A Multi-Center Group to Study Acute Liver Failure in Children

研究儿童急性肝衰竭的多中心小组

• 批准号: 7909350
• 负责人: ROBERT H SQUIRES
• 金额: $ 15万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7909350
• 关键词: Acetaminophen; Acetylcysteine; Active Sites; Acute; Acute Liver Failure; Adolescent; Adult; Age; Antidotes; Autoimmune Hepatitis; Biological; Blood Coagulation Disorders; Canada; Cells; Child; Childhood; Classification; Clinical; Clinical Data; Clinical Trials; Collaborations; Collection; DNA; Data; Data Set; Defect; Diagnosis; Double-Blind Method; Encephalopathies; Enrollment; Epidemiology; Etiology; Functional disorder; Funding; Funding Mechanisms; Future; Growth; Immune; Infant; Ingestion; Injury; Intravenous; Laboratories; Link; Liver; Liver diseases; Measures; Modeling; National Institute of Diabetes and Digestive and Kidney Diseases; Natural Killer Cells; Organ failure; Outcome; Pathogenesis; Patients; Pattern; Placebos; Population; Prevalence; Principal Investigator; Proteins; Recording of previous events; Registries; Reporting; Research Ethics Committees; Research Personnel; Resources; Role; Safety; Sampling; Serum; Site; Specimen; System; Testing; Tissues; Toxic effect; United States National Institutes of Health; Viral hepatitis; adduct; age group; cohort; fatty acid metabolism; fatty acid oxidation; follow-up; innovation; liver transplantation; male; outcome forecast; parent grant; prospective; randomized placebo controlled trial; repository; response

The Pediatric Acute Liver Failure Study Group (PALFSG) is the first multi-center, multi-national collaboration to identify, characterize, and develop management strategies for infants, children and adolescents who present with acute liver failure (ALF). Initial funding and support came through the Acute Liver Failure Study Group (NIH 1R01-DK58369-01, William Lee, MD, P.I). This proposal is to establish independent NIH funding to support the current and future activities of this pediatric consortium. PALFSG includes 24 active sites (21 in the U.S., 1 in Canada and 2 in the U.K.) which have collected detailed clinical data from 293 children. We have already redefined ALF in children, demonstrated that the etiologies of ALF in children differs greatly from those seen in adults, described unique features of autoimmune hepatitis associated ALF, and are now conducting a clinical trial using intravenous (IV) N-acetylcysteine (NAC) to treat non- acetaminophen ALF. The Specific Aims of this application are: (1) To collect, maintain, analyze and report clinical, epidemiological, and outcome data in children with ALF, including information derived from serum, tissue, and DNA specimens. Long-term outcome data on patients not enrolled in other NIH-funded pediatric consortia will be collected through the PALFSG. To conserve resources, the NIDDK repositories for tissue, DNA and serum will be utilized. These data will be used to develop predictors of prognosis, analyzetrends, and provide materials to investigators. (2) To identify unrecognized mechanisms of hepatocellular injury resulting in ALF in children. Studies will assess the impact of fatty acid oxidation defects, NK cell dysfunction, and acetaminophen on the pathogenesis of ALF. Through these studies, noveltreatment strategies may be developed. (3) To continue and complete the double-blind, randomized, placebo controlled trial of NAC to treat non-acetaminophen ALF. The purpose is to examinethe safety and efficacy of IV NAC in children with ALF for whom there is no antidote or other specific treatment.

儿科急性肝功能衰竭研究组（PALFSG）是第一个多中心，多国合作 确定、描述和制定针对以下儿童、儿童和青少年的管理策略： 急性肝衰竭（ALF）。最初的资金和支持来自急性肝衰竭研究 组（NIH 1R01-DK58369-01，William Lee，MD，P.I）。这一建议是建立独立的NIH 资助，以支持该儿科联盟的当前和未来活动。PALFSG包括24个活跃的 研究中心（21个在美国，1个在加拿大，2个在英国）他们收集了293名患者的详细临床数据， 孩子我们已经重新定义了儿童ALF，表明儿童ALF的病因 与成人中观察到的有很大不同，描述了自身免疫性肝炎相关ALF的独特特征， 目前正在进行一项临床试验，使用静脉注射（IV）N-乙酰半胱氨酸（NAC）治疗非- 对乙酰氨基酚本应用程序的具体目的是：（1）收集、维护、分析和报告 ALF儿童的临床、流行病学和结局数据，包括来自血清的信息， 组织和DNA样本未入组其他NIH资助的儿科研究的患者的长期结局数据 财团将通过PALFSG收集。为了节约资源，NIDDK组织库， 将使用DNA和血清。这些数据将被用于发展预测预后，分析趋势， 并向调查人员提供材料。(2)识别未被识别的肝细胞损伤机制 导致儿童ALF。研究将评估脂肪酸氧化缺陷、NK细胞 功能障碍和对乙酰氨基酚对ALF发病机制的影响。通过这些研究， 可以制定战略。(3)继续并完成双盲、随机化、安慰剂 NAC治疗非对乙酰氨基酚ALF的对照试验。目的是检验其安全性和有效性 在没有解毒剂或其他特定治疗的ALF儿童中静脉注射NAC。