining optimal frequency of HBV-DNA monitoring during and after chemotherapy, or for determining when to stop preemptive therapy for HBV reactivation. Thus, well-designed clinical trials should be carried out to investigate the efficacy and safety of such preemptive therapy. Additionally, assessment of viral factors such as HBV genotypes and gene mutations may assist in the development of strategies to prevent the occurrence of severe hepatitis. In this review, we summarize the characteristics of HBV reactivation after systemic chemotherapy including rituximab, and propose a management strategy for malignant lymphoma patients suffering from HBV reactivation.

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Abbreviations

HBV:

Hepatitis B virus

HBsAg:

Hepatitis B surface antigen

Anti-HBc:

hepatitis B core antibody

Anti-HBs:

Hepatitis B surface antibody

HBeAg:

Hepatitis B e antigen

Anti-HBe:

Hepatitis B e antibody

ALT:

Aminotransferase

RTD-PCR:

Real-time detection polymerase chain reaction

NAT:

Nucleic acid amplification test

CHOP:

Cyclophosphamide, doxorubicin, vincristine, prednisolone

R-CHOP:

Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone

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Acknowledgments

The authors thank Mrs. Kazumi Takagi for support with the analysis of the specimen information from the Nagoya City University Hospital. The authors also thank the ZENYAKU Company for providing clinical data on 111 patients who developed serious hepatitis B after systemic chemotherapy containing rituximab. Financial Support was provided by the Ministry of Health, Labour and Welfare of Japan (grant-in-aid H20-kanen-014 to S.·K.).

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Author notes

  1. Masashi Mizokami

    Present address: Research Center for Hepatitis and Immunology, International Medical Center of Japan Konodai Hospital, Ichikawa, Chiba, Japan

Authors and Affiliations

  1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Shigeru Kusumoto & Ryuzo Ueda

  2. Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Yasuhito Tanaka & Masashi Mizokami

Authors
  1. Shigeru Kusumoto
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Correspondence to Shigeru Kusumoto.

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Kusumoto, S., Tanaka, Y., Mizokami, M. et al. Reactivation of hepatitis B virus following systemic chemotherapy for malignant lymphoma. Int J Hematol 90, 13–23 (2009). https://doi.org/10.1007/s12185-009-0359-5

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  • DOI: https://doi.org/10.1007/s12185-009-0359-5

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