Relationship between fatty liver and subsequent development of necrosis, inflammation and fibrosis in experimental alcoholic liver disease.

Rats fed a diet varying in the amount of fat, infused with ethanol, were studied to determine the relationship among diet, degree of fatty liver, and development of necrosis, inflammation, and fibrosis. Three groups of experimental animals, male Wistar rats, were fed diets containing 25% fat, 35% fat, and 32% fat with low protein. Morphologic assessment of liver injury was performed monthly by obtaining liver biopsies. The greatest degree of fatty infiltration at 1 month was seen in the high fat-low protein group, the mean fat score (3.8 +/- 0.37) was significantly higher than in the other two groups (P less than 0.05 and P less than 0.01). When the subsequent development of necrosis, inflammation, and fibrosis was related to the degree of fatty infiltration at 1 month, a significant relationship was seen between the number of animals developing these pathologic lesions and the severity of fatty liver. Our results show that the degree of fatty infiltration of the liver, influenced by the dietary intake of both fat and protein, is related to the subsequent development of necrosis, inflammation, and fibrosis in our intragastric feeding model for alcoholic liver disease.