Table 2.

Epidemiologic studies examining environmental risk factors for NAFLD (2013–2018)

Study	Location	Study design	Time period	Study population	Exposure	Exposure assessment	Outcome	Main findings
Heavy metals
Lin et al. (2017) [33]	Taiwan	Crosssectional	2014	Hospital-based; n=1,137 individuals receiving transabdominal sonography	Heavy metals: arsenic, cadmium, chromium, copper, lead, mercury, nickel, zinc	Residential township linked with survey of soil heavy metal concentrations	NAFLD (n=301) using transabdominal sonography; exclusions for drug history of total parenteral nutrition, long-term use of estrogen, tamoxifen, amiodarone, sodium valproate, methotrexate or corticosteroids	Heavy metals exposures was associated with NAFLD among males (OR 1.83, 95% CI 1.16–2.90) but not females (OR 1.06, 95% CI 0.57–1.96) adjusting for age, BMI, metabolic syndrome, smoking, alcohol consumption, SES
Hyder et al. (2013) [83]	US	Crosssectional	1988–1994	National Health and Nutrition Examination Survey (NHANES)	Heavy metals: cadmium	Creatinine-corrected urinary cadmium	NAFLD (n=1,175 males and n=1,147 females) using gallbladder ultrasound videotapes and ALT or AST levels; exclusions for heavy alcohol consumption or zydovudine or didanosine use	Higher urinary cadmium levels (≥0.65 μg/g for males and ≥0.83 μg/g for females) compared to lower levels were associated with NAFLD among males (OR 1.30, 95% CI 1.01–1.68) but not females (OR 1.11, 95% CI 0.88–1.41) adjusting for age, race/ethnicity, education, smoking, pack years, sedentary lifestyle, BMI, alcohol consumption, total cholesterol
Trihalomethanes
Burch et al. (2015) [82]	US	Crosssectional	1999–2006	NHANES	THM	Blood THM	NAFLD (n=353) using elevated ALT levels (>40 IU/L for males; >30 IU/L for females); exclusions for heavy alcohol consumption, HBV, HCV, self-reported liver cancer, or high transferrin saturation levels	Higher total THM levels (highest tertile mean 62.0 ± 88.9 pg/mL) compared to lower levels (mean 7.4 ± 2.5 pg/mL) were not associated with NAFLD (OR 1.23, 95% CI 0.87–1.72) adjusting for age, race, smoking, BMI, alcohol consumption, selfreported high BP, diastolic BP, total cholesterol, albumin
Methyl tert-butyl ether
Yang et al. (2016) [84]	China	Crosssectional	2014	Petrol station attendants (n=71)	MTBE	Personal exposure monitoring using charcoal-based organic vapor monitor	NAFLD (n=11) using abdominal ultrasonography; exclusions for heavy alcohol consumption, HBV, HCV, autoimmune hepatitis, primary biliary cirrhosis, or other chronic liver disease	Higher MTBE exposure (≥300 μg/m3) compared to lower exposure (≤100 μg/m3) was suggestively associated with NAFLD (OR 1.52, 95% CI 0.93–1.61) adjusting for age, sex, physical activity, BMI, SBP, DBP, ALT, WBC, TC, TG, LDL, HDL
Selenium
Yang et al. (2016) [85]	China	Crosssectional	2011–2012	Shanghai subsample of Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal study (REACTION) (n=8,550)	Selenium	Plasma selenium	NAFLD (n=3,732) using ultrasonography; exclusions for heavy alcohol consumption or history of liver disease	Higher selenium levels (>247.4 μg/L) compared to lower levels (<181.6 ug/L) were associated with NAFLD (OR 1.54, 95% CI 1.13–2.18) adjusting for age, sex, BMI, smoking, alcohol consumption, physical activity, waist circumference, SBP, DBP, fasting plasma glucose, post-loading plasma glucose, HOMA-IR, lipid profiles and estimated glomerular filtration rate, ALT, AST, GGT, CRP

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CRP, C-reactive protein; DBP, diastolic blood pressure; GGT, gamma-glutamyltransferase; HDL, high-density lipoprotein; HOMA-IR, Homeostatic Model Assessment of Insulin Resistance; LDL, low-density lipoprotein; MTBE, methyl tert-butyl ether; NAFLD, nonalcoholic fatty liver disease; OR, odds ratio; SBP, systolic blood pressure; SES, socioeconomic status; TC, total cholesterol; TG, triglyceride; THM, trihalomethane; WBC, white blood cell.