Invited Perspective: PFAS and Liver Disease: Bringing All the Evidence Together

By Alan Ducatman and Suzanne E. Fenton
EHP
May 2, 2022
DOI: 10.1289/EHP11149

In this issue, Costello et al.¹ provide a meta-analysis for associations between per- and polyfluoroalkyl substances (PFAS) and human clinical biomarkers for liver injury. They simultaneously considered PFAS effects on liver biomarkers and histological data from rodent experimental studies. This integrative assessment addresses an important need.

Based on concordance between population and experimental findings, the authors concluded there is convincing evidence that perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFOS), and perfluorononanoic acid (PFNA) are hepatotoxic to humans. The authors note that, although the exact mechanisms of toxicity are uncertain, they likely feed into pathways that induce nonalcoholic fatty liver disease (NAFLD)—a reasonable hypothesis, given the abundant literature concerning PFAS and lipid disruption. Others have called attention to the similarity of experimental PFAS-induced steatosis and human biomarkers following PFAS exposure^2,3; Costello et al.¹ are the first to provide a needed methodical approach to literature-wide statistical assessment of liver data.

An important consideration is that the global epidemic of NAFLD is estimated to affect ∼25%∼25% of the human population,⁴ although this figure may still be an underestimation of the prevalence of early preclinical stages, which do not invariably progress.^4,5 Because the diagnosis requires clinical suspicion along with laboratory and imaging studies, and because it is formally made with invasive techniques, NAFLD is underdiagnosed and preventive opportunities are often lost.⁵ The strong association of NAFLD to alanine amino transferase (ALT), the biomarker of choice in this systematic review by Costello et al.,¹ diminishes the possibility that population findings are attributable to unmeasured confounding by alcohol intake.⁶ This work firmly puts PFAS exposure on the list of persistent pollutants, such as polychlorinated biphenyls,⁷ that cause hepatotoxicity and whose mechanism is linked to steatosis.⁸

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