Expression and activity of the cytochrome P450 2E1 in patients with nonalcoholic steatosis and steatohepatitis.
OBJECTIVE
Nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver (NAFL) have a different prognosis and should be dealt with differently. The pathogenesis of NASH implicates the overexpression of cytochrome P450 2E1 (CYP2E1). We investigated whether the noninvasive determination of CYP2E1 activity could replace a liver biopsy in order to differentiate NASH from NAFL.


METHODS
Forty patients referred for suspicion of NASH underwent liver biopsy. In these patients, CYP2E1 activity was determined noninvasively by the 6-hydroxychlorzoxazone/chlorzoxazone (CHZ) ratio (CHZ test). Expression of CYP2E1 on liver slides was assessed by immunohistochemistry, and immunostaining for smooth muscle actin was used to assess the activation of hepatic stellate cells (HSC).


RESULTS
Thirty patients with NASH were compared with 10 subjects with NAFL. No statistically significant difference could be identified for the clinical and biochemical parameters between the two groups. In the histology, steatosis was more important in NASH than in NAFL (P<0.0001). There was no difference either in the activity (CHZ test) or in the expression of CYP2E1 (immunohistochemistry) between patients with NASH and patients with NAFL. The degree of HSC activation was also comparable between the two groups. A positive and significant correlation was found between the activity of CYP2E1 and body mass index (P<0.001) as well as with the degree of steatosis (P=0.008).


CONCLUSIONS
For patients suspected to have NASH, noninvasive tests including the determination of the CYP2E1 activity are unable to distinguish them from patients with steatosis.
Chtioui
Haithem
H
Institute of Clinical Pharmacology, University of Bern, Bern, Switzerland.
Semela
David
D
Ledermann
Monika
M
Zimmermann
Arthur
A
Dufour
Jean-François
JF
D000328:Adult; D001706:Biopsy; D001711:Biotransformation; D002753:Chlorzoxazone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism*; D003937:Diagnosis, Differential; D005234:Fatty Liver / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006505:Hepatitis / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D006900:Hydroxylation; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011379:Prognosis
D009125:Muscle Relaxants, Central; C039289:6-hydroxychlorzoxazone; D019392:Cytochrome P-450 CYP2E1; D002753:Chlorzoxazone