title: New therapeutic concepts in bile acid transport and signaling for management of cholestasis.
abstract: 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. (Hepatology 2017;65:1393-1404).
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria.
authors.forename: Claudia Daniela
authors.initials: CD
authors.lastname: Fuchs
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria.
authors.forename: Emina
authors.initials: E
authors.lastname: Halilbasic
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria.
authors.forename: Gustav
authors.initials: G
authors.lastname: Paumgartner
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects*; D002779:Cholestasis / Q000188:drug therapy* / Q000503:physiopathology*; D015331:Cohort Studies; D004195:Disease Models, Animal; D006801:Humans; D008102:Liver Circulation / Q000502:physiology; D012720:Severity of Illness Index; D015398:Signal Transduction; D013656:Taurocholic Acid / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001647:Bile Acids and Salts; D013656:Taurocholic Acid