Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran; Middle East Liver Diseases (MELD) Center, Tehran, Iran.
Middle East Liver Diseases (MELD) Center, Tehran, Iran.
Virus Res. 2019 Jan 2;259:54-61. doi: 10.1016/j.virusres.2018.10.014. Epub 2018 Oct 25.
Resistance-associated substitutions (RASs) in the NS5A gene of hepatitis C virus (HCV) has been studied as one of the predictors of response to NS5A inhibitor-containing regimens. This study aimed to evaluate the prevalence of pre-treatment naturally-occurring NS5A RASs in HCV isolates from patients with chronic HCV genotype 1 (HCV-1) infection retrieved from GenBank.
In the search procedure, the studies with published HCV-1 NS5A sequence in GenBank were screened and evaluated for inclusion in the pooled analysis. The sequences of the included studies were retrieved from GenBank and evaluated for substitutions in amino acid positions24, 26, 28, 29, 30, 31, 32, 38, 58, 62, 92 and 93 of HCV NS5A including RASs and RASs conferring >100 resistance fold change (RASs >100X).
In the pooled analysis, 2409 isolates from patients with HCV-1 infection were included, consisting 1305 (54.2%) HCV-1a and 1104 (45.8%) HCV-1b isolates. The prevalence of NS5A RASs and RASs >100X were 16.0% (95%CI = 14.6%-17.5%) and 4.7% (95%CI = 3.9%-5.6%), respectively. The NS5A RASs were more frequently observed in HCV-1b isolates than in HCV-1a isolates (P < 0.001).
The naturally-occurring HCV NS5A RASs especially those with clinical relevance (RASs >100X) are observed in a small (4.7%) number of patients with HCV-1 infection.
丙型肝炎病毒（HCV）的 NS5A 基因中的耐药相关突变（RAS）已被研究作为预测 NS5A 抑制剂联合方案应答的指标之一。本研究旨在评估从 GenBank 中检索到的慢性 HCV 基因型 1（HCV-1）感染患者的 HCV 分离株中治疗前自然发生的 NS5A RAS 的流行率。
在搜索过程中，筛选并评估了 GenBank 中发表的 HCV-1 NS5A 序列的研究，以纳入汇总分析。从 GenBank 中检索纳入研究的序列，并评估 HCV NS5A 氨基酸位置 24、26、28、29、30、31、32、38、58、62、92 和 93 中取代的 RAS 和 RAS （>100 倍耐药变化的 RASs>100X）。
在汇总分析中，纳入了 2409 例 HCV-1 感染患者的分离株，其中包括 1305 例（54.2%）HCV-1a 和 1104 例（45.8%）HCV-1b 分离株。NS5A RAS 和 RAS>100X 的发生率分别为 16.0%（95%CI=14.6%-17.5%）和 4.7%（95%CI=3.9%-5.6%）。NS5A RAS 在 HCV-1b 分离株中比在 HCV-1a 分离株中更常见（P<0.001）。
在 HCV-1 感染患者中，自然发生的 HCV NS5A RAS （特别是那些具有临床相关性的 RAS>100X）的发生率较低（4.7%）。
