Scientists at UofL, along with colleagues from Boston University and the University of Massachusetts Lowell, have identified perfluorooctane sulfonate (PFOS) as a potential environmental factor that worsens alcohol-associated liver disease.

PFOS is a man-made chemical belonging to the group known as per- and polyfluoroalkyl substances (PFAS), often referred to as “forever chemicals” because they do not readily break down in the environment or the human body. These substances have been used for decades in products such as non-stick cookware, water-resistant clothing, fast-food packaging, stain-resistant carpets and upholstery, and firefighting foams. Their extensive use has led to widespread contamination in the environment. show that PFAS can be detected in approximately 95% of Americans, sparking increasing concern about their long-term health effects.

At the same time, alcohol consumption remains a significant global health issue. , and its consumption continues to rise globally. In the U.S. alone, excessive alcohol use is responsible for approximately 95,000 deaths annually, making it one of the leading causes of preventable death and a major contributor to liver disease.

“Given the increasing prevalence of alcohol consumption and the widespread presence of PFAS in the environment, many individuals who drink alcohol may be inevitably exposed to these persistent pollutants. This makes it critically important to study how combined exposures to alcohol and environmental chemicals like PFOS might influence liver health,” said Matthew Cave, UofL professor of medicine and publication co-author.

Although it is well known that both alcohol and PFOS cause liver damage individually, little has been understood about their combined effects until now. , indicating that additional factors such as genetics, sex, microbiome and environmental exposures may contribute to individual susceptibility.

“This work helps explain why two people with similar alcohol consumption may experience very different liver outcomes,” said Frederick Ekuban, assistant professor of medicine at UofL and first author of the study. “Environmental exposures like PFOS may be the missing link.”

Using animal models, the researchers simulated real-world exposures to both alcohol and PFOS. The study showed that co-exposure to alcohol and PFOS significantly increased fat accumulation and markers of liver damage, as well as clear signs of disrupted metabolism and activation of genes and pathways predicted to be associated with oxidative stress and cancer development.

In short, the study demonstrates that PFOS exposure can significantly worsen liver damage when combined with alcohol consumption. While this research used high levels of alcohol to understand the underlying mechanisms, the findings reveal important biological pathways that warrant further investigation across different drinking patterns.

The research team also found that PFOS interferes with the liver’s ability to manage fats, disrupts its natural protective and repair systems and activates pathways that promote liver injury.

“While the liver typically has a remarkable capacity to recover from alcohol-induced stress, PFOS appears to push that resilience beyond its limits, resulting in compounded and more severe damage,” said Jennifer Schlezinger professor of environmental health at Boston University and co-author of the publication.

Perhaps most concerning, the team discovered that 60% of all PFOS exposure ended up concentrated in the liver, exactly where alcohol damage occurs.

Ongoing research at UofL is examining how other PFAS compounds may interact with alcohol, whether males and females respond differently to these exposures and what the long-term consequences of combined exposures might be. The team is also exploring whether targeted therapies can be developed to prevent or mitigate this type of liver damage.

Although more studies are needed, people can take practical steps now to limit their exposure to PFAS. These include:

• Choose stainless steel or cast-iron cookware instead of non-stick pans
• Use water filters, especially in areas near industrial zones
• Avoid stain-resistant treatments on furniture and carpets
• Reduce consumption of packaged fast foods and microwave popcorn.
• Select household products with PFAS-free labels

Given that liver disease affects millions of Americans and is becoming more prevalent worldwide, the findings of this research support growing calls for stronger regulation and oversight of persistent chemical contaminants. By better understanding the hidden interactions between environmental toxicants and lifestyle behaviors, scientists and policymakers may be better equipped to prevent and treat liver disease.

 Article by Sarah Jump

“Research!Louisville is a great opportunity to explore the important role UofL research plays in our day-to-day lives,” said Kevin Gardner, executive vice president for research and innovation. “That work positively impacts our world, from creating meaningful educational experiences and career pathways for students to developing innovative new technologies and companies.”

This year, R!L highlighted 365 abstracts for presentation. Among the scientific poster competition participants represented were masters and doctoral engineering students, NCI R25 undergraduate students, cancer and health disparity Summer Bridge Program students, Brown Cancer Center high school scholars, dental students, masters and doctoral basic science students, medical students, distinction tract medical students, case reports, postdoctoral scholars, research associates, research staff, PharmDs, masters and doctoral public health students, nursing students, medical residents, clinical fellows and faculty.

A full list of award winners and their slide presentations, as well as photos/recording of the closing ceremony are available on the .

Richard Woychik, director of the National Institute of Environmental Science and the National Toxicology Program delivered the keynote address, “Looking to the Future of Environmental Health Sciences.” Woychik oversees federal funding for biomedical research to discover how the environment influences human health and disease. His lecture drew a full house and was preceded with an introduction by UofL President Kim Schatzel.

R!L’s symposium featured seminars, presentations and lectures on a variety of subjects, including nursing research, environmental health sciences, anti-racism research, IRB protocol and more.

The event schedule included a Q&A forum with renowned medical ethicist and author, Harriett Washington. The School of Nursing presented Imelda Wright, assistant professor of nursing, whose research focuses on the effects of perioperative nurse practice and the environment on patient safety in the operating room. UofL’s Social, ����ֱ��al and Behavioral IRB presented a workshop to provide an overview of the UofL SBE IRB and HSPP Office. The IRB also hosted a workshop geared toward biomedical researchers from the UofL Health Sciences and Shelby Campuses. The Research Integrity Office presented Leslie Hollie, a distinguished expert in health care fraud and economic crimes, including grant fraud with a concentration in foreign influence/interference and administrative conflict of interest investigations.

The Center for Integrative Environmental Health Sciences (CIEHS) hosted two forums of presentations by Pilot Project awardees and Research Voucher awardees highlighting their accomplishments from their third-year awards. The Office of HSC Diversity and Inclusion hosted a panel discussion, “The Past is Present: Slavery & Medicine in Louisville History” and an anti-racism program which supports anti-racism research occurring at the University of Louisville which encourages further research aimed at impacting racial inequities.

Juw Won Park, director of the Center for Integrative Environmental Health Sciences Biostatistics and Informatics Facility Core, director of Brown Cancer Center Bioinformatics Core, and colleagues discussed their research interest in bioinformatics and computational genomics which requires high-performance computing. Finally, R!L sponsored a seminar at the Kentucky Science Center for students in grades 7-12 with a biomedical focus. The day also included a “Pulse of Surgery” program, a real-time, open-heart surgery. The full schedule of 2023 events are on the .

The co-chairs of R!L, Jon Klein, vice dean for research, and Chris States, associate dean for research, along with the R!L Steering Committee, look forward to R!L 2024. Look for announcements of dates/agenda in UofL Today.