New research reveals how PFAS chemicals destroy human hepatocytes, causing fat accumulation, immune interference, and cancer-related changes.
They are called “eternal chemicals” for reasons. Polyfluoroalkyl substances (PFAs) used in everyday products such as non-stick pans, food wrappers and waterproof fabrics are nearly impossible to decompose when released into the environment.
Over time, they accumulate in the human body, and scientists have long suspected that they will contribute to serious health problems.
Now, new research from the USC’s Keck School of Medicine reveals exactly how these contaminants harm liver cells, providing a clearer picture of the dangers lurking beneath the surface.
Why the liver is hit
The liver is the body’s main detox organ, constantly filtering blood and disposing of harmful substances.
However, this protective role makes it extremely vulnerable to PFA, infiltrating the bloodstream through drinking water, packaging foods and consumer goods.
Unlike natural toxins that can be broken down by the liver, PFA remains intact, accumulates in tissues and interferes with normal cell function.
For years, researchers have seen a link between PFA exposure and liver disease and higher risk of cancer. What they couldn’t explain was the “method.”
That’s where new research begins. It still provides the most detailed appearance of the cellular results of PFA exposure.
Inside the lab: Reproducing the human liver
Instead of relying on animal testing, the USC team relied on advanced 3D models known as spheroids.
Made from real human liver cells donated by men and women, these miniature organs recreate the structure and behavior of a living liver. This setup gave scientists an unprecedented view of how PFA destroys organs at a minimum scale.
Four PFA compounds commonly detected in human blood were tested individually.
For 7 days, liver spheroids were exposed to these chemicals before being degraded into single cells for genetic and metabolic analysis.
Different chemicals, different damage
The results revealed that not all PFAs behave the same, but they are not harmless.
PFOA and PFHXS: Both resulted in fat accumulation in liver cells, but through different biological processes. One increased the increase in fat production, and the other slowed the release of fat, which ultimately led to the same result. This was overloaded with fat. PFOS and PFNA: these two chemicals were associated with altered cellular activity associated with cancer. PFNA in particular raised the red flag, but more than 60% of affected liver cells exhibit inflammation, oxidative stress, and disruption of pathways associated with DNA repair.
Over all four chemicals, the team observed the immune process and interference with the failure of hepatocyte communication. This may explain why long-term exposure is associated with chronic liver problems.
Amazing gender differences
Another notable finding is that liver cells from male and female donors react differently. PFOA had a strong effect on female cells, and PFO caused more damage in male cells.
These gender-specific patterns suggest that treatment for PFA-related liver damage needs to be personalized.
Impact on health and treatment
By identifying how PFA interferes with liver cells, researchers are paving the way for new medical approaches.
FDA-approved drugs that regulate liver fat processing may be reused to address conditions associated with PFA, which may accelerate treatment options.
However, prevention remains the most urgent priority. Because PFA is very persistent, reducing exposure is the most effective way to protect liver health.
This means filtering drinking water, limiting the use of non-stick cooking utensils, and paying attention to consumer products that may contain PFA.
Next chapter in PFAS research
Researchers are currently analyzing the combined effects of multiple PFAs on hepatocytes. This is a scenario that more closely reflects actual exposure.
As science reveals more about these chemicals, evidence is growing. PFA not only lasts in the environment, but also in the body.
And in the organs, they affect, but liver cells appear to be at the forefront of damage.
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