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奥比他韦和帕利瑞韦与利托那韦联用,并与达沙布韦联合用于治疗慢性丙型肝炎。

Ombitasvir and paritaprevir boosted with ritonavir and combined with dasabuvir for chronic hepatitis C.

作者信息

Flisiak Robert, Flisiak-Jackiewicz Marta

机构信息

a Department of Infectious Diseases and Hepatology , Medical University of Białystok , Białystok , Poland.

b Department of Pediatrics, Gastroenterology and Allergology , Medical University of Białystok , Białystok , Poland.

出版信息

Expert Rev Gastroenterol Hepatol. 2017 Jun;11(6):559-567. doi: 10.1080/17474124.2017.1309284. Epub 2017 Mar 24.

Abstract

Hepatitis C is a leading cause of cirrhosis and hepatocellular carcinoma responsible for almost 700,000 deaths worldwide annually. Until 2014, management of HCV infections was based on interferon alfa containing regimens, with efficacy of 40-70% and a high adverse event rate. Interferon-free therapeutic options improved sustained viral response (SVR) rate to >90% and safety profile to placebo-like levels. Areas covered: This article describes all-oral regimen consisting of three direct acting antivirals (DAA) - ombitasvir (OBV), paritaprevir (PTV) and dasabuvir (DSV), which in clinical practice is boosted with ritonavir (r) and sometimes with ribavirin (RBV). This combination is registered for treatment of patients infected with HCV genotype 1 and 4. We focused on the regimen characteristics, pharmacokinetics, risk of resistance as well as efficacy and safety in clinical trials and real world studies. Expert commentary: Combination of OBV/PTV/r±DSV±RBV provides SVR rate of about 95% and good safety profile even in patients with compensated liver cirrhosis and failure with previous therapy. Currently it should be of particular value in areas with a predominance of genotype 1b infections. Due to the complexity and risk of drug to drug interactions, it will probably be replaced in coming few years with pangenotypic combinations of next generation DAAs.

摘要

丙型肝炎是肝硬化和肝细胞癌的主要病因,每年在全球导致近70万人死亡。直到2014年,丙型肝炎病毒(HCV)感染的治疗主要基于含干扰素α的治疗方案,其疗效为40%-70%,且不良事件发生率高。不含干扰素的治疗方案将持续病毒学应答(SVR)率提高到>90%,安全性达到类似安慰剂的水平。涵盖领域:本文描述了由三种直接作用抗病毒药物(DAA)——奥比他韦(OBV)、帕利哌韦(PTV)和达沙布韦(DSV)组成的全口服方案,在临床实践中该方案与利托那韦(r)联合使用,有时还与利巴韦林(RBV)联合使用。这种联合用药已获批用于治疗HCV基因1型和4型感染患者。我们重点关注了该方案的特点、药代动力学、耐药风险以及在临床试验和真实世界研究中的疗效和安全性。专家评论:OBV/PTV/r±DSV±RBV联合用药即使在代偿期肝硬化患者和既往治疗失败的患者中也能提供约95%的SVR率和良好的安全性。目前,在基因1b型感染占主导的地区,它应具有特别的价值。由于药物相互作用的复杂性和风险,在未来几年它可能会被新一代泛基因型DAA联合用药所取代。

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