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New therapeutic concepts in bile acid transport and signaling for management of cholestasis
Author(s) -
Trauner Michael,
Fuchs Claudia Daniela,
Halilbasic Emina,
Paumgartner Gustav
Publication year - 2017
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.28991
Subject(s) - enterohepatic circulation , cholestasis , bile acid , fgf19 , farnesoid x receptor , hepatology , ursodeoxycholic acid , medicine , bile salt export pump , g protein coupled bile acid receptor , pharmacology , transporter , chemistry , receptor , endocrinology , biochemistry , fibroblast growth factor , nuclear receptor , transcription factor , gene
The identification of the key regulators of bile acid (BA) synthesis and transport within the enterohepatic circulation has revealed potential targets for pharmacological therapies of cholestatic liver diseases. Novel drug targets include the bile BA receptors, farnesoid X receptor and TGR5, the BA‐induced gut hormones, fibroblast growth factor 19 and glucagon‐like peptide 1, and the BA transport systems, apical sodium‐dependent bile acid transporter and Na + ‐taurocholate cotransporting polypeptide, within the enterohepatic circulation. Moreover, BA derivatives undergoing cholehepatic shunting may allow improved targeting to the bile ducts. This review focuses on the pathophysiological basis, mechanisms of action, and clinical development of novel pharmacological strategies targeting BA transport and signaling in cholestatic liver diseases. (H epatology 2017;65:1393‐1404).