Obesity and hepatotoxins as risk factors for fatty liver disease.

Generally fatty liver disease (FLD) is attributed either to alcohol, diabetes mellitus, or obesity. To evaluate this commonly held clinical belief, a case-control study of FLD in Western Pennsylvania was conducted with 19 cases being identified over a two year period. Cases of FLD were significantly heavier and were significantly more likely than controls to have exposures to either agents with recognised animal hepatotoxicity (odds ratio [OR] 8, p = 0.018) or to agents with potential hepatotoxicity--that is, documented in humans, animals, or expected on the basis of structure activity relations (OR = 4.5; p = 0.18). By contrast, they had not consumed significantly more alcohol than the controls. A logistic regression model of this experience suggests that both exposure to hepatotoxins and obesity are independent risk factors for FLD, which have an additive rather than a multiplicative interaction. Based upon these data, an occupational exposure to either recognised or potential hepatotoxins should be considered as a cause of liver dysfunction in subjects with FLD, independent of obesity and a history of alcohol consumption.