Pediatric liver disease has significant morbidity and mortality. Biliary atresia accounts for more than half of pediatric liver transplants. Genetic causes of neonatal cholestasis include Alagille's syndrome, alpha-1-antitrypsin deficiency, Progressive Familial Intrahepatic Cholestasis (PFIC), bile acid synthetic defects, mitochondrial hepatopathies, and cystic fibrosis. All of these diseases can progress to cirrhosis and endstage liver disease. In order to study the diagnosis, progression, and treatment of these disorders, we propose to join the CHILDREN Research Network to conduct clinical research on pediatric liver disease with the following specific aims:
Specific Aim 1 : Contribute to the existing studies in the Biliary Atresia Research Consortium (BARC), the Cholestatic Liver Diseases Research Consortium (CLiC) and Cystic Fibrosis Liver Disease Research Consortium (CFLD), which are merging to form the CHILDREN network. Research will include collecting and studying clinical data on children with these diseases, evaluating diagnostic tests, and storing biosamples for future study. We will enroll patients in the ongoing trial of corticosteroids for the treatment of biliary atresia. The hypothesis is that corticosteroids improve the outcome of Kasai operation in biliary atresia.
Specific Aim 2 : We will conduct studies of portal hypertension in children: We will study the frequency of minimum hepatic encephalopathy (MHE) in children with cirrhosis, assess their health-related quality of life (QOL), and evaluate the impact of lactulose therapy on MHE. The hypothesis is that MHE is common in children, negatively impacts QOL, and that lactulose improves MHE and QOL. We will conduct a randomized controlled trial of secondary prophylaxis of variceal bleeding comparing endoscopic band ligation (EBL) vs propranolol. The hypothesis is that EBL is superior to propranolol for secondary prophylaxis of variceal bleeding in children.
Specific Aim 3 : We will design and implement a computer module which teaches physicians key points about neonatal cholestasis;we will evaluate our outcomes by testing primary care providers and residents before and after using the curriculum. The hypothesis is that use of computer modules on neonatal cholestasis improves the knowledge of primary care physicians. Relevance: Pediatric liver disease, associated with chronic illness, malnutrition, and the need for liver transplantation, has significant public health impact. There is much need for knowledge regarding physiology, diagnosis, natural history, risk factors and treatment. Because these diseases are rare, multicenter collaborations like the CHILDREN network are crucial for studying these children and improving medical management and outcnmes.
|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|
|Ye, Wen; Narkewicz, Michael R; Leung, Daniel H et al. (2018) Variceal Hemorrhage and Adverse Liver Outcomes in Patients With Cystic Fibrosis Cirrhosis. J Pediatr Gastroenterol Nutr 66:122-127|
|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|
|Chen, Jake Y; Pandey, Ragini; Nguyen, Thanh M (2017) HAPPI-2: a Comprehensive and High-quality Map of Human Annotated and Predicted Protein Interactions. BMC Genomics 18:182|
|Schwarz, Kathleen B; Molleston, Jean P; Jonas, Maureen M et al. (2016) Durability of Response in Children Treated With Pegylated Interferon alfa [corrected] 2a ± Ribavirin for Chronic Hepatitis C. J Pediatr Gastroenterol Nutr 62:93-6|
|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|
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