Per- and Polyfluoroalkyl Substances (aka PFAS or “forever chemicals”) have been making headlines for being everywhere, from makeup and waterproof jackets to rainwater and breast milk. Now, a proof-of-concept analysis has linked PFAS to a specific type of liver cancer called hepatocellular carcinoma (HCC).

The study used data from the Multiethnic Cohort Study, which has tracked the health of around 200,000 Los Angeles and Hawaii residents since the 1990s. The results are published in the journal JHEP Reports.

Used since the 1940s for their water, oil, and heat-proof properties, PFAS take a long time to break down in the environment, and have recently been linked to various health issues. However, the true scope of their impact is still vague, with many claims being linked to animal studies rather than human studies.

“When you are looking at an environmental exposure, you need samples from well before a diagnosis because it takes time for cancer to develop,” explained study author Dr Veronica Wendy Setiawan in a statement.

So, researchers selected 50 participants who developed HCC, and 50 control participants with no history of liver disease. HCC cases that could have been linked to viral infection were excluded. Controls were matched by age, sex, and race, and had similar levels of smoking and alcohol intake to participants with liver cancer. However, the authors admit that “Because of the limited sample size, we were not able to examine effect modification by known risk factors such as race, sex, BMI, or diabetes status.”

Plasma samples taken before the participants had their cancer diagnosis (while fasting, to avoid recent diet skewing the findings) were analyzed for PFAS, with the chemicals being found in the plasma of every participant. The authors say that they “observed a positive association between prediagnostic plasma PFAS concentrations and risk of HCC.”

Levels of a specific PFAS called perfluorooctane sulfonate (PFOS) at or above 54.9 micrograms per liter were associated with a 4.5 higher HCC risk. The researchers observed five metabolic pathways that were enriched in both HCC cases and high levels of PFOS, plus four metabolites. They hypothesize that “PFAS exposure increases risk of HCC via effects on lipid, amino acid, and carbohydrate metabolism.”

In fact, a systemic review and meta-analysis published in April 2022 linked PFAS to elevated levels of an enzyme that indicates liver damage.

“We believe our work is providing important insights into the long-term health effects that these chemicals have on human health, especially with respect to how they can damage normal liver function,” said study author Dr Lida Chatzi.

“This study fills an important gap in our understanding of the true consequences of exposure to these chemicals.”