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丙型肝炎病毒的非凡历史。

The remarkable history of the hepatitis C virus.

机构信息

Université Paris Descartes, Paris, France.

Département d'Hépatologie, Hôpital Cochin, APHP, Paris, France.

出版信息

Genes Immun. 2019 May;20(5):436-446. doi: 10.1038/s41435-019-0066-z. Epub 2019 Apr 25.

Abstract

The infection with the hepatitis C virus (HCV) is an example of the translational research success. The reciprocal interactions between clinicians and scientists have allowed in 30 years the initiation of empirical treatments by interferon, the discovery of the virus, the development of serological and virological tools for diagnosis but also for prognosis (the non-invasive biochemical or morphological fibrosis tests, the predictors of the specific immune response including genetic IL28B polymorphisms). Finally, well-tolerated and effective treatments with oral antivirals inhibiting HCV non-structural viral proteins involved in viral replication have been marketed this last decade, allowing the cure of all infected subjects. HCV chronic infection, which is a public health issue, is a hepatic disease, which may lead to a cirrhosis and an hepatocellular carcinoma (HCC) but also a systemic disease with extra-hepatic manifestations either associated with a cryoglobulinemic vasculitis or chronic inflammation. The HCV infection is the only chronic viral infection, which may be cured: the so-called sustained virologic response, defined by undetectable HCV RNA 12 weeks after the end of the treatment, significantly reduces the risk of morbidity and mortality associated with hepatic and extra-hepatic manifestations, which are mainly reversible. The history of HCV ends with the pangenotypic efficacy of the multiple combinations, easy to use for 8-12 weeks with one to three pills per day and little problems of tolerance. This explains the short 30 years from the virus discovery to the viral hepatitis elimination policy proposed by the World Health Organization (WHO) in 2016.

摘要

丙型肝炎病毒(HCV)感染是转化研究成功的一个例子。临床医生和科学家之间的相互作用使得在 30 年内可以通过干扰素进行经验性治疗,发现了该病毒,并开发了用于诊断但也用于预后的血清学和病毒学工具(非侵入性生化或形态纤维化测试、包括 IL28B 基因多态性在内的特异性免疫反应的预测因子)。最后,过去十年中,市场上推出了具有良好耐受性和有效性的口服抗病毒药物,这些药物抑制参与病毒复制的 HCV 非结构病毒蛋白,从而能够治愈所有感染的患者。丙型肝炎慢性感染是一个公共卫生问题,也是一种肝脏疾病,可导致肝硬化和肝细胞癌(HCC),但也可能是一种伴有肝外表现的全身性疾病,包括冷球蛋白血症性血管炎或慢性炎症。HCV 感染是唯一可以治愈的慢性病毒感染:所谓的持续病毒学应答,定义为治疗结束后 12 周 HCV RNA 不可检测,可显著降低与肝脏和肝外表现相关的发病率和死亡率风险,这些表现主要是可逆转的。丙型肝炎病毒的历史随着多种组合的泛基因型疗效而结束,这些组合易于使用,治疗时间为 8-12 周,每天服用一到三种药物,且耐受性问题很少。这就解释了从发现病毒到世界卫生组织(WHO)在 2016 年提出消除病毒性肝炎政策,这一过程仅用了 30 年。

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