The role of environment contaminants in the development of NAFLD

18 Nov 2021

As the prevalence of non alcoholicfatty liver disease (NAFLD) is progressively increasing worldwide (reaching almost 25% of the population worldwide [Ref 1]), many risk factors are being identified in order to possibly use them as therapeutic targets. Up to now, the risk factors that have been more studied are those related to the patient themselves, i.e. connected to clinical and molecular “internal” mechanisms. In fact, the most studied factors related to NAFLD are commonly metabolic syndrome (especially diabetes mellitus), unbalanced diet (high-fructose diet, high fat diet), PNPLA3 genepolimorphism, which regulates lipolysis of hepatocyte lipid droplets and is the most strongly associated genetic variant linked to NASH, endocrine disorders such as polycystic ovary syndrome, hypothyroidism, GH deficiency, congenital and acquired lipodystrophy and drug-associated NAFLD (amiodarone, methotrexate, tamoxifen) [Ref 2-5].

Recently, the role of the so-called endocrine-disrupting chemicals (EDCs) has become of great interestas risk factors for the development of NAFLD. EDCs are chemicals or mixtures of chemicals that interfere with the normal hormonal function. For instance, some EDCs act like “hormone mimics”, other are hormone antagonists, some EDCs increase or decrease the plasmatic levels of hormones or modify the sensitivity of the body different hormones. EDCs are commonly present in the environment (i.e. air, soil, or water supply), food sources, personal care products and manufactured products. Among the most common EDCs there are certainly perfluorinated alkyl substances (PFAS), which are commonly present in many everyday objects, such as grease-resistant paper, fast food containers/wrappers, pizza boxes, nonstick cookware, water resistant clothing, cleaning products. Experimental studies demonstrate that PFAS gradually accumulate in the liver, where they interfere with glucose and lipid metabolism, elevating liver enzymes, and exacerbating the effect of a fat-rich diet [Ref 6]. A recent study by Sen P. et al. tried to investigate the impact of PFAS exposure on the human liver metabolome [Ref 7].

They analyzed liver biopsies from 105 individuals undergoing laparoscopic bariatric surgery and assessed the presence of metabolites and environmental contaminants using four mass spectrometry-based analytical platforms. According to this study, serum concentrations of PFAS were positively associated with liver fat content and were associated both with NASH and hepatic fibrosis. Moreover, PFAS were associated with content percent of hepatic macrosteatosis, HOMA index, stage of NASH, liver fibrosis, cholesterol biosynthesis. Interestingly, the  levels  of  PFAS  were  higher  in  females  with  NAFLD.

In summary, this study demonstrates how circulating PFAS concentrations are associated with perturbations in key hepatic metabolic pathways that are known to be altered in patients with NAFLD, with females being more sensitive to chemical exposure than males. It is therefore important to prevent these further possible mechanisms of liver damage by paying attention to the choices we made every day. As NAFLD prevention is not related only to food choices but also to healthy lifestyle options, intervening also on the choice of safe everyday tools becomes increasingly fundamental in this context.


  1. Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2018 Jan;67(1):123-133.
  2. Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, George J, Bugianesi E. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev GastroenterolHepatol. 2018 Jan;15(1):11-20.
  3. Portillo-Sanchez P, Bril F, Maximos M, Lomonaco R, Biernacki D, Orsak Bet al. High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels. J Clin Endocrinol Metab. 2015 Jun;100(6):2231-8.
  4. Eslam M, Valenti L, Romeo S. Genetics and epigenetics of NAFLD and NASH: Clinical impact. J Hepatol. 2018 Feb;68(2):268-279.
  5. Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies. Nat Med. 2018 Jul;24(7):908-922.
  6. Deierlein AL, Rock S, Park S. Persistent Endocrine-Disrupting Chemicals and Fatty Liver Disease. Current Environmental Health Reports 2017;4:439-449 obesity. Liver Int. 2021 Oct;41(10):2295-2307.
  7. Sen P, Qadri S, Luukkonen PK, Ragnarsdottir O, McGlinchey A, Jäntti S et al. Exposure to environmental contaminants is associated with altered hepatic lipid metabolism in non-alcoholic fatty liver disease. J Hepatol. 2021 Oct 7:S0168-8278(21)02104-8.