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Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid.
MedLine Citation:
PMID:  22911624     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Bezafibrate is a widely used hypolipidemic agent and is known as a ligand of the peroxisome proliferator-activated receptors (PPARs). Recently this agent has come to be recognized as a potential anticholestatic medicine for the treatment of primary biliary cirrhosis (PBC) that does not respond sufficiently to ursodeoxycholic acid (UDCA) monotherapy. The aim of this study was to explore the anticholestatic mechanisms of bezafibrate by analyzing serum lipid biomarkers in PBC patients and by cell-based enzymatic and gene expression assays. Nineteen patients with early-stage PBC and an incomplete biochemical response to UDCA (600 mg/day) monotherapy were treated with the same dose of UDCA plus bezafibrate (400 mg/day) for 3 months. In addition to the significant improvement of serum biliary enzymes, IgM, cholesterol and triglyceride concentrations in patients treated with bezafibrate, reduction of 7α-hydroxy-4-cholesten-3-one (C4), a marker of bile acid synthesis, and increase of 4β-hydroxycholesterol, a marker of CYP3A4/5 activity, were observed. In vitro experiments using human hepatoma cell lines demonstrated that bezafibrate controlled the target genes of PPARα, as well as those of the pregnane X receptor (PXR); downregulating CYP7A1, CYP27A1 and sinusoidal Na(+) /taurocholate cotransporting polypeptide (NTCP), and upregulating CYP3A4, canalicular multidrug resistance protein 3 (MDR3), MDR1 and multidrug resistance-associated protein 2 (MRP2). Conclusion: Bezafibrate is a dual PPARs/PXR agonist with potent anticholestatic efficacy in early-stage PBC patients with an incomplete biochemical response to UDCA monotherapy. (HEPATOLOGY 2012.).
Authors:
Akira Honda; Tadashi Ikegami; Makoto Nakamuta; Teruo Miyazaki; Junichi Iwamoto; Takeshi Hirayama; Yoshifumi Saito; Hajime Takikawa; Michio Imawari; Yasushi Matsuzaki
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-22
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  -     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 American Association for the Study of Liver Diseases.
Affiliation:
Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki, Japan; Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki, Japan.
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