{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:28:30Z","timestamp":1791178110400,"version":"4.1.0"},"reference-count":45,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2013,5,7]],"date-time":"2013-05-07T00:00:00Z","timestamp":1367884800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Infection"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:p>The treatment of hepatitis C virus (HCV) infection with pegylated interferon alpha and ribavirin leads to a sustained virologic response in around 50% of patients with HCV genotype 1, 65% with HCV genotype 4, 75% with HCV genotype 3 and around 80% with HCV genotype 2. A better understanding of the HCV lifecycle has resulted in the development of several potential direct-acting antiviral drugs (DAAs) targeting viral proteins [NS3\/4A protease inhibitors, NS5B nucleos(t)idic and non-nucleos(t)idic polymerase inhibitors, NS5A replication complex inhibitors]. This review summarizes the main clinical data for the combinations of oral DAAs. DAAs, either in combination with pegylated interferon alpha or in interferon-free regimens, have demonstrated a high level of antiviral efficacy and a generally well-tolerated safety profile in treatment-na\u00efve patients and in prior nonresponders to pegylated interferon alpha\/ribavirin. Oral combination of new DAAs is likely to become the standard of care for chronic HCV in treatment-na\u00efve or treatment-experienced patients. However, most studies so far have included small numbers of \u2018easy-to-treat\u2019 patients with short post-treatment periods for defining the sustained virologic response. Extension of the number of treated patients (including \u2018difficult-to-treat\u2019 patients, i.e. patients infected with genotype 3, who failed to respond to first-generation protease inhibitors or with cirrhosis as well as immunocompromised patients) and of the post-treatment follow up in a real-life setting could significantly worsen the rate of recovery. In these \u2018difficult-to-treat\u2019 patients, the rate of virologic cure with new DAAs could be lower than expected and consequently interferons may be still necessary in combination with the new drugs.<\/jats:p>","DOI":"10.1177\/2049936113488359","type":"journal-article","created":{"date-parts":[[2013,5,8]],"date-time":"2013-05-08T00:08:04Z","timestamp":1367971684000},"page":"107-116","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Oral antiviral therapies for chronic hepatitis C infection"],"prefix":"10.1177","volume":"1","author":[{"given":"Stanislas","family":"Pol","sequence":"first","affiliation":[{"name":"Unit\u00e9 d\u2019H\u00e9patologie, H\u00f4pital Cochin, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Corouge","sequence":"additional","affiliation":[{"name":"Unit\u00e9 d\u2019H\u00e9patologie, H\u00f4pital Cochin, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Sogni","sequence":"additional","affiliation":[{"name":"Unit\u00e9 d\u2019H\u00e9patologie, H\u00f4pital Cochin, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2013,5,7]]},"reference":[{"key":"bibr1-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009482"},{"key":"bibr2-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(11)61197-5"},{"key":"bibr3-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02701.x"},{"key":"bibr4-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.10.027"},{"key":"bibr5-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2008.05.008"},{"key":"bibr6-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.08.006"},{"key":"bibr7-2049936113488359","doi-asserted-by":"crossref","unstructured":"Coelmont, L., Hanoulle, X., Chatterji, U., Berger, C., Snoeck, J., Bobardt, M. (2010). DEB025 (Alisporivir) inhibits hepatitis C virus replication by preventing a cyclophilin A induced cis-trans isomerisation in domain II of NS5A.\n                      PLoS One\n                      . 5: e13687.","DOI":"10.1371\/journal.pone.0013687"},{"key":"bibr8-2049936113488359","first-page":"378A","volume":"54","author":"Dieterich D.","year":"2011","journal-title":"Hepatology"},{"key":"bibr9-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2010.0078"},{"key":"bibr10-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.02.023"},{"key":"bibr11-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.16.9.1345"},{"key":"bibr12-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.05.046"},{"key":"bibr13-2049936113488359","first-page":"1429A","volume":"54","author":"Fried M.","year":"2011","journal-title":"Hepatology"},{"key":"bibr14-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61384-0"},{"key":"bibr15-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1208953"},{"key":"bibr16-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1038\/nature08960"},{"key":"bibr17-2049936113488359","doi-asserted-by":"crossref","unstructured":"Gish, R.G., Meanwell, N.A. (2011) The NS5A replication complex inhibitors: difference makers?\n                      Clin Liver Dis\n                      15: 627\u2013639.","DOI":"10.1016\/j.cld.2011.05.010"},{"key":"bibr18-2049936113488359","doi-asserted-by":"crossref","unstructured":"Hezode, C., Dorival, C., Zoulim, F., Poynard, T., Mathurin, P., Pol, S.\n                      et\u00a0al.\n                      (2012a) Safety of telaprevir or boceprevir in combination with peginterferon alpha\/ribavirin, in cirrhotic non responders. First results of the French early access program (ANRS C020-CUPIC).