Determination of drug resistance mutations of NS3 inhibitors in chronic hepatitis c patients infected with genotype; [Genotip 1 ile enfekte kronik hepatit C hastalarinda NS3 inhibitörü ilaçlarin direnç mutasyonlarinin belirlenmesi]

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dc.contributor.authorŞanlidaǧ T.
dc.contributor.authorSayan M.
dc.contributor.authorAkçali S.
dc.contributor.authorKasap E.
dc.contributor.authorBuran T.
dc.contributor.authorArikan A.
dc.date.accessioned2024-07-22T08:10:54Z
dc.date.available2024-07-22T08:10:54Z
dc.date.issued2017
dc.description.abstractDirect-Acting antiviral agents (DAA) such as NS3 protease inhibitors is the first class of drugs used for chronic hepatitis C (CHC) treatment. NS3 inhibitors (PI) with low genetic barrier have been approved to be used in the CHC genotype 1 infections, and in the treatment of compensated liver disease including cirrhosis together with pegile interferon and ribavirin. Consequently, the development of drug resistance during DAA treatment of CHC is a major problem. NS3 resistant variants can be detected before treatment as they can occumaturally. The aim of this study was to investigate new and old generation NS3 inhibitors resistance mutations before DAA treatment in hepatitis C virus (HCV) that were isolated from CHC. The present study was conducted in 2015 and included 97 naive DAA patients infected with HCV genotype 1, who were diagnosed in Manisa and Kocaeli cities of Turkey. Magnetic particle based HCV RNA extraction and than RNA detection and quantification were performed using commercial real-Time PCR assay QIASypmhony + Rotorgene Q/ArtusHCV QS-RGQ and COBAS Ampliprep/COBAS TaqMan HCV Tests. HCV NS3 viral protease genome region was amplified with PCR and mutation analysis was performed by Sanger dideoxy sequencing technique of NS3 protease codons (codon 32-185). HCV NS3 protease inhibitors; asunaprevir, boceprevir, faldaprevir, grazoprevir, pariteprevir, simeprevir and telap- revir were analysed for resistant mutations by Geno2pheno-HCV resistance tool. HCV was genotyped in all patients and 88 patients (n= 88/97, 91%) had genotype 1. Eight (n= 8/97, 8.2%) and 80 (n= 80/97, 82.4%) HCC patients were subgenotyped as 1 a and 1 b, respectively. Many aminoacid substitutions and resistance mutations were determined in 39/88 (44%) patients in the study group. Q80L, SI 22C/N, SI 38W were defined as potential substitutions (6/88 patients; 7%); R109K, R117C, S122G, 1132V, 1170V, N174S were described as potential resistance (34/88 patients; 39%); V36L, T54S, V55A, Q80H were characterized as resistance (7/88 patients; 8%) and Q80K, A156S were defined as high resistance (3/88 patients; 3%) mutations. Based on resistance and high resistance mutations, clinically significant mutations were defined in 10/88 (11%) of the patients. Our study shows that it is essential to analyse HCV NS3 protease inhibitors drug resistance before DAA treatment of CHC patients. On the other hand, our results pointed out that analysis of NS5A and NS5B genome region mutations may also be required in the near future.
dc.identifier.DOI-ID10.5578/mb.53824
dc.identifier.issn03749096
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/15441
dc.language.isoTurkish
dc.publisherAnkara Microbiology Society
dc.rightsAll Open Access; Bronze Open Access
dc.subjectAdult
dc.subjectAged
dc.subjectAntiviral Agents
dc.subjectDrug Resistance, Viral
dc.subjectFemale
dc.subjectGenotype
dc.subjectHepacivirus
dc.subjectHepatitis C, Chronic
dc.subjectHumans
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectMutation
dc.subjectProtease Inhibitors
dc.subjectRNA, Viral
dc.subjectViral Nonstructural Proteins
dc.subjectYoung Adult
dc.subjectantivirus agent
dc.subjectNS3 protein, hepatitis C virus
dc.subjectproteinase inhibitor
dc.subjectviral protein
dc.subjectvirus RNA
dc.subjectadult
dc.subjectaged
dc.subjectantagonists and inhibitors
dc.subjectantiviral resistance
dc.subjectclassification
dc.subjectdrug effects
dc.subjectfemale
dc.subjectgenetics
dc.subjectgenotype
dc.subjectHepacivirus
dc.subjectHepatitis C, Chronic
dc.subjecthuman
dc.subjectisolation and purification
dc.subjectmale
dc.subjectmiddle aged
dc.subjectmutation
dc.subjectvirology
dc.subjectyoung adult
dc.titleDetermination of drug resistance mutations of NS3 inhibitors in chronic hepatitis c patients infected with genotype; [Genotip 1 ile enfekte kronik hepatit C hastalarinda NS3 inhibitörü ilaçlarin direnç mutasyonlarinin belirlenmesi]
dc.typeArticle

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