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治疗初治 HCV 基因型 6a 感染患者的丙型肝炎病毒直接作用抗病毒药物相关的自然发生耐药相关变异。

Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients.

机构信息

Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.

Guangdong Provincial Key Laboratory of Liver Disease, Guangdong, China.

出版信息

Biomed Res Int. 2017;2017:9849823. doi: 10.1155/2017/9849823. Epub 2017 Oct 15.

DOI:10.1155/2017/9849823
PMID:29164151
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5661091/
Abstract

BACKGROUND AND OBJECTIVE

The direct-acting antiviral agents (DAAs) antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV) patients. However, the viral drug resistance-associated variants (RAVs) can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients.

METHODS

Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B.

RESULTS

In NS3/4A region, we detected Q80K in 95.5% isolates (84/88) and D168E in 2.3% isolates (2/88). In NS5A region, we detected Q30R in 93.2% isolates (82/88), L31M in 4.6% isolates (4/88), and H58P in 6.8% isolates (6/88). In NS5B region, we detected A15G in 2.3% isolates (2/88), S96T in 1.1% isolates (1/88), and S282T in 20.7% isolates (17/88) and we detected I482L in 100% isolates (4/4), V494A in 50% isolates (2/4), and V499A in 100% isolates (4/4).

CONCLUSIONS

RAVs to DAAs preexist in treatment-naive HCV-6a patients. Further studies should address the issue of the impact of RAVs in response to DAA therapies for HCV-6a patients.

摘要

背景与目的

直接作用抗病毒药物(DAAs)的抗病毒治疗极大地改善了丙型肝炎病毒(HCV)患者的预后。然而,病毒耐药相关变异(RAVs)会限制 DAA 的疗效。由于 HCV-6a 不是主要流行基因型,因此关于其天然发生的 RAVs 的流行率的数据很少。本研究旨在评估初治 HCV-6a 患者中 RAVs 的流行率。

方法

对 95 例 HCV-6a 患者进行巢式 PCR 检测,以扩增 HCV 病毒 NS3、NS5A 和 NS5B 区。

结果

在 NS3/4A 区,我们在 95.5%的分离株(84/88)中检测到 Q80K,在 2.3%的分离株(2/88)中检测到 D168E。在 NS5A 区,我们在 93.2%的分离株(82/88)中检测到 Q30R,在 4.6%的分离株(4/88)中检测到 L31M,在 6.8%的分离株(6/88)中检测到 H58P。在 NS5B 区,我们在 2.3%的分离株(2/88)中检测到 A15G,在 1.1%的分离株(1/88)中检测到 S96T,在 20.7%的分离株(17/88)中检测到 S282T,在 100%的分离株(4/4)中检测到 I482L,在 50%的分离株(2/4)中检测到 V494A,在 100%的分离株(4/4)中检测到 V499A。

结论

初治 HCV-6a 患者中存在对 DAA 的耐药相关变异。进一步的研究应该解决 RAVs 对 HCV-6a 患者 DAA 治疗反应的影响问题。

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