The Childhood Liver Disease Research and Education Network (ChiLDREN) provides an unprecedented opportunity to improve the lives of children with serious liver diseases. Continued productive contributions of this Clinical Center to ChiLDREN are proposed with 3 major aims: I. Consortium Contribution: A well-organized infrastructure that enables a high level of patient enrollment and data and specimen collection is well established, integrated into one of the largest pediatric hepatology programs in the United States with experienced investigators and coordinators, and an excellent track record in clinical research. In addition, we propose leading an analysis of clinical data and biliary atresia liver tissue to better evaluate phenotypic and clinicopathological correlations and, by competing outcomes, multivariate and neural network modeling, to better predict and determine outcomes after hepatoportenterostomy. II. Ancillary Studies: Several unique studies are linked to this proposal, developing from this Clinical Center's pre-eminent strengths and preliminary studies: (i) serum fibrosis and novel imaging markers will be further evaluated to improve diagnosis and monitor liver fibrosis in ChiLDREN diseases;(ii) in parallel mechanistic studies, we are further exploring the molecular mechanisms of pathogenesis of biliary atresia and CFLD, studying epigenetic, genetic, and fundamental fibrogenetic mechanisms in liver tissue and serum, and we propose extending these studies to repository tissue and data analysis. III. Clinical Trial: To evaluate new antifibrogenic therapies, a Phase II clinical trial of pentoxyfilline (PTX), a known antifibrogenic antiinflammatory agent of proven safety in infants, is being conducted in infants with newly-diagnosed BA (registered with clinical to determine whether PTX has sufficient biological activity against BA, with minimal risk, which warrants further study. We hypothesize that PTX will be a safe and effective therapeutic agent to improve outcomes for select children with progressive biliary fibrosis/cirrhosis. Since there are currently no effective medical therapies for CHiLDREN diseases, proper exploration of the safety and efficacy of this agent would perfectly fit within the charge of ChiLDREN, which is uniquely poised to examine such novel therapies on a large scale. We hope to renew our productive contribution to achieving all the aims of ChiLDREN, helping to make a difference for children with liver diseases. We expect to provide high-value participation, capitalize on the well- developed ChiLDREN serum and tissue repository in the search for non-invasive biomarkers and better prediction of outcomes, embark upon fruitful mechanistic studies on the molecular pathogenesis of these diseases, and help lead investigations of novel safe therapies to help fill the current therapeutic void.

Public Health Relevance

The ChiLDREN Network provides a means of studying pediatric liver disorders, which carry a substantial public health burden (e.g. biliary atresia is he most common indication for liver transplant in children). Continued subject enrollment and follow-up in existing Network protocols from our high-volume Center will propel the mission of ChiLDREN and allow for high quality research of these diseases for years to come. Our proposed ancillary studies, which would make use of Consortium resources, are designed to elucidate molecular mechanisms of pathogenesis, discover non-invasive biomarkers, and test a new therapy, pentoxifylline, in ChilDREN diseases.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-7 (M1))
Program Officer
Sherker, Averell H
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
Schools of Medicine
United States
Zip Code
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
Kamath, Binita M; Abetz-Webb, Linda; Kennedy, Ciara et al. (2018) Development of a Novel Tool to Assess the Impact of Itching in Pediatric Cholestasis. Patient 11:69-82
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
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
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
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

Showing the most recent 10 out of 12 publications