Salman A, Elewa A, Marwan A, Salman MA. Hepatic exposome as an emerging contributor to metabolic dysfunction-associated steatotic liver disease. World J Transl Med 2026; 12(3): 124965 [DOI: 10.5528/wjtm.124965]
Corresponding Author of This Article
Ahmed Salman, FRACP, FRCP, MRCP, Department of Internal Medicine, Kasr Alainy School of Medicine, 1 Al-Saray Street, Al-Manial, Cairo 11562, Egypt. awea844@gmail.com
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Gastroenterology & Hepatology
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review-article
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Salman A, Elewa A, Marwan A, Salman MA. Hepatic exposome as an emerging contributor to metabolic dysfunction-associated steatotic liver disease. World J Transl Med 2026; 12(3): 124965 [DOI: 10.5528/wjtm.124965]
World J Transl Med. Sep 28, 2026; 12(3): 124965 Published online Sep 28, 2026. doi: 10.5528/wjtm.124965
Hepatic exposome as an emerging contributor to metabolic dysfunction-associated steatotic liver disease
Ahmed Salman, Ahmed Elewa, Ahmad Marwan, Mohamed A Salman
Ahmed Salman, Department of Internal Medicine, Kasr Alainy School of Medicine, Cairo 11562, Egypt
Ahmed Elewa, Department of General Surgery, National Hepatology and Tropical Medicine Research Institute, Cairo 11796, Egypt
Ahmad Marwan, Department of Internal Medicine, Faculty of Medicine, Mansoura University, Mansoura 35511, Egypt
Mohamed A Salman, Department of General Surgery, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
Author contributions: Salman A contributed to the conception and design of the review, the literature search, and drafting of the manuscript; Elewa A and Marwan A contributed to the literature search, data interpretation, and critical revision of the manuscript for important intellectual content; Salman MA contributed to the conception of the review, critical revision, and supervision; and all authors read and approved the final version of the manuscript.
AI contribution statement: During the preparation of this manuscript, the authors used a generative artificial-intelligence large language model (ChatGPT 5.6) solely to improve language clarity and formatting. No artificial-intelligence tool was used to generate scientific content, data, analyses, interpretations, or references. The authors reviewed and edited all output and take full responsibility for the content of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Ahmed Salman, FRACP, FRCP, MRCP, Department of Internal Medicine, Kasr Alainy School of Medicine, 1 Al-Saray Street, Al-Manial, Cairo 11562, Egypt. awea844@gmail.com
Received: June 29, 2026 Revised: July 30, 2026 Accepted: August 31, 2026 Published online: September 28, 2026 Processing time: 68 Days and 12.4 Hours
Abstract
Metabolic dysfunction-associated steatotic liver disease is among the most prevalent chronic liver diseases worldwide. Its increasing incidence is typically linked to over-nutrition and metabolic syndrome. However, this account remains insufficiently detailed, particularly regarding diseases in lean individuals and the generational acceleration of metabolic illnesses. The exposome encompasses the entirety of the environmental exposure throughout an individual’s life and provides a complementary framework. The liver is a pivotal organ given that it is the primary location for the biotransformation of xenobiotics. This study synthesized data suggesting that environmental chemical exposure may be a plausible and controllable factor in steatotic liver disease while distinguishing associations from causation. We reviewed the main exposure classes, including per- and polyfluoroalkyl substances, micro- and nanoplastics, endocrine-disrupting plasticizers, persistent organic pollutants, hazardous metals, and air pollution. We assessed the strength of human evidence and delineated the potential mechanisms shared by these agents, including nuclear receptor disruption, mitochondrial and oxidative injury, inflammasome activation, stellate cell fibrogenesis, gut microbiota-bile acid disruption, and developmental reprogramming, along with their documented associations with steatosis, steatohepatitis, fibrosis, and hepatocellular carcinoma. The recognition of environmental exposure redefines metabolic dysfunction-associated steatotic liver disease as chemical environment-driven. These findings have implications in risk assessment, treatment, and prevention.
Core Tip: Metabolic dysfunction-associated steatotic liver disease is typically a result of overnutrition and metabolic syndrome; the phenomenon of lean disease and its increasing prevalence remain inadequately elucidated. This review analyzes the hepatic exposome, focusing on environmental chemicals such as per- and polyfluoroalkyl substances, phthalates, bisphenols, persistent organic pollutants, toxic metals, and air pollution as potential modifiable factors contributing to steatosis, steatohepatitis, fibrosis, and hepatocellular carcinoma, while also noting that micro- and nanoplastics remain an emerging and unverified exposure. We incorporated shared mechanisms, human and experimental evidence assessed by strength, sex-specific susceptibility, and the tools necessary to implement environmental hepatology in practice.
