BARC: BILLIARY ATRESIA STUDY IN INFANTS AND CHILDREN (BASIC)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 假设1：遗传缺陷是胆道闭锁（BA）和多个先天性异常的儿童中的一个可能的致病因素。 假设二：自身免疫因素可能导致疾病进展或获得，并且可以通过将患有BA的儿童与健康对照组中的HLA相关联，以及通过将那些发生早期并发症的人与那些未发生早期并发症的人进行比较来识别，所述早期并发症包括静脉曲张出血、腹水和生长衰竭。 假设3a：与儿科终末期肝病评分（PELD）相比，静脉曲张出血、腹水和生长障碍等前哨事件是死亡或需要肝移植的早期预测因子。假设3b：与健康年龄匹配的儿童相比，健康相关的生活质量将受损，并与疾病的严重程度相关。假设3c：通过人体测量学和营养补充测量的生长障碍将预测随后24个月内哨兵事件（腹水、静脉曲张出血、死亡和移植）的发生。 关于引起胆道闭锁的因素和影响疾病进展的因素知之甚少。各种遗传、自身免疫和环境影响被认为是重要的。迄今为止，大多数研究都集中在新生儿和幼儿与BA，但年龄较大的幸存儿童与BA可以提供有关遗传学的重要信息，以及，自然史。该数据库的目的是收集相关的临床信息、遗传物质和体液样本，以使研究者能够解决上述假设和以下相关目标： 具体目标1。鉴定与BA病因学有关的基因 具体目标2。鉴定在疾病进展中可能重要的多态性，如HLA多态性i.对胆道闭锁患者进行高分辨率HLA-A、B、C、DRB 1、DRB 3、DRB 4、DRB 5、DQA 1、DQB 1、DPA 1和DPB 1分型。利用一种新的计算机算法，可以筛选大量的HLA等位基因，以检测胆道闭锁患者的共同表位。iii.使用传统的等位基因频率分析和新的共享表位算法评估HLA多态性在胆道闭锁发病率和严重程度中的作用。 具体目标3。描述年龄较大的非移植BA患儿的自然病史。

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. Hypothesis 1: A genetic defect is a likely causative factor for biliary atresia (BA) among children with BA and multiple congenital anomalies. Hypothesis 2: Autoimmune factors are likely to contribute to disease progression or acquisition and can be identified by correlating HLA among children with BA to healthy controls and by comparison of those who develop early complications including, variceal bleed, ascites, and growth failure compared to those who do not. Hypothesis 3a: Sentinel events such as variceal bleeding, ascites and growth failure are earlier predictors of death or need for liver transplantation than the pediatric end-stage liver disease score (PELD). Hypothesis 3b: Health related quality of life will be impaired compared to healthy age matched children and relate to severity of illness. Hypothesis 3c: Growth failure as measured by anthropometrics and nutritional supplementation will be predictive of onset of sentinel events (ascites, variceal bleed, death, and transplant) in the following 24 months. Little is known about the factors that cause biliary atresia nor the factors that influence disease progression. A variety of genetic, autoimmune and environmental influences have been hypothesized to be important. Most studies to date have focused on the neonate and young child with BA, yet the older surviving child with BA can provide important information about genetics, as well as, natural history. The purpose of this database is to collect the pertinent clinical information, genetic material and body fluid samples to enable investigators to address the above hypotheses and the following related aims: Specific Aim 1. To identify the gene or genes implicated in the etiology of BA Specific Aim 2. To identify polymorphisms that may be important in disease progression such as HLA polymorphisms i.To perform high resolution HLA-A, B, C, DRB1, DRB3 DRB4, DRB5, DQA1, DQB1, DPA1, and DPB1 typing on patients with biliary atresia. ii.To utilize a novel computer algorithm that permits screening large numbers of HLA alleles to detect shared epitopes in patients with biliary atresia. iii.To assess the role of HLA polymorphism in incidence and severity of biliary atresia using traditional analysis of allele frequency and a novel shared epitope algorithm. Specific Aim 3. Characterize the natural history of the older, non-transplanted child with BA.