Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Genetic Subtypes and Natural Resistance Mutations in HCV Genotype 4 Infected Saudi Arabian Patients

Version 1 : Received: 14 June 2021 / Approved: 16 June 2021 / Online: 16 June 2021 (08:21:33 CEST)

How to cite: Di Stefano, M.; Ismail, M.; Faleo, G.; Elmnan Adem, S.; Elamin, M.; Eltreifi, O.; Alwazzeh, M.; Fiore, J.R.; Santantonio, T.A. Genetic Subtypes and Natural Resistance Mutations in HCV Genotype 4 Infected Saudi Arabian Patients. Preprints 2021, 2021060423 (doi: 10.20944/preprints202106.0423.v1). Di Stefano, M.; Ismail, M.; Faleo, G.; Elmnan Adem, S.; Elamin, M.; Eltreifi, O.; Alwazzeh, M.; Fiore, J.R.; Santantonio, T.A. Genetic Subtypes and Natural Resistance Mutations in HCV Genotype 4 Infected Saudi Arabian Patients. Preprints 2021, 2021060423 (doi: 10.20944/preprints202106.0423.v1).

Abstract

This study aimed to characterize the genetic subtypes of HCV-GT4 and identify the presence of natural occurring resistance-associated substitutions (RASs) in Saudi Arabia patients. A total of 17 GT4 patients was analyzed. Sequence analysis of NS3, NS5A and NS5B regions was performed by direct sequencing. In addition, phylogenetic analysis was used to determine genetic subtypes, RAS and polymorphisms. Nine patients were infected by a GT4a, one with GT4o, 3 with GT4d. The remaining four patients were infected with a recombinant virus (GT4a+GT4o in three patients, GT4c+GT4d in a patient). Natural RASs were found in six patients (35%), including three infected by GT4a, two by GT4a+GT4o and one patient infected by GT4c+GT4d. In particular, NS3-RAS V170I was demonstrated in three patients, while NS5A-RASs (L28M, L30R, L28M+M31L) were detected in the remaining three patients. All patients were treated with sofosbuvir plus daclatasvir; three patients were lost to follow-up whereas 14 patients completed the treatment. A sustained virological response (SVR) was obtained in all but one patient carrying NS3-RAS V170I who later relapsed. GT4a is the most common subtype in this small cohort of Saudi Arabia patients infected with hepatitis C infection. Natural RASs were observed in about a third of patients, but only one of them showed a treatment failure.

Keywords

HCV; Genotypes; Subtypes; DAA

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