Biliary Atresia, Cholestatic Liver Diseases, and Cystic Fibrosis: Indiana Univers

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DESCRIPTION (provided by applicant): 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.