Alcohol consumption is a major etiology of chronic liver disease worldwide. The morphological spectrum of human alcoholic liver disease includes fatty liver, alcoholic hepatitis, and cirrhosis. In rodents, intragastric infusion of ethanol for 4-5 weeks leads to steatosis, inflammation, and to a less extent fibrosis in the liver, whereas feeding Lieber-DeCarli liquid diet containing ethanol does not cause significant liver injury except steatosis. In humans, interestingly, only a small percentage of heavy drinkers (10-15%) developed alcoholic liver injury, strongly suggesting that alcohol is a cofactor for developing chronic liver disease. Accumulating evidence suggests that many genetic and acquired factors are implicated in the susceptibility of the individual to alcohol-induced liver injury. These factors include chronic viral infection, nutritional factors, the dose and duration of alcohol consumption, pattern drinking, age of onset of drinking, genetic polymorphisms of cytokines and alcohol-metabolizing enzymes, gender, histocompatibility antigens, immunological factors, genetic predisposition to alcohol addiction, and hepatic iron overload. It has been well documented that alcohol consumption accelerates the development and progression of liver disease induced by hepatitis virus infection. Our lab is to study how chronic ethanol consumption potentiates liver injury induced by other toxins or viruses and to study the molecular mechanisms underlying alcohol-induced liver injury. We have demonstrated that alcohol consumption accelerates T cell- and MCMV virus-mediated hepatitis and that treatment with IL-6 ameliorates alcoholic fatty liver disease in mice. Currently, we are studying (1) the hepatoprotective effect of IL-6/STAT3 in alcoholic liver injury and transplantation, (2) the effect of alcohol drinking on liver fibrosis via modulation of the innate immunity, (3) the effect of alcohol drinking on liver progenitor cells. We are also collaborating with Dr. George Kunos to investigate the role of canabinoid in alcoholic liver disease, and with Dr. Jake Liang from NIDDK to study the interaction of alcohol and hepatitis viral proteins in liver injury.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Intramural Research (Z01)
Project #
1Z01AA000369-04
Application #
7146675
Study Section
(LPS)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2005
Total Cost
Indirect Cost
Name
Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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