Researchers at the University of Southern California Keck School of Medicine have discovered a potential link between exposure to a group of long-lasting chemicals and nonviral hepatocellular carcinoma. According to Veronica Wendy Setiawan, PhD, and colleagues, greater exposure to polyfluoroalkyl and perfluoroalkyl substances (PFAS) greatly increased the risk for developing this type of liver cancer, and the likely mechanisms centered on alterations in glucose, amino acid, and bile acid metabolism. These research findings were published in JHEP Reports, an open-access companion to the Journal of Hepatology.

“We believe our work is providing important insights into the long-term health effects that these chemicals have on human health, especially with respect to how they can damage normal liver function,” stated coauthor Lida Chatzi, MD, PhD, in a Keck School of Medicine press release.

Plasma PFAS were measured in 50 patients with hepatocellular carcinoma and 50 carefully selected control participants, and the risk was calculated using a conditional logistic regression. Additionally, a metabolome-wide association study and pathway enrichment analysis were performed for PFAS exposure and its correlation to hepatocellular carcinoma.

Through these methods, it was determined that high levels of perfluorooctane sulfonic acid (PFOS) contributed the most to the risk of developing hepatocellular carcinoma. The 90th percentile for PFOS concentration (determined by the National Health and Nutrition Examination Survey), measured at approximately 55 µg/L, correlated to 4.5 times the risk for developing this type of liver cancer. Through this study, it was also seen that PFOS exposure likely caused alterations in the metabolism of glucose, bile acid, and branched chain amino acids in the liver, which may contribute to the onset of nonalcoholic fatty liver disease; patients with this disease have a significantly higher risk of developing liver cancer. This study is reportedly the first to look at the effects of PFAS exposure in humans, and more research is needed to confirm these findings.