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

儿科急性肝衰竭研究小组(PALFSG)是第一个多中心、多国家合作的组织 识别、描述和制定婴幼儿、儿童和青少年的管理策略 出现急性肝功能衰竭(ALF)。最初的资金和支持来自急性肝功能衰竭研究 组(NIH 1R01-DK58369-01，William Lee，MD，P.I.)。这项提议是建立独立的NIH 为支持该儿科联盟目前和未来的活动提供资金。PALFSG包括24个活动 网站(21个在美国，1个在加拿大，2个在英国)已经收集了293份详细的临床数据 孩子们。我们已经重新定义了儿童ALF，证明了儿童ALF的病因 与成人有很大不同，描述了自身免疫性肝炎相关性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ALF。本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、流行病学和预后数据，包括来自血清的信息， 组织和DNA样本。未参加美国国立卫生研究院资助的其他儿科研究的患者的长期结果数据 财团将通过PALFSG收集。为了节约资源，NIDDK组织储存库， 将利用DNA和血清。这些数据将被用来开发预测预后的因素，分析趋势， 并向调查人员提供材料。(2)识别未被认识的肝细胞损伤机制 导致儿童发生ALF。研究将评估脂肪酸氧化缺陷对NK细胞的影响 功能障碍，以及对乙酰氨基酚在ALF发病机制中的作用。通过这些研究，新的治疗方法 可以制定战略。(3)继续并完成双盲、随机、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。

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.