Recent Advances in Primary Sclerosing Cholangitis Pathogenesis and Targets for Therapeutic Intervention

Description

Presenters in this session expound on the current understanding of the pathogenesis, diagnosis, and treatment of primary sclerosing cholangitis (PSC). Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease leading to biliary fibrosis and cirrhosis. The etiology of PSC remains unclear. Recent studies demonstrate that senescence of ductular reactive cells and epithelial cells exacerbate cholestatic liver injury and activate fibrogenic myofibroblasts. With the development of new technologies such as single cell/nucleus RNA sequencing, the complexity of liver cell interactions and immunological responses are being characterized. Specific changes in farnesoid X receptor and Takeda G protein-coupled receptor 5 (TGR5) expression in cholangiocytes critically contribute to the pathogenesis of PSC. Treatment with nor-ursodeoxycholic acid (norUDCA) and nonsteroidal farnesoid X receptor agonist (cilofexor) are being tested in phase 3 clinical trials to assess improvement of liver function in patients with PSC. Novel strategies such as targeting myeloid cells or hepatic myofibroblasts are being developed to prevent/revert cholestatic fibrosis.