Primary sclerosing cholangitis (PSC): Current concepts in biology and strategies for new therapy

Abstract

Primary sclerosing cholangitis (PSC) is characterised morphologically by fibroinflammatory stricture formation and typified phenotypically by strong clinical association with inflammatory bowel disease. Although rare, PSC harbours a significant and disproportionate clinical need, in which 50% of patients develop advancing disease necessitating transplantation. These unacceptably poor outcomes highlight a critical therapeutic shortfall in hepatology, whereby no existing intervention has been shown to improve transplant-free survival. The clinical course in PSC can be unpredictable; and advances in clinical practice highlight the breadth of disease heterogeneity, that exists, whilst equally providing a more individualised assessment of patient risk. These developments are paralleled by notable pathological discovery, wherein recognition of enteric dysbiosis, essential lymphocyte recruitment pathways, and mucosal immunogenicity have driven a resurgence in clinical trial activity for appropriately stratified patient populations.