Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2018; 24(13): 1373-1385
Published online Apr 7, 2018. doi: 10.3748/wjg.v24.i13.1373
Dissecting the molecular pathophysiology of drug-induced liver injury
Hui Ye, Leonard J Nelson, Manuel Gómez del Moral, Eduardo Martínez-Naves, Francisco Javier Cubero
Hui Ye, Eduardo Martínez-Naves, Francisco Javier Cubero, Department of Immunology, Ophtalmology and ORL, Complutense University School of Medicine, Madrid 28040, Spain
Hui Ye, Eduardo Martínez-Naves, Francisco Javier Cubero, 12 de Octubre Health Research Institute (imas12), Madrid 28041, Spain
Leonard J Nelson, Institute for BioEngineering (Human Liver Tissue Engineering), School of Engineering, Faraday Building, The University of Edinburgh, The King’s Buildings, Mayfield Road, Edinburgh EH9 3 JL, Scotland, United Kingdom
Manuel Gómez del Moral, Department of Cell Biology, Complutense University School of Medicine, Madrid 28040, Spain
Author contributions: Ye H and Cubero FJ outlined the review, wrote the manuscript and designed figures; Nelson LJ, Gómez del Moral M and Martínez-Naves E corrected the manuscript, checked English language and provided fundamental guidance.
Supported by the Spanish Ministerio de Economía y Competitividad (MINECO), No. RyC2014-15242 and No. SAF2016-78711 to Martinez-Naves E and Cubero FJ. Martinez-Naves E and Cubero FJ are part of the UCM group ¨Lymphocyte Immunobiology¨, Ref. 920631 (imas12-associated, Ref. IBL-6); Chinese Scholarship Council fellow to Ye H.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Open-Access: 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:
Correspondence to: Francisco Javier Cubero, BSc, MSc, PhD, Assistant Professor, Department of Immunology, Ophtalmology and ORL, Complutense University School of Medicine, Plaza de Ramón y Cajal s/n, Madrid 28040, Spain.
Telephone: +34-91-3941385 Fax: +34-91-3941641
Received: January 27, 2018
Peer-review started: January 28, 2018
First decision: February 10, 2018
Revised: February 16, 2018
Accepted: February 26, 2018
Article in press: February 26, 2018
Published online: April 7, 2018
Core Tip

Core tip: Drug-induced liver injury (DILI) represents a broad spectrum of clinical manifestations, and is generally divided into two subtypes: intrinsic and idiosyncratic hepatotoxicity. Drugs and their reactive metabolites covalently bind to mitochondria and cause direct hepatic toxicity through accumulation of oxidative stress (ROS and RNS), endoplasmic reticulum stress and mitochondrial dysfunction, ultimately leading to cell death. The innate and adaptive immune responses also play an important role in the occurrence of idiosyncratic immunological reactions towards the drugs. In this review, we discuss the pathophysiological mechanisms underlying DILI, specific signaling pathways and the common forms of hepatocyte death.