In this application we propose the development at Children's Hospital of Pittsburgh (CHP) of a Clinical Center as a part of the NIDDK-sponsored Biliary Atresia Clinical Research Consortium. CHP is the only tertiary pediatric medical center in Western Pennsylvania and has played a pioneering role in the development of liver transplantation for children for well over two decades. The program has cared for more than 60 patients with biliary atresia (BA) and more than 125 patients with neonatal hepatitis over the last five years. The proposal will utilize the resources available from the NIH-funded Pediatric G-CRC at CHP, the Starzl Transplantation Institute, the Office of Clinical Research within the School of Medicine of the University of Pittsburgh (Pitt), as well as, the extensive expertise for conducting collaborative clinical research programs within the School of Public Health at Pitt. We will examine the hypothesis that BA is the phenotype of several underlying disorders by proposing a large-scale database to identify subgroups within a rigorously characterized population of BA patients. Second, we propose a short-term project to screen for mutations in the human orthologue of the human inv gene in a subgroup of patients with BA who also have anomalies of visceral organ situs determination. This project has the potential to identify a genetic mechanism for abnormal morphogenesis of the hepatobiliary system and a diagnostic marker for a subgroup of BA patients. Third, we propose a longer-term project using gene chip analysis of several novel model systems to identify hepatic genes for which expression is specifically altered in BA. This third project is designed to identify new diagnostic and/or prognostic markers and to provide leads for further basic research on the pathobiology of BA.