Little-known 'forever chemical' worsens liver disease in teens

A team of scientists has found that a little-known “forever chemical” may be quietly worsening an already serious liver disease in teenagers.

The chemical, perfluoroheptanoic acid (PFHpA), isn’t one of the well-known PFAS like PFOA or PFOS, but in this study, it behaved just as harmfully.

Teens with obesity who had more PFHpA in their blood were much more likely to have metabolic dysfunction-associated steatotic liver disease (MASLD). They were also more likely to have it in a more advanced and dangerous form.

The work was led by the Keck School of Medicine of USC and the Southern California Superfund Research and Training Program for PFAS Assessment, Remediation and Prevention (the ShARP Center).

What makes the study stand out is the follow-up work. The team tested 3D liver models with real-world PFAS doses and saw the same kinds of injury. That closes the loop from exposure to mechanism.

Hidden chemical, real liver harm

The researchers analyzed blood from 137 adolescents enrolled in the Teen Longitudinal Assessment of Bariatric Surgery – the largest U.S. study following young people through weight-loss surgery.

When they compared PFHpA levels with liver diagnoses, the pattern was sharp: teens with twice as much PFHpA in their blood had an 80 percent higher chance of being diagnosed with MASLD.

Those with higher levels also showed inflammation and fibrosis – the kinds of liver changes that can march, over years, toward cirrhosis, liver failure, or even cancer.

The study’s senior author is Dr. Lida Chatzi, a professor of population and public health sciences and director of the ShARP Center.

“PFHpA is not as well-known as the legacy PFAS like PFOA or PFOS, but our findings show it may pose comparable risks to human health,” she said. “This underscores the urgency of regulating not just the PFAS compounds we already know a lot about, but the broader class of emerging chemicals.”

That warning lands in a country where PFAS are nearly everywhere – coatings, food packaging, cosmetics, nonstick cookware, and even water. Nearly half of U.S. water systems are thought to have detectable PFAS.

Add in the fact that MASLD already affects 5 to 10 percent of U.S. kids and up to a third of those with obesity, and you can see why the team is sounding the alarm.

From symptoms to cell science

“Our research goes beyond simple associations,” said lead author Brittney O. Baumert, a postdoctoral fellow at USC. “Using a translational science approach by bridging bench science and epidemiological research, we are uncovering how these chemicals alter liver biology at the cellular level.”

“That knowledge can ultimately help us protect vulnerable populations, especially children and adolescents.”

To do that, the team built 3D liver spheroids – miniature, structured liver tissues in a dish – and exposed them to PFAS at doses in the range that people actually get.

PFHpA triggered a familiar toxic trio: inflammation, oxidative stress, and disrupted lipid metabolism. In other words, the cells reacted just like the teens’ livers: stressed, inflamed, and prone to storing fat.

“By mapping the pathways PFAS activate inside liver cells, we can pinpoint potential therapeutic targets to help stop PFAS-induced liver disease before it progresses,” said Dr. Ana Maretti-Mira, who led the in vitro work.

PFAS worsens obesity’s liver toll

MASLD (formerly NAFLD) is already a disease of “too much”: too much fat in the liver, too much metabolic stress, and too much long-term risk.

Add an environmental toxicant that independently amplifies inflammation and fibrosis, and you get a steeper, faster slope toward serious liver damage.

And because these are adolescents, not adults, the window for harm is long. A 16-year-old with fatty liver and PFAS exposure could face liver disease in their 30s.

The study also fits a larger pattern emerging in environmental health: lower-profile “replacement” or “emerging” PFAS are not necessarily safer than the older ones that regulators have started to restrict.

This is another push toward regulating PFAS as a class instead of one compound at a time.

Superfund science with a purpose

This work is part of the USC Superfund Research Program, backed by the National Institute of Environmental Health Sciences, whose job is to investigate hazardous chemicals and push the findings into policy and prevention.

Here, that means blending patient data with “omics” tools – metabolomics, proteomics, and single-cell transcriptomics – to catch subtle biological signals early.

Next steps at the ShARP Center will expand from “who is harmed and how” to “how do we stop the exposure.”

These steps include engineering better PFAS treatment, working with communities to identify and reduce exposure pathways, and training young researchers who can bridge public health and environmental science.

The long-term goal is precision environmental health – being able to identify which exposures matter for which people, and what interventions will actually help.

Protecting kids from PFAS

Three things stand out. First, PFHpA is not harmless just because it’s less well-known. Second, environmental chemicals and obesity can interact to make liver disease in children far more serious than it needs to be.

And third, connecting patient cohorts to mechanistic lab work is a powerful way to turn a statistical red flag into actionable biology.

The study shows that we already know enough to start tightening PFAS controls – especially for the newer compounds we “don’t know much about.” With the right tools, we can detect problems early enough to protect the most vulnerable.

The study is published in the journal Communications Medicine.

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