Z Gastroenterol 2012; 50 - P1_19
DOI: 10.1055/s-0031-1295749

Hepatic cytochrome P–4502E1 induction correlates significantly with the degree of steatosis, inflammation, fibrosis and exocyclic etheno DNA-adducts in patients with alcoholic steatohepatitis (ASH) and non-alcoholic fatty liver disease (NAFLD)

Q Hua 1, K Glassen 1, R Waldherr 1, G Millonig 1, S Mueller 1, HK Seitz 1
  • 1Abteilung für Innere Medizin, Krankenhaus Salem, Universität Heidelberg, Heidelberg

It has been shown that cytochrome P402E1 (CYP2E1) is induced in alcoholic liver disease (ALD)1 and in non-alcoholic fatty liver disease (NAFLD)2. Hepatic CYP2E1 is responsible for the generation of reactive oxygen species (ROS) which may stimulate fibrogenesis and carcinogenesis since hepatic CYP2E1 correlates significantly with highly carcinogenic exocyclic etheno DNA-adducts (edA) 3. In experimental ALD inhibition of CYP2E1 by chlormethiazole (CMZ), a strong CYP2E1 inhibitor prevents ALD partially4 and inhibits carcinogenesis. The purpose of this study was to further investigate the role of CYP2E1 in patients with ASH and NAFLD not only with respect to carcinogenesis, but also to prove whether CYP2E1 has an effect on hepatic steatosis and fibrosis. To study this, 60 patients with ASH and 39 patients with NAFLD were biopsied and the degree of hepatic fat, fibrosis, and inflammation was evaluated according to a scoring system5. In addition, CYP2E, 4-hydroxynonenal (4HNE), and edA were determined immunohistologically. A significant correlation was found between CYP2E1, hepatic steatosis (r=0.24; p=0.017), inflammation (r=0.203; p=0.044), fibrosis (r=0.251; p=0.012) and edA (r=0.219; r=0.05). There was also a significant correlation between edA and 4HNE (r=0.260; p=0.021), between edA and fibrosis (r=0.314; p=0.005), and between fibrosis and ethanol intake (r=0.386; p=0.0001). These data emphasize a causal role of CYP2E1 in progression of ALD. They also show that the generation of highly carcinogenic etheno DNA-adducts is due to 4HNE produced via CYP2E1.

Literatur: 1. Wang et al, Hepatology 2009;50:453 2. Weltman et al, Hepatology 1998;27:128 3. Wang et al, Hepatology 2009;50:453 4. Gouillon et al, Proc Soc Biol Med 2000;224:302 5. Kleinert et al, Hepatology 2005;41:1313

4HNE - ALD - CYP2E1