This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT This longitudinal observational study will investigate the natural history and progression of four genetic causes of intrahepatic cholestasis of childhood, including alpha-1 antitrypsin deficiency (a1-AT), Alagille syndrome (AGS), progressive familial intrahepatic cholestasis (PFIC), and bile acid synthesis defects (BAD). This study will be conducted as part of the Cholestatic Liver Disease Consortium (CLiC), an NIH-funded multi-centered Rare Disease Clinical Research Consortium. In this study, we will collect defined data elements in a uniform fashion at fixed intervals for five years over a relatively large number of patients with these rare disorders. In addition, a biobank of patient specimens and DNA samples will be established for use in ancillary studies to be performed in addition to this study. By comparing outcome measures between the four liver diseases (i.e., using each disorder as a disease-control for the other disorders), the full impact of each disorder can best be determined in comparison to the other liver diseases. Using the longitudinal database in this fashion, this study will provide an improved understanding of the effects of the cholestatic liver during childhood irrespective of the underlying etiology as well as to the pathophysiology, outcome, and complications of each of the disorders. This initial characterization will allow calculation of sample sizes for future therapeutic intervention clinical trials and provide the baseline to which interventions should be compared.
Showing the most recent 10 out of 459 publications
