Per- and polyfluoroalkyl substances may be a novel environmental etiology of nonalcoholic fatty liver: a national cross-sectional study

Abstract

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has been on the rise, with nearly one-quarter of the world’s population currently affected by this condition. Per- and polyfluoroalkyl substances (PFAS) have been suggested as emerging and potentially modifiable environmental risk factors for NAFLD. However, relevant epidemiological evidence remains limited. In the present study, 5,348 adult participants were enrolled from the China National Human Biomonitoring study. The fatty liver index (FLI) was computed using waist circumference, body mass index, triglycerides and γ-glutamyltransferase. NAFLD was defined as an FLI value exceeding 30. To explore the associations of PFAS with FLI and NAFLD, weighted multiple linear regression and logistic regression analyses were performed. Weighted quantile sum regression was applied to assess the joint effects of PFAS mixtures on FLI. The weighted prevalence of NAFLD among study participants was 41.8%. Multiple PFAS congeners were positively associated with FLI. PFAS concentrations were categorized into four equal quartiles from the lowest to the highest level. When comparing the highest quartile (Q4) group with the lowest quartile (Q1) group, the adjusted regression coefficients β [95% confidence interval (CI)] for FLI were as follows: perfluorooctanoic acid (PFOA) 3.63 (1.37-5.89), perfluorooctane sulfonic acid 3.11 (0.87-5.35), perfluorononanoic acid 4.20 (1.82-6.59), perfluorohexane sulfonic acid (PFHxS) 3.62 (0.92-6.32), perfluoroheptane sulfonic acid 3.78 (1.31-6.25) and 6:2 chlorinated polyfluoropolyether sulfonic acid 3.65 (1.02-6.29). PFHxS was positively associated with NAFLD. When comparing Q4 group with Q1 group, the adjusted odds ratio (95%CI) was 1.61 (1.04-2.50). Furthermore, fish consumption appeared to attenuate the adverse effects of PFAS on NAFLD. Exposure to PFAS mixtures was positively associated with FLI, with PFOA and PFHxS identified as the major contributing compounds. These findings support that PFAS may act as an emerging and potentially modifiable environmental risk factor for NAFLD, providing new evidence for the environmental determinants of NAFLD.

Keywords

Per- and polyfluoroalkyl substances / fatty liver index / nonalcoholic fatty liver disease / mixture exposure / environmental etiology

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