{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:28:33Z","timestamp":1791260913148,"version":"4.1.0"},"reference-count":83,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2015,12,18]],"date-time":"2015-12-18T00:00:00Z","timestamp":1450396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3\/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.<\/jats:p>","DOI":"10.3390\/v7122968","type":"journal-article","created":{"date-parts":[[2015,12,18]],"date-time":"2015-12-18T10:15:04Z","timestamp":1450433704000},"page":"6716-6729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals"],"prefix":"10.3390","volume":"7","author":[{"given":"Asma","family":"Ahmed","sequence":"first","affiliation":[{"name":"Plymouth University, Peninsula School of Medicine and Dentistry, Plymouth PL6 8BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Felmlee","sequence":"additional","affiliation":[{"name":"Plymouth University, Peninsula School of Medicine and Dentistry, Plymouth PL6 8BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1002\/hep.26141","article-title":"Global epidemiology of hepatitis C virus infection: New estimates of age-specific antibody to HCV seroprevalence","volume":"57","author":"Groeger","year":"2013","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/hep.27259","article-title":"Global distribution and prevalence of hepatitis C virus genotypes","volume":"61","author":"Messina","year":"2015","journal-title":"Hepatology"},{"key":"ref_3","unstructured":"World Health Organisation Hepatitis C. 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