GENETIC AND ENVIRONMENTAL DETERMINANTS OF SUSCEPTIBILITY TO ALCOHOL-INDUCED LIVER DISEASE

Although there is an overall relationship between cumulative alcohol intake and the severity of alcohol-related liver damage, there is considerable variation in individual susceptibility to the hepatotoxic effects of alcohol. In this review I shall discuss what factors appear to influence susceptibility.Women develop liver disease after a shorter period of excessive drinking and at a lower alcohol intake than men. This is partly related to differences in body size and composition between the sexes which result in women having preportionately higher blood alcohol levels than men after a standard drink; this probably explains why women are more susceptible to a variety of alcohol-related problems. Other genetic determinants of susceptibility have until recently proved elusive, but certain HLA types, such as HLA-B8, have been shown to increase the risk of chronic liver damage by up to 50%. No genetic variations in the enzymes responsible for alcohol metabolism have been definitely associated with predisposit...

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