Pediatric liver disease is rare but can lead to other morbidities, organ transplantation, or even death. The Childhood Liver Disease Research Network (ChiLDReN) is a collaborative network dedicated to research endeavors related to eight pediatric liver diseases, namely biliary atresia (BA);Alagille syndrome (ALGS);alpha-1-antitrypsin deficiency;progressive familial intrahepatic cholestasis (PFIC);bile acid synthesis defects;mitochondrial hepatopathies;idiopathic neonatal hepatitis;and cystic fibrosis liver disease. ChiLDReN aims to promote clinical and translational research on pediatric liver diseases in hopes of elucidating the pathogenesis and natural history, and developing means of treatment and clinical management. The Network will continue to build its robust biorepository of plasma, serum, urine, DNA, and hepatobiliary tissue specimens for use in future studies and analyses. It will also continue to compile already considerable datasets on demographic, medical history, and neurocognitive characteristics of pediatric liver disease. The Network has also recently initiated a clinical trial to address key gaps in the early management of children with biliary atresia, and is on the brink of initiating several other trials, which will facilitate treatment options for children with rare liver disease. Our site aims to contribute to the goals of ChiLDReN by ensuring continued and future availability of patients for observational and interventional Network protocols. We will also continue to the intellectual needs of the Network by providing committee leadership within the consortium, actively participating in data analysis and manuscript development, and developing novel studies and protocols. To this effect, we propose a novel and exciting protocol to differentiate cholangiocytes from induced pluripotent cells, and to apply this technology to model several biliary diseases of direct relevance to the Network. Through the continuation of its longitudinal observational and interventional studies, ChiLDReN aims to discover new diagnostics, etiologies, and treatment options for children with rare liver disease and those who undergo liver transplantation. The findings from the studies and analyses conducted by ChiLDReN will ultimately help improve outcomes and quality of life for North American children who suffer from liver disease.

Public Health Relevance

Pediatric liver disease is relatively rare but can lead to liver transplantation or death. This project investigates the natural history of highly morbid pediatric liver diseases such as biliary atresia, Alagille syndrome, alpha-1-antitrypsin deficiency, Progressive Familial Intrahepatic Cholestasis syndromes, bile acid synthesis defects, mitochondrial hepatopathies, idiopathic neonatal hepatitis, and Cystic Fibrosis liver disease, in order to gain a better understanding of these rare conditions. The project also includes clinical therapy trials in order to find new and better treatments for infants and children with liver disease.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZDK1-GRB-7 (M1))
Program Officer
Sherker, Averell H
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Hospital for Sick Chldrn (Toronto)
Zip Code
M5 1-X8
Loomes, Kathleen M; Spino, Cathie; Goodrich, Nathan P et al. (2018) Bone Density in Children With Chronic Liver Disease Correlates With Growth and Cholestasis. Hepatology :
Ng, Vicky L; Sorensen, Lisa G; Alonso, Estella M et al. (2018) Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study. J Pediatr 196:139-147.e3
Wang, Kasper S; Tiao, Greg; Bass, Lee M et al. (2017) Analysis of surgical interruption of the enterohepatic circulation as a treatment for pediatric cholestasis. Hepatology 65:1645-1654
Shneider, Benjamin L; Magee, John C; Karpen, Saul J et al. (2016) Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts Short-Term Outcomes in Biliary Atresia. J Pediatr 170:211-7.e1-2
Leung, Daniel H; Ye, Wen; Molleston, Jean P et al. (2015) Baseline Ultrasound and Clinical Correlates in Children with Cystic Fibrosis. J Pediatr 167:862-868.e2
Ye, Wen; Rosenthal, Philip; Magee, John C et al. (2015) Factors Determining ?-Bilirubin Levels in Infants With Biliary Atresia. J Pediatr Gastroenterol Nutr 60:659-63
Tsai, Ellen A; Grochowski, Christopher M; Falsey, Alexandra M et al. (2015) Heterozygous deletion of FOXA2 segregates with disease in a family with heterotaxy, panhypopituitarism, and biliary atresia. Hum Mutat 36:631-7
Kamath, Binita M; Chen, Zhen; Romero, Rene et al. (2015) Quality of Life and Its Determinants in a Multicenter Cohort of Children with Alagille Syndrome. J Pediatr 167:390-6.e3
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
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

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