Scope of the problem: Alcohol abuse is a leading cause of morbidity and mortality worldwide1'2. Estimates suggest that about 18 million Americans abuse alcohol3 and that Alcoholic Liver Disease (ALD) affects over 10 million people in the United States4. Alcohol abuse's deleterious effects on the liver lead to three pathologically distinct entities: Alcoholic Fatty Liver, Alcoholic Steatohepatitis (ASH) and cirrhosis. Fatty liver occurs in up to 90% of alcoholics, of whom 10-35% have alcoholic hepatitis on liver biopsy5'6. The spectrum of alcoholic hepatitis can range from mild transaminase elevation as the only indication of disease, to severe liver dysfunction with complications such as jaundice, hepatic encephalopathy, ascites, esophageal varices, coagulopathy and coma. In severe cases, reported mortality ranges from 30 to 60%6. Progression to cirrhosis occurs at a variable rate and different studies have reported this outcome in 10 to 30% of affected subjects with ALD. Alcoholic cirrhosis remains among the most common indications for liver transplantation worldwide7.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory Grants (P20)
Project #
5P20AA017837-04
Application #
8379789
Study Section
Special Emphasis Panel (ZAA1-BB)
Project Start
Project End
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$9,399
Indirect Cost
$4,084
Name
Cleveland Clinic Lerner
Department
Type
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195
Zhou, Hao; Yu, Minjia; Zhao, Junjie et al. (2016) IRAKM-Mincle axis links cell death to inflammation: Pathophysiological implications for chronic alcoholic liver disease. Hepatology 64:1978-1993
Chaudhry, Kamaljit K; Shukla, Pradeep K; Mir, Hina et al. (2016) Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice. J Nutr Biochem 27:16-26
Sinasac, D S; Riordan, J D; Spiezio, S H et al. (2016) Genetic control of obesity, glucose homeostasis, dyslipidemia and fatty liver in a mouse model of diet-induced metabolic syndrome. Int J Obes (Lond) 40:346-55
Smathers, Rebecca L; Chiang, Dian J; McMullen, Megan R et al. (2016) Soluble IgM links apoptosis to complement activation in early alcoholic liver disease in mice. Mol Immunol 72:9-18
McCullough, Rebecca L; McMullen, Megan R; Das, Dola et al. (2016) Differential contribution of complement receptor C5aR in myeloid and non-myeloid cells in chronic ethanol-induced liver injury in mice. Mol Immunol 75:122-32
Roychowdhury, Sanjoy; McCullough, Rebecca L; Sanz-Garcia, Carlos et al. (2016) Receptor interacting protein 3 protects mice from high-fat diet-induced liver injury. Hepatology 64:1518-1533
Chaudhry, Kamaljit K; Samak, Geetha; Shukla, Pradeep K et al. (2015) ALDH2 Deficiency Promotes Ethanol-Induced Gut Barrier Dysfunction and Fatty Liver in Mice. Alcohol Clin Exp Res 39:1465-75
Berisha, Stela Z; Brubaker, Greg; Kasumov, Takhar et al. (2015) HDL from apoA1 transgenic mice expressing the 4WF isoform is resistant to oxidative loss of function. J Lipid Res 56:653-64
Golub, Haleigh M; Zhou, Qi-Gang; Zucker, Hannah et al. (2015) Chronic Alcohol Exposure is Associated with Decreased Neurogenesis, Aberrant Integration of Newborn Neurons, and Cognitive Dysfunction in Female Mice. Alcohol Clin Exp Res 39:1967-77
Latchoumycandane, Calivarathan; Nagy, Laura E; McIntyre, Thomas M (2015) Myeloperoxidase formation of PAF receptor ligands induces PAF receptor-dependent kidney injury during ethanol consumption. Free Radic Biol Med 86:179-90

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