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

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

doi:10.1016/j.heliyon.2023.e21194

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

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

Authors

Mohamed Darwish Ahmed Abd Alla¹, Reham M Dawood², Hassan Abd El-Hafeth Rashed¹, Yasser Mohammed El-Dessouky¹, Galal AbdElhameed AbuFarrag¹, Islam Abdelmawla Emran Ammar¹, Mohamed Mahmoud Abdel-Halim Mahmoud¹, Ghada M Salum², Mohamed Zakaria Abu-Amer¹, Mohamed Abd Elrafaa Hassan Sekeen¹, Mohamed Mousa Ibraheem Heggazy¹, Ahmed Mohamed Abdulhamid Altanbouly¹, Mai Abd El-Meguid², Mostafa K El Awady²

Affiliations

¹ Department of Hepatology, Gastroenterology and Infectious Diseases, Faculty of Medicine, Al-Azhar University, Egypt.
² Department of Microbial Biotechnology, National Research Centre, Cairo, Egypt.

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. Methods: 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. Results: IFNL3-(rs12979860) genotyping in post-direct acting antivirals (DAAs) SVR and HCV-relapse revealed: a) high frequency of CC-genotype and C-allele in group I compared to group II (P < 0.005) and group III(P ≤ 0.05) when hepatic-parenchyma looks normal by ultrasound b) frequent CT-genotype and T-allele in group II compared with I(P < 0.01) and III(P < 0.05) when liver tissues are bright (early cirrhotic-changes) c) frequent TT-genotype and T-allele in group III relative to I (P < 0.05) and II (P ≤ 0.08) when liver-tissues appear coarse by ultrasound. Conclusion: 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.

Keywords: DAAs; HCV-Hepatic-changes; IFNL3-Gene-SNPs; PBMCs-PCR.