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直接抗病毒药物时代的移植后丙型肝炎管理

Management of post transplant hepatitis C in the direct antiviral agents era.

作者信息

Coilly Audrey, Roche Bruno, Duclos-Vallée Jean-Charles, Samuel Didier

机构信息

Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, 12, Avenue Paul Vaillant-Couturier, 94800, Villejuif, France,

出版信息

Hepatol Int. 2015 Apr;9(2):192-201. doi: 10.1007/s12072-015-9621-5. Epub 2015 Mar 28.

Abstract

Hepatitis C virus (HCV) infection is one of the main indications for liver transplantation. Viral recurrence occurs in all patients with detectable serum HCV RNA at the time of transplantation leading to cirrhosis in 20-30% of patients within 5 years. Viral eradication using antiviral therapy has been shown to improve patient and graft survival. Pegylated interferon (PEG-IFN) and ribavirin (RBV) antiviral therapy achieved SVR in around 30% of transplant recipients. In the non-transplant setting, first generation NS3/4 protease inhibitors, boceprevir or telaprevir associated with PEG-IFN and RBV, has improved the SVR rates to 75% in genotype 1 infected patients. However, tolerability and drug-drug interactions with calcineurin inhibitors are both limiting factors of their use in transplant recipients. In the non-transplant patients, using new direct-acting antiviral therapy has dramatically improved the efficacy of antiviral C therapy over recent years leading to SVR rates over 90% in phase II and III clinical trials, without PEG-IFN and/or RBV. Preliminary results in transplant patients showed better efficacy, better tolerability and less drug-drug interactions.

摘要

丙型肝炎病毒(HCV)感染是肝移植的主要指征之一。移植时血清HCV RNA可检测到的所有患者都会出现病毒复发,导致20%至30%的患者在5年内发生肝硬化。使用抗病毒疗法根除病毒已被证明可提高患者和移植物的存活率。聚乙二醇化干扰素(PEG-IFN)和利巴韦林(RBV)抗病毒疗法在约30%的移植受者中实现了持续病毒学应答(SVR)。在非移植环境中,与PEG-IFN和RBV联合使用的第一代NS3/4蛋白酶抑制剂博赛匹韦或特拉匹韦,已将1型感染患者的SVR率提高到75%。然而,耐受性以及与钙调神经磷酸酶抑制剂的药物相互作用都是其在移植受者中使用的限制因素。在非移植患者中,近年来使用新型直接抗病毒疗法显著提高了抗HCV治疗的疗效,在II期和III期临床试验中导致SVR率超过90%,且无需使用PEG-IFN和/或RBV。移植患者的初步结果显示疗效更佳、耐受性更好且药物相互作用更少。

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