Department of Hepatology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.
Liver Int. 2018 Feb;38 Suppl 1:21-27. doi: 10.1111/liv.13638.
Direct-acting antivirals (DAAs) have transformed traditional treatment options for hepatitis C virus (HCV) infection. DAA combinations have been shown to be highly effective in reducing the burden of chronic HCV infection in clinical trials and have been recommended by the European Association for the Study of the Liver (EASL) treatment guidelines. This review examines the results of second-generation DAA combinations in real-life clinical practice in patients with genotypes 1-3 and in those co-infected with HIV (real-world data in genotypes 4-6 are rare). Second generation DAAs (sofosbuvir plus daclatasvir, sofosbuvir/ledipasvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir, sofosbuvir plus velpatasvir, glecaprevir plus pibrentasvir, grazoprevir plus elbasvir) have very high SVR rates and good safety profiles, higher resistance barriers and are more convenient. Real-world data in all 3 genotypes generally support the EASL guidelines and high overall sustained virological response rates are reported with recommended regimens. However, real-world data are only available for sofosbuvir plus daclatasvir, sofosbuvir/ledipasvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir. Furthermore, because of the existing level of evidence, it is difficult to define optimal regimens based on real-world data (ie, treatment duration, when to include ribavirin and options for patients with cirrhosis). The real-life challenges of managing HIV-coinfected patients are also discussed showing the additional burden of avoiding drug-drug interactions between DAAs and antiretrovirals.
直接作用抗病毒药物(DAAs)改变了丙型肝炎病毒(HCV)感染的传统治疗选择。临床试验表明,DAA 联合治疗在降低慢性 HCV 感染负担方面非常有效,已被欧洲肝脏研究协会(EASL)治疗指南推荐。这篇综述考察了第二代 DAA 联合治疗在 1-3 基因型患者和合并 HIV 感染(基因型 4-6 的真实世界数据罕见)患者中的真实临床实践结果。第二代 DAA(索非布韦加达拉他韦、索非布韦/雷迪帕韦、奥比他韦/帕利他韦/利托那韦加达卡他韦、索非布韦加维帕他韦、格卡瑞韦/哌仑他韦)具有非常高的 SVR 率和良好的安全性特征,更高的耐药屏障,且更方便。所有 3 种基因型的真实世界数据通常都支持 EASL 指南,且推荐方案报告的总体持续病毒学应答率较高。然而,只有索非布韦加达拉他韦、索非布韦/雷迪帕韦、奥比他韦/帕利他韦/利托那韦加达卡他韦的真实世界数据可用。此外,由于现有证据水平,很难根据真实世界数据确定最佳方案(即治疗持续时间、何时包括利巴韦林以及肝硬化患者的选择)。还讨论了合并 HIV 感染患者管理方面的真实世界挑战,表明需要避免 DAA 与抗逆转录病毒药物之间的药物相互作用,从而带来额外的负担。