(NAFLD), say the authors of a comprehensive evidence review.
They found “consistent” evidence for PFAS hepatotoxicity from rodent studies. In addition, exposure to PFAS was found to be associated with markers of liver function in observational studies in people.
The review, published online in Environmental Health Perspectives, may be the first systematic analysis of PFAS exposure and liver damage.
Possible contributor to growing NAFLD epidemic
In their analysis, the authors included 85 rodent studies and 24 epidemiologic studies, primarily involving people from the United States and largely focusing on four “legacy” PFAS: perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS).
Meta-analyses of human studies found that higher levels of alanine aminotransferase were significantly associated with exposure to three of the older chemicals – PFOA, PFOS, and PFNA.
The “positive” and “convincing” associations between exposure to these synthetic chemicals and higher ALT levels suggest that exposure may contribute to the growing NAFLD epidemic, the researchers write.
Exposure to one of the chemicals, PFOA, was also associated with higher aspartate aminotransferase and gamma-glutamyl transferase levels in people.
In rodents, exposure to these synthetic chemicals consistently resulted in higher ALT levels and steatosis.
“The mechanism is not well understood yet, but there are a few proposed theories,” first author Elizabeth Costello, MPH, PhD student, department of population and public health sciences, University of Southern California, Los Angeles, told this news organization.
“PFAS are similar to fatty acids in chemical structure, so it’s possible that they activate some of the same receptors or otherwise interfere with fat metabolism. This might lead to inflammation or fat accumulation in the liver,” Ms. Costello explained.
People widely exposed
PFAS are ubiquitous in the environment. They have been detected in the blood of most people and have been linked to a variety of health concerns. Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and even drinking water.
“We are exposed to PFAS in so many ways – through water, food, and products we use. It can be very difficult for individuals to control their own exposure,” Ms. Costello commented.
“At this point, it’s important to look for ways to remove PFAS from the environment and phase them out of our products and carefully consider the safety of any replacement chemicals,” she said.
Although most of the research to date has been limited to the four older PFAS (PFOA, PFOS, PFNA, and PFHxS), there are thousands of different PFAS chemicals.
“We don’t know very much about the effects of exposure to multiple PFAS at the same time or how newer replacement PFAS might affect liver disease or other health conditions,” Ms. Costello said.
Reached for comment, Lisa B. VanWagner, MD, with Northwestern University, Chicago, said this analysis is “very interesting,” but she is also “left wondering how we could do anything since it seems from my reading that these chemicals are ubiquitous and used regularly in the environment.”
Dr. VanWagner, who was not involved in the study, said the major limitation is the small number of human studies and the high heterogeneity between studies, “meaning it is hard to come to a firm conclusion about whether what has been observed in the animal studies does truly apply to humans.
“Overall, this study provides important proof of concept for future work to look more specifically at PFAS exposure, and more specific markers of fatty liver disease and liver damage, like liver biopsy, are needed in humans,” Dr. VanWagner said.
“If data accumulate showing that these chemicals do in fact contribute to fatty liver and worsening inflammation or liver damage as a result of exposure, then public health interventions to remove or reduce use of these chemicals could have wide-ranging public health effects,” Dr. VanWagner added.