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丙型肝炎病毒(HCV)的治疗结果取决于IFNL3基因多态性(rs12979860)的单核苷酸多态性(SNPs)以及肝实质的肝硬化改变。

HCV treatment outcome depends on SNPs of IFNL3-Gene polymorphisms (rs12979860) and cirrhotic changes in liver parenchyma.

作者信息

Abd Alla Mohamed Darwish Ahmed, Dawood Reham M, Rashed Hassan Abd El-Hafeth, El-Dessouky Yasser Mohammed, AbuFarrag Galal AbdElhameed, Ammar Islam Abdelmawla Emran, Mahmoud Mohamed Mahmoud Abdel-Halim, Salum Ghada M, Abu-Amer Mohamed Zakaria, Sekeen Mohamed Abd Elrafaa Hassan, Heggazy Mohamed Mousa Ibraheem, Altanbouly Ahmed Mohamed Abdulhamid, Abd El-Meguid Mai, El Awady Mostafa K

机构信息

Department of Hepatology, Gastroenterology and Infectious Diseases, Faculty of Medicine, Al-Azhar University, Egypt.

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

出版信息

Heliyon. 2023 Oct 19;9(11):e21194. doi: 10.1016/j.heliyon.2023.e21194. eCollection 2023 Nov.

Abstract

The allelic discrimination of IFNL3-(rs12979860 C > T) polymorphism reveals ambiguous associations with the effectiveness of oral HCV treatment. Solitary intra peripheral-blood-mononuclear-cells (PBMCs) HCV-RNA antisense-strands are independently detected in naïve and experienced cases regardless of viremia or hepatic-parenchymal alterations. We examined the frequencies of IFNL3-genetic variants with chronic-HCV-induced liver changes during the sustained virologic response (SVR) by evaluating the PBMCs- HCV-PCR after oral antiviral therapy. : Twelve weeks after finishing oral antiviral therapy, the effects of IFNL3-genetic variants were evaluated in three groups of patients: Group-I (n = 25) showed HCV-RNA negativity in both serum and PBMCs-, group II (n = 52) showed positivity of HCV-RNA in PBMCs, and group-III (n = 25) had positive HCV-RNA in serum. The genetic variants of the IFNL3-gene were estimated for all the enrolled cases and correlated with their hepatic image changes. : IFNL3-(rs12979860) genotyping in post-direct acting antivirals (DAAs) SVR and HCV-relapse revealed: high frequency of CC-genotype and C-allele in compared to group (P < 0.005) and group (P ≤ 0.05) when hepatic-parenchyma looks normal by ultrasound frequent CT-genotype and T-allele in compared with (P < 0.01) and (P < 0.05) when liver tissues are bright (early cirrhotic-changes) frequent TT-genotype and T-allele in relative to (P < 0.05) and (P ≤ 0.08) when liver-tissues appear coarse by ultrasound. : Outcomes of HCV treatment depend on host IFNL3-gene polymorphism and hepatic-parenchymal changes. A high frequency of wild-CC-genotype and C-allele is observed in patients with normal hepatic parenchyma and that achieved SVR. Solitary relapse in PBMCs occurs on increasing CT-genotype frequency when liver tissues are bright. Serologic relapse is detected when TT-genotype and T-allele are dominant in association with the cirrhotic liver. Therefore, IFNL3-gene-SNP analysis as a genetic predictor in relation to ultra-sonographic hepatic-parenchymal changes could be valuable for selecting the patients with the highest priority for treatment.

摘要

IFNL3-(rs12979860 C>T)多态性的等位基因鉴别显示其与口服丙肝治疗效果的关联并不明确。无论病毒血症或肝实质改变情况如何,在初治和经治病例中均可独立检测到外周血单个核细胞(PBMC)中的丙肝病毒(HCV)RNA反义链。我们通过评估口服抗病毒治疗后的PBMC-HCV-PCR,研究了IFNL3基因变异与慢性丙肝导致的肝脏变化在持续病毒学应答(SVR)期间的频率。口服抗病毒治疗结束12周后,在三组患者中评估了IFNL3基因变异的影响:第一组(n=25)血清和PBMC中的HCV-RNA均为阴性;第二组(n=52)PBMC中的HCV-RNA为阳性;第三组(n=25)血清中的HCV-RNA为阳性。对所有纳入病例的IFNL3基因变异进行了评估,并将其与肝脏影像变化相关联。在直接作用抗病毒药物(DAA)治疗后的SVR和HCV复发患者中进行IFNL3-(rs12979860)基因分型显示:当超声检查肝实质正常时,与第二组(P<0.005)和第三组(P≤0.05)相比,第一组中CC基因型和C等位基因的频率较高;当肝脏组织呈明亮表现(早期肝硬化改变)时,与第一组(P<0.01)和第三组(P<0.05)相比,第二组中CT基因型和T等位基因的频率较高;当超声检查肝脏组织粗糙时,与第一组(P<0.05)和第二组(P≤0.08)相比,第三组中TT基因型和T等位基因的频率较高。丙肝治疗结果取决于宿主IFNL3基因多态性和肝实质变化。肝实质正常且实现SVR的患者中观察到野生型CC基因型和C等位基因的高频率。当肝脏组织呈明亮表现时,随着CT基因型频率增加,PBMC中出现单独复发。当TT基因型和T等位基因在肝硬化肝脏中占主导时,检测到血清学复发。因此,IFNL3基因单核苷酸多态性分析作为与超声检查肝实质变化相关的遗传预测指标,对于选择治疗优先级最高的患者可能具有重要价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f632/10623284/3423f6df387e/gr1.jpg

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