Arsenic exposure and risk of nonalcoholic fatty liver disease (NAFLD) among US adolescents and adults: an association modified by race/ethnicity, NHANES 2005-2014

Background: While associated with obesity, the cause of the rapid rise in prevalence of nonalcoholic fatty liver disease (NAFLD) in children, which is highest among Hispanics, is not well understood. Animal experiments have demonstrated that arsenic exposure contributes to liver injury. Our objective was to examine the association between arsenic exposure and NAFLD in humans and to determine if race/ethnicity modifies the association. Methods: Urinary inorganic arsenic concentrations among those >= 12 years in the National Health and Nutrition Examination Survey, 2005-2014 were used to assess the cross-sectional association with serum alanine aminotransferase (ALT) levels, a marker of liver dysfunction. We excluded high alcohol consumers (>4-5 drinks/day; n = 939), positive hepatitis B or C (n = 2330), those missing body mass index (n = 100) and pregnant women (n = 629) for a final sample of 8518. Arsenic was measured using liquid chromatography coupled with mass spectrometry and ALT was measured using standard methods. Sampling weights were used to obtain national estimates. Due to lack of normality, estimates were log transformed and are presented as geometric means. Logistic regression models controlling for age, sex, income, and weight category estimate adjusted odd ratios (aOR) of elevated ALT by quartile of arsenic and tested for effect modification by race/ethnicity and weight. Elevated ALT was defined as >25 IU/L and >22 IU/L for boys and girls >= 17 years, respectively and >30 IU/L and >19 IU/L for men and women, respectively. Results: Among all, aOR of elevated ALT were higher among those in the highest vs. lowest arsenic quartile (referent), 1.4 (95% confidence interval [CI]: 1.1, 1.7) with a borderline significant interaction (p = 0.07) by race/ethnicity but not weight (p = 0.4). In analysis stratified by race/ethnicity, aOR of elevated ALT among those in the 4th quartile were higher among Mexican Americans, 2.0 (CI: 1.3, 3.1) and non-Hispanic whites only, aOR 1. 4 (CI: 1.1, 1.8) despite the fact that obesity prevalence was highest among non-Hispanic blacks. Conclusions: Our findings demonstrate a positive association between urinary arsenic exposure and risk of NAFLD among U.S. adolescents and adults that is highest among Mexican Americans and among those obese, regardless of race/ethnicity.