The ubiquity of the toxic class of substances commonly known as “forever chemicals” is well established. Now, medical researchers have zeroed in on their effects on a crucial component of the human body’s internal filtration system: the liver.

In a peer-reviewed study published this month in JHEP Reports, a sister publication of the Journal of Hepatology, researchers at the Keck School of Medicine at the University of Southern California found that people who had the highest levels of exposure to the chemical perfluorooctane sulfonic acid were 4.5 times more likely to develop liver cancer than those with the lowest exposure.

Scientists’ understanding of the effects of “forever chemicals” has steadily evolved since 2015, when researchers observed that the chemicals—varieties of perfluoroalkyl and polyfluoroalkyl substances, known by the acronym PFAS (pronounced PEE-fahs”)—were present in over 95% of blood serum samples collected from the general U.S. population. Last year, scientists noted the presence of PFAS for the first time in the snow and melted water at the summit of Mount  Everest.

PFAS are known as forever chemicals because of the slow rate at which they break down in the environment and their persistence in accumulating in the human body and other organisms. Commonly used in such household items as nonstick pans, cleaning products and stain-resistant coatings on fabrics and carpet, they have been shown to increase the risk of certain cancers, suppress immune system response, decrease fertility and lead to developmental delays in children. 

Although earlier research had linked occurrences of liver cancer in animals to PFAS, the study is one of the first that connects the most common form of liver cancer in humans, hepatocellular carcinoma, to the chemicals.

Jesse Goodrich, an environmental epidemiologist who served as one of the study’s lead authors, said he and his colleagues examined blood samples collected from participants in a large-scale research project conducted in 1999-2000 and then tracked the health histories of those participants two decades later.

Goodrich and his fellow researchers identified 50 participants who over time were diagnosed with liver cancer and compared their 20-year-old blood samples with those of 50 people in the project who did not develop cancer. The results showed that those whose blood samples placed them in the top 10% of participants registering PFAS exposure in 2000 had a higher risk of developing liver cancer than those who had the lowest exposure.

“A really important part of the studies is actually being able to say that before these people got cancer, they had higher levels” of the chemicals, Goodrich said. “And that helps us to determine that it’s more likely in this situation that it’s actually PFAS that are associated with the cancer as opposed to just some sort of random chance.”

Goodrich said that one of the more critical implications of the findings was the high mortality rate associated with liver cancer, which in 2020 was the world’s third-deadliest form of cancer. The five-year survival rate for those diagnosed with liver cancer is about 20%.

“Any increase in risk is unacceptable,” Goodrich said.

Researchers also found that PFAS disrupts the normal metabolic functions of the liver, which can lead to a condition known as nonalcoholic fatty liver disease. The study noted that cases of fatty liver disease have been on the rise globally in recent years; by 2030, researchers said, nearly a third of all American adults may be diagnosed with the condition.

The findings on PFAS and liver cancer were made public roughly a week after the release of a report by the National Academies calling for increased testing among people with a history of elevated exposure to the chemicals.

That includes those with “occupational exposure, those who have lived in communities with documented contamination and those who have lived where contamination may have occurred,” the academies’ study said, like people living near airports, military bases, wastewater treatment plants, farms, landfills and incinerators.

For those with 2 nanograms per milliliter of PFAS in their blood, the academies recommend routine screening for high cholesterol and breast cancer. For those with higher levels, annual thyroid testing is recommended, as is regular screening for kidney and testicular cancer.

“What these recommendations are doing is helping us start the conversation about what kinds of medical care people who have had this exposure should start to receive,” said Jane Hoppin, a member of the academies committee that issued the recommendations. Hoppin, who is also an environmental epidemiologist at North Carolina State University, said the recommendations are intended to supplement guidance from the Centers for Disease Control and Prevention.

Beyond the health risks of PFAS, the economic toll of regular exposure to the chemicals can be steep. Researchers at New York University’s Grossman School of Medicine found that the combined toll of medical bills and lost worker productivity resulting from ailments linked to PFAS is at least $5.5 billion nationwide. 

Their peer-reviewed study, published in the journal Exposure and Health, identified 13 conditions, including cancer, thyroid disease, infertility and diabetes, that will cost Americans as much as $63 billion over the lifetimes of the nation’s current population.

Leonardo Trasande, the report’s senior author, said his team’s research underscored the need for policy measures and steps to curtail the use of products that contain PFAS. “There’s a large body of evidence that’s rapidly accumulated supporting the effects of PFAS on the entire U.S. population from cradle to grave,” he said.

Trasande noted that some policymakers have questioned the expense of moving away from the use of products containing the chemicals, commonly found in food packing, furniture and oil- and water-resistant clothing.

“A lot of people say it’s too costly,” said Trasande. “But the reality is that we are paying in the form of disease and disability at the present if we don’t do anything. And so this study really adds to the case for action.”

Trasande estimates that 100 million Americans have enough PFAS in their water to contribute to disease and disability and argues that exploring techniques to reduce such contamination is crucial, even if many consider it too costly. 

Potential methods are emerging. On Aug. 18 researchers at Northwestern University announced they had developed a new way to break down a group of PFAS compounds. In a study published in the journal Science, they detailed how they were able to destroy the PFAS compounds by heating them in dimethyl sulfoxide with sodium hydroxide.

PFAS “are persistent, bioaccumulative pollutants found in water resources at concentrations harmful to human health,” the researchers noted. They called the combination “forever chemicals’ Achilles’ heel.”

Linda Birnbaum, the former director of the National Institute of Environmental Health Sciences, said that thousands of new chemicals have been and are still being introduced into the environment, even though “we have so little information about their long-term impacts on our health.”

“Some of them we know have led to climate change—we know that’s a problem,” said Birnbaum, a toxicologist and scholar in residence at Duke University’s Nicholas School of the Environment. “But many of these contaminants are ubiquitous.

“These chemicals are everywhere, and they’re in all of us.”