Document Detail

Primary biliary cirrhosis and bile acids.
MedLine Citation:
PMID:  23141888     Owner:  NLM     Status:  In-Data-Review    
The dihydroxylated bile acid ursodeoxycholic acid (UDCA) has now been regarded for 20 years as the standard treatment for primary biliary cirrhosis (PBC), a chronic cholestatic immune-mediated condition marked by progressive destruction of small intrahepatic bile ducts, impaired biliary secretion, hepatocellular retention of toxic endogenous bile acids and, ultimately, the development of fibrosis leading to cirrhosis that commonly requires liver transplantation. At first sight, it seems intriguing that a bile acid could be considered for use as a therapeutic agent in a bile-acid secretion disorder. Yet, in addition to its inherently greater hydrophilic nature and competitive effect on endogenous bileacid recycling, UDCA has indeed been demonstrated to be a potent post-transcriptional secretagogue as well as a potential anti-inflammatory and anti-apoptotic agent. While the combined glucocorticoid receptor/pregnane X receptor (PXR) agonist budesonide, in combinaison with UDCA, has been shown to exert additional beneficial effects in PBC, significant progress in understanding the regulatory mechanisms involved in bile-acid homeostasis has led to the identification of nuclear [farnesoid X receptor (FXR), PXR, peroxisome proliferator-activated receptor alpha (PPARα)] and membrane (the membrane G protein-coupled bile acid receptor TGR5) receptors as critical pharmacological targets for future therapeutic approaches. Encouraging data from recent experimental and phase-II studies tend to confirm that the FXR agonist obeticholic acid and the PPARα agonists bezafibrate and fenofibrate may be used as add-on therapies in PBC patients with inadequate responses to UDCA or even as alternative first-line agents. These results could mark the beginning of a new therapeutic era for PBC.
Christophe Corpechot
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinics and research in hepatology and gastroenterology     Volume:  36 Suppl 1     ISSN:  2210-741X     ISO Abbreviation:  Clin Res Hepatol Gastroenterol     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-11-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101553659     Medline TA:  Clin Res Hepatol Gastroenterol     Country:  France    
Other Details:
Languages:  eng     Pagination:  S13-20     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Service d'Hépatologie, Centre de référence des maladies inflammatoires des voies biliaires, Hôpital Saint-Antoine, 184 rue du Faubourg-Saint-Antoine, 75571 Paris cedex 12, France. Electronic address:
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