Who gets alcoholic liver disease: nature or nurture?

The factors determining why fewer than 10% of drinkers develop advanced alcoholic liver disease remain largely unknown. There is a weak relationship between disease risk and the dose and pattern of alcohol consumed. Obesity increases the risk of all stages of alcoholic liver disease, probably reflecting the role of steatosis in the pathogenesis of more advanced disease. Women develop disease at a lower intake than men due, in part, to their lower volume of distribution for alcohol, but also potentially to increased gut permeability to endotoxin. Recent studies suggest a non-gender-linked genetic component to disease susceptibility and recent case-control studies have suggested that polymorphisms of genes encoding cytokines and other immunoregulatory molecules may exert a significant effect. The pattern of polymorphisms associated with risk suggests that antibody-mediated mechanisms play a role in disease pathogenesis. This has implications for treatment and for identifying high risk individuals at an early stage.