The Pittsburgh Cholestatic Liver Disease Consortium

匹兹堡胆汁淤积性肝病联盟

• 批准号: 8013469
• 负责人: BENJAMIN L SHNEIDER
• 金额: $ 15.41万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-05 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8013469
• 关键词: Alagille Syndrome; Bile Acid Biosynthesis Pathway; Bile Acids; Bile fluid; Biliary Atresia; Child; Child health care; Childhood; Clinical; Clinical Course of Disease; Clinical Trials; Cross-Over Studies; Cystic Fibrosis; Databases; Defect; Diagnosis; Disease; Disease Progression; Double-Blind Method; Education; Etiology; Funding; Goals; Hepatology; Infant; Intestines; Investigation; Lead; Liver; Liver diseases; Methods; Mitochondria; Morbidity - disease rate; Neonatal; Outcome; Pathogenesis; Patients; Pattern; Pediatric Hospitals; Pennsylvania; Performance; Placebo Control; Principal Investigator; Progressive intrahepatic cholestasis; Pruritus; Randomized; Relative (related person); Research; Research Activity; Research Infrastructure; Research Personnel; Serum; Severity of illness; Time; Transplantation; Treatment Factor; United States; alpha 1-Antitrypsin Deficiency; base; improved; inhibitor/antagonist; liver transplantation; mortality; novel; outcome forecast; population based; prospective; randomized trial; secondary outcome; total measurement Bilirubin; transport inhibitor

DESCRIPTION (provided by applicant): Neonatal cholestatic liver diseases including Alagille syndrome, alpha-1 antitrypsin deficiency, bile acid synthesis defects, biliary atresia, cystic fibrosis, mitochondrial hepatopathies and progressive familial intrahepatic cholestasis, lead to significant morbidity and mortality in childhood and frequently necessitate liver transplantation. No single United States clinical center sees a large enough number of patients with these disorders to permit a rigorous answer to unresolved questions including etiology and pathogenesis, optimal methods of diagnosis and treatment, and factors that influence disease severity and prognosis. This competitive renewal proposal from the Pittsburgh Cholestatic Liver Disease Consortium at Children's Hospital of Pittsburgh of UPMC seeks to continue ongoing research activities in the Biliary Atresia Research Consortium (BARC) and the Cholestatic Liver Disease Consortium (CLiC) as part of a newly constituted Childhood Liver Disease Research and Education Network (ChiLDREN). This application for renewal funding includes a strong commitment to continuing the on-going research efforts and two new proposals, one based upon the existing research infrastructure, the other a novel clinical trial. The clinical center at CHP includes an outstanding group of clinician investigators with well-documented expertise in basic, translational and clinical investigation. Performance to date in the on-going studies of BARC and CLiC has been exemplary and has taken full advantage of the population base within Western Pennsylvania and the unique referral patterns to CHP as a quaternary center for Pediatric Hepatology and Liver Transplantation. The existing BARC database will be analyzed to assess the clinical course of children with biliary atresia who have poor bile flow. It is hypothesized that pre-emptive liver transplantation in this group of patients will yield superior overall outcome. A randomized trial of an inhibitor of intestinal bile acid transport in the management of pruritus associated with familial intrahepatic cholestasis 1 disease is also proposed. The primary end-point of this trial will be change in pruritus score, while secondary outcomes will include changes in serum and fecal bile acids. Relevance: Diseases in infants that impair the liver's ability to secrete bile (e.g. biliary atresia) are the leading indication for liver transplantation in childhood. Multi-centered prospective investigations are essential to improve the health of children afflicted by these disorders. The Pittsburgh Cholestatic Liver Disease Consortium at Children's Hospital of Pittsburgh is ideally suited to participate in these prospective investigations.

描述（由申请人提供）： 新生儿胆汁淤积性肝病，包括 Alagille 综合征、α-1 抗胰蛋白酶缺乏症、胆汁酸合成缺陷、胆道闭锁、囊性纤维化、线粒体肝病和进行性家族性肝内胆汁淤积，导致儿童期显着的发病率和死亡率，并且经常需要肝移植。美国没有一个临床中心拥有足够多的患有这些疾病的患者，无法对尚未解决的问题提供严格的答案，包括病因和发病机制、最佳诊断和治疗方法以及影响疾病严重程度和预后的因素。 UPMC 匹兹堡儿童医院匹兹堡胆汁淤积性肝病联盟的这项竞争性更新提案旨在继续胆道闭锁研究联盟 (BARC) 和胆汁淤积性肝病联盟 (CLiC) 中正在进行的研究活动，作为新成立的儿童肝脏的一部分疾病研究和教育网络 (ChiLDREN)。这项更新资金申请包括对继续正在进行的研究工作的坚定承诺和两项新提案，一项基于现有的研究基础设施，另一项基于新颖的临床试验。 CHP临床中心拥有一批优秀的临床医生 在基础、转化和临床研究方面拥有丰富专业知识的研究人员。迄今为止，BARC 和 CLiC 正在进行的研究的表现堪称典范，并充分利用了宾夕法尼亚州西部的人口基础以及 CHP 作为儿科肝病学和肝移植四级中心的独特转诊模式。将分析现有的 BARC 数据库，以评估胆汁流动不良的胆道闭锁儿童的临床病程。据推测，对这组患者进行先发性肝移植将产生更好的总体结果。还提出了一项肠道胆汁酸转运抑制剂治疗与家族性肝内胆汁淤积 1 疾病相关的瘙痒的随机试验。该试验的主要终点是瘙痒评分的变化，而次要终点是 包括血清和粪便胆汁酸的变化。 相关性：损害肝脏分泌胆汁能力的婴儿疾病（例如胆道闭锁）是儿童期肝移植的主要适应症。多中心前瞻性研究对于改善受这些疾病困扰的儿童的健康至关重要。匹兹堡儿童医院的匹兹堡胆汁淤积性肝病联盟非常适合参与这些前瞻性研究。