Ubiquitous Environmental Exposures and Risk of Hepatocellular Carcinoma: A Narrative Review

Hepatocellular carcinoma (HCC) is among the most prevalent and deadly cancers worldwide. Chronic liver disease is the most established risk factor for HCC, but environmental exposures are increasingly recognized as contributor. In this narrative review, we sought to analyze data linking three substances to HCC: polycyclic aromatic hydrocarbons (PAHs), per- and polyfluoroalkyl substances (PFAS), and cadmium.

We performed a literature search of MEDLINE for this narrative review. Two reviewers screened titles and abstracts for relevance. We focused on articles published within the last three years.

PAH, PFAS, and cadmium have been linked to chronic liver disease, liver injury, and to a lesser extent, HCC. Major limitations in existing data are small sample sizes, lack of longitudinal follow up (most studies are cross-sectional), and heterogeneity in the species assayed and the methods of assay.

Further studies in large, prospective cohorts with longitudinal follow up are needed. Given existing evidence linking these substances to liver injury and HCC, a multi-faceted prevention and intervention strategy is needed, incorporating research, public education and engagement, legal frameworks, decontamination and medical interventions to mitigate deleterious effects of these substances.