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.
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