{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T22:36:14Z","timestamp":1778711774095,"version":"3.51.4"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T00:00:00Z","timestamp":1650585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>The advent of direct-acting antiviral drugs (DAAs) was a breakthrough in the treatment of patients with chronic hepatitis C, yet high viral replication errors can lead to the development of resistance associated variants (RAVs). Thus, assessment of RAV in infected patients is necessary to monitor treatment effectiveness. The aim of our study was to investigate the presence of primary resistance mutations in the NS3 and NS5 regions of HCV in treatment-naive patients. Samples were taken from 42 patients with HCV who had not previously received DAA treatment. In the present study, we used the method for determining drug resistance mutations based on direct sequencing of the NS3, NS5A, and NS5B genes developed by the Saint Petersburg Pasteur Institute. Primary mutations associated with resistance were detected in 5 patients (12%). According to the Geno2pheno [hcv] 0.92 database, nucleotide substitutions were identified in various viral genes conferring resistance or decreased sensitivity to the respective inhibitors. This study has shown different mutations in the analyzed genes in patients with HCV who had not previously received DAA treatment. These mutations may increase the likelihood of treatment failure in the future.<\/jats:p>","DOI":"10.3390\/diagnostics12051054","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T08:14:06Z","timestamp":1650701646000},"page":"1054","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Distribution of Primary Resistance Mutations in Saint Petersburg in Patients with Chronic Hepatitis C"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0931-102X","authenticated-orcid":false,"given":"Diana","family":"Valutite","sequence":"first","affiliation":[{"name":"Saint Petersburg Pasteur Institute, 197101 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2270-8897","authenticated-orcid":false,"given":"Yulia","family":"Ostankova","sequence":"additional","affiliation":[{"name":"Saint Petersburg Pasteur Institute, 197101 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3223-8219","authenticated-orcid":false,"given":"Alexandr","family":"Semenov","sequence":"additional","affiliation":[{"name":"FSBI State Scientific Center of Virology and Biotechnology \u00abVector\u00bb of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor), 620030 Ekaterinburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liudmila","family":"Lyalina","sequence":"additional","affiliation":[{"name":"Saint Petersburg Pasteur Institute, 197101 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Areg","family":"Totolian","sequence":"additional","affiliation":[{"name":"Saint Petersburg Pasteur Institute, 197101 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,22]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021, May 02). Hepatitis C. Key Facts. Available online: http:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-c."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"92","DOI":"10.4254\/wjh.v8.i2.92","article-title":"Chronic hepatitis C: This and the new era of treatment","volume":"8","author":"Bertino","year":"2016","journal-title":"World J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8374","DOI":"10.1128\/JVI.00690-07","article-title":"Hepatitis C Virus p7 and NS2 Proteins Are Essential for Production of Infectious Virus","volume":"81","author":"Jones","year":"2007","journal-title":"J. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrmicro1645","article-title":"Replication of hepatitis C virus","volume":"5","author":"Moradpour","year":"2007","journal-title":"Nat. Rev. MicroBiol."},{"key":"ref_5","first-page":"1","article-title":"The Origin of Hepatitis C Virus","volume":"369","author":"Simmonds","year":"2013","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_6","first-page":"5","article-title":"Viktorovna Virus gepatita S: Mekhanizmy izmenchivosti, klassifikaciya, evolyuciya","volume":"60","year":"2015","journal-title":"Vopr. Virusologii."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cld.2009.11.009","article-title":"Epidemiology of Hepatitis B and C Viruses: A Global Overview","volume":"14","author":"Te","year":"2010","journal-title":"Clin. Liver Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"583","DOI":"10.4254\/wjh.v7.i3.583","article-title":"Variations and mutations in the hepatitis B virus genome and their associations with clinical characteristics","volume":"7","author":"Yano","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Andernach, I.E., Jutavijittum, P., Samountry, B., Yousukh, A., Thammavong, T., H\u00fcbschen, J.M., and Muller, C.P. (2012). A High Variability of Mixed Infections and Recent Recombinations of Hepatitis B Virus in Laos. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030245"},{"key":"ref_10","unstructured":"EASL (2021, May 12). 46th Annual Congress, 30 March\u20133 April 2011. Available online: http:\/\/www.hepmag.com\/archive\/currentNews_2596.shtml."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1002\/hep.26371","article-title":"New horizons in hepatitis C antiviral therapy with direct-acting antivirals","volume":"58","author":"Aghemo","year":"2013","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1111\/jvh.12422","article-title":"Interferon-free, direct-acting antiviral therapy for chronic hepatitis C","volume":"22","author":"Gutierrez","year":"2015","journal-title":"J. Viral Hepat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1073\/pnas.88.8.3392","article-title":"Nucleotide sequence and mutation rate of the H strain of hepatitis C virus","volume":"88","author":"Ogata","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.jhep.2011.01.011","article-title":"Hepatitis C virus resistance to protease inhibitors","volume":"55","author":"Halfon","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1093\/infdis\/jis761","article-title":"Antiviral Resistance and the Future Landscape of Hepatitis C Virus Infection Therapy","volume":"207","author":"Wyles","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Khan, H.U., Khan, S., Shah, M.A., Attaullah, S., and Malik, M.A. (2020). Pre-existing resistance associated polymorphisms to NS3 protease inhibitors in treatment na\u00efve HCV positive Pakistani patients. