The sex-specific effects of blood lead, mercury, and cadmium levels on hepatic steatosis and fibrosis: Korean nationwide cross-sectional study

Aim: The potential effects of heavy metals on non-alcoholic fatty liver disease (NAFLD) remain unknown. We investigated the sex-specific relationships of blood lead (BPb), mercury (BHg), and cadmium (BCd) levels with hepatic steatosis (HS) and fibrosis (HF). Method: We included 4420 participants from the 2016-2017 Korea National Health and Nutrition Examination Survey. High-risk alcoholics and patients with chronic hepatitis B or C infections or liver cirrhosis were excluded. We calculated the hepatic steatosis index (HSI) and fibrosis-4 index (FIB-4) values; we defined the presence of HS and HF as an HSI >= 36 and FIB-4 score > 2.67, respectively. We adjusted for age, smoking and alcohol consumption statuses, hypertension, obesity, diabetes, hypertriglyceridemia, and BPb, BHg, and BCd levels. Result: In males (n = 1860), the HSI was correlated negatively with the BPb level and positively with the BHg level (both p < 0.01). The FIB-4 score was correlated positively with the BPb and BCd levels (both p < 0.01). In females (n = 2560), the HSI and FIB-4 score were correlated positively with the BPb, BHg, and BCd levels (all p < 0.01). After adjustments, the BHg level increased the risk of HS in both males (OR = 1.065, p = 0.003) and females (OR = 1.061, p = 0.048), and the BCd level increased the risk of HF in females (OR = 1.668, p = 0.012). Conclusion: Blood heavy metal levels were generally correlated positively with the HSI and FIB4 score, more so in females than males. The BHg level was associated with HS in males and females, and the BCd level was associated with HF in females. Further studies on NAFLD progression according to heavy metal status and sex are warranted.