Neonatal cholestatic liver diseases including Alagille syndrome, alpha-1 antitrypsin deficiency, bile acid synthesis defects, biliary atresia, cystic fibrosis, mitochondrial hepatopathies and progressive familial intrahepatic cholestasis, lead to significant morbidity and mortality in childhood and frequently necessitate liver transplantation. No single United States clinical center sees a large enough number of patients with these disorders to permit a rigorous answer to unresolved questions including etiology and pathogenesis, optimal methods of diagnosis and treatment, and factors that influence disease severity and prognosis. This competitive renewal proposal from the Pittsburgh Cholestatic Liver Disease Consortium at Children's Hospital of Pittsburgh of UPMC seeks to continue ongoing research activities in the Biliary Atresia Research Consortium (BARC) and the Cholestatic Liver Disease Consortium (CLiC) as part of a newly constituted Childhood Liver Disease Research and Education Network (ChiLDREN). This application for renewal funding includes a strong commitment to continuing the on-going research efforts and two new proposals, one based upon the existing research infrastructure, the other a novel clinical trial. The clinical center at CHP includes an outstanding group of clinician investigators with well-documented expertise in basic, translational and clinical investigation. Performance to date in the on-going studies of BARC and CLiC has been exemplary and has taken full advantage of the population base within Western Pennsylvania and the unique referral patterns to CHP as a quaternary center for Pediatric Hepatology and Liver Transplantation. The existing BARC database will be analyzed to assess the clinical course of children with biliary atresia who have poor bile flow. It is hypothesized that pre-emptive liver transplantation in this group of patients will yield superior overall outcome. A randomized trial of an inhibitor of intestinal bile acid transport in the management of pruritus associated with familial intrahepatic cholestasis 1 disease is also proposed. The primary end-point of this trial will be change in pruritus score, while secondary outcomes will include changes in serum and fecal bile acids. Relevance: Diseases in infants that impair the liver's ability to secrete bile (e.g. biliary atresia) are the leading indication for liver transplantation in childhood. Multi-centered prospective investigations are essential to improve the health of children afflicted by these disorders. The Pittsburgh Cholestatic Liver Disease Consortium at Children's Hospital of Pittsburgh is ideally suited to participate in these prospective investigations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01DK062466-08
Application #
7743651
Study Section
Special Emphasis Panel (ZDK1-GRB-S (M1))
Program Officer
Robuck, Patricia R
Project Start
2002-09-15
Project End
2014-05-31
Budget Start
2009-09-10
Budget End
2010-05-31
Support Year
8
Fiscal Year
2009
Total Cost
$238,473
Indirect Cost
Name
University of Pittsburgh
Department
Pediatrics
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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
Alonso, Estella M; Ye, Wen; Hawthorne, Kieran et al. (2018) Impact of Steroid Therapy on Early Growth in Infants with Biliary Atresia: The Multicenter Steroids in Biliary Atresia Randomized Trial. J Pediatr 202:179-185.e4
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; Moore, Jeff; Kerkar, Nanda et al. (2017) Initial assessment of the infant with neonatal cholestasis-Is this biliary atresia? PLoS One 12:e0176275
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
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
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
Teckman, Jeffrey H; Rosenthal, Philip; Abel, Robert et al. (2015) Baseline Analysis of a Young ?-1-Antitrypsin Deficiency Liver Disease Cohort Reveals Frequent Portal Hypertension. J Pediatr Gastroenterol Nutr 61:94-101
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

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