Molecular Mechanisms of Progressive Familial Intrahepatic Cholestasis.

Bile secretion is dependent on the structural and functional integrity of membrane transport systems in hepatocytes and cholangiocytes. Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of disorders resulting from mutations in genes responsible for the makeup and stability of proteins critical to the bile acid transport system. Defects impair bile flow through a variety of mechanisms, including impaired expression, function, and intracellular trafficking of critical proteins, resulting in a phenotype of either primary cholestasis or cholangiopathy. Advances in genetics and pathophysiology have enabled an expansion of causative genes to be identified. Subsequently, the characterization of PFIC is moving away from the traditional numerical classification and instead differentiating by the distinct molecular pathways implicated in disease. In conclusion, this review aims to provide an update on the molecular spectrum of the PFIC phenotype.