Gentile Ivan, Buonomo Antonio R, Borgia Guglielmo
Department of Clinical Medicine and Surgery (Ed. 18) - University of Naples "Federico II", via S. Pansini 5, I-80131 Naples, Italy.
Rev Recent Clin Trials. 2014;9(2):115-23. doi: 10.2174/1574887109666140529222602.
Hepatitis C virus (HCV) chronically infects about 2% of the world's population. Approximately a quarter of these patients will develop, during their life, liver cirrhosis, which entails a high risk of complications and death. Successful antiviral therapy can reduce the risk of disease progression, but it is feasible only in a minority of patients because it includes interferon which is contraindicated in the most advanced stages of the disease and in patients with severe impairment of other organs. Consequent to the launch of the first direct antiviral agents (DAA), namely the protease inhibitors telaprevir and boceprevir, several molecules are in an advanced phase of clinical development to be used in association with interferon or with other DAA (in interferon-free combinations). This review focuses on the mechanism of action, pharmacokinetics, efficacy, safety and resistance of dasabuvir, a non-nucleoside inhibitor of NS5B viral RNA-dependent RNA polymerase. Thanks to its pharmacokinetics, dasabuvir can be administered twice daily. In combinations with other oral DAAs, dasabuvir results in very high rates of SVR (about 95%) in patients with HCV genotype 1 infection with a good tolerability and safety. In conclusion, dasabuvir is a good agent to be used in interferon-free combinations for the treatment of chronic hepatitis C.
丙型肝炎病毒(HCV)慢性感染着全球约2%的人口。这些患者中约有四分之一在其一生中会发展为肝硬化,这会带来较高的并发症风险和死亡风险。成功的抗病毒治疗可以降低疾病进展的风险,但仅在少数患者中可行,因为该治疗包括干扰素,而在疾病的最晚期以及其他器官严重受损的患者中,干扰素是禁忌的。随着首批直接抗病毒药物(DAA)即蛋白酶抑制剂特拉匹韦和博赛匹韦的推出,有几种分子正处于临床开发的后期阶段,可与干扰素联合使用或与其他DAA联合使用(无干扰素联合用药)。本综述重点关注达沙布韦的作用机制、药代动力学、疗效、安全性和耐药性,达沙布韦是一种非核苷类NS5B病毒RNA依赖性RNA聚合酶抑制剂。由于其药代动力学特性,达沙布韦可以每天给药两次。在与其他口服DAA联合使用时,达沙布韦在HCV基因1型感染患者中导致非常高的持续病毒学应答率(约95%),且耐受性和安全性良好。总之,达沙布韦是一种用于无干扰素联合用药治疗慢性丙型肝炎的良好药物。