We propose to transition our membership status from the Biliary Atresia Research Consortium (BARC) and the Cholestatic Liver Consortium (CLiC) to the new Childhood Liver Disease Research and Education Network (ChiLDREN). Our proposal represents a logical extension of the long-standing commitment of our Center to improve the care of children with chronic liver disease through innovative patient-based research. We have been a charter member of BARC and CLiC since their creation in 2002 and 2004, respectively. We worked collaboratively with consortium investigators to build the infrastructure to conduct patient-based studies on biliary atresia and cholestatic syndromes. Our key contributions included data submission and analysis of two retrospective studies, leadership in the development of a clinical trial, high enrollment and retention of subjects into three prospective studies and one interventional study, completion of an ancillary study of novel molecular phenotypes of biliary atresia, completion of a pilot project on defects in bile acid synthesis, and participation in working groups and committees related to project reviews, writing of manuscripts, and development of core resources. We look forward to significantly contributing to the operation of ChiLDREN through three aims.
In Aim 1, we will combine the expertise and resources of BARC and CLiC to form ChiLDREN. This will be done by transitioning the operation of ongoing study protocols to the working structure developed by the Steering Committee and the Data Coordinating Center, develop new study protocols, and continue to enroll subjects into approved studies.
In Aim 2, we will promote specialty training, develop two core services (Bile Acid Biochemistry Core and Histopathology Core), and significantly expand access to study subjects by collaborating with investigators in the Hepatology and Liver Transplant Program at the Hospital for Sick Children, Toronto. And in Aim 3, we will use state-of-the-art molecular and cellular systems to study pathogenesis of liver disease and identify novel therapeutic targets for children with biliary atresia and cholestatic syndromes using data and tissue collected by ChiLDREN protocols. Relevance: We propose to become a member of the Childhood Liver Disease Research and Education Network and to contribute to the development of the infrastructure for clinical research in children with chronic liver disease. This infrastructure will facilitate innovative patient-based studies addressing etiology, pathogenesis, and clinical outcome of children with biliary atresia and inherited cholestatic syndromes.

Public Health Relevance

We propose to become a member of the Childhood Liver Disease Research and Education Network and to contribute to the development of the infrastructure for clinical research in children with chronic liver disease. This infrastructure will facilitate innovative patient-based studies addressing etiology, pathogenesis, and clinical outcome of children with biliary atresia and inherited cholestatic syndromes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK062497-12
Application #
8545791
Study Section
Special Emphasis Panel (ZDK1-GRB-S (M1))
Program Officer
Sherker, Averell H
Project Start
2002-09-15
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
12
Fiscal Year
2013
Total Cost
$684,456
Indirect Cost
$191,476
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Ng, Vicky Lee; Haber, Barbara H; Magee, John C et al. (2014) Medical status of 219 children with biliary atresia surviving long-term with their native livers: results from a North American multicenter consortium. J Pediatr 165:539-546.e2
Bessho, Kazuhiko; Mourya, Reena; Shivakumar, Pranavkumar et al. (2014) Gene expression signature for biliary atresia and a role for interleukin-8 in pathogenesis of experimental disease. Hepatology 60:211-23
Venkat, Veena L; Shneider, Benjamin L; Magee, John C et al. (2014) Total serum bilirubin predicts fat-soluble vitamin deficiency better than serum bile acids in infants with biliary atresia. J Pediatr Gastroenterol Nutr 59:702-7
Bezerra, Jorge A; Spino, Cathie; Magee, John C et al. (2014) Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trial. JAMA 311:1750-9
Sundaram, Shikha S; Alonso, Estella M; Haber, Barbara et al. (2013) Health related quality of life in patients with biliary atresia surviving with their native liver. J Pediatr 163:1052-7.e2
Molleston, Jean P; Sokol, Ronald J; Karnsakul, Wikrom et al. (2013) Evaluation of the child with suspected mitochondrial liver disease. J Pediatr Gastroenterol Nutr 57:269-76
Setchell, Kenneth D R; Heubi, James E; Shah, Sohela et al. (2013) Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency. Gastroenterology 144:945-955.e6; quiz e14-5
Saxena, Vijay; Shivakumar, Pranavkumar; Sabla, Gregg et al. (2011) Dendritic cells regulate natural killer cell activation and epithelial injury in experimental biliary atresia. Sci Transl Med 3:102ra94
Bessho, Kazuhiko; Bezerra, Jorge A (2011) Biliary atresia: will blocking inflammation tame the disease? Annu Rev Med 62:171-85
Superina, Riccardo; Magee, John C; Brandt, Mary L et al. (2011) The anatomic pattern of biliary atresia identified at time of Kasai hepatoportoenterostomy and early postoperative clearance of jaundice are significant predictors of transplant-free survival. Ann Surg 254:577-85

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