BACKGROUND The effect of baseline resistance-associated substitutions (RAS) on the sustained virologic response at 12 weeks (SVR12) among chronic hepatitis C (CHC) patients receiving the second generation, pan-genotypic glecaprevir/pibrentasvir (G/P) regimen is unclear. AIM To assess the effect of RAS on the SVR12 in CHC patients treated with G/P regimen. METHODS The EMBASE, MEDLINE and Cochrane central register of controlled trials databases were searched for relevant studies published before 1 March 2019. The principal outcome was to compare the SVR12 in CHC patients with and without baseline RAS, particularly in genotype-1, genotype-3 and direct-acting anti-virals (DAAs) failure patients. The outcomes were pooled using a random-effects model and odds ratio (OR) was calculated. The risk of bias was assessed using the Cochrane risk of bias tools for randomised and nonrandomised interventional studies. RESULTS After initially identifying 410 studies, 3302 patients from 17 studies were included. Among 50 cases of virologic failures, 48% had genotype-3 infection, 44% genotype-1 infection and 36% DAA-failure patients. Baseline RAS were present in 44(88%) patients. The most common NS5a and NS3 mutations were Y93H and A166S respectively. The odds of SVR12 were significantly reduced in patients with any baseline RAS (NS3 and/or NS5a) (OR 0.32, 95%C I[0.15, 0.65], I2 = 0%) and NS5a substitutions (OR 0.36, 95%CI [0.18,0.73]). The impact of RAS on SVR12 was significant among genotype-3 patients, but not among genotype-1 or DAA-failure cases. The presence of Y93H and A30K mutations significantly impacted SVR12 rates in genotype-3 patients. CONCLUSION Baseline NS3 or NS5a RAS, especially the NS5a substitutions-A30K, Y93H, decrease the odds of achieving SVR12 in genotype-3 CHC patients.

中文翻译：

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荟萃分析的系统评价：基线耐药相关替代对慢性丙型肝炎患者中 glecaprevir/pibrentasvir 疗效的影响。

背景 基线耐药相关替代 (RAS) 对接受第二代泛基因型 glecaprevir/pibrentasvir (G/P) 方案的慢性丙型肝炎 (CHC) 患者 12 周时持续病毒学应答 (SVR12) 的影响尚不清楚. 目的评估RAS对G/P方案治疗的CHC患者SVR12的影响。方法 检索 EMBASE、MEDLINE 和 Cochrane 对照试验数据库中央注册数据库，查找 2019 年 3 月 1 日之前发表的相关研究。主要结果是比较有和没有基线 RAS 的 CHC 患者的 SVR12，特别是基因型 1、基因型 3和直接作用抗病毒药物 (DAA) 失败的患者。使用随机效应模型汇总结果并计算优势比 (OR)。使用随机和非随机干预研究的 Cochrane 偏倚风险工具评估偏倚风险。结果 在初步确定了 410 项研究后，纳入了 17 项研究的 3302 名患者。在 50 例病毒学失败的病例中，48% 的患者有基因 3 型感染，44% 的基因型 1 感染和 36% 的 DAA 失败患者。44 例（88%）患者存在基线 RAS。最常见的 NS5a 和 NS3 突变分别是 Y93H 和 A166S。在有任何基线 RAS（NS3 和/或 NS5a）（OR 0.32, 95%CI[0.15, 0.65], I2 = 0%）和 NS5a 替代（OR 0.36, 95%CI [0.18）的患者中，SVR12 的几率显着降低,0.73])。RAS 对 SVR12 的影响在基因型 3 患者中显着，但在基因型 1 或 DAA 失败病例中不显着。Y93H 和 A30K 突变的存在显着影响基因型 3 患者的 SVR12 率。结论 基线 NS3 或 NS5a RAS，尤其是 NS5a 替代物-A30K、Y93H，降低了基因型 3 CHC 患者实现 SVR12 的几率。