Invited Perspective. Per- and Polyfluoroalkyl Substances, Hepatotoxicity, and Liver Disease: Evidence and Clinical Responses
Main Article Content
Abstract
Background: This perspective concerning hepatoxicity of per- and polyfluoroalkyl substances (PFAS) aims to provide a current understanding of the damage and reasonable clinician responses to the needs of concerned patients and affected communities.
Methods: Search strategy included PFAS and the following: human liver toxicity/disease; relevant biomarkers including transaminases, lipids, uric acid; predictive equations (for liver disease), liver imaging modalities, and histologic findings. Experimental data concerning liver outcomes and disrupted hepatic metabolic pathways was also reviewed. Recommended clinical approaches to patients and communities was sought in both the National Library of Medicine and relevant organizational websites.
Results: Several PFAS reliably cause adverse changes in human liver biomarkers, with strong consistency between human and experimental data. Adverse population changes include human transaminases, cholesterol and LDL cholesterol, and uric acid. This biomarker triad suggests that mechanisms and outcomes are or resemble metabolic associated steatotic liver disease, which is found across species following experimental PFAS exposure. Human imaging studies and sparse human histologic studies mostly support the inference that the toxicant damage is or resembles a pathway that can lead from steatosis to more serious stages of liver disease due to disrupted liver metabolism of fatty acids. Advice to patients and clinicians was reviewed from various agencies and nonprofits organizations including a committee of the US National Academies of Sciences, Engineering, and Medicine, and the nonprofit/university collaboration PFAS REACH.
Discussion: Converging lines of evidence indict PFAS as human (and trans-species) hepatotoxins and mostly support a metabolic associated steatotic liver disease continuum as the nature of the injury. Increases in abnormal transaminases and sparser imaging and biopsy findings support that the damage is clinically important and a contributing cause of a public health problem. It is still challenging to decide which of many definitively disrupted metabolic pathways is/are most important to the injury. Many PFAS in use remain virtually unstudied, a research and public health emergency. Simple clinical responses to the concerns of the most heavily contaminated patients and communities, which are within the capabilities of most clinical offices, are reviewed.
Keywords:
Per- and polyfluoroalkyl substances (PFAS), Liver Diseases, Liver steatosis, Non-alcoholic fatty Liver disease (NAFLD), Alanine aminotransferase (ALT), Review
Article Details
How to Cite
DUCATMAN, Alan; CHATZI, Lida.
Invited Perspective. Per- and Polyfluoroalkyl Substances, Hepatotoxicity, and Liver Disease: Evidence and Clinical Responses.
Medical Research Archives, [S.l.], v. 11, n. 12, dec. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4819>. Date accessed: 23 nov. 2024.
doi: https://doi.org/10.18103/mra.v11i12.4819.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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