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在 GT3 和 GT1/4/6 HCV 感染复发后,用 Elbasvir、Grazoprevir、Sofosbuvir ± 利巴韦林进行再治疗是有效的。

Retreatment with elbasvir, grazoprevir, sofosbuvir ± ribavirin is effective for GT3 and GT1/4/6 HCV infection after relapse.

机构信息

St Vincent's Hospital and the University of Melbourne, Fitzroy, Vic., Australia.

The Austin Hospital, Melbourne, Vic., Australia.

出版信息

Liver Int. 2019 Dec;39(12):2285-2290. doi: 10.1111/liv.14201. Epub 2019 Aug 13.

Abstract

INTRODUCTION

Despite highly effective direct-acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection, some patients experience virological relapse. Salvage regimens should include multiple agents to suppress emergence of resistance-associated substitutions (RAS) and minimise treatment failure. The combination of sofosbuvir (SOF) and elbasvir/grazoprevir (ELB/GZR) ±ribavirin (RBV) is an effective retreatment strategy for HCV genotype (GT)1 and 4 infection. We hypothesised that SOF and ELB/GZR (±RBV) would also be an effective salvage regimen for DAA-experienced GT3 patients.

METHODS

We evaluated the efficacy and safety of SOF/ELB/GZR ± RBV in DAA-experienced participants with chronic HCV infection who had prior relapse. Participants were treated at four hospitals between December 2016 and March 2018 for either 12- or 16-weeks. The primary endpoint was sustained virological response at week 12 post-treatment (SVR12) using intention-to-treat analysis.

RESULTS

There were 40 participants included in the analysis. The mean age was 53 years, 53% had GT3, 33% had GT1 infection and 63% had cirrhosis. Fifty-eight percent were treated for 12 weeks, 42% were treated for 16 weeks and 90% received RBV. The SVR12 rate was 98% overall, 100% in non-GT3 participants and 95% in GT3 participants. One GT3 cirrhotic participant relapsed. ELB/GZR was stopped at week 6 in one GT3 cirrhotic participant who switched to SOF/velpatasvir/RBV for a further 12 weeks and achieved SVR12. RBV dose reduction was required in two participants. Treatment was otherwise well tolerated.

DISCUSSION

The combination of SOF/ELB/GZR ± RBV is effective and safe for difficult-to-cure patients who relapse after first-line DAA, including those with cirrhosis and GT3 infection.

摘要

简介

尽管直接作用抗病毒药物(DAA)治疗慢性丙型肝炎病毒(HCV)感染非常有效,但有些患者会出现病毒学复发。补救方案应包括多种药物,以抑制耐药相关替代(RAS)的出现并最大限度地减少治疗失败。索磷布韦(SOF)和艾尔巴韦/格拉瑞韦(ELB/GZR)±利巴韦林(RBV)联合方案是治疗 HCV 基因型(GT)1 和 4 感染的有效再治疗策略。我们假设 SOF 和 ELB/GZR(±RBV)对 DAA 治疗后复发的 GT3 患者也是一种有效的补救方案。

方法

我们评估了 SOF/ELB/GZR±RBV 在 DAA 治疗后复发的慢性 HCV 感染患者中的疗效和安全性。2016 年 12 月至 2018 年 3 月,共有 4 家医院的患者接受了为期 12 或 16 周的治疗。主要终点是治疗后 12 周持续病毒学应答(SVR12),采用意向治疗分析。

结果

共有 40 名患者纳入分析。平均年龄为 53 岁,53%为 GT3,33%为 GT1 感染,63%为肝硬化。58%的患者接受 12 周治疗,42%的患者接受 16 周治疗,90%的患者接受 RBV 治疗。总体 SVR12 率为 98%,非 GT3 患者为 100%,GT3 患者为 95%。一名 GT3 肝硬化患者复发。一名 GT3 肝硬化患者在治疗 6 周时停止使用 ELB/GZR,转而接受 SOF/velpatasvir/RBV 治疗 12 周,实现 SVR12。两名患者需要减少 RBV 剂量。治疗耐受性良好。

讨论

SOF/ELB/GZR±RBV 联合方案对于 DAA 一线治疗后复发的难治性患者(包括肝硬化和 GT3 感染患者)有效且安全。

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