D'Ambrosio Roberta, Aghemo Alessio, Colombo Massimo
Università degli Studi di Milano, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milano, Via F. Sforza 35, 20122 Milan , Italy +39 0255035432 ; +39 0250320410 ;
Expert Opin Drug Saf. 2015 Mar;14(3):473-84. doi: 10.1517/14740338.2015.1009035. Epub 2015 Feb 3.
IFN-free regimens with direct antiviral agents (DAAs) against hepatitis C virus (HCV) are likely to greatly expand patients' access and response to hepatitis C therapy, while safety and tolerability of treatments seem substantially improved. Sofosbuvir (SOF), a NS5B nucleotide polymerase inhibitor with pan-genotypic activity and a high-barrier to resistance, has been approved by FDA and EMA in an all oral combination therapy for chronic hepatitis C with ribavirin (RBV) alone, or in combination with either pegylated interferon/RBV or other DAAs.
This paper provides an overview of SOF-based therapy in chronic hepatitis C as it emerges from the published clinical trials. Data on special populations are included (i.e., decompensated patients, patients on liver transplant waiting lists, patients with renal impairment). The data has been analyzed according to the different HCV-genotypes and comprehensively covers both safety and efficacy treatment profiles.
Clinical trials have highlighted the safety and efficacy of SOF-based regimens, leading to the rapid approval of this therapy and its incorporation in the recommendations of the international societies on treatment of HCV infection. However, additional data are still needed to optimize both combination therapies' efficacy and duration in some categories of patients who have been under-represented in the registration trials.
使用直接抗病毒药物（DAA）的无干扰素方案治疗丙型肝炎病毒（HCV），可能会极大地扩大患者接受丙型肝炎治疗的机会并提高治疗反应率，同时治疗的安全性和耐受性似乎也有显著改善。索磷布韦（SOF）是一种具有泛基因型活性且耐药屏障高的NS5B核苷酸聚合酶抑制剂，已获美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准，可用于单独与利巴韦林（RBV）联合，或与聚乙二醇干扰素/RBV或其他DAA联合，进行全口服联合治疗慢性丙型肝炎。
本文根据已发表的临床试验，概述了基于索磷布韦的慢性丙型肝炎治疗方法。文中纳入了特殊人群的数据（即失代偿患者、等待肝移植的患者、肾功能损害患者）。数据根据不同的HCV基因型进行了分析，全面涵盖了安全性和疗效治疗概况。
临床试验突出了基于索磷布韦方案的安全性和有效性，促使该疗法迅速获批，并被纳入国际社会关于HCV感染治疗的推荐意见中。然而，对于在注册试验中代表性不足的某些患者类别，仍需要更多数据来优化联合治疗的疗效和疗程。
