USC Superfund researchers identify “forever chemical” PFHpA as risk factor for severe liver disease in adolescents

Scientists at the Keck School of Medicine of USC, working within the Southern California Superfund Research and Training Program for PFAS Assessment, Remediation and Prevention (ShARP) Center, have uncovered compelling evidence that exposure to perfluoroheptanoic acid (PFHpA), a lesser-known member of the PFAS family of “forever chemicals, is linked to a significantly higher risk and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in adolescents with obesity. The study, published in Communications Medicine (Nature Portfolio), integrates clinical data from adolescents undergoing bariatric surgery with advanced 3D liver models to reveal the biological mechanisms by which PFHpA may drive disease progression.

PFHpA and liver disease

The researchers examined blood samples from 137 adolescents enrolled in  Teen Longitudinal Assessment of Bariatric Surgery, the largest U.S. study of pediatric bariatric surgery. They found that adolescents with twice the amount of PFHpA in their blood faced an 80% greater likelihood of being diagnosed with MASLD compared to their peers with lower levels. Teens with higher exposures also showed more advanced liver injury, including inflammation and fibrosis—early signs of disease progression that can eventually lead to cirrhosis, liver failure, or even liver cancer. To strengthen these findings, the team tested PFAS on laboratory-grown liver spheroids using doses comparable to typical human exposure, showing that PFHpA disrupts critical biological pathways, including inflammation, oxidative stress and lipid metabolism. This dual approach allowed the researchers to connect exposure to mechanism, producing a distinctive molecular signature of PFHpA-related liver damage.

Rising rates of MASLD and PFAS exposures

MASLD, once referred to as nonalcoholic fatty liver disease, is one of the most common liver disorders in young people, affecting an estimated five to 10% of U.S. children and adolescents and more than 30% of those with obesity. It is also a condition on the rise, placing many young people at risk of severe long-term health consequences, including type 2 diabetes and cardiovascular disease. The fact that exposure to PFHpA can worsen this trajectory is particularly concerning given how widespread these chemicals are. PFAS are used in products ranging from food packaging and waterproof clothing to cosmetics and nonstick cookware, and they contaminate drinking water supplies across the country. Nearly half of all U.S. water systems are now believed to contain detectable PFAS levels.

“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,” said the study’s senior author, Lida Chatzi, MD, PhD, professor of population and public health sciences and director of the ShARP Center at the Keck School of Medicine. “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 communities are being exposed to every day.”

A translational approach from patients to mechanisms

“Our research goes beyond simple associations,” said Brittney O. Baumert, PhD, MPH, lead author and 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.”

Ana C. Maretti-Mira, PhD, who led the in vitro experiments, added, “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.”

Reducing PFAS exposure through Superfund research

This study reflects the mission of the USC Superfund Research Program, funded by the National Institute of Environmental Health Sciences, to uncover the health impacts of hazardous chemicals and translate discoveries into prevention and policy. By integrating patient-based data with advanced exposomics technologies such as metabolomics, proteomics and single-cell transcriptomics, USC researchers are bridging laboratory science and public health.

Looking ahead, the ShARP Center will focus on reducing PFAS exposures in real-world communities. Future ShARP Center projects will advance engineering innovations for PFAS treatment, increase community engagement efforts to raise awareness about exposure pathways and strategies for reducing risk, and train the next generation of environmental health and engineering scientists. A central goal of all these studies is to advance the fields of precision environmental health and precision medicine, ensuring that research findings can be translated into targeted interventions, personalized prevention strategies and evidence-based policies that protect the most vulnerable.

About this research

In addition to Baumert, the study’s other authors are Zhenjiang Li, Hongxu Wang, Yinqi Zhao, Qiran Jia, Jiawen Carmen Chen, Sarah Rock, Sandrah P. Eckel, Max M. Aung, Rob McConnell, Jesse Goodrich, David V. Conti and Lida Chatzi from the Department of Population and Public Health Sciences, Keck School of Medicine of USC, University of Southern California; Ana C. Maretti-Mira, Matthew P. Salomon and Lucy Golden-Mason from the USC Research Center for Liver Diseases, Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine of USC, University of Southern California; Douglas I. Walker from the Rollins School of Public Health, Emory University; Nikos Stratakis from the Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain; Fabian Christoph Fischer from the University of Rhode Island; Damaskini Valvi from the Icahn School of Medicine at Mount Sinai; Scott M. Bartell from the University of California, Irvine; Thomas Inge and Justin R. Ryder from the Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children’s Hospital of Chicago; Todd Jenkins and Stavra Xanthakos from Cincinnati Children’s Hospital Medical Center; Stephanie Sisley from Baylor College of Medicine; David E. Kleiner from the National Cancer Institute, National Institutes of Health; Rohit Kohli from Children’s Hospital Los Angeles; and Michele A. La Merrill from the University of California, Davis.

This work was supported by the National Institute of Environmental Health Sciences [P42ES036506]. Additional funding came from the National Institutes of Health [R01ES030691, R01ES029944, R01ES030364, U01HG013288, P30ES007048, T32-ES013678, R01ES033688, R21ES035148, P30ES023515, U2CES030859, R01ES032831, P2C ES033433, R21ES029681, P01CA196569, R01DK128117−01A1, R01DK117004]; the European Union: Advancing Tools for Human Early Lifecourse Exposome Research and Translation (ATHLETE) project [874583]; the European Union’s Horizon Research and Innovation Programme [101059245]; the California Environmental Protection Agency [20-E0017]; and the U.S. Department of Agriculture [6250-51000-053]. Funding for Teen-LABS was provided by the National Institutes of Health [U01DK072493, UM1 DK072493, UM1 DK095710] and the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH [8UL1TR000077]. Additional support came from the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH [UL1TR000114]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.