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

Mariantonietta Di Stefano,Thomas Leitner,Mohamed O M E Elamin,Marwan J Alwazzeh,Mona H Ismail,Saada A Elmnan Adem,Jose R Fiore,Teresa A Santantonio,Giuseppina Faleo,Obeidi Eltreifi

doi:10.3390/v13091832

Abstract

This study aimed to characterize the HCV genetic subtypes variability and the presence of natural occurring resistance-associated substitutions (RASs) in Saudi Arabia patients. A total of 17 GT patients were analyzed. Sequence analysis of NS3, NS5A, and NS5B regions was performed by direct sequencing, and phylogenetic analyses were used to determine genetic subtypes, RAS, and polymorphisms. Nine patients were infected by GT 4a, two with GT 4o and three with GT 4d. Two patients were infected with apparent recombinant virus (4a/4o/4a in NS3/NS5A/NS5B), and one patient was infected with a previously unknown, unclassifiable, virus of GT 4. Natural RASs were found in six patients (35%), including three infected by GT 4a, two by GT 4a/GT 4o/GT 4a, and one patient infected by an unknown, unclassifiable, virus of GT 4. 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. GT 4a is the most common subtype in this small cohort of Saudi Arabia patients infected with hepatitis C infection. Natural RASs were observed in about one-third of patients, but only one of them showed a treatment failure.

Highlights

Hepatitis C virus (HCV) is a leading cause of cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related death worldwide [1]
This study aimed to characterize the genetic subtypes of HCV-GT4 in Saudi Arabian patients and analyze the prevalence and characteristics of resistance-associated substitutions (RASs) in direct-acting antivirals (DAAs)-naïve patients by the use of Sanger sequencing with a RAS detection limit of around 15/20% of the viral population
The study of genotype, subtype characteristics, and circulation is critical to defining HCV epidemiology and driving more appropriate therapy choices

Summary

Introduction

Hepatitis C virus (HCV) is a leading cause of cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related death worldwide [1]. The epidemic caused by HCV affects all regions, with significant differences between and within countries. An estimated 71 million people are chronically infected by HCV. The WHO Eastern Mediterranean Region and the European Region have the highest reported prevalence of HCV [1,2,3]. HCV exhibits high genetic diversity and is currently classified into eight genotypes (GT 1 to GT 8), with varied geographic prevalence [4]. The distribution of HCV genotypes in the Middle East is highly variable, with a higher prevalence of GT 1 in Iran, Oman, and UAE. GT 2 is prevalent in Bahrain and Libya, GT 3 is prevalent in Afghanistan, and GT 4 is prevalent in Egypt, Iraq, Jordan, Palestine, Qatar, Saudi Arabia, and Syria

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