Cadmium Exposure and Liver Disease among US Adults

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. 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. The cutoffs for highest quartile of urinary cadmium per gram of urinary creatinine were 0.65 and 0.83 mu g/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). 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.