Advancing our Understanding of Rare Pediatric Liver Diseases

Summary

Principal Investigator: KATHLEEN MARY LOOMES
Abstract: The overall goal of this application is to ensure the continued success of the Biliary Atresia Research Consortium (BARC) and the Cholestatic Liver Consortium (CLiC). Through a coordinated effort, investigations of eight cholestatic pediatric disorders will be advanced while sharing common resources Including a data coordinating center. National collaborative processes have been used in the area of acquired immuno-deficiency syndrome (AIDS) research and oncology with dramatic and rapid progress made for diagnosis and treatment. A similar collaborative process will be helpful for rare pediatric liver disorders. For many of these diseases little is known about the pathogenesis, natural history or optimal treatment strategies. Much of the scientific and therapeutic progress has been hampered by the lack of sufficient patients needed to carry out quality, significant research. We propose to continue to participate in the national collaborative process focusing on biliary atresia (BA), hepatic mitochondropathies, Alagille syndrome (AGS), alpha-one antitrypsin deficiency, progressive familial intrahepatic cholestasis, bile acid synthetic disorders, cystic fibrosis liver disease and neonatal hepatitis. The ultimate gains are obvious both for individual patients and in terms of health care dollars.
Funding Period: 2002-09-01 - 2015-05-31
more information: NIH RePORT

Top Publications

  1. ncbi A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000
    Benjamin L Shneider
    Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029, Department of Biostatistics, University of Michigan, Ann Arbor, MI, and Department of Pediatrics, Children s Hospital of Philadelphia, PA, USA
    J Pediatr 148:467-474. 2006
  2. pmc Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia
    Ellen A Tsai
    Genomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Hum Genet 133:235-43. 2014
  3. pmc Health related quality of life in patients with biliary atresia surviving with their native liver
    Shikha S Sundaram
    Departments of Gastroenterology, Hepatology, and Nutrition, Children s Hospital of Colorado, University of Colorado School of Medicine, Aurora, CO Electronic address
    J Pediatr 163:1052-7.e2. 2013
  4. pmc Evidence from human and zebrafish that GPC1 is a biliary atresia susceptibility gene
    Shuang Cui
    Division of Gastroenterology, Hepatology, and Nutrition, The Children s Hospital of Philadelphia Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Gastroenterology 144:1107-1115.e3. 2013
  5. pmc Portal hypertension in children and young adults with biliary atresia
    Benjamin L Shneider
    Children s Hospital Pittsburgh of UPMC, Division of Pediatric Gastoenterology, Hepatology and Nutrition, PA 15224
    J Pediatr Gastroenterol Nutr 55:567-73. 2012
  6. pmc Efficacy of fat-soluble vitamin supplementation in infants with biliary atresia
    Benjamin L Shneider
    Department of Pediatrics, Children s Hospital Pittsburgh of UPMC, Pittsburgh, PA 15224, USA
    Pediatrics 130:e607-14. 2012
  7. pmc Pancreatic insufficiency is not a prevalent problem in Alagille syndrome
    Binita M Kamath
    Hospital for Sick Children, Toronto, Canada
    J Pediatr Gastroenterol Nutr 55:612-4. 2012
  8. pmc Notch signaling in human development and disease
    Andrea L Penton
    Department of Pathology and Laboratory Medicine, The Children s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    Semin Cell Dev Biol 23:450-7. 2012
  9. pmc 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
    Riccardo Superina
    Children s Memorial Hospital, Chicago, IL, USA
    Ann Surg 254:577-85. 2011
  10. pmc Design and validation of the biliary atresia research consortium histologic assessment system for cholestasis in infancy
    Pierre Russo
    Department of Pathology and Laboratory Medicine, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Clin Gastroenterol Hepatol 9:357-362.e2. 2011

