{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:36:44Z","timestamp":1787319404756,"version":"build-2736575974"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T00:00:00Z","timestamp":1574899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01 AA016258"],"award-info":[{"award-number":["R01 AA016258"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["U01 AA021908"],"award-info":[{"award-number":["U01 AA021908"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alcohol\u2010related liver disease is the main cause of liver\u2010related mortality worldwide. The development of novel targeted therapies for patients with advanced forms (i.e., alcoholic hepatitis, AH) is hampered by the lack of suitable animal models. Here, we developed a novel mouse model of acute\u2010on\u2010chronic alcohol liver injury with cholestasis and fibrosis and performed an extensive molecular comparative analysis with human AH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>For the mouse model of acute\u2010on\u2010chronic liver injury, we used 3,5\u2010diethoxycarbonyl\u20101,4\u2010dihydrocollidine (DDC, 0.05% w\/w) diet for 8\u00a0weeks to establish cholestatic liver fibrosis. After 1\u2010week washout period, male mice were fed intragastrically for 4\u00a0weeks with up to 24\u00a0g\/kg of ethyl alcohol in a high\u2010fat diet. This animal model was phenotyped using histopathology, clinical chemistry, microbiome, and gene expression approaches. Data were compared to the phenotypes of human alcohol\u2010related liver disease, including AH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mice with cholestatic liver fibrosis and subsequent alcohol exposure (DDC\u00a0+\u00a0EtOH) exhibited exacerbated liver fibrosis with a pericellular pattern, increased neutrophil infiltration, and ductular proliferation, all characteristics of human AH. DDC administration had no effect on urine alcohol concentration or liver steatosis. Importantly, DDC\u2010 and alcohol\u2010treated mice showed a transcriptomic signature that resembled that of patients with AH. Finally, we show that mice in the DDC\u00a0+\u00a0EtOH group had an increased gut barrier dysfunction, mimicking an important pathophysiological mechanism of human AH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We developed a novel mouse model of acute\u2010on\u2010chronic cholestatic alcoholic liver injury that has considerable translational potential and can be used to test novel therapeutic modalities for AH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.14234","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:17Z","timestamp":1573430417000},"page":"87-101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A Novel Mouse Model of Acute\u2010on\u2010Chronic Cholestatic Alcoholic Liver Disease: A Systems Biology Comparison With Human Alcoholic Hepatitis"],"prefix":"10.1111","volume":"44","author":[{"given":"Shinji","family":"Furuya","sequence":"first","affiliation":[{"name":"From the  Department of Veterinary Integrative Biosciences (SF, IR) Texas A&amp;M University College Station Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josepmaria","family":"Argemi","sequence":"additional","affiliation":[{"name":"Center for Liver Diseases (JA, RB) Pittsburgh Research Center University of Pittsburgh Medical Center Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeki","family":"Uehara","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology (TU, YK) Osaka Prefecture University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuuki","family":"Katou","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology (TU, YK) Osaka Prefecture University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick E.","family":"Fouts","sequence":"additional","affiliation":[{"name":"J. 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