S1065 Arsenic Exposure and Risk of Liver Injury Among U.S. Adults: An Association Modified by Gender

Abstract

INTRODUCTION: Arsenic has toxic effects on multiple organ systems; however, arsenic toxicity on the liver has not been well explored. Therefore, we examined the association between arsenic exposure and serum ALT, a marker for liver injury and effect modification by gender. METHODS: Individuals >19 years of age from 7 cycles of the National Nutrition and Health Examination Survey (NHANES 2003–16) were included. Associations between serum ALT and creatinine-standardized urinary concentrations of total and 7 arsenic forms were examined. Data were summarized with mean (standard deviation) or frequencies. Urinary arsenic and serum ALT were log-transformed due to right-skewed distributions. We used survey-weighted linear regression without and with adjustments for gender, age, diabetes, hypertension, race, smoking, alcohol use, estimated GFR, and body mass index(BMI). Effect-modification by gender was examined by with an interaction term between gender and arsenic forms. RESULTS: Of the 12,439 participants, 52% were females, 33% hypertensives, 9% were diabetics, 54% were non-smokers, and 68% were whites. The mean age was 48 years. BMI 29 Kg/m2, ALT 26 U/L, and total urinary arsenic 18.4 ug/L. As compared to females, males had significantly higher ALT (30.3 vs 21.9; P < 0.001) and total urinary arsenic levels (19.7 vs 17.3 P = 0.02). In adjusted models, each 10% increase in urinary total arsenic, dimethylarsonic acid, trimethylarsine oxide was associated with 0.1%, 0.4%, and 0.2% increase in serum ALT respectively (all P-values< 0.01); ALT increase with other urinary arsenic forms was not significant. Females had larger increases in ALT than males for 5 arsenic forms; for each 10% increase in arsenous acid, arsenic acid, arsenocholine, monomethylarsonic acid, and dimethylarsenic acid were associated with 0.3%, 0.6%, 0.4%, 0.6%, and 0.4% larger increase in ALT than males (all P < 0.05) (Figure). CONCLUSION: Urinary arsenic levels within an acceptable range (total urinary arsenic< 100ug/L) are associated with a small but significant risk of liver injury as measured by elevation in serum ALT. Females are particularly at a higher risk of liver injury than males. The clinical significance of this liver injury needs examination in longitudinal studies.Figure 1