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This concept, albeit not novel, is becoming widely accepted by the field, and more research is directed toward identifying and characterizing the interfaces of the cross\u2010interactions to help understand individual predisposition to the disease. Another pivotal development is the begin ning of cell type\u2010specific research to elucidate specific contributions not only of hepatocytes, but also of hepatic macrophages, liver\u2010associated lymphocytes, si nusoidal endothelial cells, and hepatic stellate cells to sensitizing and priming mechanisms. In particular, the critical role of hepatic macrophages has been high lighted and the priming mechanisms concerning this paracrine effect have been proposed. Glutathione de pletion in hepatocyte mitochondria is considered the most important sensitizing mechanism. One of the contributing factors is decreased methionine metabo lism. Remaining key questions include how altered methionine metabolism contribute to the pathogenesis of ALD; how cross\u2010talk among nonparenchymal liver cells or between nonparenchymal cells and hepatocytes leads to ALD; how dysfunctional mitochondria deter mine the type of cell death in ALD; and what secondary factors are critical for the development of advanced ALD such as alcoholic hepatitis and cirrhosis.\u2014Tsukamoto, H., Lu, S. C. Current concepts in the pathogenesis of alcoholic liver injury.\n                    <jats:italic>The FASEB J.<\/jats:italic>\n                    15, 1335\u20131349 (2001)\n                  <\/jats:p>","DOI":"10.1096\/fj.00-0650rev","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:03:24Z","timestamp":1027710204000},"page":"1335-1349","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":301,"title":["Current concepts in the pathogenesis of alcoholic liver injury"],"prefix":"10.1096","volume":"15","author":[{"given":"Hidekazu","family":"Tsukamoto","sequence":"first","affiliation":[{"name":"USC\u2010UCLA Research Center for Alcoholic Liver and Pancreatic Diseases, USC Research Center for Liver Diseases Department of Pathology Keck School of Medicine of USC Los Angeles California 90033 USA"},{"name":"USC\u2010UCLA Research Center for Alcoholic Liver and Pancreatic Diseases, USC Research Center for Liver Diseases Department of Medicine Keck School of Medicine of USC Los Angeles California 90033 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelly C.","family":"Lu","sequence":"additional","affiliation":[{"name":"USC\u2010UCLA Research Center for Alcoholic Liver and Pancreatic Diseases, USC Research Center for Liver Diseases Division of Gastrointestinal and Liver Diseases Los Angeles California 90033 USA"},{"name":"USC\u2010UCLA Research Center for Alcoholic Liver and Pancreatic Diseases, USC Research Center for Liver Diseases Department of Medicine Keck School of Medicine of USC Los Angeles California 90033 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,6]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1093\/jn\/101.4.533","article-title":"Ethanol feeding and choline deficiency as influences on he patic choline uptake","volume":"101","author":"Barak A. 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