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

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.

Beyond genotype‐4: Direct‐acting antiviral agents in patients with chronic hepatitis C infection from the Eastern Province of Saudi Arabia

“…A meta‐analysis of HCV genotypes in 18 studies from Saudi Arabia also found that 52.6% of HCV infections were due to GT‐4 22 . Together, these studies confirmed the predominance and regional variability of HCV GT‐4 (60%–80%) in Saudi Arabia, but little data is available on the HCV‐4 subtype 23,24 . Furthermore, pangenotypic DAAs have some drawbacks, such as higher costs and the potential for the development of drug‐resistant strains of HCV.…”

“…22 Together, these studies confirmed the predominance and regional variability of HCV GT-4 (60%-80%) in Saudi Arabia, but little data is available on the HCV-4 subtype. 23,24 Furthermore, pangenotypic DAAs have some drawbacks, such as higher costs and the potential for the development of drugresistant strains of HCV. Therefore, further studies on resistanceassociated variants (RAVs) are needed.…”

‘Unusual’ HCV genotype subtypes: origin, distribution, sensitivity to direct-acting antiviral drugs and behaviour on antiviral treatment and retreatment

“…61 Genotype 4 subtypes, including 4d and 4o, have been identified in Saudi Arabia with a low prevalence. 64 Only subtype 5a and one yet unassigned subtype of genotype 5 are known. Subtype 5a is the most common genotype in South Africa, where the majority of cases are found (figure 2).…”

Determination of hepatitis C virus subtype prevalent in Sindh, Pakistan: a phylogenetic analysis

“…Pattern one is characterized by high genetic diversity and involves the geographically discrete areas with different genotypes, such as in West Africa the most predominant types are 1, and 2, Central Africa with type 4, and Asia with types 3, and 6. According to a study based on the small genotypes 4 (GT 4) cohort, the most predominant genotype in Middle East region was observed as genotype 4 19 . However, HCV genotype 1 is the most prevalent among non-Arab countries in the region including Turkey, Iran, Cyprus, and Israel 20 .The genotype 6 is mainly distributed in southeast Asia and southern China 21 .…”