Journal of Pediatric Gastroenterology & Nutrition:
News and Views
Professor and Vice Chair of Pediatrics
The Children's Hospital, Denver and the
University of Colorado Health Sciences Center
The National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health of the United States (NIDDK) has initiated funding of a 5-year, multicenter study of biliary atresia, neonatal hepatitis, and related neonatal liver diseases. Neonatal liver disease affects approximately 1 in 2,500 liver births. The etiology of many of these liver diseases is not known and current treatments are inadequate; therefore, these disorders account for more than 60% of all liver transplants performed in children (Studies of Pediatric Liver Transplantation Annual Report, 2002). Moreover, a poor understanding of the pathogenesis of these disorders hampers the development of improved diagnostic and therapeutic strategies. Because biliary atresia and its related disorders are relatively uncommon, no single center in North America cares for enough new patients each year to allow for intensive analysis of etiology and risk factors or to critically assess novel means of diagnosis or treatment. Therefore, in 2001, the NIH issued a request for applications to establish a clinical research consortium that would establish and maintain the infrastructure for accruing sufficient numbers of biliary atresia and neonatal hepatitis patients to perform adequately powered studies. The overall goal of this consortium is to gather clinical and biochemical data and adequate numbers of serum, tissue, and DNA samples in a prospective manner to facilitate research and generate new hypotheses and test existing hypotheses on the pathogenesis and optimal diagnostic and treatment modalities of these disorders. It is also hoped that the establishment of this consortium and the serum and tissue bank will stimulate other scientists to develop an interest in investigating the etiology and pathogenesis of these disorders and collaborate with the consortium, with serum and tissue being made available for appropriate studies.
In September 2002, the NIDDK announced the nine clinical centers chosen through competitive review for this collaborative effort. Those centers include the following principal investigators and institutions: Barbara Haber of Children's Hospital of Philadelphia, David Perlmutter of Children's Hospital of Pittsburgh, Peter Whitington of Children's Memorial Hospital in Chicago, Jorge Bezerra of Cincinnati Children's Hospital and Medical Center, Kathleen Schwarz of Johns Hopkins Hospital, Benjamin Shneider of Mount Sinai Hospital of NYC, Ross Shepherd of St. Louis Children's Hospital/Washington University, Phillip Rosenthal of University of California at San Francisco, and Ronald Sokol of University of Colorado/The Children's Hospital of Denver. The Data Coordinating Center will be located at the University of Michigan in Ann Arbor under the direction of Morton Brown. This network will be funded through a cooperative NIH agreement grant (U01), in which substantial NIH scientific or programmatic involvement is expected to support and stimulate the productivity of the research consortium. During the first year of this grant award, the Steering Committee (composed of all Clinical Center Principal Investigators, the Data Coordinating Center PI, and the NIDDK Project Officer, Pat Robuck) will be developing and implementing a clinical database and the collection of tissue, serum, and DNA specimens, and developing and initiating clinical studies. The Chair of the Steering Committee is Ronald Sokol, MD, of Denver; the co-chair is Ross Shepherd, MD, of St. Louis. Funding of this consortium is being provided by the National Institute of Diabetes, Digestive and Kidney Diseases and the Office of Rare Disorders.
The initiation of this Clinical Research Network for biliary atresia and neonatal liver diseases should be viewed as an accomplishment for the pediatric gastroenterology and hepatology communities. Hopefully other NIH requests for proposals and program announcements specifically targeted at pediatric GI disorders will follow. Suggested research areas of focus have been published in the “Pediatric Gastroenterology and Nutrition Research Agenda” of NASPGHAN and the Children's Digestive Health and Nutrition Foundation and the “Pediatric Liver Research Agenda” of the American Liver Foundation (endorsed by NASPGHAN), both published this year as supplements to The Journal of Pediatric Gastroenterology and Nutrition. Now that this new biliary atresia research network is in place, a large body of collaborative work remains to be done to achieve the objectives of the network and to improve the health and lives of children afflicted with biliary atresia and related disorders.