{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:32:21Z","timestamp":1789651941034,"version":"4.0.0"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T00:00:00Z","timestamp":1537920000000},"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","award":["15K19345"],"award-info":[{"award-number":["15K19345"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>It remains unclear whether there is an association between single\u2010nucleotide polymorphisms (SNPs) and development of hepatocellular carcinoma (HCC) during entecavir (ETV) treatment in nucleos(t)ide analog\u2010na\u00efve patients with chronic hepatitis B virus infection. We investigated the risk factors for HCC, especially host factors, during ETV treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 127 Japanese patients undergoing ETV treatment were enrolled in this study. Univariate and multivariate analyses for clinical factors, hepatic fibrosis markers, and SNPs associated with HCC development were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 10 patients developed HCC during the follow\u2010up period (median duration, 3.3\u00a0years). The 3\u2010, 5\u2010, and 7\u2010year cumulative rates of HCC development were 4.8%, 10.6%, and 13.6%, respectively. Liver fibrosis (cirrhosis; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0005), age (\u2265\u00a049\u00a0years; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0048), platelet count (\u2264\u00a0115\u00a0\u00d7\u00a010\/mm<jats:sup>3<\/jats:sup>; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0007), \u03b1\u2010fetoprotein (\u2265\u00a08.0\u00a0ng\/mL; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.030), type IV collagen (\u2265\u00a0200\u00a0ng\/mL; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.043), fibrosis\u20104 index (\u2265\u00a04.14; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0006), and <jats:italic>human leukocyte antigen (HLA)\u2010DQA1\/DRB1<\/jats:italic>\u2010SNP (AA genotype; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0092) were significantly associated with HCC development according to the log\u2010rank test. In multivariate analysis, AA genotype in the <jats:italic>HLA\u2010DQA1\/DRB1<\/jats:italic> gene (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.013; hazard ratio 4.907; 95% confidence interval 1.407\u201317.113) and cirrhosis (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.019; hazard ratio 4.789; 95% confidence interval 1.296\u201317.689) were significantly associated with HCC development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggested that patients with AA genotype in the <jats:italic>HLA\u2010DQA1\/DRB1<\/jats:italic> gene or cirrhosis should be carefully followed up as a population potentially at higher risk of HCC during ETV treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.14454","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T18:30:36Z","timestamp":1535653836000},"page":"937-946","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Association between <i>HLA\u2010DQA1\/DRB1<\/i> polymorphism and development of hepatocellular carcinoma during entecavir treatment"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0763-6760","authenticated-orcid":false,"given":"Ritsuzo","family":"Kozuka","sequence":"first","affiliation":[{"name":"Department of Hepatology Osaka City University Graduate School of Medicine  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Enomoto","sequence":"additional","affiliation":[{"name":"Department of Hepatology Osaka City University Graduate School of Medicine  Osaka 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