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The growing rates of <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> may be partially attributable to increased numbers of people with non\u2010alcoholic fatty liver disease (<jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>) and non\u2010alcoholic steatohepatitis (<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>). However, details of the liver\u2010specific molecular mechanisms responsible for the <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> progression remain unclear, and mouse models that can be used to explore the exact factors that influence the progression of <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> to the more chronic stages of liver disease and subsequent <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> are not yet fully established. We have previously reported a choline\u2010deficient, L\u2010amino acid\u2010defined, high\u2010fat diet (<jats:styled-content style=\"fixed-case\">CDAHFD<\/jats:styled-content>) as a dietary <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> model with rapidly progressive liver fibrosis in mice. The current study in C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6J mice fed <jats:styled-content style=\"fixed-case\">CDAHFD<\/jats:styled-content> provided evidence for the chronic persistence of advanced hepatic fibrosis in <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> and disease progression towards <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> in a period of 36\u00a0weeks. When mice fed <jats:styled-content style=\"fixed-case\">CDAHFD<\/jats:styled-content> were switched back to a standard diet, hepatic steatosis was normalized and <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content> activity score improved, but <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> incidence increased and the phenotype of fibrosis\u2010associated <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> development was observed. Moreover, when mice continued to be fed <jats:styled-content style=\"fixed-case\">CDAHFD<\/jats:styled-content> for 60\u00a0weeks, <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> further developed without severe body weight loss or carcinogenesis in other organs. The autochthonous tumours showed a variety of histological features and architectural patterns including trabecular, pseudoglandular and solid growth. The <jats:styled-content style=\"fixed-case\">CDAHFD<\/jats:styled-content> mouse model might be a useful tool for studying the development of <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> from <jats:styled-content style=\"fixed-case\">NAFLD<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>, and potentially useful for better understanding pathological changes during hepatocarcinogenesis.<\/jats:p>","DOI":"10.1111\/iep.12240","type":"journal-article","created":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T09:02:42Z","timestamp":1505206962000},"page":"221-233","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["Hepatocellular carcinoma in a mouse model fed a choline\u2010deficient, L\u2010amino acid\u2010defined, high\u2010fat diet"],"prefix":"10.1111","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0072-0094","authenticated-orcid":false,"given":"Ayae","family":"Ikawa\u2010Yoshida","sequence":"first","affiliation":[{"name":"Chugai Research Institute for Medical Science, Inc. Gotemba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saori","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Fuji\u2010Gotemba Research Laboratories Chugai Pharmaceutical Co., Ltd. Gotemba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuhiko","family":"Kato","sequence":"additional","affiliation":[{"name":"Fuji\u2010Gotemba Research Laboratories Chugai Pharmaceutical Co., Ltd. Gotemba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Ohmori","sequence":"additional","affiliation":[{"name":"Fuji\u2010Gotemba Research Laboratories Chugai Pharmaceutical Co., Ltd. Gotemba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Higashida","sequence":"additional","affiliation":[{"name":"Chugai Research Institute for Medical Science, Inc. 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