Recent developments in alcoholism:the liver.
The past decade has witnessed major gains in our understanding of the pathogenesis and therapy of alcoholic liver disease. The molecular biology of alcohol-metabolizing enzymes is well understood. Older concepts of liver injury, e.g., hypermetabolism, generation of free radicals, mitochondrial and microtubular dysfunction, and impairment of liver regeneration by ethanol, have been studied in greater detail. The fibrotic response to alcoholic liver injury has been explored, revealing complex interrelationships between the nonparenchymal cells of the liver and showing the importance of cytokines in regulating these cells. New mechanisms of injury have been appreciated, most prominently the association between hepatitis C infection and alcoholic liver disease, and the formation of protein-acetaldehyde adducts in the liver of alcohol-fed subjects. A new animal model of alcoholic liver injury, the alcohol infusion rat model developed by French and Tsukomoto, promises to provide a relatively simple model for researchers. The clinical management of alcoholic liver disease continues to evolve. Focal fatty change is recognized as a variant of alcoholic fatty liver. Nonalcoholic steatohepatitis has been described as a mimic of alcoholic liver disease, and may provide insight into the mechanisms of perivenular liver injury. The presence of perivenular fibrosis may predict at an early stage which patients are at risk for serious liver injury. Nutritional and corticosteroid therapy of alcoholic hepatitis are now established. Other therapies such as propylthiouracil, glucagon plus insulin infusion, and colchicine have been studied in large trials. Alcoholic liver disease can now be treated in selected cases by liver transplantation.
Crabb
D W
DW
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202.
D000426:Alcohol Dehydrogenase / Q000502:physiology; D000428:Alcohol Drinking / Q000009:adverse effects / Q000503:physiopathology; D000444:Aldehyde Dehydrogenase / Q000502:physiology; D000818:Animals; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D000431:Ethanol / Q000493:pharmacokinetics; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008104:Liver Cirrhosis, Alcoholic / Q000503:physiopathology / Q000534:rehabilitation; D008108:Liver Diseases, Alcoholic / Q000503:physiopathology* / Q000534:rehabilitation; D010089:Oxidoreductases, N-Demethylating / Q000502:physiology
D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D000444:Aldehyde Dehydrogenase; D010089:Oxidoreductases, N-Demethylating