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细胞毒性治疗导致的乙型肝炎病毒复制再激活:一项为期五年的前瞻性研究。

Reactivation of hepatitis B virus replication due to cytotoxic therapy: a five-year prospective study.

作者信息

Francisci Daniela, Falcinelli Flavio, Schiaroli Elisabetta, Capponi Monia, Belfiori Barbara, Cecchini Enisia, Baldelli Franco

机构信息

Section of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.

出版信息

Tumori. 2012 Mar-Apr;98(2):220-4. doi: 10.1177/030089161209800207.

Abstract

BACKGROUND AND AIMS

In hepatitis B virus (HBV) carriers receiving chemotherapy, the risk of reactivation is high, particularly if rituximab is given alone or in combination with steroids. The aim of this study was to assess the incidence, prevalence, and clinical course of HBV infection in a cohort of patients with hematological malignancies receiving cytotoxic therapy as well as to propose a strategy for managing HBV reactivation.

METHODS

This is a prospective observational study. All consecutive patients with hematological malignancies receiving intravenous cytotoxic chemotherapy between October 2005 and June 2010 and followed up for at least six months were enrolled in the study. Viral hepatitis markers and liver function indexes were monitored prospectively.

RESULTS

We enrolled 478 patients, including 263 males (55%) and 465 (97.3%) Italians. Non-Hodgkin's lymphoma was the most frequent diagnosis (66%). At least one HBV marker was positive in 96 patients (20%): 21 (4.4%) patients were HBsAg positive, 17 (3.5%) were anti-HBc positive, and 58 (12.1%) were anti-HBc/anti-HBs positive. All but one HBsAg-positive patient received therapy with nucleoside/nucleotide analogs prior to chemotherapy. All but three reached complete virological suppression at six months from the start of treatment. Of the 17 HBsAg-negative/anti-HBc-positive patients, three (18%) had reactivation with seroreversion. All three obtained viral suppression with adefovir. Regarding the 58 anti-HBc/anti-HBs-positive patients, two (3.4%) experienced seroreversion and were treated successfully with nucleoside analogs; both were taking rituximab. No severe ALT flares were observed during or after antiviral therapy.

CONCLUSION

Our data suggest that pre-treatment screening of patients at risk of viral reactivation yields benefit and therefore should be practiced by clinicians treating patients with malignancies.

摘要

背景与目的

在接受化疗的乙型肝炎病毒(HBV)携带者中,病毒再激活的风险很高,尤其是在单独使用利妥昔单抗或与类固醇联合使用时。本研究的目的是评估接受细胞毒性治疗的血液系统恶性肿瘤患者队列中HBV感染的发生率、患病率和临床病程,并提出管理HBV再激活的策略。

方法

这是一项前瞻性观察性研究。纳入了2005年10月至2010年6月期间所有接受静脉细胞毒性化疗且随访至少6个月的连续性血液系统恶性肿瘤患者。前瞻性监测病毒性肝炎标志物和肝功能指标。

结果

我们纳入了478例患者,其中男性263例(55%),意大利人465例(97.3%)。非霍奇金淋巴瘤是最常见的诊断(66%)。96例患者(20%)至少一种HBV标志物呈阳性:21例(4.4%)患者HBsAg阳性,17例(3.5%)抗-HBc阳性,58例(12.1%)抗-HBc/抗-HBs阳性。除1例HBsAg阳性患者外,所有患者在化疗前均接受了核苷/核苷酸类似物治疗。除3例患者外,所有患者在治疗开始后6个月均达到完全病毒学抑制。在17例HBsAg阴性/抗-HBc阳性患者中,3例(18%)出现血清学逆转的再激活。所有3例患者使用阿德福韦后均获得病毒抑制。对于58例抗-HBc/抗-HBs阳性患者,2例(3.4%)出现血清学逆转,使用核苷类似物治疗成功;两者均在使用利妥昔单抗。抗病毒治疗期间或之后未观察到严重的ALT升高。

结论

我们的数据表明,对有病毒再激活风险的患者进行预处理筛查有益,因此治疗恶性肿瘤患者的临床医生应进行此项筛查。

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