en
Scientific article
English

Liver kidney microsomal type 1 antibodies reduce the CYP2D6 activity in patients with chronic hepatitis C virus infection

Published inJournal of viral hepatitis, vol. 19, no. 8, p. 568-573
Publication date2012
Abstract

Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease the CYP2D6 activity in vitro and are present in a minority of patients with chronic hepatitis C infection. We investigated whether LKM-1 antibodies might reduce the CYP2D6 activity in vivo. All patients enrolled in the Swiss Hepatitis C Cohort Study and tested for LKM-1 antibodies were assessed (n = 1723): 10 eligible patients were matched with patients without LKM-1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specific substrate using the dextromethorphan/dextrorphan metabolic ratio to classify patients into four activity phenotypes. All patients had a CYP2D6 extensive metabolizer genotype. The observed phenotype was concordant with the CYP2D6 genotype in most LKM-negative patients, whereas only three LKM-1 positive patients had a concordant phenotype (six presented an intermediate and one a poor metabolizer phenotype). The median DEM/DOR ratio was sixfold higher in LKM-1 positive than in LKM-1 negative patients (0.096 vs. 0.016, P = 0.004), indicating that CYP2D6 metabolic function was significantly reduced in the presence of LKM-1 antibodies. In chronic hepatitis C patients with LKM-1 antibodies, the CYP2D6 metabolic activity was on average reduced by 80%. The impact of LKM-1 antibodies on CYP2D6-mediated drug metabolism pathways warrants further translational studies.

Keywords
  • Adult
  • Aged
  • Autoantibodies/immunology
  • Cohort Studies
  • Cytochrome P-450 CYP2D6/genetics/metabolism
  • Dextromethorphan/metabolism
  • Dextrorphan/metabolism
  • Female
  • Genotype
  • Hepatitis C, Chronic/pathology
  • Humans
  • Male
  • Middle Aged
  • Switzerland
Citation (ISO format)
GIRARDIN, François et al. Liver kidney microsomal type 1 antibodies reduce the CYP2D6 activity in patients with chronic hepatitis C virus infection. In: Journal of viral hepatitis, 2012, vol. 19, n° 8, p. 568–573. doi: 10.1111/j.1365-2893.2011.01578.x
Main files (1)
Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1352-0504
570views
0downloads

Technical informations

Creation03/12/2013 4:20:00 PM
First validation03/12/2013 4:20:00 PM
Update time03/14/2023 8:05:15 PM
Status update03/14/2023 8:05:14 PM
Last indexation01/16/2024 1:20:03 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack