Abstract

INTRODUCTION: Industrial chemical exposure is an increasingly recognized entity in NAFLD and NASH. Perfluorooctanoate (PFOA) has been widely used in industrial manufacturing, and is linked to cardiovascular, thyroid, oncologic, and liver disease. This study examines its association with NAFLD and Advanced Fibrosis using U.S. nationally representative data. METHODS: A population of 2,833 non-pregnant individuals ages 18-74 were included in this secondary analysis of NHANES 2011-2016. Exclusion criteria: AST/ALT > 500 IU/L, alcohol > 10 drinks/week (females)/ >20 drinks/week (males), transferrin saturation > 50%, positive hepatitis B and C serology. NAFLD was defined by Fatty Liver Index score > 60. Advanced fibrosis was defined by National Fibrosis Score > 0.676. Student’s T-test was used for continuous and Rao-Scott Chi-Square test for categorical variables. Comparison across quartiles were done with simple linear regression for continuous, Rao-Scott Chi-Square test for categorical variables. Demographics and patient confounders were adjusted using multivariate logistic regression (SAS 9.4) for odds of NAFLD/Advanced Fibrosis with respect to PFOA quartile. RESULTS: NAFLD compared to non-NAFLD cohort were significantly more likely to be older, male, less educated, obese, have higher HbA1C, rates of diabetes, hypertension, insulin resistance, more likely Latino, and have higher total cholesterol (see Table 1). For NAFLD, adjusted regression analysis show a positive trend for NAFLD with increased PFOA quartile (Q3, OR 1.16, 95% CI 0.60–2.22), (Q4, OR 1.63, 95% CI 0.88–3.03), and on stratification the association was significant for BMI >30 (Q4 OR 3.25, 95% C.I. 1.33–7.95). Unadjusted regression analysis, participants with increased PFOA exposure were more likely to have Advanced Fibrosis (Q4 OR 1.74, 95% CI 1.03–2.98), and this association was seen particularly in females, smokers, and the obese with advanced fibrosis (Q4 OR 2.99, 95% CI 1.90–4.72), (Q4 OR 2.71, 95% CI 1.30–5.68), (Q4 OR 2.09, 95% CI 1.17–3.72), but was attenuated after adjustment. CONCLUSION: Our findings show a significant association for NAFLD in obese patients with increased PFOA exposure. Both NAFLD and Advanced fibrosis show a positive trend with increased PFOA exposure. This study highlights that PFOA, an established carcinogen and toxic industrial contaminant, may play a role in NAFLD and related comorbidities in the US population. Further studies are needed for confirmation.

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