The Pittsburgh Cholestatic Liver Disease Consortium

Summary

Principal Investigator: Benjamin L Shneider
Abstract: 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.
Funding Period: 2002-09-15 - 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 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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

Detail Information

Publications9

  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 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
    ....
  3. 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...
  4. 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...
  5. 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...
  6. 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...
  7. 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
    ....
  8. 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. 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. ..
  2. The role of regulatory T cells in biliary atresia
    Alexander Miethke; Fiscal Year: 2013
    ....
  3. Clinical Center: Childhood Liver Disease Research and Education Network (ChiLDREN
    PETER FRANK WHITINGTON; Fiscal Year: 2013
    ..Children with biliary atresia or any of the five genetic cholestatic liver diseases studied by ChiLDREN account for the majority of pediatric liver transplantations performed in the United States. ..
  4. Revolutionizing Biomedical and Clinical Research through Innovative Technology
    Michael N Mindrinos; Fiscal Year: 2013
    ....
  5. Circulating miRNA as a biomarker for biliary atresia
    Joshua R Friedman; Fiscal Year: 2013
    ..It may also lead to insights regarding BA pathogenesis and progress, as well as applications in other liver diseases. ..
  6. 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. ..
  7. North American Mitochondrial Disease Consortium (NAMDC)
    JOHN L THOMPSON; Fiscal Year: 2013
    ....
  8. Molecular Subtypes for Targeted Therapies in Alcoholic Hepatitis
    Ramon Bataller; Fiscal Year: 2013
    ..We anticipate that the systematic approach and translational nature of this consortium will advance the understanding of AH, and provide novel approaches for its prevention and treatment. ..
  9. MMC and VICC: Partnership for Survivorship (1 of 2)
    Maureen Sanderson; Fiscal Year: 2013
    ..abstract_text> ..
  10. Role of Bile Acids in the Initiation of Liver Regeneration
    Willscott E Naugler; Fiscal Year: 2013
    ....
  11. 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. ..
  12. Immunologic dysfunction in biliary atresia
    Jorge A Bezerra; Fiscal Year: 2013
    ..These results will identify an array of targets for new therapies that block progression of disease, restore the biliary epithelium, and foster long-term survival of patients with biliary atresia. ..
  13. Spinal Cord Injury, Plasticity and Transplant Mediated Repair
    John D Houle; Fiscal Year: 2013
    ..This Program Project has direct relevance to the design and implementation of future treatment programs for acute and delayed intervention after SCI. ..
  14. Regulation of Hepatic Metabolic Function by Parenteral Nutrition
    Douglas G Burrin; Fiscal Year: 2013
    ..These studies in premature pigs are highly translational and will lead to new clinical practices in nutritional support and prevention of liver disease in infants. ..
  15. Genetic Modifiers of Liver Disease Severity in Alagille Syndrome
    Nancy Bettina Spinner; Fiscal Year: 2013
    ....
  16. 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. ..