Exposure to per- and polyfluoroalkyl substances associated with increased risk of HCC

Recent research revealed that exposure to high levels of per- and polyfluoroalkyl substances was associated with an increased risk of non-viral Hepatocellular carcinoma due to alterations in glucose, amino acid, and bile acid metabolism. The study was published in the Journal JHEP Reports. 

Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants. Exposure to these is inescapable. Previous literature shows that PFAS exposure in animals has shown an increased risk of fatty liver and hepatocellular carcinoma (HCC) due to its impact on hepatic lipid, amino acid, and glucose metabolism. But there is no similar research on humans. Hence researchers from the U.S.A. conducted a study to examine the associations between PFAS exposure, altered metabolic pathways, and risk of non-viral HCC. 

A case-control study was done to measure the prediagnostic plasma PFAS and metabolomics in 50 incident HCC cases and 50 individually matched controls from the Multiethnic Cohort Study (MEC). Cases/controls were matched by age, sex, race, and study area. Using the conditional logistic regression PFAS exposure and risk of HCC were examined. A metabolome-wide association study and pathway enrichment analysis were performed for PFAS exposure and HCC risk, and key metabolites/metabolic pathways were identified using a meet-in-the-middle approach. 

Key findings:

• High perfluoro octane sulfonic acid (PFOS) levels were associated with a 4.5-fold increased risk of HCC.
• Pathway enrichment analysis showed that PFOS exposure was associated with alterations in amino acid and glycan biosynthesis pathways, which were also associated with HCC risk.
• Four metabolites linking PFOS exposure with HCC were identified, including glucose, butyric acid, α-Keto isovaleric acid, and 7α-Hydroxy-3-oxo-4-cholestenoate which is a bile acid, each of which was positively associated with PFOS exposure and risk of HCC. 

Thus, the researchers concluded from the study that exposure to high PFOS levels was associated with an increased risk of non-viral HCC due to alterations in glucose, amino acid, and bile acid metabolism. 

To read the full article, click here: https://doi.org/10.1016/j.jhepr.2022.100550 

Goodrich JA, Walker D, Lin X, et al. Exposure to perfluoroalkyl substances and risk of hepatocellular carcinoma in a multiethnic cohort. JHEP Reports. Published online August 2022:100550.