{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:10:20Z","timestamp":1792807820674,"version":"4.5.0"},"reference-count":39,"publisher":"BMJ","issue":"2","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Gut"],"accepted":{"date-parts":[[2016,9,28]]},"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The clinical significance of polymorphisms in the interleukin-28B gene encoding interferon (IFN)-\u03bb3, which has antiviral effects, is known in chronic HCV but not in HBV infection. Thus, we measured IFN-\u03bb3 levels in patients with HBV and investigated its clinical significance and association with nucleos(t)ide (NUC) analogue administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Serum IFN-\u03bb3 level was measured in 254 patients with HBV with varying clinical conditions using our own high sensitivity method. The resulting values were compared with various clinical variables. In addition, cell lines originating from various organs were cultured with NUCs, and the production of IFN-\u03bb3 was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Higher serum IFN-\u03bb3 levels were detected in the patients treated with nucleotide analogues (adefovir or tenofovir) compared with those treated with nucleoside analogues (lamivudine or entecavir). There were no other differences in the clinical background between the two groups. A rise in the serum IFN-\u03bb3 levels was observed during additional administration of the nucleotide analogues. In vitro experiments showed that the nucleotide analogues directly and dose-dependently induced IFN-\u03bb3 production only in colon cancer cells. Furthermore, the supernatant from cultured adefovir-treated colon cancer cells significantly induced IFN-stimulated genes (ISGs) and inhibited hepatitis B surface antigen (HBsAg) production in hepatoma cells, as compared with the supernatant from entecavir-treated cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We discovered that the nucleotide analogues show an additional pharmacological effect by inducing IFN-\u03bb3 production, which further induces ISGs and results in a reduction of HBsAg production. These findings provide novel insights for HBV treatment and suggest IFN-\u03bb3 induction as a possible target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gutjnl-2016-312653","type":"journal-article","created":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T22:43:37Z","timestamp":1477608217000},"page":"362-371","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":171,"title":["Induction of IFN-\u03bb3 as an additional effect of nucleotide, not nucleoside, analogues: a new potential target for HBV infection"],"prefix":"10.1136","volume":"67","author":[{"given":"Kazumoto","family":"Murata","sequence":"first","affiliation":[{"name":"The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Asano","sequence":"additional","affiliation":[{"name":"The Research Center for Hepatitis and 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