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While interferon therapy is problematic in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> cirrhosis, the era of direct\u2010acting anti\u2010viral (<jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content>) therapy provides effective treatment for patients with cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To systematically review the results of <jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content> therapy to date in patients with <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> cirrhosis, and highlight the ongoing challenges for <jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content> therapy in this population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A structured Medline search was conducted to obtain phase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">III HCV<\/jats:styled-content> trials in patients with cirrhosis. Citations from review articles were cross\u2010referenced and conference abstracts from <jats:styled-content style=\"fixed-case\">EASL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AASLD<\/jats:styled-content> liver meetings for the preceding 3 years were reviewed manually. Keywords used included hepatitis C, cirrhosis and the <jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content>'s: sofosbuvir, ledipasvir, velpatasvir, grazoprevir, elbasvir, daclatasvir, beclabuvir, asunaprevir, simeprevir, paritaprevir, ombitasvir and dasabuvir.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Successful direct\u2010acting anti\u2010viral treatment is now possible in patients with <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010related cirrhosis including those with liver decompensation with several regimens now offering sustained virological response (<jats:styled-content style=\"fixed-case\">SVR<\/jats:styled-content>) of 90\u201395%. Overall success rates in <jats:styled-content style=\"fixed-case\">GT<\/jats:styled-content>1 cirrhosis are excellent while <jats:styled-content style=\"fixed-case\">GT<\/jats:styled-content>3\u2010infected patients with cirrhosis remain hard to cure. The pangenotypic combination of sofosbuvir and velpatasvir holds promise for <jats:styled-content style=\"fixed-case\">GT<\/jats:styled-content>3 cirrhosis achieving <jats:styled-content style=\"fixed-case\">SVR<\/jats:styled-content> of ~90%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Potent <jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content> therapies provide much needed, safe and highly effective treatment options for persons with <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> cirrhosis including those previously deemed unsuitable for treatment. Combination therapy with two or more classes of drug is essential to achieve high efficacy and minimise viral resistance, with the role of ribavirin still under evaluation. However, several challenges remain including the hard\u2010to\u2010cure groups of <jats:styled-content style=\"fixed-case\">GT<\/jats:styled-content>3 cirrhosis and direct\u2010acting anti\u2010viral failures, and managing drug\u2013drug interactions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.13633","type":"journal-article","created":{"date-parts":[[2016,4,18]],"date-time":"2016-04-18T10:44:37Z","timestamp":1460976277000},"page":"1276-1292","source":"Crossref","is-referenced-by-count":118,"title":["Systematic review: current concepts and challenges for the direct\u2010acting antiviral era in hepatitis C cirrhosis"],"prefix":"10.1111","volume":"43","author":[{"given":"A.","family":"Majumdar","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Alfred Hospital Melbourne Vic. 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