Perfluoroalkyl Substances (PFASs) and Liver Inflammation and Fibrosis in Children with Nonalcoholic Fatty Liver Disease (NAFLD)

摘要

Background: Perfluoroalkyl substances (PFASs) cause liver toxicity in rodents and might contribute to the increased prevalence of NAFLD. Children appear to have higher body burden of PFASs and a more progressive form of NAFLD; however, no previous studies have examined effects of PFASs on liver histology, the gold standard for NAFLD assessment. Methods: Concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonic acid (PFHxS) were quantified in serum of 70 children (7-19 years of age) with biopsy-proven NAFLD, and their associations with liver histological features were examined using multinomial logistic regression models with adjustments for age, sex, ethnicity and BMI Z score. Liver histological features, including grade of steatosis (0-3), lobular inflammation (0-3), portal inflammation (0-2) and fibrosis stage (0-4), were scored according to the NASH Clinical Research Network scoring system. 'Liver inflammation score' was calculated as sum of scores for lobular inflammation and portal inflammation. Results: NAFLD patients were mostly boys (71.4%) and Hispanics (51.4%). The median and interquartile range (IQR) of serum PFOA, PFOS and PFHxS concentrations were 3.42 (1.58), 3.67 (4.48) and 1.53 (3.17) ng/ml, respectively. The odds of having moderate-to-severe inflammation (score >1) compared with no inflammation (score =0) increased with each IQR increase of PFHxS (OR: 3.38, 95% CI: 1.04-10.9). Similarly, the odds of having significant fibrosis (score >2) compared to no fibrosis (score =0) increased by 3.95 (95% CI: 1.23-12.7) with each IQR increase of PFHxS. No statistically significant associations of PFOA and PFOS levels with severity of steatosis, inflammation or fibrosis were observed. Conclusions: PFHxS exposure was associated with severity of liver inflammation and fibrosis in children with NAFLD.