Associations between perfluoroalkyl substances and the severity of non-alcoholic fatty liver disease

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide and the determinants driving its severity remain to be elucidated. Perfluoroalkyl substances (PFAS) are synthetic chemical compounds. They are used in commonplace products and persistent in water, soil and the human body. In vitro and animal studies suggest a pathogenic role for PFAS in metabolic diseases such as NAFLD. OBJECTIVES: We aimed to evaluate the association between NAFLD severity and serum PFAS concentrations in humans. METHODS: One hundred biopsy-proven NAFLD patients were included with a well-balanced distribution between the different stages of severity: 25 patients with simple steatosis, 25 with early non-alcoholic steatohepatitis (NASH and F0-F1 fibrosis), 33 with fibrotic NASH (NASH and F2-F3 fibrosis), and 17 with cirrhotic NASH (NASH and F4 fibrosis). Liver histological features were evaluated according to the NASH Clinical Research Network classification. Seventeen PFAS were measured by high-performance liquid chromatography coupled with tandem mass spectrometry on serum samples stored at -80 °C. RESULTS: . Long-chain PFAS were associated with steatosis grade (p = 0.03). Among the nine PFAS detected in > 50 % of the patients, Perfluoro-n-heptanoic acid (PFHpA) showed significantly higher concentrations in grade 3 steatosis versus grade 1 (p = 0.02). Perfluoro-n-dodecanoic acid (PFDoA) concentrations were higher in patients with significant fibrosis (p = 0.04) and PFHpA in patients with advanced fibrosis (p = 0.02). The association between PFHpA and steatosis grade remained significant in multivariate analysis adjusted for age, gender, BMI, diabetes presence and dyslipidemia (p = 0.004). DISCUSSION: Our study showed a significant association between PFHpA and liver steatosis in NAFLD. According to data available in the literature, PFHpA could be implicated in liver steatosis through β-oxidation and biosynthesis of fatty acids.