Non-alcoholic fatty liver disease (NAFLD) is a public health epidemic. In parallel with the growing obesity epidemic, prevalence of NAFLD has significantly increased in recent years and become one of the most common causes of chronic liver disease globally. The prevalence of NAFLD is estimated to be about 25% worldwide, whereas cases in the United States are expected to number , or about one-third of all adults, by 2030. Untreated, NAFLD may progress to more serious liver injury such as non-alcoholic steatohepatitis (NASH), cirrhosis, and end-stage liver disease.
Exposure to environmental chemicals has emerged as a significant contributor to liver disease, including NAFLD. Experimental evidence indicates that exposure to per- and polyfluorinated substances (PFAS), a class of endocrine-disrupting chemicals, has the ability to promote metabolic changes that can result in fatty liver. PFAS are synthetic chemicals widely used in industry and consumer products such as stain-resistant fabric and fire retardants. The stable chemical properties that make PFAS ideal for industrial use also allow them to persist and accumulate in the environment, which is of concern because of the potential for long-term human health effects. Recent biomonitoring studies have emphasized the ubiquitous nature of PFAS exposure and have indicated that four congeners of PFAS account for most known human exposure: perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and perfluorononanoic acid (PFNA).
Significant sources of exposure include drinking water, food, indoor and outdoor air, and early life placental or breast milk exposure. PFAS are detected in the serum of nearly all U.S. adults and accumulate in body tissues, such as in the liver. This bioaccumulation, coupled with the long half-lives of many PFAS, leads to concern about the potential for PFAS to disrupt liver homeostasis should they continue to accumulate in human tissue even if industrial use is abated.