Yang D, Kim B, Kim JW. Mechanistic insights into hepatic cell type-specific contributions to acetaminophen-induced acute liver injury. World J Gastroenterol 2025; 31(45): 112720 [DOI: 10.3748/wjg.v31.i45.112720]
Corresponding Author of This Article
Jong-Won Kim, PhD, Assistant Professor, Department of Pharmacology, Institute of Medical Sciences, College of Medicine, Gyeongsang National University, 15, Jinjudae-ro 816 Beon-gil, Jinju 52727, South Korea. kimjw@gnu.ac.kr
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Gastroenterology & Hepatology
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Review
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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/
Dec 7, 2025 (publication date) through Dec 6, 2025
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World Journal of Gastroenterology
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1007-9327
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Yang D, Kim B, Kim JW. Mechanistic insights into hepatic cell type-specific contributions to acetaminophen-induced acute liver injury. World J Gastroenterol 2025; 31(45): 112720 [DOI: 10.3748/wjg.v31.i45.112720]
World J Gastroenterol. Dec 7, 2025; 31(45): 112720 Published online Dec 7, 2025. doi: 10.3748/wjg.v31.i45.112720
Mechanistic insights into hepatic cell type-specific contributions to acetaminophen-induced acute liver injury
Daram Yang, Bumseok Kim, Jong-Won Kim
Daram Yang, Bumseok Kim, Biosafety Research Institute and College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, South Korea
Jong-Won Kim, Department of Pharmacology, Institute of Medical Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, South Korea
Jong-Won Kim, Department of Convergence Medical Science, Gyeongsang National University Graduate School, Jinju 52727, South Korea
Co-corresponding authors: Bumseok Kim and Jong-Won Kim.
Author contributions: Yang D drafted the original manuscript and prepared all figures and visual summaries; Yang D and Kim B jointly secured the research funding; Kim B and Kim JW contributed to writing - review & editing and supervision. All the authors have read and approved the final manuscript. Both Kim B and Kim JW have made indispensable and complementary contributions as corresponding authors. Kim B ensured financial support, administrative management, and structural guidance of the manuscript. Kim JW offered scientific supervision, strategic direction, and final oversight of the manuscript’s academic content. Therefore, they qualify as co-corresponding authors for this work.
Supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), Funded by the Ministry of Education, No. RS-2023-00275922; and the Ministry of Science and ICT, Republic of Korea, No. RS-2025-00556031.
Conflict-of-interest statement: The authors declare that they have no conflict 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: Jong-Won Kim, PhD, Assistant Professor, Department of Pharmacology, Institute of Medical Sciences, College of Medicine, Gyeongsang National University, 15, Jinjudae-ro 816 Beon-gil, Jinju 52727, South Korea. kimjw@gnu.ac.kr
Received: August 4, 2025 Revised: September 4, 2025 Accepted: October 27, 2025 Published online: December 7, 2025 Processing time: 121 Days and 9.2 Hours
Abstract
Acetaminophen [N-acetyl-p-aminophenol (APAP)] overdose is a leading cause of acute liver failure worldwide, chiefly due to its hepatotoxic effects. The pathogenesis of APAP-induced acute liver injury (ALI) involves complex interactions among various hepatic cell types, each playing a distinct role in the progression of the injury. Hepatocytes, the primary targets of APAP toxicity, undergo oxidative stress, mitochondrial dysfunction, and necrosis following the formation of the toxic metabolite N-acetyl-p-benzoquinone imine. Additionally, other hepatic cells and infiltrating immune cells responding to liver injury significantly contribute to the pathogenesis of APAP-induced ALI. This review synthesizes current mechanistic insights to offer a detailed understanding of the specific contributions of hepatic cells to APAP-induced liver injury, emphasizing potential therapeutic targets designed to reduce liver damage and enhance patient outcomes. Additionally, it identifies potential therapeutic targets within these cellular pathways that could be leveraged to alleviate liver damage and enhance clinical outcomes for patients affected by APAP overdose.
Core Tip: This review provides a comprehensive overview of the cellular mechanisms underlying acetaminophen (APAP)-induced acute liver injury (ALI). It highlights the distinct yet interconnected roles of hepatocytes, Kupffer cells, monocyte-derived macrophages, hepatic stellate cells, liver sinusoidal endothelial cells, and adaptive immune cells in the initiation and progression of ALI. The review also explores how these cells contribute to both liver injury and repair, offering insight into the dynamic cellular crosstalk during APAP hepatotoxicity. By integrating recent findings, it identifies potential therapeutic targets and strategies that modulate cell-specific responses to improve clinical outcomes in drug-induced liver injury.
