Insecticide and metal exposures are associated with a surrogate biomarker for non-alcoholic fatty liver disease in the National Health and Nutrition Examination Survey 2003-2004

Environ Sci Pollut Res Int. 2020 Feb;27(6):6476-6487. doi: 10.1007/s11356-019-07066-x. Epub 2019 Dec 23.


Non-alcoholic fatty liver disease (NAFLD), the most common form of liver disease, affects over 30% of the US population. Our group and others have previously demonstrated that low-level environmental pollutant exposures were associated with increased odds ratios for unexplained alanine aminotransferase (ALT) elevation, a surrogate biomarker for NAFLD, in the adult National Health and Nutrition Examination Survey (NHANES). However, recently, more sensitive and lower ALT cutoffs have been proposed. The objective of this observational study is to utilize these ALT cutoffs to determine new associations between environmental chemicals and the surrogate NAFLD biomarker. Adult NHANES 2003-2004 participants without viral hepatitis, hemochromatosis, or alcoholic liver disease were analyzed in this cross-sectional study. ALT elevation was defined as > 30 IU/L in men and > 19 IU/L in women. Odds ratios adjusted for potential confounders for ALT elevation were determined across exposure quartiles for 17 pollutant subclasses comprised of 111 individual pollutants. The overall prevalence of ALT elevation was 37.6%. Heavy metal and organochlorine insecticide subclasses were associated with dose-dependent increased adjusted odds ratios for ALT elevation of 1.6 (95% CI 1.2-2.3) and 3.5 (95% CI 2.3-5.5) respectively, for the highest vs. lowest exposure quartiles (ptrend < 0.01). Within these subclasses, increasing whole blood levels of lead and mercury, and lipid-adjusted serum levels of dieldrin, and the chlordane metabolites, heptachlor epoxide, and trans-nonachlor, were associated with increased odds ratios for ALT elevation. In conclusion, organochlorine insecticide, lead, and mercury exposures were associated with ALT elevation and suspected NAFLD in adult NHANES 2003-2004.

Keywords: ALT; Insecticides; Metals; NHANES; Non-alcoholic fatty liver disease (NAFLD); Toxicant-associated steatohepatitis (TASH).

MeSH terms

  • Adult
  • Alanine Transaminase
  • Biomarkers / metabolism
  • Cross-Sectional Studies
  • Environmental Exposure / statistics & numerical data*
  • Environmental Pollutants / metabolism
  • Environmental Pollutants / toxicity*
  • Female
  • Humans
  • Insecticides / metabolism
  • Insecticides / toxicity*
  • Male
  • Metals / metabolism
  • Metals / toxicity*
  • Non-alcoholic Fatty Liver Disease / epidemiology
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Nutrition Surveys
  • United States / epidemiology


  • Biomarkers
  • Environmental Pollutants
  • Insecticides
  • Metals
  • Alanine Transaminase