Published online Jul 6, 2019. doi: 10.12998/wjcc.v7.i13.1571
Peer-review started: January 10, 2019
First decision: January 30, 2019
Revised: June 5, 2019
Accepted: June 10, 2019
Article in press: June 10, 2019
Published online: July 6, 2019
Recently the field of cholestasis has expanded enormously reflecting an improved understanding of the molecular mechanisms underlying bile secretion and its perturbation in chronic cholestatic disease. Novel anti-cholestatic therapeutic options have been developed for patients not favorably responding to ursodeoxycholic acid (UDCA), the current standard treatment for cholestatic liver disease. Important novel treatment targets now also include nuclear receptors involved in bile acid (BA) homoeostasis like farnesoid X receptor and G protein-coupled receptors e.g., the G-protein-coupled BA receptor “transmembrane G coupled receptor 5”. Fibroblast growth factor-19 and enterohepatic BA transporters also deserve attention as additional drug targets as does the potential treatment agent norUDCA. In this review, we discuss recent and future promising therapeutic agents and their potential molecular mechanisms in cholestatic liver disorders.
Core tip: Anti-cholestatic therapeutic options now go beyond ursodeoxycholic acid (UDCA) and target nuclear receptors regulating bile acid (farnesoid X receptor) and G protein-coupled receptor and fibroblast growth factor-19. Additionally, enterohepatic bile acid transporters and norUDCA represent potential targets in cholestatic disease.