{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:42:44Z","timestamp":1791362564944,"version":"4.3.1"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T00:00:00Z","timestamp":1543881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"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":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human alcoholic hepatitis (AH) carries a high mortality rate. AH is an acute-on-chronic form of liver injury characterized by hepatic steatosis, ballooned hepatocytes, neutrophil infiltration, and pericellular fibrosis. We aimed to study the pathogenesis of AH in an animal model which combines chronic hepatic fibrosis with intragastric alcohol administration. Adult male C57BL6\/J mice were treated with CCl4 (0.2\u2009ml\/kg, 2\u00d7weekly by intraperitoneal injections for 6\u2009weeks) to induce chronic liver fibrosis. Then, ethyl alcohol (up to 25\u2009g\/kg\/day for 3\u2009weeks) was administered continuously to mice via a gastric feeding tube, with or without one-half dose of CCl4. Liver and serum markers and liver transcriptome were evaluated to characterize acute-on-chronic-alcoholic liver disease in our model. CCl4 or alcohol treatment alone induced liver fibrosis or steatohepatitis, respectively, findings that were consistent with expected pathology. Combined treatment resulted in a marked exacerbation of liver injury, as evident by the development of inflammation, steatosis, and pericellular fibrosis, pathological features of human AH. E. coli and Candida were also detected in livers of mice cotreated with CCl4 and alcohol, indicating pathogen translocation from gut to liver, similar to human AH. Importantly, liver transcriptomic changes specific to combined treatment group demonstrated close concordance with pathways perturbed in patients with severe AH. Overall, mice treated with CCl4 and alcohol displayed key molecular and pathological characteristics of human AH\u2014pericellular fibrosis, increased hepatic bacterial load, and dysregulation of the same molecular pathways. This model may be useful for developing therapeutics for AH.<\/jats:p>","DOI":"10.1093\/toxsci\/kfy292","type":"journal-article","created":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T15:17:45Z","timestamp":1543504665000},"page":"427-437","source":"Crossref","is-referenced-by-count":26,"title":["Histopathological and Molecular Signatures of a Mouse Model of Acute-on-Chronic Alcoholic Liver Injury Demonstrate Concordance With Human Alcoholic Hepatitis"],"prefix":"10.1093","volume":"170","author":[{"given":"Shinji","family":"Furuya","sequence":"first","affiliation":[{"name":"Department of Veterinary Integrative Biosciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A","family":"Cichocki","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kranti","family":"Konganti","sequence":"additional","affiliation":[{"name":"Texas A&M Institute for Genome Sciences and Society, Texas A&M University, College Station, Texas 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kostiantyn","family":"Dreval","sequence":"additional","affiliation":[{"name":"Program in Cancer Genetics, Epigenetics and Genomics, Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico 87102"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeki","family":"Uehara","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuuki","family":"Katou","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisataka","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kono","sequence":"additional","affiliation":[{"name":"First Department of Surgery, University of Yamanashi, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor P","family":"Pogribny","sequence":"additional","affiliation":[{"name":"National Center for Toxicological Research, U.S. FDA, Jefferson, Arkansas 72079"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josepmaria","family":"Argemi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Bataller","sequence":"additional","affiliation":[{"name":"Department of Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Rusyn","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,12,4]]},"reference":[{"key":"2020071622051017800_kfy292-B1","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1136\/gutjnl-2011-301146","article-title":"Transcriptome analysis identifies TNF superfamily receptors as potential therapeutic targets in alcoholic hepatitis","volume":"62","author":"Affo","year":"2013","journal-title":"Gut"},{"key":"2020071622051017800_kfy292-B2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.cgh.2011.09.011","article-title":"Acute kidney injury is an early predictor of mortality for patients with alcoholic hepatitis","volume":"10","author":"Altamirano","year":"2012","journal-title":"Clin. 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