Albeit each is relatively rare, congenital cholestatic liver diseases collectively impact pediatric health significantly. Amongst them, biliary atresia (BA) is the most common cause of pediatric end-stage liver disease and the leading indication for pediatric liver transplantation. The Childhood Liver Disease Research Network (ChiLDReN) was established in 2009 to expand the scope of the Biliary Atresia Research Consortium to study numerous rare congenital cholestatic liver diseases including Alagille syndrome, Progressive Familial Intrahepatic Cholestasis, a1- Antitrypsin Deficiency, Mitochodrial Hepatopathies, and Bile Salt Synthesis Defects. Since then, numerous high impact observations have been reported by the NIDDK-funded consortium. Primary Sclerosing Cholangitis is currently being added as a disease of focus by the network. The Children’s Hospital Los Angeles (CHLA) clinical research center has been very active in all aspects of the network’s efforts. In this application, we restate our commitment to improve the clinical outcomes of patients with congenital liver diseases. The overall objectives of this application are to impact survival of children with rare liver diseases via (1) the enrollment of subjects into the various clinical studies and trials within the ChiLDREN consortium and (2) a translational ancillary study focused on CoQ10, as a biomarker of liver fibrosis. The central hypothesis of objective #2 is that serum levels of CoQ10 correlate with extent of liver fibrosis. This project is innovative because (1) CHLA has the only Principal Investigator who is a pediatric surgeon, thus providing surgical insight and perspective for a Steering Committee otherwise comprised of pediatric hepatologists and (2) CoQ10 is a novel potential biomarker for liver fibrosis.

Infant and pediatric cholestatic liver diseases are rare and individual hospitals cannot accumulate sufficient experience to make meaningful scientific contributions which are the basis for the management algorithms of these diseases. ChiLDReN will continue to facilitate the accrual of larger cohorts of patients with these rare diseases. This research proposal details our continued commitment to the enrollment of subjects into the various ChiLDReN studies and a project focused on a new and potentially novel marker of liver fibrosis.