title: Alcoholic disease: liver and beyond.
abstract: The harmful use of alcohol is a worldwide problem. It has been estimated that alcohol abuse represents the world's third largest risk factor for disease and disability; it is a causal factor of 60 types of diseases and injuries and a concurrent cause of at least 200 others. Liver is the main organ responsible for metabolizing ethanol, thus it has been considered for long time the major victim of the harmful use of alcohol. Ethanol and its bioactive products, acetaldehyde-acetate, fatty acid ethanol esters, ethanol-protein adducts, have been regarded as hepatotoxins that directly and indirectly exert their toxic effect on the liver. A similar mechanism has been postulated for the alcohol-related pancreatic damage. Alcohol and its metabolites directly injure acinar cells and elicit stellate cells to produce and deposit extracellular matrix thus triggering the "necrosis-fibrosis" sequence that finally leads to atrophy and fibrosis, morphological hallmarks of alcoholic chronic pancreatitis. Even if less attention has been paid to the upper and lower gastrointestinal tract, ethanol produces harmful effects by inducing: (1) direct damaging of the mucosa of the esophagus and stomach; (2) modification of the sphincterial pressure and impairment of motility; and (3) alteration of gastric acid output. In the intestine, ethanol can damage the intestinal mucosa directly or indirectly by altering the resident microflora and impairing the mucosal immune system. Notably, disruption of the intestinal mucosal barrier of the small and large intestine contribute to liver damage. This review summarizes the most clinically relevant alcohol-related diseases of the digestive tract focusing on the pathogenic mechanisms by which ethanol damages liver, pancreas and gastrointestinal tract.
authors.affiliation: Alba Rocco, Debora Compare, Debora Angrisani, Marco Sanduzzi Zamparelli, Gerardo Nardone, Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy.
authors.forename: Alba
authors.initials: A
authors.lastname: Rocco
authors.affiliation: Alba Rocco, Debora Compare, Debora Angrisani, Marco Sanduzzi Zamparelli, Gerardo Nardone, Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Compare
authors.affiliation: Alba Rocco, Debora Compare, Debora Angrisani, Marco Sanduzzi Zamparelli, Gerardo Nardone, Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Angrisani
authors.affiliation: Alba Rocco, Debora Compare, Debora Angrisani, Marco Sanduzzi Zamparelli, Gerardo Nardone, Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sanduzzi Zamparelli
authors.affiliation: Alba Rocco, Debora Compare, Debora Angrisani, Marco Sanduzzi Zamparelli, Gerardo Nardone, Gastroenterology Unit, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Nardone
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects* / Q000378:metabolism; D000437:Alcoholism / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D018450:Disease Progression; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010182:Pancreatic Diseases / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000431:Ethanol
keywords: Alcohol and gastrointestinal tract; Alcoholic liver disease; Alcoholic pancreatitis