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

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.

Distribution of hepatitis С virus drug resistance mutations among patients with recurrence of the disease during therapy with direct antiviral drugs

“…Присутствие мутаций резистентности хотя бы в одном регионе были обнаружены в 60% случаев. Распределение генотипов среди устойчивых штаммов было следующим: 1а -26,7%, 1b -46,6%, 3a -26,7% [23]. Как и в нашем исследовании, обращало на себя внимание преобладание мутации Y93H в регионе NS5A среди ВГС генотипов 1b и 3a.…”