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0231480"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e20180237","DOI":"10.1590\/1678-4685-gmb-2018-0237","article-title":"Resistance mutations of NS3 and NS5b in treatment-na\u00efve patients infected with hepatitis C virus in Santa Catarina and Rio Grande do Sul states, Brazil","volume":"43","author":"Andrade","year":"2020","journal-title":"Genet. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1186\/1743-422X-10-355","article-title":"Naturally occurring resistance mutations to inhibitors of HCV NS5A region and NS5B polymerase in DAA treatment-na\u00efve patients","volume":"10","author":"Paolucci","year":"2013","journal-title":"Virol. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1128\/JVI.02294-12","article-title":"Hepatitis C Virus Variants with Decreased Sensitivity to Direct-Acting Antivirals (DAAs) Were Rarely Observed in DAA-Naive Patients prior to Treatment","volume":"87","author":"Bartels","year":"2013","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3851\/IMP2821","article-title":"Naturally Occurring Dominant Drug Resistance Mutations Occur Infrequently in the Setting of Recently Acquired Hepatitis C","volume":"20","author":"Applegate","year":"2015","journal-title":"Antivir. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1002\/hep.22549","article-title":"Naturally occurring dominant resistance mutations to hepatitis C virus protease and polymerase inhibitors in treatment-na\u00efve patients","volume":"48","author":"Kuntzen","year":"2008","journal-title":"Hepatology"},{"key":"ref_22","first-page":"e14248","article-title":"Prevalence of NS5B Resistance Mutations in Hepatitis C Virus (HCV) Treatment Naive South Africans","volume":"17","author":"Gededzha","year":"2017","journal-title":"Zahedan J. Res. Med Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.drup.2018.01.004","article-title":"Hepatitis C virus drug resistance associated substitutions and their clinical relevance: Update 2018","volume":"37","author":"Sorbo","year":"2018","journal-title":"Drug Resist. Updat."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Loggi, E., Galli, S., Vitale, G., Di Donato, R., Vukotic, R., Grandini, E., Margotti, M., Guarneri, V., Furlini, G., and Galli, C. (2017). Monitoring the treatment of hepatitis C with directly acting antivirals by serological and molecular methods. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0187755"},{"key":"ref_25","first-page":"97","article-title":"Primary HCV Drug Resistance Mutations in Patients with Newly Diagnosed HIV Infection","volume":"3","author":"Ostankova","year":"2020","journal-title":"Probl. Part. Danger. Infect."},{"key":"ref_26","unstructured":"(2022, February 14). Available online: https:\/\/hcv.geno2pheno.org\/index.php."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/jmv.20828","article-title":"Genetic characterization of hepatitis C virus strains in Estonia: Fluctuations in the predominating subtype with time","volume":"79","author":"Tallo","year":"2007","journal-title":"J. Med. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"64","DOI":"10.17116\/molgen20193702164","article-title":"Rekombinantnye varianty virusa gepatita S v Sibiri","volume":"37","author":"Chub","year":"2019","journal-title":"Mol. Genet. Mikrobiol. Virusologiya."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.jhep.2005.05.032","article-title":"Mutagenic effects of ribavirin and response to interferon\/ribavirin combination therapy in chronic hepatitis C","volume":"43","author":"Asahina","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"197778","DOI":"10.1016\/j.virusres.2019.197778","article-title":"A novel molecular mechanism to explain mutations of the HCV protease associated with resistance against covalently bound inhibitors","volume":"274","author":"Grotto","year":"2019","journal-title":"Virus Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S1473-3099(16)00052-9","article-title":"Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: A multicentre, open-label, randomised, phase 2 trial","volume":"16","author":"Manns","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ahmed, H.R., Waly, N.G.F.M., El-Baky, R.M.A., Yahia, R., Hetta, H.F., Elsayed, A.M., and Ibrahem, R.A. (2021). Distribution of naturally -occurring NS5B resistance-associated substitutions in Egyptian patients with chronic Hepatitis C. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0249770"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1128\/AAC.01874-12","article-title":"In Vitro Activity of Daclatasvir on Hepatitis C Virus Genotype 3 NS5A","volume":"57","author":"Wang","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","first-page":"001496","article-title":"A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir","volume":"102","author":"Campos","year":"2021","journal-title":"J. Gen. Virol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/5\/1054\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:59:11Z","timestamp":1760137151000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/5\/1054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,22]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["diagnostics12051054"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12051054","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,22]]}}}