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glecaprevir和pibrentasvir复方药用于治疗丙型肝炎病毒感染合并重度肾功能损害患者
Glecaprevir and Pibrentasvir in Patients with HCV and Severe Renal Impairment


Edward Gane ... 其他 • 2017.10.12
相关阅读
• 用glecaprevir-pibrentasvir 8周对慢性HCV基因型1或3感染有效 • 对重度肾疾病患者进行安全且有效的抗丙型肝炎治疗 • 出生队列筛查是否能有效识别丙型肝炎患者 • 使用直接作用的抗病毒药治疗丙型肝炎后肝癌的发生风险 • 丙型肝炎病毒根除的远期结局

摘要


背景

慢性肾脏病患者与非慢性肾脏病患者相比,其慢性丙型肝炎病毒(HCV)感染更加普遍。慢性肾脏病合并HCV感染的患者与不存在HCV感染的慢性肾脏病患者相比,其进展为终末期肾病的风险更高。患者同时存在HCV感染和晚期慢性肾脏病时的治疗选择比较有限。

 

方法

我们开展了一项多中心、开放标签、3期临床试验,在存在HCV基因1型、2型、3型、4型、5型或6型感染和代偿性肝病(存在或不存在肝硬化)伴重度肾功能损害,或肾透析依赖,或同时合并两者的成年患者中,评估NS3/4A蛋白酶抑制剂glecaprevir和NS5A抑制剂pibrentasvir联合用药12周的疗效和安全性。患者存在慢性肾脏病4期或5期,或曾接受干扰素或聚乙二醇干扰素、利巴韦林、索非布韦或这些药物联合治疗。研究主要终点是治疗结束12周后的持续病毒学应答。

 

结果

在临床试验纳入的104名患者中,52%存在基因1型HCV感染、16%存在基因2型感染、11%存在基因3型感染、19%存在基因4型感染、2%存在基因5型或6型感染。持续病毒学应答率达98%(102/104;95%置信区间,95%~100%)。治疗过程中没有患者出现病毒学失败,治疗结束时没有患者出现病毒学复发。至少10%患者曾报告过的不良事件包括瘙痒症、疲劳和恶心。24%的患者曾报告过严重不良事件。4名患者因不良事件提前终止试验,其中3名患者存在持续病毒学应答。

 

结论

在慢性肾脏病4期或5期合并HCV感染的患者中,glecaprevir和pibrentasvir联合治疗12周能获得高持续病毒学应答率(由艾伯维[AbbVie]资助;在ClinicalTrials.gov注册号为NCT02651194)。





作者信息

Edward Gane, M.D., Eric Lawitz, M.D., David Pugatch, M.D., Georgios Papatheodoridis, M.D., Norbert Bräu, M.D., Ashley Brown, M.D., Stanislas Pol, M.D., Ph.D., Vincent Leroy, M.D., Ph.D., Marcello Persico, M.D., Christophe Moreno, M.D., Ph.D., Massimo Colombo, M.D., Eric M. Yoshida, M.D., David R. Nelson, M.D., Christine Collins, Ph.D., Yang Lei, Ph.D., Matthew Kosloski, Ph.D., and Federico J. Mensa, M.D.
From the Liver Unit, Auckland City Hospital, Auckland, New Zealand (E.G.); the Texas Liver Institute, University of Texas Health, San Antonio (E.L.); AbbVie, North Chicago, IL (D.P., C.C., Y.L., M.K., F.J.M.); the Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens (G.P.); the James J. Peters Veterans Affairs Medical Center, Bronx, and Icahn School of Medicine at Mount Sinai, New York — both in New York (N.B.); Imperial College Healthcare, London (A.B.); Groupe Hospitalier Cochin–Saint Vincent de Paul, Paris (S.P.), and Centre Hospitalier Universitaire de Grenoble, Grenoble (V.L.) — both in France; the Internal Medicine and Hepatology Unit, University of Salerno, Salerno (M.P.), Humanitas Clinical and Research Center, Rozzano (M.C.), and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca’ Granda Ospedale Maggiore Policlinico, Università di Milano, Milan (M.C.) — all in Italy; Cliniques Universitaires de Bruxelles Hôpital Erasme, Université Libre de Bruxelles, Brussels (C.M.); University of British Columbia, Vancouver, Canada (E.M.Y.); and the Department of Medicine, University of Florida, Gainesville (D.R.N.). Address reprint requests to Dr. Gane at Auckland City Hospital, 2 Park Rd., Auckland 1023, New Zealand, or at edgane@adhb.govt.nz.

 

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