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: 7122342
• 负责人: ROBERT H SQUIRES
• 金额: $ 64.62万
• 依托单位: CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
• 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/7122342
• 关键词: acetaminophen; acetylcysteine; adolescence (12-20); child (0-11); clinical research; clinical trials; cooperative study; disease /disorder etiology; drug adverse effect; epidemiology; fatty acid metabolism; human subject; human therapy evaluation; liver disorder chemotherapy; liver failure; natural killer cells; pathologic process; patient /disease registry; patient oriented research; prognosis; tissue resource /registry

DESCRIPTION (provided by applicant): 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, analyze trends, 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, novel treatment 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 examine the safety and efficacy of IV NAC in children with ALF for whom there is no antidote or other specific treatment

描述（由申请人提供）： 儿科急性肝衰竭研究小组 (PALFSG) 是第一个多中心、跨国合作组织，旨在识别、描述和制定患有急性肝衰竭 (ALF) 的婴儿、儿童和青少年的管理策略。最初的资金和支持来自急性肝衰竭研究小组（NIH 1R01-DK58369-01，William Lee，MD，P.I）。该提案旨在建立独立的 NIH 资金来支持该儿科联盟当前和未来的活动。 PALFSG 包括 24 个活动站点（21 个在美国、1 个在加拿大、2 个在英国），收集了 293 名儿童的详细临床数据。我们已经重新定义了儿童 ALF，证明儿童 ALF 的病因与成人的病因有很大不同，描述了自身免疫性肝炎相关 ALF 的独特特征，现在正在进行一项使用静脉注射 (IV) N-乙酰半胱氨酸 (NAC) 的临床试验) 治疗非对乙酰氨基酚 ALF。该应用程序的具体目标是： (1) 收集、维护、分析和报告 ALF 儿童的临床、流行病学和结果数据，包括来自血清、组织和 DNA 样本的信息。未加入其他 NIH 资助的儿科联盟的患者的长期结果数据将通过 PALFSG 收集。为了节约资源，将利用 NIDDK 的组织、DNA 和血清存储库。这些数据将用于开发预后预测因子、分析趋势并为研究人员提供材料。 (2) 确定导致儿童 ALF 的肝细胞损伤的尚未认识的机制。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，可能会开发出新的治疗策略。 (3)继续并完成NAC治疗非对乙酰氨基酚ALF的双盲、随机、安慰剂对照试验。目的是检查 IV NAC 对于没有解毒剂或其他特异性治疗的 ALF 儿童的安全性和有效性