engleski

High prevalence of NS3 resistance associated substitutions in treatment naïve patients infected with genotype 1 of hepatitis C virus in Croatia

It is estimated that between 35000 and 45000 of the Croatian population is chronically infected with HCV, with genotype 1 being the most widely distributed (57%) followed by genotype 3 (37%). Antiviral therapy for hepatitis C virus has been considerably improved with the introduction of direct-acting antivirals (DAA) that selectively target nonstructural proteins of the virus, among which is serine protease (NS3/4A). Resistance- associated substitutions (RAS) can be associated with inadequate treatment outcomes with DAA. The aim of this study was to analyze the frequency of substitutions associated with HCV resistance to NS3 inhibitors in treatment naive patients infected with HCV subtype 1a, 1b and 3a in Croatia The study included 40 patients with chronic HCV genotype 1 and 18 patients with genotype 3 infection receiving clinical care at the Department of Viral Hepatitis of the University Hospital for Infectious Diseases, Zagreb between January 2019 and March 2020. HCV subtype was determined by using VERSANT HCV Genotype 2.0 Assay LiPA. Detection of substitutions associated with resistance to NS3 inhibitors was performed by population-based sequencing while resistance profile was analyzed in Geno2Pheno algorithm. Resistance to NS3 inhibitors was detected in 13 of 40 (32, 5%) of genotype 1 patients, 10 patients with subtype 1a (41, 67%) and 3 patients with subtype 1b (18, 75%). Additionally, 14 patients (35.0%) carried only mutations that cause reduced susceptibility to NS5A inhibitors, 7 patients in subtype 1a (21, 17%) and 7 patients in subtype 1b (43, 75%). Clade I of subtype 1a was detected in 18, and clade II in 6 patients with RAS present exclusively in clade I. All subtype 1a patients carried the same RAS, Q80K, associated with resistance to simeprevir. Resistance to NS3 inhibitors was detected in 1 of 18 (5, 56%) of subtype 3a patients. High prevalence of NS3 RAS was detected in patients infected with HCV genotype 1, especially subtype 1a. It is necessary to choose appropriate DAA combination in these patients in order to facilitate the achievement of sustained virological response.

Hepatitis C virus ; Genotype 1 ; Resistance-associated substitutions ; Direct-acting antivirals ; Population-based sequencing

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