Childhood Liver Disease Research Network (ChiLDReN) Clinical Centers

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Project Summary/Abstract Liver disease is a major cause of infant and childhood morbidity and mortality. The diseases comprising “pediatric liver diseases” are individually rare, which has hindered the study of their causes/pathophysiologies. As a result of this basic defect in understanding effective therapeutic strategies are lacking for most of them. This in turn results in many children with progressing to end-stage liver disease necessitating orthotopic liver transplantation. Pediatric liver transplants comprise approximately 10% of all liver transplants performed, and the indications for most of them lie among the diseases to be studied in the Childhood Liver Disease Research Network (ChiLDReN). This network combines the efforts of several large and individually successful clinical research enterprises to recruit subjects and carry them through rigorous clinical studies and trials with the expectation of establishing well-characterized patient cohorts that can be followed through the natural history of their disease process and which can be accessed for trials of emerging therapies. In addition, the biological specimens linked to clinical data provide the fuel for studies of etiology (genetic and other) and the influences of gene expression and epigenomics on disease expression and progression, as well as response to therapy. We propose to participate in ChiLDReN as a center wherein investigators have substantial expertise in several of the key areas of investigation within the consortium as a whole. Our center has been one of the top contributors of subjects to studies undertaken by ChiLDReN over the term of its existence. We expect to continue to contribute substantially to the performance of ChiLDReN in achieving its goal of successfully eliminating pediatric liver disease as a major cause of infant and childhood morbidity and mortality. The specific aims at our center include: a) to participate fully as a leading clinical center in ChiLDReN; b) To pilot a double-blind, randomized, placebo controlled, cross-over trial testing the efficacy of rifaximin therapy to reduce symptoms of minimal hepatic encephalopathy (MHE) and improve Health Related Quality of Life (HRQOL) in school aged patients in the ChiLDReN network with portal hypertension (PHTN); c) To characterize the impact of systemic inflammatory markers and measures of bacterial translocation on both PROs and the growth hormone axis in school age children with and without PHTN.