{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:32:08Z","timestamp":1791106328233,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,6,7]],"date-time":"2012-06-07T00:00:00Z","timestamp":1339027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Naturally occurring pre\u2010S deletion mutants have been identified in hepatitis B virus (<jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>)\u2010related hepatocellular carcinoma (<jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>This study investigated whether specific deletions within the pre\u2010<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content> region were associated with <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The virologic characteristics of 56 <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> chronic carriers and 112 age\u2010matched patients with <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>\u2010related <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> were examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> patients had a significantly higher frequency of high viral load, basal core promoter mutation and pre\u2010S deletion than chronic carriers. Sequencing analysis showed that the deleted regions were clustered mainly in the C terminus of pre\u2010S1 (70.5%) and the N terminus of pre\u2010S2 (72.7%) in <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> patients. Immuno\u2010epitope mapping of these pre\u2010S deletion sequences showed that all the deletion regions encompassed T\u2010 and B\u2010 cell epitopes and the B\u2010cell epitope at amino acid 1\u20136 of pre\u2010S2 was significantly deleted in <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> patients (60.0% vs. 0.0%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.036). Functional mapping of these deletion mutants showed that most of <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> patients lost one or more functional sites and the deletion of site for viral secretion (aa 1\u20135 of pre\u2010S2 domain) was significantly detected in <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> patients than chronic carriers (62.5% vs. 0.0%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.029). Computational protein function prediction indicated that these mutants may have different molecular functions and participate in other biological processes compared with wild\u2010type pre\u2010S.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Deletion of B\u2010cell epitope at amino acid 1\u20136 of pre\u2010S2 region and the site for virion secretion are significantly associated with the development of <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> carriers.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1478-3231.2012.02826.x","type":"journal-article","created":{"date-parts":[[2012,6,8]],"date-time":"2012-06-08T03:55:20Z","timestamp":1339127720000},"page":"1373-1381","source":"Crossref","is-referenced-by-count":31,"title":["Fine mapping of hepatitis B virus pre\u2010S deletion and its association with hepatocellular carcinoma"],"prefix":"10.1111","volume":"32","author":[{"given":"Jia\u2010Horng","family":"Kao","sequence":"first","affiliation":[{"name":"Division of Gastroenterology Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan"},{"name":"Graduate Institute of Clinical Medicine National Taiwan University College of Medicine Taipei Taiwan"},{"name":"Hepatitis Research Center National Taiwan University Hospital Taipei Taiwan"},{"name":"Department of Medical Research National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Jen","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guey\u2010Mei","family":"Jow","sequence":"additional","affiliation":[{"name":"School of Medicine Fu Jen Catholic University New Taipei City 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