{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:59:12Z","timestamp":1784807952947,"version":"3.55.0"},"reference-count":24,"publisher":"American Physiological Society","issue":"2","funder":[{"name":"European Union's 2020 Framework Programme","award":["668031"],"award-info":[{"award-number":["668031"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union's Horizon 2020 Societal Challenges","award":["731875"],"award-info":[{"award-number":["731875"]}]},{"name":"Cellex Foundation (PREDICT)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:p> Metabolic and alcoholic liver injuries result in nonalcoholic (NAFLD) or alcoholic (ALD) fatty liver disease, respectively. In particular, presence of fibrosis in NAFLD and ALD requires treatment, but development of drugs is hampered by the lack of suitable models with significant fibrosis. The carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) liver fibrosis model does not reflect human NAFLD or ALD, but CCl<jats:sub>4<\/jats:sub> may serve as a fibrosis accelerator in addition to another injury. Ethanol in drinking water (16%) or Western diet (WD) were administered for 7 wk in mice either alone or in combination with CCl<jats:sub>4<\/jats:sub> intoxications. Extent of fibrosis, steatosis, and inflammation was assessed by histology, transcription, and biochemistry. Furthermore, transcription of fibrosis, proliferation, and inflammation-related genes was studied on human liver samples with fibrosis resulting from hepatitis C virus infection ( n = 7), NAFLD ( n = 8), or ALD ( n = 7). WD or ethanol alone induced only mild steatosis and inflammation. Combination of CCl<jats:sub>4<\/jats:sub> and WD induced the most severe steatosis together with significant liver fibrosis and moderate inflammation. Combination of CCl<jats:sub>4<\/jats:sub> and ethanol induced the strongest inflammation, with significant liver fibrosis and moderate steatosis. The relationship pattern between fibrosis, proliferation, and inflammation of human ALD was mostly similar in mice treated with CCl<jats:sub>4<\/jats:sub> and ethanol. The combination of CCl<jats:sub>4<\/jats:sub> intoxication with WD validates previous data suggesting it as an appropriate model for human nonalcoholic steatohepatitis. Especially, CCl<jats:sub>4<\/jats:sub> plus ethanol for 7 wk induces ALD in mice, providing a model suitable for further basic research and drug testing. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Alcoholic fatty liver disease with significant fibrosis is generated within 7 wk using carbon tetrachloride as a fibrosis accelerator and administering gradually ethanol (up to 16%) in mice. The similarity in the pattern of steatosis, inflammation, and fibrosis involved in alcoholic fatty liver disease to those of the human condition renders this mouse model suitable as a preclinical model for drug development. <\/jats:p>","DOI":"10.1152\/ajpgi.00361.2018","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T14:17:31Z","timestamp":1560349051000},"page":"G182-G194","source":"Crossref","is-referenced-by-count":55,"title":["Combination of CCl<sub>4<\/sub> with alcoholic and metabolic injuries mimics human liver fibrosis"],"prefix":"10.1152","volume":"317","author":[{"given":"Maximilian Joseph","family":"Brol","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, University of Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicitas","family":"R\u00f6sch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University of Bonn, 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