Advancing our Understanding of Rare Pediatric Liver Diseases
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
- A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000Benjamin 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...
- Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresiaEllen 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...
- Health related quality of life in patients with biliary atresia surviving with their native liverShikha 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....
- Evidence from human and zebrafish that GPC1 is a biliary atresia susceptibility geneShuang 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...
- Portal hypertension in children and young adults with biliary atresiaBenjamin 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...
- Efficacy of fat-soluble vitamin supplementation in infants with biliary atresiaBenjamin 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...
- Pancreatic insufficiency is not a prevalent problem in Alagille syndromeBinita 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...
- Notch signaling in human development and diseaseAndrea 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...
- The anatomic pattern of biliary atresia identified at time of Kasai hepatoportoenterostomy and early postoperative clearance of jaundice are significant predictors of transplant-free survivalRiccardo 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...
- Design and validation of the biliary atresia research consortium histologic assessment system for cholestasis in infancyPierre Russo
Department of Pathology and Laboratory Medicine, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
Clin Gastroenterol Hepatol 9:357-362.e2. 2011....
- Genomic alterations in biliary atresia suggest region of potential disease susceptibility in 2q37.3Melissa 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...
- Growth failure and outcomes in infants with biliary atresia: a report from the Biliary Atresia Research ConsortiumPatricia 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...
- Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trialJorge 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...
- Novel molecular and cellular approaches for alcoholism medication developmentRobert 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. ..
- Center for the Study of Pediatric CholestasisRonen 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. ..
- Colorado Center for Childhood Liver Disease Research and EducationRonald J Sokol; Fiscal Year: 2013..We will also train the researchers of the future who will study these rare diseases. ..
- Hereditary Causes of Nephrolithaisis and Kidney FailureDAWN SCHMAUTZ MILLINER; Fiscal Year: 2013..This work will address barriers of rare diseases research through vigorous multidisciplinary cooperation. ..
- University of Maryland Greenebaum Cancer Center Support GrantKevin 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. ..
- The Pittsburgh Cholestatic Liver Disease ConsortiumBenjamin 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. ..
- Molecular Mechanisms of Intrahepatic CholestasisBenjamin 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. ..
- North American Mitochondrial Disease Consortium (NAMDC)JOHN L THOMPSON; Fiscal Year: 2013....
- Clinical Research on Nonalcoholic Fatty Liver DiseaseJOEL EDWARD LAVINE; Fiscal Year: 2013..abstract_text> ..
- Hypoxic Adenosine ResponsesMichael 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. ..
- 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. ..
- CENTER FOR AIDS RESEARCHDouglas 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. ..
- DRUG DEPENDENCE CLINICAL RESEARCH PROGRAMReese T Jones; Fiscal Year: 2013..abstract_text> ..
- NUTRITION OBESITY RESEARCH CENTERMichael 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 ..
- Silvio O. Conte Digestive Diseases Research Core CentersMichael 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. ..
- B-cell Biology of Mucosal Immune Protection from SIV ChallengeEric Hunter; Fiscal Year: 2013....
- Collaborative Clinical Research on Non Alcoholic StratohepatitisNaga P Chalasani; Fiscal Year: 2013..g., proteomics, lipodimics, clinical prediction rules) and disease pathogenesis (cytokine analyses, genome-wide association studies, tissue proteomics). ..