Genetics of Biliary Atresia: A Work in Progress for a Disease with an Unavoidable Sequela into Liver Cirrhosis following Failure of Hepatic Portoenterostomy

The bile duct development may not be fully completed at birth, and this is quite a common event. Moreover, bile formation is immature, and there is a propensity for the neonate to develop cholestasis in the presence of a wide variety of insults that can damage the liver. A biliary atresia is a correctable form of infantile cholangiopathies. The Kasai hepatic portoenterostomy (HPE) is often performed and is successful if it is done at an early stage. However, HPE can fail, and the liver fate is inevitably a cirrhotic change. Biliary atresia is heterogeneous and may result from a combination of genetic factors, vascular, infective or toxic insults with activation of different genetic and immunological pathways. In this chapter, we will review some genes that may be highly relevant to biliary atresia, including not only PKHD1, JAG1, and CFTR, but also GPC1, ADD3 and others. Four genetic loci are considered as predisposition loci in biliary atresia, despite the absence of an etiologic mutation. The rare occurrence of biliary atresia in well-known genetic syndromes seems to suggest coincidental finding, but epigenetic aspects might play a significant role in contributing to the increase of biliary atresia rate.