Pathology of Progressive Familial Intrahepatic Cholestasis: An update

Abstract

Progressive familial intrahepatic cholestasis (PFIC) comprises a heterogeneous group of rare, autosomal recessive liver disorders characterised by defective bile formation and secretion, leading to progressive cholestasis, pruritus, growth impairment, and early onset liver failure. Advances in molecular genetics have identified distinct causative pathogenic variants involving key hepatocellular transporters of bile salts, and phospholipids, giving rise to multiple PFIC subtypes. Early recognition is crucial, as timely medical management and surgical interventions may delay disease progression, while liver transplantation remains the definitive therapy for advanced cases. Through this comprehensive review, we seek to strengthen pathologists understanding of the disease by outlining its morphomolecular and immunohistochemical features, together with the subtleties and diagnostic hallmarks critical for accurate diagnosis.