Serum ALT and AST levels were elevated less than two-fold by ethanol in the WT mice and a similar increase was found with the KO mice (Fig. 2A,2B). Serum ALT and AST levels were increased about four- five-fold by ethanol in the KI mice, an increase greater than the increase by ethanol in the WT or KO mice. Histopathology observation revealed the expected presence of steatosis in the ethanol-fed WT mice but little or no indication for necrosis (Fig. 3A,3B). Steatosis was much lower and necrosis was not observed in the ethanol-fed KO mice. However, both necrosis and steatosis were found with the ethanol-fed KI mice; areas with cell swelling, focus necrosis and inflammatory infiltration were observed (Fig. 3A,3B). Necroinflammation scores were elevated only for the ethanol-fed KI mice (Fig. 2C). No changes in the activity of caspases 3 or 9 nor TUNEL staining were found in the ethanol-fed KI mice compared to dextrose controls (data not shown) suggesting necrotic but not apoptotic liver injury was occurring under these conditions.
