Sequential production of fatty liver, hepatitis, and cirrhosis in sub-human primates fed ethanol with adequate diets.
This study reproduces in experimental animals the sequential development of all the liver lesions seen in the human alcoholic: in 15 baboons fed ethanol, all developed fatty liver, five progressed to hepatitis, and five had cirrhosis. Maintenance of a nutritionally adequate regimen despite the intake of inebriating amounts of ethanol (50% of total calories) was achieved by incorporation of the ethanol in a totally liquid diet. Upon ethanol withdrawal, signs of physical dependence, such as seizures and tremors, developed. Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis) and differed from the alterations produced by choline and protein defiencies. At the fatty liver stage, some "adaptive" increases in activity of microsomal enzymes [aniline hydroxylase (EC 1.14.14.1) and the microsomal ethanol oxidizing system] were observed, but these tended to disappear with the development of hepatitis and cirrhosis. Fat accumulation was also much more pronounced in the animals with the hepatitis as compared with those with simple fatty liver (an 18-fold compared with 3- to 4-fold increase in liver triglycerides). The demonstration that these lesions can develop despite an adequate diet indicates that in addition to correction of the nutritional status, control of alcohol intake is mandatory for the management of patients with alcoholic liver injury.
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000473:pathology; D004032:Diet; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005234:Fatty Liver / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000473:pathology; D008930:Mitochondria, Liver / Q000648:ultrastructure; D010215:Papio
D000431:Ethanol