{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:19:13Z","timestamp":1787818753346,"version":"build-2784847793"},"reference-count":92,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"abstract":"<jats:p>Vitamin A (VitA) is a fat\u2010soluble micronutrient involved in various physiological processes. Its sustained intake exceeding physiological needs leads to increased hepatic accumulation warranting careful monitoring for potential health implications. Despite being widely studied in animal models, there are limited data on histopathology associated with VitA toxicity in human liver that are essential to understand organ response and its pathogenesis to guide clinical management. A literature search was conducted, focusing on peer\u2010reviewed articles that explored the histological effects of excessive liver VitA accumulation in humans, excluding veterinary studies, reviews and articles without histological findings. Data on demographic, clinical, laboratory and histological information were extracted. Thirty\u2010nine studies, including results from 84 liver tissue samples, were reviewed (1960s\u20132025). Patients' mean age was 40 (3\u201378) years, with a balanced gender distribution. The majority of cases were due to medical therapy (67.9%) or dietary supplements (27.4%). The mean VitA intake was 112,006 international units (IU)\/day (equivalent to 33,600\u2009\u03bcg\/day) over 6.8\u2009years. The most common histological findings were hepatic stellate cell (HSC) hypertrophy\/hyperplasia (90.1%), sinusoidal fibrosis (44.1%), cirrhosis (25.0%), chronic hepatitis (23.8%) and variable steatosis, fibrosis and cholestasis. In humans, the hepatic response to excess VitA begins with HSC hypertrophy and hyperplasia, which represent the main adaptive storage mechanism; hepatotoxicity subsequently manifests through sinusoidal dilatation, chronic inflammation and fibrosis, occasionally progressing to cirrhosis. The severity of liver injury correlates with the duration and dose of VitA intake, with genetic and environmental factors potentially influencing clinical outcomes.<\/jats:p>","DOI":"10.1111\/his.70271","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T07:54:36Z","timestamp":1787817276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Histological manifestations of vitamin A toxicity in the liver"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5373-0611","authenticated-orcid":false,"given":"Giorgio","family":"Cazzaniga","sequence":"first","affiliation":[{"name":"Department of Pathology Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens  Athens Greece"},{"name":"Pathology Fondazione IRCCS San Gerardo dei Tintori  Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2103-0335","authenticated-orcid":false,"given":"Georg","family":"Lietz","sequence":"additional","affiliation":[{"name":"Human Nutrition Research Centre Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4657-7780","authenticated-orcid":false,"given":"Dina G.","family":"Tiniakos","sequence":"additional","affiliation":[{"name":"Department of Pathology Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens  Athens Greece"},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23031014","article-title":"The role of vitamin A in retinal diseases","volume":"23","author":"Sajovic J","year":"2022","journal-title":"Int. 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