Vallet-Pichard Anaïs, Pol Stanislas
Université Paris Descartes, Hepatology Department Cochin Hospital, APHP, INSERM U1213 and USM-20 Institut Pasteur, Paris, France.
Département d'Hépatologie, Hôpital Cochin, AP-HP, 27 rue du faubourg Saint-Jacques, 75679 Paris Cedex 14, France.
Therap Adv Gastroenterol. 2017 Jan;10(1):155-167. doi: 10.1177/1756283X16671293. Epub 2016 Oct 17.
Interferon-free regimens combine different second-wave direct-acting antiviral agents (DAAs), which target the main viral proteins involved in the replication cycle of hepatitis C virus (HCV): NS3/4A protease inhibitors (simeprevir or paritaprevir boosted by ritonavir), NS5B nucleos(t)idic (sofosbuvir) and nonnucleos(t)idic (dasabuvir) polymerase inhibitors, NS5A replication complex inhibitors (daclatasvir, ledipasvir, elbasvir, velpatasvir). Combinations of two or three DAAs, given for 8-24 weeks reach sustained virology response (SVR) rates greater than 90% with good tolerance. SVR rates and safety are similar in clinical trials and in real life, usually higher than 95% in the per-protocol analysis. Next-generation DAAs are now expected. To be competitive, these new combinations need to prove their added value regarding the pill burden, the reduced duration of treatment, the drug-drug interaction profile and safety. Zepatier is a fixed-dose combination product coformulating MK-5172 [grazoprevir (GZR), 100 mg QD] and MK-8742 [elbasvir or (EBR) 50 mg QD]: it combines highly potent inhibitors of the HCV NS3/4A protease and NS5A replication complex, respectively. This review provides a summary of the main evidence available for the use of GZR/EBR and highlights the strength of this combination.
无干扰素方案联合使用不同的第二代直接抗病毒药物（DAA），这些药物靶向丙型肝炎病毒（HCV）复制周期中涉及的主要病毒蛋白：NS3/4A蛋白酶抑制剂（simeprevir或由ritonavir增强的paritaprevir）、NS5B核苷（酸）（sofosbuvir）和非核苷（酸）（dasabuvir）聚合酶抑制剂、NS5A复制复合体抑制剂（daclatasvir、ledipasvir、elbasvir、velpatasvir）。两种或三种DAA联合使用8至24周，可达到持续病毒学应答（SVR）率大于90%，耐受性良好。SVR率和安全性在临床试验和现实生活中相似，在符合方案分析中通常高于95%。现在期待新一代DAA。为了具有竞争力，这些新组合需要在服药负担、缩短治疗疗程、药物相互作用谱和安全性方面证明其附加价值。Zepatier是一种固定剂量复方产品，共同配方为MK-5172[grazoprevir（GZR），每日100毫克]和MK-8742[elbasvir或（EBR）每日50毫克]：它分别结合了HCV NS3/4A蛋白酶和NS5A复制复合体的高效抑制剂。本综述总结了使用GZR/EBR的主要现有证据，并强调了这种组合的优势。
