Exposure to Per- and Polyfluoroalkyl Substances and Liver Cancer: A Systematic Review of Animal and Epidemiological...

The global incidence and mortality rates of liver cancer are rising, necessitating research into environmental and lifestyle risk factors. Early onset liver cancer, diagnosed before the age of 50, is becoming prevalent, suggesting the potential influence of emerging environmental exposures. Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants that have been linked to liver toxicity in humans and shown to cause hepatotoxic effects in animals, but their role in liver cancer remains unclear. This systematic review synthesizes evidence from animal and epidemiological studies to evaluate associations between PFAS exposure and liver cancer risk. PubMed and Embase were searched through November 2025 for studies on PFAS and liver cancer. Data were independently extracted by two reviewers, and quality was assessed using the U.S. Environmental Protection Agency (EPA) guidelines. Twenty-three studies (seven animal, 16 human) met inclusion criteria. Most studies focused on legacy PFAS, primarily perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). Animal studies demonstrated increased liver tumor incidence with high-dose PFAS exposure. Human epidemiological findings were mixed: three studies reported positive associations between PFAS and liver cancer, while others showed null associations.While animal studies strongly suggest hepatocarcinogenic effects of PFAS, epidemiological evidence remains inconsistent. Large, prospective studies with robust exposure assessment are needed to clarify these associations and inform public health policy.