engleski

Resistance to NS3 protease inhibitors in persons with chronic hepatitis C virus subtype 1a from Croatia

Background: An NS3 inhibitor simeprevir is one of the treatment options for chronic hepatitis C in Croatia (in combination with pegylated interferon alpha and ribavirin). Mutation Q80K in persons infected with HCV subtype 1a is associated with reduced treatment response to simeprevir. The aim of this study was to analyze the frequency of Q80K mutations in persons with HCV subtype 1a infection prior to treatment with direct acting antivirals and to analyze other mutations associated with HCV resistance to NS3 inhibitors. Methods: The study included 85 persons with chronic hepatitis C infected with HCV subtype 1a receiving clinical care at the Department of Viral Hepatitis of the University Hospital for Infectious Diseases, Zagreb and Croatian Reference Center for Viral Hepatitis. HCV subtype was determined by using Inno LiPA genotyping test. Detection of Q80K and other mutations associated with resistance to NS3 inhibitors was performed as a part of pre-treatment diagnostic workup by population-based sequencing on ABI PRISM - 3100 Genetic Analyzer. Geno2Pheno algorithm was used for the interpretation of resistance analysis results. Results: Resistance to Simeprevir was detected in 36 of 85 (42 %) of patients. Subtype 1a clade I was detected in 41 patients and clade II in 44 patients. Mutation Q80K was detected only in patients infected with HCV subtype 1a clade I (32 of 41 patients). The majority of patients with clade I (n = 21) were infected with strains carrying Q80K mutation only whereas 11 patients carried a combination of Q80K and other mutations associated with NS3 resistance mutations. Mutations associated with resistance to NS3 inhibitors excluding Q80K were detected in 4 of 44 patients infected with subtype 1a clade II. The patterns of resistance mutations included: 155 T and 170 V (n = 1 patient), 36 L, 155 K and 170 V (n = 1), 138A, 155S, 168G, 170C and 43S (n = 1) and 36 L (n = 1, possible resistance). Conclusion: The results of this study have shown a high prevalence of Q80K in patients with chronic hepatitis C infected with clade I subtype 1a from Croatia. The contribution of other mutations to NS3 inhibitors resistance was limited.

Resistance ; chronic hepatitis C ; Croatia

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