Genetic Contributions to Biliary Atresia: A Developmental Cholangiopathy

Abstract

Biliary atresia (BA) is the most prevalent serious liver disease of infancy and childhood, and the principal indication for liver transplantation in pediatrics. BA is best considered as an idiopathic panbiliary cholangiopathy characterized by obstruction of bile flow and consequent cholestasis presenting during fetal and perinatal periods. While a number of etiologies have been proposed, each has significant drawbacks that have limited understanding of disease progression and the development of effective treatments. Recently, modern genetic analyses have uncovered gene variants contributing to BA, thereby shifting the paradigm for explaining the BA phenotype from an acquired etiology (e.g., virus, toxin) to one that results from genetically-altered cholangiocyte development and function. Herein we review recently reported genetic contributions to BA, highlighting the enhanced representation of variants in biological pathways involving ciliary function, cytoskeletal structure, and inflammation. Finally, we blend these findings as a new framework for understanding the resultant BA phenotype as a developmental cholangiopathy.

Recent Advances in Liver Tissue Engineering as an Alternative and Complementary Approach for Liver Transplantation

“…Biliary atresia is a major disorder affecting infants and one of the diseases benefiting from liver transplantation [9]. Its etiology is due to the obstruction of bile flow leading to cholangiopathy during fetal and prenatal stages [9].…”

“…Biliary atresia is a major disorder affecting infants and one of the diseases benefiting from liver transplantation [9]. Its etiology is due to the obstruction of bile flow leading to cholangiopathy during fetal and prenatal stages [9]. Recent studies have identified the role of genetic contributions along with the previously known causes, including viral infections and toxins [9].…”