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利妥昔单抗含化疗后乙型肝炎病毒再激活:个案报告。

Late reactivation of hepatitis B virus after rituximab-containing chemotherapy for mantle cell lymphoma: a case report.

机构信息

Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168, Rome, Italy.

Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Agostino Gemelli Hospital, Catholic University, Rome, Italy.

出版信息

Infection. 2019 Apr;47(2):313-316. doi: 10.1007/s15010-018-1242-1. Epub 2018 Oct 27.

DOI:10.1007/s15010-018-1242-1
PMID:30368733
Abstract

BACKGROUND

Hepatitis B virus (HBV) reactivation is commonly observed in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Recent guidelines recommend antiviral prophylaxis to be continued for up to 12 months after the discontinuation of the anticancer regimen.

CASE PRESENTATION

We report a case of a patient who underwent antiviral prophylaxis for 26 months after the discontinuation of a rituximab-containing chemotherapy regimen for a lymphoma and was admitted in the infectious diseases department with a 3-day history of jaundice, itching, and dark urine. After excluding other possible causes of acute liver damage, HBV reactivation was suspected. HBV-DNA was 4497000 IU/mL. Following reintroduction of entecavir, we observed a steady decline of ALT, AST, bilirubin and HBV-DNA serum levels, with a rapid resolution of acute hepatitis and an improvement in clinical conditions; one year after the event of HBV reactivation and beginning of antiviral therapy, the patient was virologically suppressed.

DISCUSSION

Our study demonstrates that the risk of HBV reactivation in HBsAg-positive patients with undetectable HBV-DNA can occur even after three years from the last administration of rituximab and several months after the withdrawal of prophylactic antiviral therapy in patients with hematological malignancies. This implies that a close monitoring of HBV-related markers including HBV-DNA must continue after the withdrawal of prophylactic NA therapy.

摘要

背景

HBV 病毒(HBV)再激活在接受免疫抑制化疗的 HBsAg 阳性血液学患者中很常见。最近的指南建议在抗癌方案停药后,抗病毒预防应持续长达 12 个月。

病例介绍

我们报告了一例患者,在接受含利妥昔单抗的化疗方案治疗淋巴瘤后,抗病毒预防持续了 26 个月,并因黄疸、瘙痒和深色尿 3 天而入住传染病科。排除其他急性肝损伤的可能原因后,怀疑为 HBV 再激活。HBV-DNA 为 4497000 IU/ml。在重新引入恩替卡韦后,我们观察到 ALT、AST、胆红素和 HBV-DNA 血清水平持续下降,急性肝炎迅速缓解,临床状况改善;HBV 再激活和开始抗病毒治疗一年后,患者病毒学得到抑制。

讨论

我们的研究表明,即使在接受利妥昔单抗治疗的最后一次给药后三年,以及在血液恶性肿瘤患者停止预防性抗病毒治疗后几个月,HBV-DNA 不可检测的 HBsAg 阳性患者也可能发生 HBV 再激活风险。这意味着在停止预防性 NA 治疗后,必须继续密切监测 HBV 相关标志物,包括 HBV-DNA。

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本文引用的文献

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Hepatitis B in patients with hematological diseases: An update.血液系统疾病患者的乙型肝炎:最新进展
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2
EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.EASL 2017 临床实践指南:乙型肝炎病毒感染管理。
J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.
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Prevention of Hepatitis B reactivation in the setting of immunosuppression.免疫抑制情况下乙肝再激活的预防。
Clin Mol Hepatol. 2016 Jun;22(2):219-37. doi: 10.3350/cmh.2016.0024. Epub 2016 Jun 13.
4
Reactivation of hepatitis B virus during targeted therapies for cancer and immune-mediated disorders.癌症和免疫介导性疾病的靶向治疗期间乙型肝炎病毒再激活。
Expert Opin Biol Ther. 2016 Jul;16(7):917-26. doi: 10.1080/14712598.2016.1177017. Epub 2016 May 3.
5
Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial.恩替卡韦与拉米夫定预防未治疗弥漫性大 B 细胞淋巴瘤接受 R-CHOP 化疗患者乙型肝炎病毒再激活:一项随机临床试验。
JAMA. 2014 Dec 17;312(23):2521-30. doi: 10.1001/jama.2014.15704.
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American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy.美国胃肠病学会关于免疫抑制药物治疗期间预防和治疗乙型肝炎病毒再激活的指南。
Gastroenterology. 2015 Jan;148(1):215-9; quiz e16-7. doi: 10.1053/j.gastro.2014.10.039. Epub 2014 Oct 31.
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Ann Hematol. 2011 Oct;90(10):1219-23. doi: 10.1007/s00277-011-1241-0. Epub 2011 Apr 26.
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