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恶性淋巴瘤全身化疗后乙型肝炎病毒再激活

Reactivation of hepatitis B virus following systemic chemotherapy for malignant lymphoma.

作者信息

Kusumoto Shigeru, Tanaka Yasuhito, Mizokami Masashi, Ueda Ryuzo

机构信息

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

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

出版信息

Int J Hematol. 2009 Jul;90(1):13-23. doi: 10.1007/s12185-009-0359-5. Epub 2009 Jun 23.

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.

摘要

不仅在接受全身化疗的乙肝表面抗原(HBsAg)阳性患者中报道了乙肝病毒(HBV)再激活,而且在一部分具有乙肝核心抗体和/或乙肝表面抗体的HBsAg阴性患者中也有报道。最近,利妥昔单抗联合类固醇化疗(R-CHOP等)已被确定为恶性淋巴瘤HBsAg阴性患者HBV再激活的危险因素。对于预防HBsAg阳性患者的HBV再激活,使用抗病毒药物进行预防至关重要,但在药物选择或适当的预防持续时间方面几乎没有证据可供依据。关于HBsAg阴性患者的临床数据也很少,对于此类HBV再激活患者也没有既定的护理标准。基于先前有限的报道数量,在连续HBV-DNA监测的指导下进行抢先治疗是预防HBsAg阴性患者HBV再激活的合理策略。然而,仅凭临床证据不足以确定化疗期间及化疗后HBV-DNA监测的最佳频率,也不足以确定何时停止针对HBV再激活的抢先治疗。因此,应该开展精心设计的临床试验来研究这种抢先治疗的疗效和安全性。此外,评估病毒因素如HBV基因型和基因突变可能有助于制定预防严重肝炎发生的策略。在本综述中,我们总结了包括利妥昔单抗在内的全身化疗后HBV再激活的特征,并提出了针对发生HBV再激活的恶性淋巴瘤患者的管理策略。

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