Genetic architecture of primary sclerosing cholangitis: shared pathways with inflammatory bowel disease and gut–liver axis mediation

This study delineates PSC's genetic architecture by identifying novel causal genes and confirms the gut-liver axis's central role in its pathogenesis. We propose an integrated "dual-hit" model where host genetic susceptibility constitutes the "first hit" and subsequent gut dysbiosis acts as a "second hit." These findings offer novel therapeutic targets and a mechanistic framework with potential implications for patient management in liver transplantation.