Pestalardo ML, Bevilacqua CS, Amante MF. Vitamin A toxicity and hepatic pathology: A comprehensive review. World J Hepatol 2025; 17(8): 107738 [DOI: 10.4254/wjh.v17.i8.107738]
Corresponding Author of This Article
Marcelo Fabián Amante, MD, Chief Physician, Professor, División Patología, Hospital General de Agudos Cosme Argerich, Pi y Margall 480, Buenos Aires C1155AHA, Argentina. marcelofabianamante@gmail.com
Research Domain of This Article
Pathology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Aug 27, 2025; 17(8): 107738 Published online Aug 27, 2025. doi: 10.4254/wjh.v17.i8.107738
Vitamin A toxicity and hepatic pathology: A comprehensive review
María L Pestalardo, Cecilia S Bevilacqua, Marcelo Fabián Amante
María L Pestalardo, Marcelo Fabián Amante, División Patología, Hospital General de Agudos Cosme Argerich, Buenos Aires C1155AHA, Argentina
Cecilia S Bevilacqua, División Patología, Nuevo Hospital Iturraspe, Santa Fe S2800XAH, Argentina
Co-first authors: María L Pestalardo and Cecilia S Bevilacqua.
Author contributions: Pestalardo ML and Bevilaqua CS have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper; Pestalardo ML and Amante MF made equal contributions to the conceptualization and design of the study, creation of the artwork, supervision, and making critical revisions to the various versions of the manuscript, underlying their role; Bevilaqua CS conducted the literature review, performed the analysis and interpretation of data, and drafted the original manuscript; Bevilacqua CS and Amante MF contributed equally in the overall completion of this work; all authors prepared the draft and approved the submitted version.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Marcelo Fabián Amante, MD, Chief Physician, Professor, División Patología, Hospital General de Agudos Cosme Argerich, Pi y Margall 480, Buenos Aires C1155AHA, Argentina. marcelofabianamante@gmail.com
Received: April 9, 2025 Revised: May 21, 2025 Accepted: July 23, 2025 Published online: August 27, 2025 Processing time: 152 Days and 10.2 Hours
Abstract
Vitamin A is essential for vision, immunity, and cellular function, but excessive intake, known as hypervitaminosis A, leads to liver toxicity. Toxicity can be acute (from high single doses) or chronic (from prolonged overconsumption), causing symptoms like nausea, bone pain, and liver damage. The normal values of vitamin A in adults, measured as serum retinol, can range from 0.3 mg/L to 1.2 mg/L. The liver, which stores vitamin A in hepatic stellate cells, becomes overwhelmed, leading to retinoid accumulation, oxidative stress, and inflammation. Pathologically, vitamin A toxicity progresses from hepatic steatosis (fatty liver) to fibrosis and cirrhosis. Histological changes include hepatocellular ballooning, stellate cell activation, and perisinusoidal fibrosis. Molecular mechanisms involve oxidative stress from reactive oxygen species, apoptosis, and dysregulated pathways (tumor growth factor-beta, nuclear factor-kappa B), which drive fibrogenesis. Chronic toxicity also disrupts lipid metabolism, worsening liver injury. Clinically, management includes limiting vitamin A intake and exploring antioxidants (e.g., N-acetylcysteine) or anti-fibrotic therapies. Research gaps include the need for better biomarkers, personalized risk assessment, and refined dietary guidelines. Future studies should focus on therapeutic interventions and experimental models to improve outcomes. In conclusion, while vitamin A is vital, its toxicity poses serious hepatic risks. Understanding its mechanisms and developing targeted treatments are crucial for preventing liver damage and ensuring safe consumption.
Core Tip: Vitamin A toxicity (hypervitaminosis A) causes serious liver damage, progressing from steatosis to fibrosis and cirrhosis. The liver’s storage capacity is overwhelmed, leading to retinoid accumulation, oxidative stress, and inflammation. Key mechanisms include reactive oxygen species generation, apoptosis, and dysregulated pathways (tumor growth factor-beta, nuclear factor-kappa B), which drive stellate cell activation and fibrosis. Clinically, chronic toxicity manifests as hepatomegaly, portal hypertension, and potential liver failure. Management involves limiting vitamin A intake and exploring antioxidants (e.g., N-acetylcysteine) or anti-fibrotic therapies. Future research should focus on biomarkers, personalized risk assessment, and safer dietary guidelines. Public awareness and therapeutic advancements are crucial to prevent liver disease.
