Southern California Alcoholic Hepatitis Consortium Administrative Core

描述（申请人提供）：酒精性肝炎是一种肝脏炎症性疾病，发生在少数慢性酒精中毒患者中，原因不明。酒精性肝炎的病理生理学尚不完全清楚，推荐用于治疗重度酒精性肝炎的泼尼松龙在很大一部分患者中无效。 患者酒精性肝炎的改善将需要使用广泛的、假设独立的方法（例如，蛋白质组学和转录组学）以及有重点的假设驱动的研究。行政核心的总体目标是为科学任务和各个U01项目的具体目标提供行政支持，协助外部咨询委员会监督联合体，并确保实现NIAAA的目标。特别是，该联盟专注于了解和治疗肝脏炎症，并探索酒精性肝炎中肝细胞损伤和再生的途径。该联盟的主要项目是酒精性肝炎新疗法的临床试验。其他五个翻译项目将探索免疫状态，肝脏转录组学，肝脏蛋白质组学，肝细胞线粒体损伤，肝细胞损伤途径和肝细胞再生抑制。项目之间的合作是了解酒精性肝炎病理生理学的核心。行政核心将负责监督项目，鼓励合作，监测单个项目的进展，解决冲突，评估新研究人员的增加，回应与研究有关的科学询问，并保持与NIAAA的沟通。这个U01联盟和管理核心支持NIAAA了解酒精对健康影响的使命，包括酒精性肝损伤的病理生理学和治疗。 公共卫生相关性：该联盟将测试酒精性肝炎的新疗法，并对免疫异常、肝细胞损伤途径和再生抑制进行详细研究。这些研究将有助于更好地了解肝脏是如何受损的，并为更好地治疗酒精性肝炎奠定基础。需要新的治疗方法，因为高达30%的酒精性肝炎患者在目前治疗的前6个月内死亡。

DESCRIPTION (provided by applicant): Alcoholic hepatitis is an inflammatory disease of the liver that occurs for unknown reasons in a minority of chronic alcoholic patients. The pathophysiology of alcoholic hepatitis is incompletely understood and prednisolone, the recommended treatment for severe alcoholic hepatitis, is ineffective in a significant proportion of patients. Improvements in alcoholic hepatitis will require testing of new drugs and detailed investigations of liver and blood using broad, hypothesis independent approaches (e.g., proteomics and transcriptomics) as well as focused, hypothesis driven investigations. The overall aims of the administrative core are to provide administrative support for the scientific missions and specific aims of the individual U01 projects, to assist the External Advisory Board with oversight of the consortium, and to ensure the objectives of the NIAAA are achieved. In particular, this consortium is focused on understanding and treating hepatic inflammation and exploring pathways of hepatocyte injury and regeneration in alcoholic hepatitis. The main project in the consortium is a clinical trial of new treatments for alcoholic hepatitis. The five oher translational projects will explore immune status, transcriptomics of the liver, proteomics of the liver, hepatocyte mitochondrial damage, pathways of hepatocyte injury, and inhibition of hepatocyte regeneration. Collaboration among projects is central to understanding the pathophysiology of alcoholic hepatitis. The administrative core will be responsible for oversight of the projects, encouraging collaboration, monitoring progress of individual projects, resolving conflicts, evaluating the addition of new investigators, responding to scientific inquiries relatedto the research, and maintaining communication with the NIAAA. This U01 consortium and the administrative core support the NIAAA's mission of understanding the health effects of alcohol, including the pathophysiology and treatment of alcoholic liver injury. PUBLIC HEALTH RELEVANCE: This consortium will test new treatments for alcoholic hepatitis and perform detailed studies of the immune abnormalities, pathways of hepatocyte injury and inhibition of regeneration. These studies will lead to a better understanding of how the liver is damaged and will lay the groundwork for better treatments of alcoholic hepatitis. New treatments are needed because up to 30% of patients with alcoholic hepatitis die during the first 6 months with current treatments.