在真实世界中治疗丙型肝炎病毒基因型 1A 感染中，使用艾尔巴韦格拉瑞韦和检测耐药相关替换的效果：来自德国丙型肝炎注册研究的结果。

Utilization and effectiveness of elbasvir/grazoprevir and adoption of resistance-associated substitutions testing in real-world treatment of hepatitis C virus genotype 1A infection: results from the German Hepatitis C-Registry.

机构信息

Gastroenterology-Hepatology Center Kiel, Kiel.

ifi - Institute for Interdisciplinary Medicine, Study Centre St. Georg, Hamburg.

出版信息

Eur J Gastroenterol Hepatol. 2021 Mar 1;33(3):415-423. doi: 10.1097/MEG.0000000000001759.

DOI:10.1097/MEG.0000000000001759

PMID:32345848

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7846287/

Abstract

BACKGROUND

For treatment of genotype 1a (GT1a) infection with elbasvir/grazoprevir, the German guidelines recommend a differentiated approach depending on baseline viral load (BVL). For low BVL ≤800 000 IU/mL, treatment with 12 weeks elbasvir/grazoprevir should be considered, whereas for high BVL >800 000 IU/mL, this regimen is only recommended in nonstructural protein 5A (NS5A) resistance-associated substitutions (RAS) absence. With present NS5A RAS or when RAS-testing is not available, 16 weeks elbasvir/grazoprevir + ribavirin is preferred. Here, we investigated the adherence to these recommendations and the effectiveness of elbasvir/grazoprevir in a large German Hepatitis C-Registry GT1a cohort.

METHODS

From September 2016 until July 2018, 195 GT1a-infected patients were treated with elbasvir/grazoprevir ± ribavirin for 12-16 weeks. The primary outcome was per protocol SVR12 or SVR24.

RESULTS

Mean age was 50 years, 89% were male, 19% had cirrhosis, 72% were treatment-naïve. Forty-five percent had low BVL ≤800 000 IU/mL, 55% high BVL >800 000 IU/mL, of whom 49 vs. 42% were baseline RAS-tested. Four patients with high (7.7%) and two with low BVL (5%) had NS5A RAS of whom 50% received elbasvir/grazoprevir+ribavirin, respectively. Ninety-four percent of patients with low and 65% with high BVL received elbasvir/grazoprevir without ribavirin. Thirty-five percent of patients with high BVL received ribavirin, mostly without prior RAS-testing. Per protocol sustained virologic response (SVR) by low vs. high BVL was 98.8 and 95.1%. All patients with NS5A RAS achieved SVR.

CONCLUSIONS

In German, real-world most patients received elbasvir/grazoprevir without ribavirin. Ribavirin was mainly added in GT1a patients >800 000 IU/mL, who were not NS5A RAS tested. SVR rates were consistently high and comparable to clinical trial results.

摘要

背景

对于基因型 1a（GT1a）感染的治疗，使用 Elbasvir/grazoprevir，德国指南建议根据基线病毒载量（BVL）进行差异化治疗。对于低 BVL≤800000IU/ml，应考虑使用 12 周 Elbasvir/grazoprevir 治疗，而对于高 BVL＞800000IU/ml，只有在非结构蛋白 5A（NS5A）耐药相关取代（RAS）不存在的情况下才推荐使用该方案。对于目前存在 NS5A RAS 或无法进行 RAS 检测的患者，推荐使用 16 周 Elbasvir/grazoprevir+利巴韦林。在这里，我们调查了这些建议的遵循情况以及 Elbasvir/grazoprevir 在德国 HCV 登记处 GT1a 队列中的有效性。

方法

从 2016 年 9 月至 2018 年 7 月，195 名 GT1a 感染患者接受 Elbasvir/grazoprevir±利巴韦林治疗 12-16 周。主要结局是根据方案检测的 SVR12 或 SVR24。

结果

平均年龄为 50 岁，89%为男性，19%有肝硬化，72%为初治患者。45%的患者 BVL 低（≤800000IU/ml），55%的患者 BVL 高（＞800000IU/ml），其中 49%与 42%的患者进行了基线 RAS 检测。4 名高 BVL（7.7%）和 2 名低 BVL（5%）患者有 NS5A RAS，其中 50%的患者接受了 Elbasvir/grazoprevir+利巴韦林治疗。94%的低 BVL 患者和 65%的高 BVL 患者接受了 Elbasvir/grazoprevir 治疗，未接受利巴韦林治疗。35%的高 BVL 患者接受了利巴韦林治疗，其中大多数患者未进行 RAS 检测。根据低 BVL 与高 BVL 的方案检测的持续病毒学应答（SVR）分别为 98.8%和 95.1%。所有有 NS5A RAS 的患者均达到 SVR。