Emerging forever chemical may drive fatty liver disease
PFHpA exposure may increase risk in obese adolescents: Study
Exposure to a human-made chemical called perfluoroheptanoic acid (PFHpA) may increase the risk and severity of fatty liver disease in adolescents with obesity, according to a study in the U.S.
PFHpA is part of a group of industrial chemicals known as per- and polyfluorinated substances (PFAS). These chemicals are used in many common household and industrial products but are considered persistent pollutants, or “forever chemicals,” as they accumulate in the environment and within living organisms.
Some PFAS, including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), have been voluntarily phased out in the U.S. and other countries because of health concerns. However, other PFAS like PFHpA are still in use.
“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,” Lida Chatzi, MD, PhD, the study’s senior author at the University of Southern California (USC), said in a university press release. “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.”
The study, “Translational framework linking perfluoroheptanoic acid (PFHpA) exposure to metabolic dysfunction associated steatotic liver disease in adolescents,” was published in Communications Medicine.
PFAS exposure adds new concern to fatty liver disease in youth
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a type of fatty liver disease where too much fat builds up in the liver. This condition is typically associated with underlying metabolic conditions such as obesity or diabetes.
Over time, MASLD can worsen and become metabolic dysfunction-associated steatohepatitis (MASH) — a more serious form marked by liver inflammation and scarring (fibrosis). These changes can eventually lead to irreversible liver fibrosis (cirrhosis), liver cancer, and liver failure.
Studies have shown MASLD is becoming more common in children. This increase isn’t fully explained by traditional risk factors (such as excess energy intake, sedentary lifestyle, and genetics), suggesting other factors like environmental toxins may also be at play.
“PFAS are man-made chemicals widely used by industrial processes and consumer products, and nearly everyone in the United States has detectable levels of PFAS in their blood,” the researchers wrote.
There’s data that these forever chemicals — including PFOA and PFOS — can cause a range of health problems. PFOA is thought to affect hormonal balance and increase cancer risk, while PFOS has been linked to fertility issues. But the health effects of PFHpA, which is still in use, are not fully understood.
Higher exposure tied to worse liver health in obese adolescents
In this study, Chatzi and her colleagues looked for potential associations between PFAS and MASLD using data from a U.S.-based clinical trial called Teen-LABS (NCT00465829). The trial examined the long-term safety and efficacy of bariatric, or weight-loss, surgery in obese adolescents.
The analysis specifically included data from 136 participants. More than a third (38%) had MASLD, and 22% had MASH. The researchers measured PFAS levels in blood samples collected at the time of surgery and then used statistical analyses to look for associations between PFAS and MASLD.
This revealed a statistically significant association between higher PFHpA levels in the blood and an increased MASLD risk: each doubling in PFHpA levels was associated with an 80% increase in the risk of developing MASLD.
In addition, higher PFHpA levels were significantly associated with signs of more advanced liver disease, including a higher degree of liver inflammation, the presence of fibrosis, and more severe MALSD activity.
“Our study established a robust association between PFHpA exposure and MASLD,” the researchers wrote.
Lab tests show chemical may disrupt liver cell metabolism and repair
Additional analyses of biomarkers from human samples and tests using three-dimension lab-grown human liver cells indicated PFHpA exposure can boost biological pathways involved in chronic inflammation and liver fibrosis and disrupt how liver cells process fat.
This provided a biological mechanism for how this forever chemical could increase the likelihood of MASLD.
“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 Ana C. Maretti-Mira, PhD, a USC professor who led the cell experiments.
Further analyses allowed the identification of metabolism- and protein-related signatures of PFHpA-induced MASLD. The metabolism-related profile was linked to a 49% lower chance of MASLD, while the protein-related profile was linked to a 600% higher likelihood of MASLD.
“Our research goes beyond simple associations,” said Brittney O. Baumert, PhD, the study’s first 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.”
Epidemiology is the study of the causes, occurrence, and distribution of health and disease in a defined population.
The scientists are also hoping to explore strategies to reduce exposure to PFHpA and other PFAS in communities.
This work was supported by the USC Superfund Research Program, funded by the National Institute of Environmental Health Sciences to investigate the health effects of hazardous chemicals and inform public health policy.
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