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巴西里约热内卢患者的 Pre-S/S 和聚合酶突变与急性和慢性乙型肝炎病毒感染的关系。

Association of Pre-S/S and Polymerase Mutations with Acute and Chronic Hepatitis B Virus Infections in Patients from Rio de Janeiro, Brazil.

机构信息

Laboratory of Molecular Virology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Brasil Av., 4365 Manguinhos, Rio de Janeiro 21040-360, Brazil.

Department of Social Medicine, Espírito Santo Federal University, Espírito Santo 29075-910, Brazil.

出版信息

Viruses. 2022 Jun 24;14(7):1375. doi: 10.3390/v14071375.

DOI:10.3390/v14071375
PMID:35891356
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9315576/
Abstract

Several hepatitis B virus (HBV)-related factors, including the viral load, genotype, and genomic mutations, have been linked to the development of liver diseases. Therefore, in this study we aimed to investigate the influence of HBV genetic variability during acute and chronic infection phases. A real-time nested PCR was used to detect HBV DNA in all samples (acute, n = 22; chronic, n = 49). All samples were sequenced for phylogenetic and mutation analyses. Genotype A, sub-genotype A1, was the most common genotype in the study population. A total of 190 mutations were found in the pre-S/S gene area and the acute profile revealed a greater number of nucleotide mutations (p < 0.05). However, both profiles contained nucleotide mutations linked to immune escape and an increased risk of hepatocellular carcinomas (acute, A7T; chronic, A7Q). Furthermore, 17 amino acid substitutions were identified in the viral polymerase region, including the drug resistance mutations lamivudine and entecavir (rtL180M), with statistically significant differences between the mutant and wild type strains. Owing to the natural occurrence of these mutations, it is important to screen for resistance mutations before beginning therapy.

摘要

一些乙型肝炎病毒(HBV)相关因素,包括病毒载量、基因型和基因组突变,与肝脏疾病的发展有关。因此,本研究旨在探讨 HBV 遗传变异在急性和慢性感染阶段的影响。使用实时嵌套 PCR 检测所有样本(急性,n=22;慢性,n=49)中的 HBV DNA。对所有样本进行测序进行系统发育和突变分析。在研究人群中,最常见的基因型是 A 型,亚基因型 A1。在 Pre-S/S 基因区域发现了总共 190 个突变,急性组显示出更多的核苷酸突变(p<0.05)。然而,这两种模式都包含与免疫逃逸和肝细胞癌风险增加相关的核苷酸突变(急性,A7T;慢性,A7Q)。此外,在病毒聚合酶区域发现了 17 个氨基酸取代,包括拉米夫定和恩替卡韦的耐药突变(rtL180M),突变株和野生型株之间存在统计学差异。由于这些突变的自然发生,在开始治疗之前,筛选耐药突变非常重要。

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本文引用的文献

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Global Epidemiology of Viral Hepatitis.全球病毒性肝炎流行病学。
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Immune-Escape Hepatitis B Virus Mutations Associated with Viral Reactivation upon Immunosuppression.免疫逃逸乙型肝炎病毒突变与免疫抑制时病毒激活相关。
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Accumulation of mutations in reverse transcriptase of hepatitis B virus is associated with liver disease severity in treatment-naïve Chinese patients with chronic hepatitis B.初治慢性乙型肝炎中国患者中,乙型肝炎病毒逆转录酶突变的积累与肝脏疾病严重程度相关。
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Profile of Mutations in the Reverse Transcriptase and Overlapping Surface Genes of Hepatitis B Virus (HBV) in Treatment-Naïve Indonesian HBV Carriers.初治印度尼西亚乙肝病毒(HBV)携带者中乙肝病毒逆转录酶和重叠表面基因的突变谱
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The virological aspects of hepatitis B.乙型肝炎的病毒学方面
Best Pract Res Clin Gastroenterol. 2017 Jun;31(3):257-264. doi: 10.1016/j.bpg.2017.04.013. Epub 2017 May 5.
8
Natural history of acute and chronic hepatitis B: The role of HBV genotypes and mutants.急慢性乙型肝炎的自然史:乙肝病毒基因型和突变体的作用
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Naturally occurring mutations in the reverse transcriptase region of hepatitis B virus polymerase from treatment-naïve Korean patients infected with genotype C2.来自未经治疗的韩国 C2 基因型感染患者乙型肝炎病毒聚合酶逆转录酶区的自然发生突变。
World J Gastroenterol. 2017 Jun 21;23(23):4222-4232. doi: 10.3748/wjg.v23.i23.4222.
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Selection of the highly replicative and partially multidrug resistant rtS78T HBV polymerase mutation during TDF-ETV combination therapy.TDF-ETV 联合治疗中选择高度复制和部分多药耐药 rtS78T HBV 聚合酶突变。
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