Association between heavy metal exposure and biomarkers for non-alcoholic fatty liver disease in Korean adolescents

Objectives: The global prevalence of non-alcoholic fatty liver disease (NAFLD) in adolescents has increased. In addition to childhood obesity, environmental risk factors, such as heavy metals that are known to be involved in hepatotoxicity, play role in NAFLD occurrence. However, their association with NAFLD remains unclear. This study aimed to investigate the association between heavy metal exposure and NAFLD biomarkers in adolescents.

Methods: In this cross-sectional study, we used the data of a total of 1505 adolescents aged 12-17 years who participated in the Korean National Environmental Health Survey III (2015-2017) and IV (2018-2020). The presence of blood lead (BPb), blood mercury (BHg), urinary mercury (UHg), and urinary cadmium (UCd) were measured. Liver enzymes including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were evaluated. For NAFLD biomarkers, the hepatic steatosis index (HSI) was calculated. Multivariate linear regression models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) model were used to investigate the association between heavy metals and NAFLD biomarkers.

Results: Among heavy metals, mercury presence showed a significant association with NAFLD biomarkers. Two-fold increases in BHg and UHg were associated with 0.21 points (95 % confidence interval [CI]: 0.08-0.35) and 0.19 points (95 % CI: 0.09-0.30) higher HSI, respectively. In the WQS model, heavy metal mixture was significantly associated with increased HSI (β = 0.06, 95 % CI: 0.01-0.11). Similarly, in the BKMR model, heavy metal mixture was positively associated with NAFLD biomarkers, and BHg was the most important contributor in the association.

Conclusions: BHg and UHg were significantly associated with NAFLD biomarkers in adolescents, indicating that organic and inorganic mercury exposure could potentially be a risk factor for NAFLD. To mitigate and address the risk of NAFLD associated with heavy metal exposure, it is imperative to take measure to reduce avoidable mercury exposure is necessary.