PFAS exposure linked to liver disease

About 24% of the world population has non-alcoholic fatty liver disease or NAFLD (Nat. Rev. Gastroenterol. Hepatol. 2017, DOI: 10.1038/nrgastro.2017.109). The condition can progress to more serious liver damage and failure. High-fat diets contribute to the disease, but lifestyle and dietary changes alone don’t account for the prevalence of NAFLD, says Elizabeth Costello, an epidemiology PhD student at the University of Southern California. She and her colleagues found a potential environmental factor.

Costello’s team reviewed the growing body of evidence from epidemiological and animal studies linking liver toxicity to exposure to a class of persistent pollutants called per- and polyfluoroalkyl substances or PFAS (Environ. Health Perspect. 2022, DOI: 10.1289/EHP10092). The human studies typically explored whether elevated levels of PFAS in the blood correlated with elevated levels of three enzymes linked with liver damage. The animal studies were more direct, with researchers dissecting the liver to look for signs of damage and probe biochemical mechanisms.

The researchers found a compelling connection between NAFLD and exposure to three PFAS: perfluorooctanesulfonic acid, perfluorooctanoic acid, and perfluorononanoic acid (PFNA). The evidence for newer PFAS is not as strong, Costello says, but there are not as many studies on these compounds, especially in humans. “Because their chemical structures are similar, we expect the toxic effects will be similar,” she says.

PFAS’ chemical structures resemble those of fatty acids, and in lab studies, they bind to receptors that are typically activated by fatty acids. So exposure to PFAS may have a similar impact on the liver to eating a high-fat diet, Costello says.

In a perspective published with the paper, West Virginia University public health researcher Alan Ducatman and National Institute of Environmental Health Sciences toxicologist Suzanne Fenton write that the work “firmly places PFAS exposure on the list of persistent pollutants” that cause liver damage (Environ. Health Perspect. 2022, DOI: 10.1289/EHP11149).

Costello says her team’s review of studies raises more questions than it answers. For example, more research is needed on how exposure to mixtures of PFAS and other persistent pollutants affects the liver. Most studies focus on single chemicals, but people are exposed to complex mixtures in the environment.