Background: Effects of chronic cadmium exposure on liver disease and liver-related mortality are unknown. We evaluated the association of creatinine-corrected urinary cadmium levels with hepatic necroinflammation, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver-related mortality, and liver cancer mortality in the US general population. Methods: We analyzed the relationship of individuals in the top quartile for urinary cadmium measured in 12,732 adults who participated in the Third National Health and Nutrition Examination Survey in 1988-1994 (NHANES III), and hepatic necroinflammation, NAFLD, and NASH. Associations between cadmium, liver-related mortality, and liver cancer mortality were evaluated in the NHANES III mortality follow-up study. Results: The cutoffs for highest quartile of urinary cadmium per gram of urinary creatinine were 0.65 and 0.83 μg/g for men and women, respectively (P < 0.001). After multivariate adjustment for other factors including smoking, the odds ratios [95 % confidence intervals (CI)] for hepatic necroinflammation, NAFLD, and NASH associated with being in the top quartile of cadmium levels by gender, were 2.21 (95 % CI, 1.64-3.00), 1.30 (95 % CI, 1.01-1.68) and 1.95 (95 % CI, 1.11-3.41) for men and 1.26 (95 % CI, 1.01-1.57), 1.11 (95 % CI, 0.88-1.41) and 1.34 (95 % CI, 0.72-2.50) for women, respectively. The hazard ratios for liver-related mortality and liver cancer mortality for both genders were 3.42 (95 % CI, 1.12-10.47) and 1.25 (95 % CI, 0.37-4.27). Conclusions: Environmental cadmium exposure was associated with hepatic necroinflammation, NAFLD, and NASH in men, and hepatic necroinflammation in women. Individuals in the top quartile of creatinine-corrected urinary cadmium had over a threefold increased risk of liver disease mortality but not in liver cancer related mortality.
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