Pol Stanislas, Corouge Marion, Vallet-Pichard Anaïs
Université Paris Descartes, Liver Department, Assistance Publique Hôpitaux de Paris, Cochin Hospital, French Institute of Health and Medical Research UMS20, Institut Pasteur, Paris, France.
Hepat Med. 2016 Mar 4;8:21-6. doi: 10.2147/HMER.S62014. eCollection 2016.
The treatment of hepatitis C virus has changed dramatically with the rapid advent of numerous new antiviral agents, including direct-acting antivirals and agents with non-viral targets (cyclophilin inhibitors, interferon-lambda, vaccine therapy). Given the better safety profile and high antiviral potency of direct-acting antivirals, their combination in interferon-free oral regimens is becoming the standard of care for hepatitis C virus infection, tailored to individual patients according to the degree of disease progression (fibrosis), hepatitis C virus genotype and subtype, resistance profile, and prior therapeutic history. Results from clinical studies as well as preliminary real-life data regarding the combination of sofosbuvir (a nucleotide polymerase inhibitor) and daclatasvir, a first-in-class NS5A replication complex inhibitor, demonstrate that it is one of the most promising antiviral therapies, with once-daily oral dosing, a low pill burden, good tolerability, and limited drug-drug interactions, in addition to high antiviral potency, with >90% sustained virologic response rates. This combination has high pangenotypic antiviral potency regardless of the severity and patient characteristics. The combination of sofosbuvir and an NS5A inhibitor with ribavirin for 12 weeks appears to be a very good further treatment option in both cirrhotic and treatment-experienced patients whatever the stage of fibrosis.
随着众多新型抗病毒药物的迅速出现，丙型肝炎病毒的治疗发生了巨大变化，这些药物包括直接作用抗病毒药物和具有非病毒靶点的药物（环孢菌素抑制剂、干扰素-λ、疫苗疗法）。鉴于直接作用抗病毒药物具有更好的安全性和高抗病毒效力，它们在不含干扰素的口服方案中的联合应用正成为丙型肝炎病毒感染的标准治疗方法，并根据疾病进展程度（纤维化）、丙型肝炎病毒基因型和亚型、耐药情况以及既往治疗史为个体患者量身定制。关于索磷布韦（一种核苷酸聚合酶抑制剂）和第一代NS5A复制复合物抑制剂达卡他韦联合应用的临床研究结果以及初步的实际数据表明，它是最有前景的抗病毒治疗方法之一，每日一次口服给药，药片负担低，耐受性良好，药物相互作用有限，此外还具有高抗病毒效力，持续病毒学应答率>90%。无论严重程度和患者特征如何，这种联合用药都具有高泛基因型抗病毒效力。索磷布韦与一种NS5A抑制剂联合利巴韦林治疗12周，对于肝硬化患者和有治疗经验的患者，无论纤维化处于何种阶段，似乎都是一个非常好的进一步治疗选择。
