Significant liver injury generally does not occur in most oral models of ethanol intake, and there is a need to develop such models for mechanistic and preventive/therapeutic designs. A modified low carbohydrate ethanol liquid diet caused mild liver injury in rats [59,60]. A two-fold elevation in ALT levels and mild liver injury occurred in female rats fed fish oil plus ethanol orally [61]. Although CYP2E1 was elevated in these models, whether the elevated CYP2E1 played a role in the liver injury was not directly evaluated. ALT, AST and necroinflammatory scores were higher in ethanol-fed CYP2E1 KI mice compared to WT and CYP2E1 KO mice. Increases in smooth muscle actin and collagen type 1 protein were observed in the ethanol-fed KI mice which may be suggestive of an initiation of fibrosis. Perhaps longer periods of ethanol feeding in the KI mice may provide a valuable model of ethanol-induced fibrosis and stellate cell activation. CYP2E1 levels and activity were about two-fold higher in the CYP2E1 KI mice compared to the wild type mice after the ethanol feeding suggesting the elevated liver injury
