Abstract
Primary sclerosing cholangitis (PSC) is a rare, progressive cholestatic disease of
unknown etiology and characterized by inflammation and stricturing of intrahepatic
and/or extrahepatic bile ducts. This process leads to bile duct scarring, progressive
liver fibrosis, and end-stage liver disease. PSC is often associated with a specific
form of inflammatory bowel disease and patients face a significant risk of developing
cholangiocarcinoma and colorectal cancer. The clinical course of PSC can differ significantly
between subtypes and affected individuals, representing a major obstacle to successful
medical treatment trials. Numerous innovative therapeutic targets have been identified
and, at least in part, explored, including nuclear and membrane receptors regulating
bile acid metabolism and transport, modulation of gut microbiota, and signaling molecules
involved in liver inflammation and fibrosis. Successful drug testing in preclinical
PSC models as well as positive signals from some clinical studies justify hope. However,
no medical treatment has so far been proven to improve transplant-free survival or
overall survival in PSC patients. Disease-modifying drugs are urgently awaited. Despite
ongoing efforts to improve study designs and implement treatment trials for novel
drug targets, a central breakthrough has not yet been convincingly achieved. This
situation might change in the near future. This article summarizes current research
efforts aimed at developing medical treatments for PSC.
Keywords
primary sclerosing cholangitis - treatment - NCA - UDCA - FXR
