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

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Serval ID
serval:BIB_E5D4FC978C7C
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
J Viral Hepat
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
ISSN
1365-2893 (Electronic)
ISSN-L
1352-0504
Publication state
Published
Issued date
08/2012
Volume
19
Number
8
Pages
568-73
Language
english
Notes
Girardin, F
Daali, Y
Gex-Fabry, M
Rebsamen, M
Roux-Lombard, P
Cerny, A
Bihl, F
Binek, J
Moradpour, D
Negro, F
Desmeules, J
eng
Research Support, Non-U.S. Gov't
England
J Viral Hepat. 2012 Aug;19(8):568-73. doi: 10.1111/j.1365-2893.2011.01578.x. Epub 2012 Jan 26.
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
Pubmed
Create date
10/02/2021 12:24
Last modification date
24/10/2022 13:39
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