Alcoholic liver disease (ALD) represents a major health problem associated with alcohol abuse. It is a progressive disease with the first stage being steatosis and culminating in cirrhosis. An important factor in the development of ALD is metabolism of alcohol. Products of ethanol metabolism including acetaldehyde and reactive oxygen species are toxic to the liver. CYP2E1 is the major catalyst of such reactions and elevated levels of the enzyme which occur in alcoholism. leads to greater production of these toxic metabolites. Much of the hepatocyte damage is believed to be caused by reactive oxygen species Furthermore, one intermediate, 1alpha-hydroxyethyl radical (HER) alkylates to CYP2E1 and results in the formation of HER adducts. These adducts lead to the development of immune reactions and the generation of autoantibodies. In subjects with ALD, high antibody titers against HER adducts are present. Currently, early detection of ALD or identification of individuals predisposed to this disease is suboptimal. Therefore, a convenient screening procedure aimed at identification of patients with early on-set ALD is needed. To address this. we will develop a procedure to detect the autoantibody to the HER adduct in human sera This diagnostic will provide a two-fold advantage. The first being detection of the early stages of ALD, the second to assess hepatic CYP2E1 induction The ability to predict these parameters with a single easy-to-use diagnostic represents a significant contribution to public health. PROPOSED COMMERCIAL APPLICATIONS: The commercial applications of the proposed diagnostic include the ability to screen individuals at risk for ALD. It is a convenient diagnostic that will identify early stages of ALD and hepatic levels of CYP2E1 by detection of a serum autoantibody to the hydroxyethyl radical adduct The prevalence of alcohol abuse throughout the world.and the lack of effective screening tests for ALD suggests the potential for a large market and a public health approach for identifying subjects predisposed to ALD
