Direct-acting antivirals: the endgame for hepatitis C?
Direct-acting antivirals: the endgame for hepatitis C?
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DOI：
10.1016/j.coviro.2017.03.017
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发表时间：
2017-06-01
影响因子：
5.9
通讯作者：
Aghemo, Alessio
中科院分区：
文献类型：
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作者：
D'Ambrosio, Roberta;Degasperi, Elisabetta;Aghemo, Alessio
直接作用的抗病毒药物（DAA）最终使所有患者都有可能从慢性丙型肝炎（HCV）感染中治愈。全口服无干扰素（IFN）方案是基于靶向HCV复制过程不同位点的分子组合。存在三类DAA：蛋白酶抑制剂（抗NS 3/4A）、RNA依赖性聚合酶抑制剂（抗NS 5 B）和抗NS 5A抑制剂，其特征在于不同的抗病毒效力和耐药性屏障，因此通常在不同的治疗方案中组合。治疗方案仍然在很大程度上取决于HCV基因型和肝病阶段，持续时间在12周至24周之间，而大多数患者组的总体治疗疗效已攀升至近95%，包括历史上难以治疗的类别（HCV基因型1，晚期肝病）。IFN的消除使得以前禁忌抗病毒治疗的患者，如失代偿性肝硬化和实体器官移植受者，得到安全有效的治疗。有效和安全的抗病毒药物的可用性，加上全球范围内获得治疗的改善，最终可能导致在未来几十年内消除HCV。
Directly-acting antivirals (DAA) have finally allowed all patients to be potentially cured from chronic hepatitis C (HCV) infection. All-oral, Interferon (IFN)-free regimens are based upon the combination of molecules targeting different sites of the HCV replication process. Three classes of DAA exist: protease inhibitors (anti-NS3/4A), RNA-dependent polymerase inhibitors (anti-NS5B) and anti-NS5A inhibitors, which are characterized by different antiviral potency and barrier to resistance and therefore are usually combined in different treatment schedules. Treatment regimens are still largely dependent on HCV genotype and stage of liver disease, with duration ranging between 12 weeks and 24 weeks, while overall treatment efficacy has climbed to nearly 95% in most patient groups, including historically difficult-to-treat categories (HCV genotype 1, advanced liver disease). The elimination of IFN has allowed safe and efficacious treatment of patients formerly contraindicated to antiviral therapy, such as decompensated cirrhosis and solid organ transplant recipients. Availability of potent and safe antiviral drugs combined with improvement of worldwide access to treatment could finally lead to HCV elimination in the next decades.