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Early-phase alcoholic liver disease: An update on animal models, pathology, and pathogenesis

Journal

INTERNATIONAL JOURNAL OF TOXICOLOGY
Volume 23, Issue 4, Pages 217-231

Publisher

SAGE PUBLICATIONS INC
DOI: 10.1080/10915810490502069

Keywords

alcoholic hepatitis; alcoholic liver disease; animal models; cirrhosis; CYP2E1; endotoxin; fatty liver; fibrosis; Kupffer cells; Lieber-DeCarli liquid diet; LPS; neutrophils; osteopontin; steatohepatitis

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Alcoholic liver disease (ALD) remains to be one of the most common etiology of liver disease and is a major cause of morbidity and mortality worldwide. The pathologic stages of ALD comprises of steatosis, steatohepatitis, and fibrosis/cirrhosis. Steatosis and steatohepatitis represents the early phase of ALD and are precursor stages for fibrosis/cirrhosis. Numerous research efforts have been directed at recognizing cofactors interacting with alcohol in the pathogenesis of steatosis and steatohepatitis. This review will elucidate the constellation of complex pathogenesis, available animal models, and microscopic pathologic findings mostly in the early-phase of ALD. The role of endotoxin, reactive oxygen species, alcohol metabolism, and cytokines are discussed. Understanding the mechanisms of early-phase ALD should provide insight into the development of therapeutic strategies and thereby decrease the morbidity and mortality associated with ALD.

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