Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan.
J Gastroenterol. 2019 Oct;54(10):916-927. doi: 10.1007/s00535-019-01575-9. Epub 2019 Mar 22.
Glecaprevir and pibrentasvir (GLE/PIB) are potent antiviral agents for hepatitis C virus (HCV) pan-genotypic infections; however, their clinical effectiveness and safety remain limited in the real-world. This study aimed to evaluate viral responses and the safety of GLE/PIB for patients with chronic HCV-1/2/3 infections during both initial- (Arm A) and re-treatment (Arm B) with all-oral direct-acting antiviral agents (DAAs).
This prospective-observational cohort study included Japanese patients with chronic HCV-1/2/3 infections (n = 271: 183 in Arm A and 83 in Arm B), who had started receiving GLE/PIB. Primary end point was a sustained virological response (SVR) rate at week 12 (SVR12) after the end of GLE/PIB treatment (EOT).
SVR12 was achieved by 99.4% of patients (180/181: modified intention-to-treat (mITT) analysis excluding 2 patients lost to follow-up) in Arm A. One patient with an HCV-3b infection who discontinued at week 8 failed to achieve SVR12. SVR12 was achieved by 97.7% of patients (85/87: mITT excluding 1 patient lost to follow-up) in Arm B. Virological relapse occurred in 2 patients with HCV-1b, presenting common 5 loci of resistance-associated substitutions (RASs) including A92 RASs in the NS5A lesion at baseline. Any adverse events (AEs) (grade ≥ 3) occurred in 8 patients (3.0%). 8 patients (3.0%) discontinued due to AEs, however, all of them achieved SVR12.
Initial and re-treatment with GLE/PIB are effective and safe for Japanese patients with HCV-1/2/3 in real-life settings. Further studies are required to elucidate the mechanism underlying treatment failures of GLE/PIB to completely eradicate HCV worldwide.
格卡瑞韦和哌仑他韦（GLE/PIB）是针对丙型肝炎病毒（HCV）全基因型感染的强效抗病毒药物；然而，在真实世界中，它们的临床疗效和安全性仍受到限制。本研究旨在评估 GLE/PIB 对初治（Arm A）和再治疗（Arm B）所有口服直接作用抗病毒药物（DAA）的慢性 HCV-1/2/3 感染患者的病毒学应答和安全性。
这是一项前瞻性观察性队列研究，纳入了 271 例慢性 HCV-1/2/3 感染的日本患者（Arm A 组 183 例，Arm B 组 83 例），他们开始接受 GLE/PIB 治疗。主要终点是 GLE/PIB 治疗结束后第 12 周（EOT）的持续病毒学应答（SVR12）率。
Arm A 组 181 例患者（改良意向治疗（mITT）分析排除 2 例失访患者）中，99.4%的患者达到 SVR12。1 例 HCV-3b 感染患者在第 8 周停药，未能达到 SVR12。Arm B 组 87 例患者（mITT 排除 1 例失访患者）中，97.7%的患者达到 SVR12。2 例 HCV-1b 患者发生病毒学复发，均存在基线时 NS5A 区常见的 5 个耐药相关取代（RAS），包括 A92 RAS。8 例（3.0%）患者出现任何不良事件（AE）（≥3 级）。8 例（3.0%）患者因 AE 停药，但均达到 SVR12。
在真实环境中，GLE/PIB 对日本 HCV-1/2/3 患者的初始和再治疗是有效和安全的。需要进一步研究阐明 GLE/PIB 治疗失败的机制，以在全球范围内彻底消除 HCV。
