{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:26:09Z","timestamp":1790108769733,"version":"4.0.1"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T00:00:00Z","timestamp":1488153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007416","name":"Japan Health Sciences Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007416","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec><jats:label\/><jats:p>Single nucleotide polymorphisms (SNPs) within or near <jats:italic>interferon lambda 4<\/jats:italic> (<jats:italic>IFNL4<\/jats:italic>) gene located upstream of <jats:italic>IFNL3<\/jats:italic> are associated with response to anti\u2010HCV therapy both in interferon (IFN)\u2010based and IFN\u2010free regimens. <jats:italic>IFNL4<\/jats:italic> encodes IFN\u03bb4, a newly discovered type III IFN, and its expression is controlled by rs368234815\u2010TT\/\u0394G, which is in strong linkage disequilibrium (LD) with other tag SNPs within or near <jats:italic>IFNL4<\/jats:italic> such as rs12979860 and rs8099917. Intrahepatic expression levels of IFN\u2010stimulated genes (ISGs) affect the responsiveness to IFN\u03b1 and are also associated with <jats:italic>IFNL4<\/jats:italic> genotype. However, <jats:italic>IFNL4<\/jats:italic> expressions and its role in intrinsic antiviral innate immunity remain unclear. This study evaluated the effect of <jats:italic>IFNL4<\/jats:italic> on intrahepatic ISG expression and investigated its relationship with treatment outcomes in liver samples obtained from 49 chronic hepatitis C patients treated with pegylated (PEG)\u2010IFN\/ribavirin therapy. <jats:italic>IFNL4<\/jats:italic> mRNA was detected in 11 of 22 patients with <jats:italic>IFNL4<\/jats:italic>\u2010unfavorable SNPs but not in patients with favorable genotypes. <jats:italic>IFNL4<\/jats:italic> expression was associated with non\u2010response to PEG\u2010IFN\/ribavirin therapy. Intrahepatic expression of antiviral ISGs (<jats:italic>ISG15<\/jats:italic> and <jats:italic>MX1<\/jats:italic>) was significantly higher in <jats:italic>IFNL4<\/jats:italic>\u2010unfavorable patients with detectable <jats:italic>IFNL4<\/jats:italic> mRNA than in patients with undetectable <jats:italic>IFNL4<\/jats:italic> mRNA, whereas the expression of suppressive ISGs (<jats:italic>RNF125<\/jats:italic>, <jats:italic>SOCS1<\/jats:italic>, <jats:italic>SOCS3<\/jats:italic>, and <jats:italic>RNF11<\/jats:italic>) was lower in patients with detectable <jats:italic>IFNL4<\/jats:italic> mRNA. In summary, intrahepatic expression of <jats:italic>IFNL4<\/jats:italic> was associated with increased antiviral ISG expression and decreased suppressive ISG expression at baseline, resulting in poor responsiveness to IFN\u03b1\u2010based therapy in HCV infection.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.24763","type":"journal-article","created":{"date-parts":[[2016,12,30]],"date-time":"2016-12-30T16:08:15Z","timestamp":1483114095000},"page":"1241-1247","source":"Crossref","is-referenced-by-count":11,"title":["Hepatic <i>IFNL4<\/i> expression is associated with non\u2010response to interferon\u2010based therapy through the regulation of basal interferon\u2010stimulated gene expression in chronic hepatitis C patients"],"prefix":"10.1002","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0468-4409","authenticated-orcid":false,"given":"Miyako","family":"Murakawa","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tokyo Medical and Dental University Tokyo Japan"},{"name":"Department of Clinical Laboratory, Medical Hospital Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Asahina","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tokyo Medical and Dental University Tokyo Japan"},{"name":"Department of Liver Disease Control Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fukiko","family":"Kawai\u2010Kitahata","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tokyo Medical and Dental University Tokyo 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