Biliary atresia and the other cholestatic liver diseases of childhood are important causes of pediatric liver disease. Encouraged by the significance of the research of the current BARC and CLiC consortia, the NIDDK is creating ChiLDREN, a new consortium that will replace BARC and CLiC and expand the number of research sites. Dr. Murray and her research team propose to establish a Clinical Center in Seattle as part of ChiLDREN. This Clinical Center brings together the patients of the Northwest and Alaska, investigators experienced in pediatric liver disease research and the BARC trials, the diagnosis and management of childhood cholestatic diseases, the only pediatric liver transplant center in the Northwest, and the resources of Seattle Children's and the University of Washington. The scope of the patient population, coupled with the richness of the clinical programs and experience of the investigators of this Seattle Clinical Center;assure that this research team will successfully enroll a large number of children with biliary atresia and other cholestatic liver diseases into the network's longitudinal natural history and database studies, the biliary atresia corticosteroid treatment trial, and future ancillary and pilot studies. The ability to train the next generation of pediatric liver disease researchers and contribute to the scientific understanding of the diseases via the clinical and laboratory research expertise relevant to biliary atresia at Seattle Children's, assure the contributions by the Clinical Center to forwarding the understanding of these conditions. Dr. Murray plans to establish the ChiLDREN Clinical Center in Seattle, and continue the currently approved longitudinal and treatment studies of the current BARC and CLiC Networks (Specific Aim 1). She has included a proposal for a pilot/feasibility study (Specific Aim 2) evaluating maternal microchimerism in biliary atresia and the resultant allogeneic peripheral immune response as a possible pathogenic etiology underlying this condition. Dr. Murray has also proposed training opportunities unique to the Seattle Clinical Center to help educate and train the pediatric liver disease researchers of the future (Specific Aim 3). Relevance: Biliary atresia and the other childhood cholestatic liver diseases are important causes of chronic liver disease in children, and the leading cause for liver transplantation. The initial funding period for the two relevant clinical research networks has been successful, however, expansion of the work is necessary. This next funding period will expand the currently ongoing research of natural history, genetics, and treatment, and explore answers to new questions relevant to these conditions.
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