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

Details

Serval ID
serval:BIB_8CD86952BD69
Type
Article: article from journal or magazin.
Collection
Publications
Title
Liver kidney microsomal type 1 antibodies reduce the CYP2D6 activity in patients with chronic hepatitis C virus infection.
Journal
Journal of Viral Hepatitis
Author(s)
Girardin F., Daali Y., Gex-Fabry M., Rebsamen M., Roux-Lombard P., Cerny A., Bihl F., Binek J., Moradpour D., Negro F., Desmeules J.
Working group(s)
Swiss Hepatitis C Cohort Study Group
Contributor(s)
Negro F., Hadengue A., Kaiser L., Rubbia-Brandt L., Moradpour D., Burgisser P., Francioli P., Rickenbach M., Martinetti G., Cerny A., Gorgievski M., Dufour JF., Hirsch H., Heim M., Helbling B., Mullhaupt B., Regenass S., Malinverni R., Gerlach T., Dollenmaier G., Cathomas G.
ISSN
1365-2893 (Electronic)
ISSN-L
1352-0504
Publication state
Published
Issued date
2012
Volume
19
Number
8
Pages
568-573
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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, Cytochrome P-450 CYP2D6/metabolism, Dextromethorphan/metabolism, Dextrorphan/metabolism, Female, Genotype, Hepatitis C, Chronic/pathology, Humans, Male, Middle Aged, Switzerland
Pubmed
Web of science
Create date
29/07/2012 15:05
Last modification date
20/08/2019 15:51
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