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[慢性丙型肝炎感染——病毒根除]

[Chronic hepatitis C infection--eradication of the virus].

作者信息

Ben Ari Ziv

出版信息

Harefuah. 2014 Jul;153(7):392-3, 433.

PMID:25189028
Abstract

Hepatitis C virus (HCV) infection, a worldwide public health problem affecting 180 million patients, is Likely the cause of chronic hepatitis, liver cirrhosis, liver failure, and hepatocellular carcinoma. In Israel it is estimated that 100,000 people are infected with HCV, 25% are diagnosed and 20-22% were treated with antiviral agents. Advances in our understanding of the HCV lifecycle have led to development of direct acting antiviral agents (DAAs) therapies capable of increasing significantly the curative SVR rates in patients with HCV. New standard-of-care treatment has been approved in 2011 for HCV genotype 1 that has markedly improved treatment results, based on a triple combination of pegylated IFN-alpha, ribavirin, and either telaprevir or boceprevir, two inhibitors of the HCV protease. Two new oral antiviral agents, simeprevir and sofosbuvir, have already been approved and are now available. Other antiviral agents will be available during 2014-2015 and many others, are in phase II or III clinical development. The results of nine phase-3 interferon-free combination regimens of DAAs were reported in the NEJM 2014. These studies demonstrated unequivocal superiority of such regimens over the standard-of-care treatment with an SVR rate of > or = 90% in HCV genotype 1 and 2, naïve, experienced and cirrhotics patients. Interferon-free regimens are associated with lower rate and severity of side effects and a shorter duration of treatment. A number of unanswered questions remain treating special populations, the role of ribavirin, genotype 3, the role of HCV resistance, and how to re-treat failures of treatment. The Ministry of Health wills have to consider: 1. HCV screening in high risk populations. 2. The strategic choices based on cost issues (the predicted costs of the new oral DAAs is extremely high) and on the severity of the liver disease.

摘要

丙型肝炎病毒(HCV)感染是一个全球性的公共卫生问题,影响着1.8亿患者,很可能是慢性肝炎、肝硬化、肝衰竭和肝细胞癌的病因。在以色列,估计有10万人感染了HCV,其中25%被诊断出来,20%-22%接受了抗病毒药物治疗。我们对HCV生命周期认识的进展导致了直接作用抗病毒药物(DAAs)疗法的发展,这种疗法能够显著提高HCV患者的持续病毒学应答(SVR)治愈率。2011年,基于聚乙二醇化干扰素-α、利巴韦林以及两种HCV蛋白酶抑制剂特拉匹韦或博赛匹韦的三联组合,新的标准治疗方案被批准用于HCV基因1型,显著改善了治疗效果。两种新的口服抗病毒药物simeprevir和索非布韦已经获批并上市。其他抗病毒药物将在2014 - 2015年上市,还有许多药物正处于II期或III期临床开发阶段。《新英格兰医学杂志》2014年报道了9种DAAs无干扰素联合治疗方案的结果。这些研究表明,在HCV基因1型和2型、初治、经治和肝硬化患者中,此类方案相对于标准治疗具有明确的优越性,SVR率≥90%。无干扰素方案的副作用发生率和严重程度较低,治疗时间较短。在治疗特殊人群、利巴韦林的作用、基因3型、HCV耐药性的作用以及如何重新治疗治疗失败患者等方面仍有一些未解决的问题。卫生部将不得不考虑:1. 对高危人群进行HCV筛查。2. 基于成本问题(新口服DAAs的预计成本极高)和肝脏疾病严重程度的战略选择。

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