The purpose of this competing renewal application is to continue, expand and merge the Biliary Atresia Research Consortium (BARC) and the Cholestatic Liver Consortium (CLiC) to form the Childhood Liver Disease Research and Education Network (ChiLDREN). ChiLDREN will have as its overall objectives to further define the epidemiology, clinical features, and pathophysiology of the major cholestatic liver diseases afflicting children, and develop new therapies to improve and prolong the life of these patients. The proposal consists of the following Specific Aims:
Aim 1) Continue with the work of the Biliary Atresia Research Consortium: a) the trial of corticosteroids post portoenterostomy, b) acquire new information on epidemiology, clinical features, factors affecting outcome post portoenterostomy, and histopathology of biliary atresia, c) define the role of modifier genes in influencing outcome, and d) develop new therapies to attenuate or prevent the development of biliary cirrhosis post portoenterostomy;
Aim 2) Study the natural history, clinical features, the correlation of genotype with phenotype, and prognosis of inherited forms of intrahepatic cholestasis including Alagille syndrome, alpha-1-antitrypsin deficiency, progressive familial intrahepatic cholestasis (PFIC), and bile acid synthesis defects;
and Aim 3) Determine overall frequency, full clinical spectrum and natural history of the mitochondrial hepatopathies. For all studies a repository of serum, urine, tissue, and DNA specimens will be available for use in future ancillary studies. The infrastructure and collaborations within ChiLDREN offer unique training opportunities for young investigators. Small pilot grants and demonstration projects will allow new hypotheses to be tested that could lead to more substantial funding from the National Institutes of Health through an independent grant or a larger study involving all of the ChiLDREN centers. There is also a need to increase public awareness about pediatric liver disease to primary care physicians and the lay public through our publications and website. Relevance: Biliary atresia and a group of inherited cholestatic syndromes remain poorly understood, and are associated with significant morbidity, mortality, and need for liver tranplantation. The ChiLDREN program will produce new knowledge on the clinical features and causes of these diseases, and develop therapies to improve and prolong the life of these patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK062445-12
Application #
8545784
Study Section
Special Emphasis Panel (ZDK1-GRB-S (M1))
Program Officer
Sherker, Averell H
Project Start
2002-09-30
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
12
Fiscal Year
2013
Total Cost
$245,000
Indirect Cost
$112,758
Name
Icahn School of Medicine at Mount Sinai
Department
Pediatrics
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Russo, Pierre; Magee, John C; Anders, Robert A et al. (2016) Key Histopathologic Features of Liver Biopsies That Distinguish Biliary Atresia From Other Causes of Infantile Cholestasis and Their Correlation With Outcome: A Multicenter Study. Am J Surg Pathol 40:1601-1615
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
Ye, Wen; Rosenthal, Philip; Magee, John C et al. (2015) Factors Determining δ-Bilirubin Levels in Infants With Biliary Atresia. J Pediatr Gastroenterol Nutr 60:659-63
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
Teckman, Jeffrey H; Rosenthal, Philip; Abel, Robert et al. (2015) Baseline Analysis of a Young α-1-Antitrypsin Deficiency Liver Disease Cohort Reveals Frequent Portal Hypertension. J Pediatr Gastroenterol Nutr 61:94-101
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
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
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
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
Schwarz, Kathleen B; Haber, Barbara H; Rosenthal, Philip et al. (2013) Extrahepatic anomalies in infants with biliary atresia: results of a large prospective North American multicenter study. Hepatology 58:1724-31

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