Research Grants

Detail Information

Publications14

  1. ncbi A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000
    Benjamin L Shneider
    Department of Pediatrics, Mount Sinai Medical Center, New York, NY 10029, Department of Biostatistics, University of Michigan, Ann Arbor, MI, and Department of Pediatrics, Children s Hospital of Philadelphia, PA, USA
    J Pediatr 148:467-474. 2006
    ..To determine the prognostic factors and optimal approaches to the diagnosis and management of biliary atresia, the leading indication for liver transplantation in children...
  2. pmc Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia
    Ellen A Tsai
    Genomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Hum Genet 133:235-43. 2014
    ..The role of ADD3 in biliary development is unclear, but our findings suggest that this gene may be functionally relevant for the development of BA...
  3. pmc Health related quality of life in patients with biliary atresia surviving with their native liver
    Shikha S Sundaram
    Departments of Gastroenterology, Hepatology, and Nutrition, Children s Hospital of Colorado, University of Colorado School of Medicine, Aurora, CO Electronic address
    J Pediatr 163:1052-7.e2. 2013
    ....
  4. pmc Evidence from human and zebrafish that GPC1 is a biliary atresia susceptibility gene
    Shuang Cui
    Division of Gastroenterology, Hepatology, and Nutrition, The Children s Hospital of Philadelphia Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Gastroenterology 144:1107-1115.e3. 2013
    ..Genome-wide association studies previously identified a potential region of interest at 2q37. We continued these studies to narrow the region and identify BA susceptibility genes...
  5. pmc Portal hypertension in children and young adults with biliary atresia
    Benjamin L Shneider
    Children s Hospital Pittsburgh of UPMC, Division of Pediatric Gastoenterology, Hepatology and Nutrition, PA 15224
    J Pediatr Gastroenterol Nutr 55:567-73. 2012
    ..The Childhood Liver Disease Research and Education Network was used to perform a cross-sectional multicentered analysis of PHT in children with BA...
  6. pmc Efficacy of fat-soluble vitamin supplementation in infants with biliary atresia
    Benjamin L Shneider
    Department of Pediatrics, Children s Hospital Pittsburgh of UPMC, Pittsburgh, PA 15224, USA
    Pediatrics 130:e607-14. 2012
    ..In this prospective multicenter study, we assessed the prevalence of FSV deficiency in infants with BA who received this FSV/TPGS preparation...
  7. pmc Pancreatic insufficiency is not a prevalent problem in Alagille syndrome
    Binita M Kamath
    Hospital for Sick Children, Toronto, Canada
    J Pediatr Gastroenterol Nutr 55:612-4. 2012
    ..FE measurements were normal (>200  μg/g) in 40 (95%) and indeterminate (100-200  μg/g) in 2 (5%). As FE is the most reliable screen for PI, these data suggest that PI is not a prevalent problem in ALGS...
  8. pmc Notch signaling in human development and disease
    Andrea L Penton
    Department of Pathology and Laboratory Medicine, The Children s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    Semin Cell Dev Biol 23:450-7. 2012
    ..Studies of these human disorders and their inheritance patterns and types of mutations reveal insights into the mechanisms of Notch signaling...
  9. pmc 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
    Riccardo Superina
    Children s Memorial Hospital, Chicago, IL, USA
    Ann Surg 254:577-85. 2011
    ..The goals of this study were to describe the clinical and anatomic features of infants undergoing Kasai portoenterostomy (KPE) for biliary atresia (BA) and to examine associations between these parameters and outcomes...
  10. pmc Design and validation of the biliary atresia research consortium histologic assessment system for cholestasis in infancy
    Pierre Russo
    Department of Pathology and Laboratory Medicine, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Clin Gastroenterol Hepatol 9:357-362.e2. 2011
    ....
  11. pmc Genomic alterations in biliary atresia suggest region of potential disease susceptibility in 2q37.3
    Melissa Leyva-Vega
    Division of Gastroenterology, Hepatology and Nutrition, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Am J Med Genet A 152:886-95. 2010
    ..The overlapping 1.76 Mb deletion on chromosome 2q37.3 from 240,936,900 to 242,692,820 constitutes the critical region and the genes within this region could be candidates for susceptibility to BA...
  12. pmc Growth failure and outcomes in infants with biliary atresia: a report from the Biliary Atresia Research Consortium
    Patricia A DeRusso
    Johns Hopkins School of Medicine and The Johns Hopkins Children s Center, Baltimore, Maryland, USA
    Hepatology 46:1632-8. 2007
    ..The combination of intermediate bilirubin concentrations and poor mean weight z-scores 3 months after HPE was also associated with poor clinical outcome...
  13. ncbi Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trial
    Jorge A Bezerra
    Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio
    JAMA 311:1750-9. 2014
    ..Biliary atresia is the most common cause of end-stage liver disease in children. Controversy exists as to whether use of steroids after hepatoportoenterostomy improves clinical outcome...

