Review Links PFAS to Nonalcoholic Fatty Liver Disease

Exposure to environmental chemicals is a significant contributor to liver disease, including nonalcoholic fatty liver disease (NAFLD), according to research by Leda Chatzi, M.D., Ph.D., professor of population and public health sciences at the University of Southern California Keck School of Medicine.

Chatzi and a team of researchers said that their research published in Environmental Health Perspectives is the first to systematically review the data on exposure to per- and polyfluorinated substances (PFAS), a class of endocrine-disrupting chemicals, and harm they may do to the liver.

Leda Chatzi

PFAS are synthetic chemicals widely used in industry and consumer products such as stain-resistant fabric and fire retardants, Chatzi wrote. “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.”

They researchers evaluated 111 peer-reviewed studies of both humans and rodents, determining whether PFAS exposure was associated with elevated levels of alanine aminotransferase (ALT), a liver enzyme that is elevated in humans with NFALD

The researchers concluded that three of the most commonly detected PFAS in humans — perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorononanoic acid (PFNA) — are all connected with elevated levels of ALT in the blood of both humans and rodents.

“PFAS are ubiquitous, and we know that all adults in the United States have detectable levels of PFAS in their bodies,” Chatzi said in a press release. “There is growing interest in the long-term health effects of PFAS exposure, and this study supports that there is evidence that PFAS are associated with liver injury.”

The research “clearly shows that PFAS need to be taken seriously as a human health concern because, even after they are phased out, they persist in the environment,” said Elizabeth Costello, M.PH, Ph.D., a student in the Department of Population and Public Health Sciences at the Keck School of Medicine and lead author of the study. “There is enough evidence, we believe, to demonstrate a need to clean up sources of exposure to PFAS and to prevent future exposures.”

The researchers point out that while animal research consistently shows PFAS exposure is connected to abnormal accumulation of fat in the liver, it is difficult to make the same conclusion about humans because there is little biopsy-confirmed data about NAFLD in the existing human research.

“We see that the prevalence of NAFLD in humans is increasing but the explanations are unclear,” said Sarah Rock, M.P.H., a Ph.D. student in the department of population and public health sciences at the Keck School of Medicine, and one of study authors. “Though the human research connecting PFAS to liver disease is limited, there is much evidence in animal research showing hepatotoxicity of PFAS.”

A challenge for PFAS researchers is that humans are “exposed to mixtures of hundreds if not thousands of these chemicals. Mixture analyses is one potential tool for addressing this complexity in the future,” Rock said.