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乙型肝炎病毒感染的认识与诊断的最新进展

Recent advances in understanding and diagnosing hepatitis B virus infection.

作者信息

Fourati Slim, Pawlotsky Jean-Michel

机构信息

National Reference Center for Viral Hepatitis B, C, and D, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France.

出版信息

F1000Res. 2016 Sep 6;5. doi: 10.12688/f1000research.8983.1. eCollection 2016.

DOI:10.12688/f1000research.8983.1
PMID:27635243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5017294/
Abstract

Hepatitis B virus (HBV) infects approximately 240 million individuals worldwide. Recent advances in the virology, immunopathogenesis, and diagnosis of HBV infection are summarized in this review article. The identification of a hepatocyte-specific cellular receptor for HBV, the sodium taurocholate co-transporting polypeptide (NTCP), made it possible to develop reliable cell culture systems and better understand the early steps of the viral lifecycle. Viral and host factors involved in covalently closed circular DNA synthesis, stability, and transcriptional regulation have also been identified and provide potential targets for new drugs. Based on recent evidence showing trained immunity in immune-tolerant patients, the immune tolerance and immune clearance phases have been renamed the non-inflammatory and inflammatory phases, respectively. New diagnostic and monitoring tools are now available, including rapid diagnostic tests for hepatitis B surface antigen (HBsAg) detection, HBsAg quantification assays, anti-HBc antibody quantification assays, an HBV core-related antigen (HBcrAg) quantification test, new HBV DNA detection and quantification assays, and an HBV RNA quantification test. Their clinical utility is under study. Finally, new antiviral and immune modulation approaches are in the preclinical or early clinical developmental stages, with the goal to achieve functional cure or ideally (if possible) eradication of HBV infection.

摘要

全球约有2.4亿人感染乙型肝炎病毒(HBV)。本文综述了HBV感染在病毒学、免疫发病机制及诊断方面的最新进展。乙型肝炎病毒肝细胞特异性细胞受体——牛磺胆酸钠共转运多肽(NTCP)的鉴定,使得开发可靠的细胞培养系统以及更好地理解病毒生命周期的早期步骤成为可能。参与共价闭合环状DNA合成、稳定性及转录调控的病毒和宿主因子也已得到鉴定,并为新药提供了潜在靶点。基于近期在免疫耐受患者中发现的训练免疫的证据,免疫耐受期和免疫清除期分别被重新命名为非炎症期和炎症期。目前已有新的诊断和监测工具,包括用于检测乙型肝炎表面抗原(HBsAg)的快速诊断试验、HBsAg定量检测、抗-HBc抗体定量检测、HBV核心相关抗原(HBcrAg)定量检测、新的HBV DNA检测和定量检测以及HBV RNA定量检测。它们的临床实用性正在研究中。最后,新的抗病毒和免疫调节方法正处于临床前或早期临床开发阶段,目标是实现功能性治愈,理想情况下(如果可能)根除HBV感染。

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本文引用的文献

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Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications.乙型肝炎病毒和丁型肝炎病毒进入肝细胞:基本见解与临床意义。
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Experimental in vitro and in vivo models for the study of human hepatitis B virus infection.用于研究人类乙型肝炎病毒感染的体外和体内实验模型。
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HBcrAg predicts hepatocellular carcinoma development: An analysis using time-dependent receiver operating characteristics.HBcrAg 可预测肝细胞癌的发生:基于时间依赖的受试者工作特征分析。
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Global strategies are required to cure and eliminate HBV infection.需要采取全球策略来治愈和消除乙肝病毒感染。
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AASLD guidelines for treatment of chronic hepatitis B.美国肝病研究学会慢性乙型肝炎治疗指南。
Hepatology. 2016 Jan;63(1):261-83. doi: 10.1002/hep.28156. Epub 2015 Nov 13.
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Comparative Performance of Three Rapid HBsAg Assays for Detection of HBs Diagnostic Escape Mutants in Clinical Samples.三种快速乙肝表面抗原检测方法在临床样本中检测乙肝诊断逃逸突变体的比较性能
J Clin Microbiol. 2015 Dec;53(12):3954-5. doi: 10.1128/JCM.02117-15. Epub 2015 Sep 16.
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Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013.全球慢性乙型肝炎病毒感染患病率的估计:1965 年至 2013 年发表数据的系统评价。
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