A Multi-Center Group to Study Acute Liver Failure

 描述（由申请人提供）：自1998年以来，急性肝衰竭研究组（ALFSG）在美国提供了一个网站网络，致力于学习和传播有关急性肝衰竭的新知识，急性肝衰竭是一种超级孤儿疾病，经常杀死年轻人，并涉及高资源利用率，尽管它很罕见。几乎没有任何治疗方法可以保护肝功能，避免肝细胞质量突然丧失的可怕后果。ALFSG已经收集和传播了2,500多名患者的重要临床信息和生物样本，并进行了N-乙酰半胱氨酸对照试验和鸟氨酸苯乙酸盐（OPA）的安全性试验作为假定的治疗选择。此外，ALFSG还为对乙酰氨基酚（APAP）在美国患者ALF中的核心作用提供了新的见解，并进一步表征了许多其他病因，如甲型肝炎、B型肝炎、自身免疫性肝炎和缺血性肝病，以及关注疾病结局和移植的作用。利用我们的数据和生物样本已经启动了90多项辅助研究，产生了约70篇关于ALF各个方面的原创文章。随着我们在2010年对研究中心的重新调整和随后增加的4个研究中心，入组人数增加，这将有助于更快地完成即将进行的试验。入院时正确评估病因和预后是治疗ALF的关键。我们的新举措旨在加强我们的诊断和预后评估，通过即时检测进行进一步测试：对乙酰氨基酚加合物测定，肝脏质量的动态测量（美沙西丁呼吸试验），凝血因子在病情中的作用的评估（利用ROTEM血栓弹力图），以及最终测试OPA作为氨捕获剂改善脑病和脑水肿的疗效。其他方法将包括仔细分析因果关系，微调预后评估，并可能在补助周期的后半部分引入肝脏支持机。基因组学、细胞因子、凝血和肝再生的持续研究补充了临床工作，并继续使ALFSG成为其他研究者的里程碑式研究网络和资源。

 DESCRIPTION (provided by applicant): Since 1998, the Acute Liver Failure Study Group (ALFSG) has provided a network of sites across the United States, dedicated to learning and disseminating new knowledge about acute liver failure, a super-orphan condition that frequently kills young people and involves high resource utilization, despite its rarity. Few, if any, treatments have become available to preserve liver function and avoid the dire consequences of the sudden loss of hepatocyte mass. ALFSG has collected and disseminated important clinical information and bio-samples on more than 2,500 patients and conducted a controlled trial of N-acetylcysteine and a safety trial of ornithine phenylacetate (OPA) as putative treatment options. In addition, ALFSG has provided new insights into the central role of acetaminophen (APAP) in ALF in United States patients and further characterized many of the other etiologies such as hepatitis A, hepatitis B, autoimmune hepatitis and ischemic liver disease as well as focusing on disease outcomes and the role of transplantation. More than 90 ancillary studies have been initiated utilizing our data and bio- samples, generating ~70 original articles on all aspects of ALF. With our realignment of sites in 2010 and subsequent addition of 4 more sites, enrollment has increased, and this will facilitate more rapid completion of forthcoming trials. The correct assessment of etiology and prognosis on admission are vital to the management of ALF. Our new initiatives are directed at strengthening our diagnostic and prognostic assessments with further testing via point-of-care assays: the acetaminophen adduct assay, a dynamic measure of hepatic mass (methacetin breath test), evaluation of the role of coagulation factors in the condition (utilizing the ROTEM thromboelastogram), and finally testing the efficacy of OPA as an ammonia-trapping agent to ameliorate encephalopathy and brain edema. Additional approaches will include careful analyses of causality, fine tuning of prognostic assessments and, possibly, and the possible introduction of a liver support machine in the latter part of the grant cycle. Continuing studies of genomics, cytokines, coagulation and hepatic regeneration, compliment the clinical work and continue to make ALFSG a landmark research network and resource for other investigators.