Centrilobular distribution of acetaldehyde and collagen in the ethanol-fed micropig.

We established a new animal model of alcoholic liver disease in the micropig, a species that consumes ethanol voluntarily in the diet. Ten micropigs were pair-fed diets containing 40% of calories as ethanol or cornstarch with identical amounts of fat, protein and micronutrients for 12 mo. Liver histopathology in the ethanol-fed pigs included steatonecrosis in all five and interstitial and perivenous fibrosis in three. Electron microscopy showed Ito-cell transformation with perisinusoidal collagen accumulation. Acetaldehyde adducts were found by immunofluorescence in the centrilobular region and were focused in perivenous zone 3 of all ethanol-fed animals. Protein and triglyceride levels were increased, whereas vitamin A and iron levels were decreased in liver homogenates from ethanol-fed animals. Thus, in this new animal model of alcoholism, ethanol feeding produced the features of alcoholic liver disease concurrent with hepatic deficiency of selected nutrients. Histological and immunofluorescent studies provide in vivo evidence that perivenous collagen deposition is linked to ethanol metabolism and acetaldehyde production.