Carcinogenic Etheno DNA Adducts in Alcoholic Liver Disease: Correlation with Cytochrome P‐4502E1 and Fibrosis

Background One mechanism by which alcoholic liver disease (ALD) progresses is oxidative stress and the generation of reactive oxygen species, among others due to the induction of cytochrome P‐4502E1 (CYP2E1). Experimental data underline the key role of CYP2E1 because ALD could be partially prevented in rats by the administration of the specific CYP2E1 inhibitor chlormethiazole. As CYP2E1 is linked to the formation of carcinogenic etheno DNA adducts in ALD patients, a causal role of alcohol‐induced CYP2E1 in hepatocarcinogenesis is implicated. The purpose of this study was to investigate CYP2E1 induction in ALD, and its correlation with oxidative DNA lesions and with hepatic histology. Methods Hepatic biopsies from 97 patients diagnosed with ALD were histologically scored for steatosis, inflammation, and fibrosis. CYP2E1 and the exocyclic etheno DNA adduct 1,N6‐etheno‐2′deoxyadenosine (εdA) were determined immunohistochemically. In addition, in 42 patients, 8‐hydroxydeoxyguanosine (8‐OHdG) was also evaluated using immunohistochemistry. Results A significant positive correlation was found between CYP2E1 and εdA (p