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

Girardin, F; Daali, Y; Gex-Fabry, M; Rebsamen, M; Roux-Lombard, P; Cerny, A; Bihl, F; Binek, J; Moradpour, D; Negro, F; Desmeules, J; Swiss Hepatitis C Cohort Study Group, (2012). Liver kidney microsomal type 1 antibodies reduce the CYP2D6 activity in patients with chronic hepatitis C virus infection. Journal of viral hepatitis, 19(8), pp. 568-73. Oxford: Blackwell Science 10.1111/j.1365-2893.2011.01578.x

Full text not available from this repository. (Request a copy)

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology

UniBE Contributor:

Dufour, Jean-François

ISSN:

1352-0504

Publisher:

Blackwell Science

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:38

Last Modified:

17 Mar 2015 21:30

Publisher DOI:

10.1111/j.1365-2893.2011.01578.x

PubMed ID:

22762141

Web of Science ID:

000306006600006

URI:

https://boris.unibe.ch/id/eprint/15233 (FactScience: 222526)

Actions (login required)

Edit item Edit item
Provide Feedback