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通过外周血单个核细胞内巢式丙型肝炎病毒RNA聚合酶链反应在诊断为对直接抗病毒药物治疗无反应者中识别7基因特征(肝硬化风险评分)。

Recognition of 7 genes signature (Cirrhosis Risk Score) in the diagnosed non-responders to DAAs therapy by intra-PBMCs nested HCV RNA PCR.

作者信息

Galal Al-Shazly Gaber Mohamed, Dawood Reham M, Awady Mostafa K El, El-Dessouky Yasser Mohamed Mohamed, Mahmoud Mohamed Mahmoud Abdel-Halim, Alla Mohamed Darwish Ahmed Abd

机构信息

Horus Specialized Hospital, General Authority of Health Care, Waburat Armant, Egypt.

Department of Microbial Biotechnology, National Research Center, Cairo, Egypt.

出版信息

J Genet Eng Biotechnol. 2023 Aug 30;21(1):89. doi: 10.1186/s43141-023-00544-3.

DOI:10.1186/s43141-023-00544-3
PMID:37646837
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10468448/
Abstract

BACKGROUND AND AIMS

Predictors of chronic HCV response to oral antiviral therapy (OAT) are related to host genetic variations. Single nucleotide polymorphisms (SNP) and alleles variations of host genes in association with hepatic fibro-cirrhotic changes have a distinct role in OAT outcomes. The current research evaluated the association of Cirrhosis-Risk-Scores (CRS) values, based on the correlation of seven genes signature-SNPs, with sonographic liver parenchymal changes in determining OAT outcomes.

METHODS

All study subjects (n = 54) were recruited three months after completing OAT and classified into three groups. Group I (n = 21) had negative HCV PCR, group II (n = 17) showed positive solitary intra-PBMCs HCV infection, and group III(n = 16) was serum HCV RNA PCR-positive. All study-population were subjected to examination by hepatic-ultrasound (US), FIB-4-scoring, and screening for 7 gene-signature that addressed CRS values as low, intermediate, and high depending on gene SNPs identification.

RESULTS

Group I showed a significant association with low CRS values compared to other groups (P < 0.001). Solitary intra- PBMCs HCV infection in group II was significantly combined with intermediate CRS values in comparison to groups I and III (P < 0.001). The high CRS values were significantly found in group III when compared to groups I and II (P < 0.01). On US imaging, low CRS values were common in normally appeared hepatic parenchyma (P < 0.001) and high CRS values were frequent in coarse-liver (P < 0.001), while bright-liver-tissues appearance was mainly detected in the intermediate CRS category (P = 0.09). On FIB-4 scoring, high CRS value were associated with hepatic fibro-cirrhosis compared to intermediate (P < 0.001) and low (P = 0.08) CRS-categories.

CONCLUSION

The current study concluded the association of (a) high CRS values with coarse liver in viral-RNA serologic relapse, (b) low CRS values with normal liver tissues in sustained virologic response (SVR), (c) intermediate CRS values with bright liver in solitary PBMCs relapse.

摘要

背景与目的

慢性丙型肝炎病毒(HCV)对口服抗病毒治疗(OAT)反应的预测因子与宿主基因变异有关。宿主基因的单核苷酸多态性(SNP)和等位基因变异与肝纤维化 - 肝硬化变化相关,在OAT治疗结果中具有独特作用。本研究基于七个基因特征性SNP的相关性,评估肝硬化风险评分(CRS)值与肝脏实质超声变化在确定OAT治疗结果中的关联。

方法

所有研究对象(n = 54)在完成OAT三个月后入组,并分为三组。第一组(n = 21)HCV PCR检测为阴性,第二组(n = 17)显示单个外周血单核细胞内HCV感染阳性,第三组(n = 16)血清HCV RNA PCR检测为阳性。所有研究人群均接受肝脏超声(US)检查、FIB - 4评分,并筛查7个基因特征,根据基因SNP鉴定将CRS值分为低、中、高。

结果

与其他组相比,第一组与低CRS值显著相关(P < 0.001)。与第一组和第三组相比,第二组单个外周血单核细胞内HCV感染与中等CRS值显著相关(P < 0.001)。与第一组和第二组相比,第三组中显著发现高CRS值(P < 0.01)。在超声成像中,正常肝脏实质中低CRS值常见(P < 0.001),粗肝中高CRS值常见(P < 0.001),而明亮肝脏组织外观主要在中等CRS类别中检测到(P = 0.09)。在FIB - 4评分中,与中等(P < 0.001)和低(P = 0.08)CRS类别相比,高CRS值与肝纤维化 - 肝硬化相关。

结论

本研究得出以下关联:(a)高CRS值与病毒RNA血清学复发时的粗肝相关;(b)低CRS值与持续病毒学应答(SVR)时的正常肝组织相关;(c)中等CRS值与单个外周血单核细胞复发时的明亮肝脏相关。

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本文引用的文献

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Development of a gene signature for predicting cirrhosis risk score of chronic liver disease associated with HCV infection in Egyptians.开发一种基因特征,用于预测埃及人 HCV 感染相关慢性肝病的肝硬化风险评分。
Microb Pathog. 2021 Apr;153:104805. doi: 10.1016/j.micpath.2021.104805. Epub 2021 Feb 18.
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Treatment of hepatitis C virus infection with direct-acting antivirals plus ribavirin eliminates viral RNA from peripheral blood mononuclear cells and reduces virologic relapse in diverse hepatic parenchymal changes.直接作用抗病毒药物联合利巴韦林治疗丙型肝炎病毒感染可从外周血单核细胞中消除病毒 RNA,并减少各种肝实质变化中的病毒学复发。
Arch Virol. 2021 Apr;166(4):1071-1081. doi: 10.1007/s00705-021-04969-4. Epub 2021 Feb 3.
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Key Players of Hepatic Fibrosis.肝纤维化的关键参与者。
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Recipient interleukin 6 gene polymorphism and expression predict HCV recurrence post liver transplantation.受体白细胞介素6基因多态性与表达可预测肝移植后丙型肝炎病毒复发。
Gene. 2020 Sep 5;754:144887. doi: 10.1016/j.gene.2020.144887. Epub 2020 Jun 10.
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Extrahepatic Upregulation of Transforming Growth Factor Beta 2 in HCV Genotype 4-Induced Liver Fibrosis.肝外转化生长因子β 2 在 HCV 基因型 4 诱导的肝纤维化中的上调。
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Hepatitis C virus serologic relapse after treatment with direct-acting antivirals is dependent on viral RNA levels in peripheral blood mononuclear cells and the grade of liver cirrhosis.直接作用抗病毒药物治疗后丙型肝炎病毒血清学复发取决于外周血单核细胞中的病毒 RNA 水平和肝硬化的程度。
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