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Liver kidney microsomal type 1 antibodies reduce the CYP2D6 activity in patients with chronic hepatitis C virus infection.
MedLine Citation:
PMID:  22762141     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Summary.  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.
Authors:
F Girardin; Y Daali; M Gex-Fabry; M Rebsamen; P Roux-Lombard; A Cerny; F Bihl; J Binek; D Moradpour; F Negro; J Desmeules;
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-26
Journal Detail:
Title:  Journal of viral hepatitis     Volume:  19     ISSN:  1365-2893     ISO Abbreviation:  -     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-7-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9435672     Medline TA:  J Viral Hepat     Country:  -    
Other Details:
Languages:  ENG     Pagination:  568-573     Citation Subset:  -    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
Affiliation:
Division of Clinical Pharmacology and Toxicology, University of Geneva, University Hospitals of Geneva, Switzerland Division of Primary Care, Department of Community Medicine, University Hospitals of Geneva, Switzerland Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland Division of Laboratory Medicine, University Hospitals of Geneva, Switzerland Division of Immunology and Allergy, University Hospitals of Geneva, Switzerland Liver Unit, Clinica Luganese Moncuco, Lugano, Switzerland Division of Gastroenterology and Hepatology, University Hospitals of Geneva, Switzerland Gastroenterology and Hepatology Unit, Ospedale San Giovanni, Bellinzona, Switzerland Gastroenterology Unit, Department of Internal Medicine, Kantonsspital, St. Gallen, Switzerland Division of Gastroenterology and Hepatology, University Hospital Centre, University of Lausanne, Lausanne, Switzerland Division of Clinical Pathology, University Hospitals of Geneva, Switzerland.
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