Role of the Ito cell in liver parenchymal fibrosis in rats fed alcohol and a high fat-low protein diet.

Eight pairs of young adult rats were pair-fed a high fat-low protein diet and ethanol or isocaloric glucose by permanent intragastric cannula for up to 6 months. Biopsies of the liver were taken monthly and the fibrosis was quantitated morphometrically using the sirius red polarization method of collagen visualization by light microscopy. Morphometric analysis of the sinusoids and scars were performed on electron micrographs made from the liver biopsies. An increase in the collagen in both the central and portal areas was found when the livers of the alcohol-fed rats were compared with controls. The predominant cell in the scars was the Ito cell. An increase in the percentage of the total Ito cell square area made up of rough endoplasmic reticulum (RER) was noted when the sinusoids of the liver of the ethanol-fed rats were compared with controls. No difference in the RER was found when the sinusoidal Ito cells were compared with the Ito cells located within the scars of the ethanol-fed rats. It was concluded that Ito cell "activation" by chronic ethanol feeding in the sinusoids of rats accurately predicts "activation" of the Ito cells within scars. The Ito cells are diffusely activated even though the scarring is localized. This implies that local factors as well as Ito cell activation are necessary for scar formation. In the case of alcoholic liver disease, scar formation may be initiated by centrilobular necrosis.