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Background and Aims: Alcoholic Liver Disease (ALD) and Non-Alcoholic Fatty Liver Disease (NAFLD) are highly prevalent liver diseases that may coexist and contribute significantly to liver disease related mortality. We recently reported chronic moderate alcohol exacerbated liver injury in our mouse model of high fat diet (HFD) compared to either alcohol or HFD alone (Duly AMP, Nutr Diab 2015). We have also shown Osteopontin (OPN), increased in patients as the disease progressed to advanced alcoholic cirrhosis. OPN is associated with hepatocellular carcinoma and presence of cirrhosis is a risk for liver cancer. Others have also found elevated OPN expression in NAFLD/NASH patients, suggesting a common pathway between the two diseases. Furthermore, alcohol metabolism generates reactive oxygen species (ROS) and these lipid peroxidation products complex with DNA to form mutagenic and carcinogenic etheno-DNA adducts. Nonetheless, there is little information on the mechanisms of liver injury due to alcohol+HFD and whether co-existence of NAFLD and ALD enhances the risk of liver cancer.

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