\n                      J Hepatol\n                      56(Suppl. 2): S4.","DOI":"10.1016\/S0168-8278(12)60022-1"},{"key":"bibr19-2049936113488359","first-page":"553A","volume":"56","author":"Hezode C.","year":"2012","journal-title":"Hepatology"},{"key":"bibr20-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1012912"},{"key":"bibr21-2049936113488359","doi-asserted-by":"crossref","unstructured":"Kowdley, K., Lawitz, E., Crespo, I., Hassanein, T., Davis, M., DeMicco, M.\n                      et\u00a0al\n                      . (2013) Sofosbuvir, an NS5 nucleotide polymerase inhibitor, with peginterferon alpha-2a and ribavirin in treatment-na\u00efve patients with hepatitis C genotypes 1, 4, and 6 infection (ATOMIC): an open-label, randomised, multicentre, phase 2 trial.\n                      Lancet Infect Dis.\n                      DOI: 10.1016\/S0140-6736(13)60247-0.","DOI":"10.1016\/S0140-6736(13)60247-0"},{"key":"bibr22-2049936113488359","doi-asserted-by":"crossref","first-page":"abstract LB","DOI":"10.1002\/hep.24804","volume":"56","author":"Kowdley K.","year":"2012","journal-title":"Hepatology"},{"key":"bibr23-2049936113488359","doi-asserted-by":"crossref","unstructured":"Lenz, O., Fevery, B., Vijgen, L., Verbeeck, J., Peeters, M., Beumont-Mauviel, M.\n                      et\u00a0al.\n                      (2012) TMC435 in patients infected with HCV genotype 1 who have failed previous pegylated interferon\/ribavirin treatment: virological analysis of the ASPIRE trial.\n                      J Hepatol\n                      56(Suppl. 2): S5.","DOI":"10.1016\/S0168-8278(12)60023-3"},{"key":"bibr24-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.10.028"},{"key":"bibr25-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1104430"},{"key":"bibr26-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25743"},{"key":"bibr27-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1645"},{"key":"bibr28-2049936113488359","doi-asserted-by":"crossref","unstructured":"Pawlotsky, J.M., Chevaliez, S., McHutchison, J.G. (2007) The hepatitis C virus life cycle as a target for new antiviral therapies.\n                      Gastroenterology\n                      132: 1979\u201398.","DOI":"10.1053\/j.gastro.2007.03.116"},{"key":"bibr29-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(12)61217-3"},{"key":"bibr30-2049936113488359","doi-asserted-by":"publisher","DOI":"10.4155\/cli.12.158"},{"key":"bibr31-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70138-X"},{"key":"bibr32-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1208809"},{"key":"bibr33-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1010494"},{"key":"bibr34-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31824f5506"},{"key":"bibr35-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(12)61219-7"},{"key":"bibr36-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(12)60010-5"},{"key":"bibr37-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(12)61431-7"},{"key":"bibr38-2049936113488359","doi-asserted-by":"crossref","unstructured":"Sulkowski, M., Asselah, T., Lalezari, J., Ferenci, P., Fainboim, H., Legett, B.\n                      et\u00a0al.\n                      (2013) Faldaprevir combined with peginterferon alpha-2a and ribavirin in treatment na\u00efve patients with chronic genotype-1 HCV: SILEN-C1 trial.\n                      Hepatology.\n                      DOI: 10.1002\/hep.26276.","DOI":"10.1002\/hep.26276"},{"key":"bibr39-2049936113488359","first-page":"abstract LB","volume":"56","author":"Sulkowski M.","year":"2012","journal-title":"Hepatology"},{"key":"bibr40-2049936113488359","first-page":"S560","volume":"56","author":"Sulkowski M.","year":"2012","journal-title":"J Hepatol"},{"key":"bibr41-2049936113488359","doi-asserted-by":"crossref","first-page":"1441A","DOI":"10.1002\/hep.24481","volume":"54","author":"Suzuki F.","year":"2011","journal-title":"Hepatology"},{"key":"bibr42-2049936113488359","doi-asserted-by":"crossref","unstructured":"Tellinghuisen, T.L., Marcotrigiano, J., Rice, C.M. (2005) Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase.\n                      Nature\n                      435: 374\u2013379.","DOI":"10.1038\/nature03580"},{"key":"bibr43-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2011.10.019"},{"key":"bibr44-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1013086"},{"key":"bibr45-2049936113488359","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.08.051"}],"container-title":["Therapeutic Advances in Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/2049936113488359","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/2049936113488359","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/2049936113488359","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:56:49Z","timestamp":1777593409000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/2049936113488359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,7]]},"references-count":45,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,6]]}},"alternative-id":["10.1177\/2049936113488359"],"URL":"https:\/\/doi.org\/10.1177\/2049936113488359","relation":{},"ISSN":["2049-9361","2049-937X"],"issn-type":[{"value":"2049-9361","type":"print"},{"value":"2049-937X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,7]]}}}