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: 7500567
• 负责人: ROBERT H SQUIRES
• 金额: $ 20万
• 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/7500567
• 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; Etiology; Functional disorder; Funding; Funding Mechanisms; Future; Growth; Immune; Infant; Ingestion; Injury; Intravenous; Laboratories; Link; Liver; Liver Failure; 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; Purpose; 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.

小儿急性肝衰竭研究组 (PALFSG) 是第一个多中心、跨国合作组织 识别、描述和制定针对婴儿、儿童和青少年的管理策略 出现急性肝衰竭（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）。该提案是建立独立的NIH 提供资金支持该儿科联盟当前和未来的活动。 PALFSG 包括 24 个活跃的 站点（美国 21 个、加拿大 1 个、英国 2 个）收集了 293 个患者的详细临床数据 孩子们。我们已经重新定义了儿童ALF，证明了儿童ALF的病因 与成人中看到的有很大不同，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 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。未参加其他 NIH 资助的儿科项目的患者的长期结果数据 联合体将通过 PALFSG 收集。为了节约资源，NIDDK 组织存储库， 将使用 DNA 和血清。这些数据将用于开发预后预测、分析趋势、 并向调查人员提供材料。 (2) 鉴定尚未认识的肝细胞损伤机制 导致儿童出现 ALF。研究将评估脂肪酸氧化缺陷、NK 细胞的影响 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，新的治疗方法 可以制定策略。 (3) 继续并完成双盲、随机、安慰剂研究 NAC 治疗非对乙酰氨基酚 ALF 的对照试验。目的是检查安全性和有效性 对没有解毒剂或其他特异性治疗的 ALF 儿童进行 IV NAC 治疗。