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圣彼得堡慢性丙型肝炎患者原发性耐药突变的分布情况

Distribution of Primary Resistance Mutations in Saint Petersburg in Patients with Chronic Hepatitis C.

作者信息

Valutite Diana, Ostankova Yulia, Semenov Alexandr, Lyalina Liudmila, Totolian Areg

机构信息

Saint Petersburg Pasteur Institute, 197101 St. Petersburg, Russia.

FSBI State Scientific Center of Virology and Biotechnology «Vector» of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor), 620030 Ekaterinburg, Russia.

出版信息

Diagnostics (Basel). 2022 Apr 22;12(5):1054. doi: 10.3390/diagnostics12051054.

DOI:10.3390/diagnostics12051054
PMID:35626210
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9139387/
Abstract

The advent of direct-acting antiviral drugs (DAAs) was a breakthrough in the treatment of patients with chronic hepatitis C, yet high viral replication errors can lead to the development of resistance associated variants (RAVs). Thus, assessment of RAV in infected patients is necessary to monitor treatment effectiveness. The aim of our study was to investigate the presence of primary resistance mutations in the NS3 and NS5 regions of HCV in treatment-naive patients. Samples were taken from 42 patients with HCV who had not previously received DAA treatment. In the present study, we used the method for determining drug resistance mutations based on direct sequencing of the NS3, NS5A, and NS5B genes developed by the Saint Petersburg Pasteur Institute. Primary mutations associated with resistance were detected in 5 patients (12%). According to the Geno2pheno [hcv] 0.92 database, nucleotide substitutions were identified in various viral genes conferring resistance or decreased sensitivity to the respective inhibitors. This study has shown different mutations in the analyzed genes in patients with HCV who had not previously received DAA treatment. These mutations may increase the likelihood of treatment failure in the future.

摘要

直接作用抗病毒药物(DAA)的出现是慢性丙型肝炎患者治疗的一项突破,但高病毒复制错误可导致耐药相关变异体(RAV)的产生。因此,评估感染患者中的RAV对于监测治疗效果很有必要。我们研究的目的是调查初治患者中丙型肝炎病毒(HCV)NS3和NS5区域的原发性耐药突变的存在情况。样本取自42例未曾接受过DAA治疗的HCV患者。在本研究中,我们使用了圣彼得堡巴斯德研究所开发的基于NS3、NS5A和NS5B基因直接测序来确定耐药突变的方法。在5例患者(12%)中检测到与耐药相关的原发性突变。根据Geno2pheno [hcv] 0.92数据库,在各种病毒基因中鉴定出核苷酸替代,这些替代赋予了对相应抑制剂的耐药性或敏感性降低。本研究显示,在未曾接受过DAA治疗的HCV患者中,所分析的基因存在不同的突变。这些突变可能会增加未来治疗失败的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb9c/9139387/3f5ce4bf1e13/diagnostics-12-01054-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb9c/9139387/f785e7c3422a/diagnostics-12-01054-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb9c/9139387/2c6707a9f20d/diagnostics-12-01054-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb9c/9139387/3f5ce4bf1e13/diagnostics-12-01054-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb9c/9139387/f785e7c3422a/diagnostics-12-01054-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb9c/9139387/2c6707a9f20d/diagnostics-12-01054-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb9c/9139387/3f5ce4bf1e13/diagnostics-12-01054-g003.jpg

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A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir.一种新型 NS5A 取代可增强丙型肝炎病毒基因型 3 对达卡他韦的耐药性。
J Gen Virol. 2021 Jan;102(1). doi: 10.1099/jgv.0.001496. Epub 2020 Nov 3.
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Pre-existing resistance associated polymorphisms to NS3 protease inhibitors in treatment naïve HCV positive Pakistani patients.
几内亚共和国医护人员中艾滋病毒和病毒性肝炎标志物的流行情况。
Diagnostics (Basel). 2023 Jan 19;13(3):378. doi: 10.3390/diagnostics13030378.
治疗初治的 HCV 阳性巴基斯坦患者中与 NS3 蛋白酶抑制剂相关的预先存在的耐药性相关的多态性。
PLoS One. 2020 Apr 10;15(4):e0231480. doi: 10.1371/journal.pone.0231480. eCollection 2020.
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Resistance mutations of NS3 and NS5b in treatment-naïve patients infected with hepatitis C virus in Santa Catarina and Rio Grande do Sul states, Brazil.巴西圣卡塔琳娜州和南里奥格兰德州初治丙型肝炎病毒感染患者中NS3和NS5b的耐药突变
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