CHOLESTATIC LIVER DISEASE CONSORTIUM (CLIC): LONGITUDINAL STUDY OF GENETIC CAUSE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项纵向观察研究将探讨儿童肝内胆汁淤积症的四种遗传病因的自然历史和进展，包括α-1抗胰蛋白酶缺乏(A1-AT)、Alagille综合征(AGS)、进行性家族性肝内胆汁淤积症(PFIC)和胆汁酸合成缺陷(BAD)。这项研究将作为胆汁淤积性肝病联盟(CLIC)的一部分进行，该联盟是由NIH资助的多中心罕见疾病临床研究联盟。在这项研究中，我们将在五年的固定间隔内以统一的方式收集相对大量的这些罕见疾病患者的已定义数据元素。此外，还将建立患者样本和DNA样本的生物库，以供在本研究之外进行的辅助研究中使用。通过比较四种肝病之间的结果衡量标准(即，使用每种疾病作为其他疾病的疾病控制)，可以最好地确定每种疾病与其他肝病相比的全部影响。以这种方式使用纵向数据库，这项研究将提供对儿童时期胆汁淤积肝脏的影响的更好的理解，而不考虑潜在的病因以及每种疾病的病理生理学、结果和并发症。这一初步特征将允许计算未来治疗干预临床试验的样本量，并提供干预措施应与之比较的基线。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.