Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Gastroenterology & Hepatology, PBC, PSC, cholestasis, second-line therapy, FXR, OCA, PPAR, PRIMARY SCLEROSING CHOLANGITIS, DOSE URSODEOXYCHOLIC ACID, TRANSPORTER INHIBITOR GSK2330672, PLACEBO-CONTROLLED TRIAL, SURROGATE END-POINTS, DOUBLE-BLIND, BILE-ACIDS, NUCLEAR RECEPTORS, OBETICHOLIC ACID, 24-NORURSODEOXYCHOLIC ACID, Humans, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Cholestasis, Receptors, Cytoplasmic and Nuclear, Membrane Transport Proteins, Cholestatic liver disease, second line therapy, 1103 Clinical Sciences, 1117 Public Health and Health Services, 3202 Clinical sciences

Abstract:

The discovery of nuclear receptors and transporters has contributed to the development of new drugs for the treatment of cholestatic liver diseases. Particular progress has been made in the development of second-line therapies for PBC. These new drugs can be separated into compounds primarily targeting cholestasis, molecules targeting fibrogenesis and molecules with immune-mediated action. Finally, drugs aimed at symptom relief (pruritus and fatigue) are also under investigation. Obeticholic acid is currently the only approved second-line therapy for PBC. Drugs in the late phase of clinical development include peroxisome proliferator-activated receptor agonists, norursodeoxycholic acid and NADPH oxidase 1/4 inhibitors.