Research Grants30

  1. Novel molecular and cellular approaches for alcoholism medication development
    Robert A Harris; Fiscal Year: 2013
    ..The PPG has both internal and external advisory board members, providing expert guidance from scientists with a wide range of expertise in drug development and therapeutics. ..
  2. Center for the Study of Pediatric Cholestasis
    Ronen Arnon; Fiscal Year: 2013
    ..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. ..
  3. Colorado Center for Childhood Liver Disease Research and Education
    Ronald J Sokol; Fiscal Year: 2013
    ..We will also train the researchers of the future who will study these rare diseases. ..
  4. Hereditary Causes of Nephrolithaisis and Kidney Failure
    DAWN SCHMAUTZ MILLINER; Fiscal Year: 2013
    ..This work will address barriers of rare diseases research through vigorous multidisciplinary cooperation. ..
  5. University of Maryland Greenebaum Cancer Center Support Grant
    Kevin J Cullen; Fiscal Year: 2013
    ..Reflecting our remarkable and continued growth, UMGCC seeks to renew its CCSG to enhance and expand its efforts in high-quality and clinically relevant cancer research. ..
  6. The Pittsburgh Cholestatic Liver Disease Consortium
    Benjamin L Shneider; Fiscal Year: 2013
    ..The Pittsburgh Cholestatic Liver Disease Consortium at Children's Hospital of Pittsburgh is ideally suited to participate in these prospective investigations. ..
  7. Molecular Mechanisms of Intrahepatic Cholestasis
    Benjamin L Shneider; Fiscal Year: 2013
    ..Recent molecular discoveries provide an opportunity to understand this disease (providing new therapies) and to explore basic physiology of the liver, pancreas, gastrointestinal tract and lungs. ..
  8. North American Mitochondrial Disease Consortium (NAMDC)
    JOHN L THOMPSON; Fiscal Year: 2013
    ....
  9. Clinical Research on Nonalcoholic Fatty Liver Disease
    JOEL EDWARD LAVINE; Fiscal Year: 2013
    ..abstract_text> ..
  10. Hypoxic Adenosine Responses
    Michael R Blackburn; Fiscal Year: 2013
    ..Three Component Projects, Two Scientific Cores and an Administrative Core are planned to facilitate the research goals and interactions of this PPG. ..
  11. UCLA CENTER FOR AIDS RESEARCH (CFAR)
    Jerome A Zack; Fiscal Year: 2013
    ..Inclusion of this resource will be highly beneficial to clinical, behavioral and basic science studies. ..
  12. CENTER FOR AIDS RESEARCH
    Douglas D Richman; Fiscal Year: 2013
    ..We continue to be guided by our External Advisory and Executive Committees, as well as the CFAR Director and Co-Directors, Core Directors, Scientific Focus Groups and our membership. ..
  13. DRUG DEPENDENCE CLINICAL RESEARCH PROGRAM
    Reese T Jones; Fiscal Year: 2013
    ..abstract_text> ..
  14. NUTRITION OBESITY RESEARCH CENTER
    Michael W Schwartz; Fiscal Year: 2013
    ..However, over the past several years, Als have tended to focus their research in the following major areas: 1. Body Weight Regulation and Obesity 2. Adipose Tissue Biology and Inflammation 3. Lipids and Atherosclerosis 4. Diabetes ..
  15. Silvio O. Conte Digestive Diseases Research Core Centers
    Michael H Nathanson; Fiscal Year: 2013
    ..A Pilot Feasibility Program supports 1-2 year small grants for new scientific initiatives. The Enrichment Program consists of research seminars, symposia, and retreats. ..
  16. B-cell Biology of Mucosal Immune Protection from SIV Challenge
    Eric Hunter; Fiscal Year: 2013
    ....
  17. Collaborative Clinical Research on Non Alcoholic Stratohepatitis
    Naga P Chalasani; Fiscal Year: 2013
    ..g., proteomics, lipodimics, clinical prediction rules) and disease pathogenesis (cytokine analyses, genome-wide association studies, tissue proteomics). ..