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.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZAA1-JJ (07))
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Orosz, Andras
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Southern California Institute for Research/Education
Long Beach
United States
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Thursz, Mark; Morgan, Timothy R (2016) Treatment of Severe Alcoholic Hepatitis. Gastroenterology 150:1823-34
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