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治疗丙型肝炎的药物——是神话还是可预见的未来?

A pill for HCV - myth or foreseeable future?

机构信息

Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland.

出版信息

Liver Int. 2014 Jan;34(1):6-11. doi: 10.1111/liv.12294. Epub 2013 Sep 2.

Abstract

Weekly injections with pegylated-IFNa (PegIFN) combined with daily ribavirin (RBV) are still the standard of care for chronic hepatitis C in most of the world. Sustained virological response (SVR) of 40-50% for patients infected with HCV genotypes (GT) 1 or 4 and 70-90% for genotypes 2-3 are achieved with this regimen. Triple therapy, registered in both the EU and USA, utilizing the first-generation direct protease inhibitors is able to increase the SVR rates to 75%, but its use is restricted to patients infected with HCV GT1. Additional limitations include challenging dosing schedules, complex treatment algorithms, limited efficacy in patients with previous null response to PegIFN/RBV therapy and additional side effects. There is also an important need for more effective antiviral therapy for difficult-to-treat populations with PEG-IFN intolerance, particularly those with cirrhosis and non-responders to previous therapies. All-oral, IFN-free therapies are an evolutionary step for future anti-HCV therapies. Initial results of clinical studies conducted during the last year give hope for 'a pill for HCV' at least in selected CHC populations. In 2013 several clinical trials of all-oral anti-HCV therapies had been completed, first all-oral combination submitted for registration and some conclusions could be drawn. However, there is not yet a clear direction for IFN-free therapies in treatment naïve patients or more complex non-responders.

摘要

每周注射聚乙二醇干扰素 α(PegIFN)联合每日利巴韦林(RBV)仍然是世界上大多数地区慢性丙型肝炎的标准治疗方法。该方案可使感染 HCV 基因型(GT)1 或 4 的患者获得 40-50%的持续病毒学应答(SVR),感染基因型 2-3 的患者获得 70-90%的 SVR。三联疗法在欧盟和美国注册,使用第一代直接蛋白酶抑制剂,能够将 SVR 率提高到 75%,但仅限于感染 HCV GT1 的患者。其使用还存在一些限制,包括剂量方案复杂、对既往 PegIFN/RBV 治疗无应答的患者疗效有限以及存在其他副作用。对于不能耐受 PEG-IFN 的难治性人群,如肝硬化和既往治疗无应答的患者,还需要更有效的抗病毒治疗。无干扰素的全口服治疗是未来抗 HCV 治疗的一个重要进展。过去一年开展的临床研究的初步结果为至少在某些 CHC 人群中“针对 HCV 的药丸”带来了希望。2013 年完成了多项全口服抗 HCV 治疗的临床试验,首个全口服联合方案已提交注册,并且得出了一些结论。然而,在治疗初治患者或更复杂的无应答者时,无干扰素治疗还没有明确的方向。

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