Bile Acids in Cholestasis and its Treatment

Abstract

Bile acids (BA) are key molecules in generating bile flow, which is an essential function of the liver. In the last decades there have been great advances in the understanding of the role of a number of specific transport proteins present at the sinusoidal and canalic-ular membrane domains of hepatocytes and cholangiocytes in generating and maintaining bile flow. Also, a clearer understanding on how BA regulate their own synthesis and the expression and/or function of transporters has been reached. This new knowledge has helped to better delineate the pathophysiology of cholestasis and the adaptive responses of hepatocytes to cholestatic liver injury as well as of the mechanisms of injury of biliary epithelia. In this context, therapeutic approaches including the use of new hydrophilic BA such as the conjugation-resistant nor- ursodeoxycholic acid, nuclear receptor (FXR, PPAR-alpha) agonists, FGF19 analogues, inhibitors of the apical sodium-depend bile acid transporter (ASBT) and modulators of the inflammatory cascade triggered by BA are being studied as novel treatments of cholestasis. In the present review we summarize recent experimental and clinical data on the role of BA in cholestasis and its treatment.

Keywords: Bile acids; Bile flow; Cell injury; Cholestasis; Inflammation; Innate immunity; Liver diseases; Neutrophils; Signaling.