Primary biliary cholangitis as a roadmap for the development of novel treatments of cholestatic liver diseases.

The discovery of nuclear receptors and transporters has contribute to the development of new drugs for the treatment of cholestatic liver diseases. Especially progress has been made in the second line therapy of PBC. These new drugs can be separated into compounds primarily targeting cholestasis, molecules targeting fibrogenesis and molecules with immune-mediated action. Finally, also drugs aimed at symptom relief ( pruritus and fatigue) are further under investigation. Obeticholic acid is currently the only approved second line therapy for PBC. Drugs in the late phase of clinical development are the PPAR agonists, NorUDCA and the NOX 1&4 inhibitors.