Review
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 8, 2017; 9(10): 491-502
Published online Apr 8, 2017. doi: 10.4254/wjh.v9.i10.491
Drug-induced liver injury: Do we know everything?
Tamara Alempijevic, Simon Zec, Tomica Milosavljevic
Tamara Alempijevic, Simon Zec, Tomica Milosavljevic, University of Belgrade, School of Medicine, 11000 Belgrade, Serbia
Tamara Alempijevic, Tomica Milosavljevic, Clinical Center of Serbia, Clinic for Gastroenterology and Hepatology, 11000 Belgrade, Serbia
Author contributions: All authors contributed equally to the conception, design, literature review, drafting, editing and critical revision of the final manuscript; as a native English speaker, Zec S also provided additional English language polishing.
Conflict-of-interest statement: Authors declare no potential conflicts of interest and no financial support.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Tamara Alempijevic, MD, PhD, Professor, University of Belgrade, School of Medicine, 2 Dr Koste Todorovica Street, 11000 Belgrade, Serbia. tamara.alempijevic@med.bg.ac.rs
Telephone: +381-11-3628582 Fax: +381-11-3628582
Received: August 25, 2016
Peer-review started: August 26, 2016
First decision: November 11, 2016
Revised: February 28, 2017
Accepted: March 14, 2017
Article in press: March 17, 2017
Published online: April 8, 2017
Processing time: 223 Days and 9.5 Hours
Abstract

Interest in drug-induced liver injury (DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged. Clinically ranging from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure, DILI remains a leading causes of emergent liver transplant. The consumption of unregulated herbal and dietary supplements has introduced new challenges in epidemiological assessment and clinician management. As such, numerous registries have been created, including the United States Drug-Induced Liver Injury Network, to further our understanding of all aspects of DILI. The launch of LiverTox and other online hepatotoxicity resources has increased our awareness of DILI. In 2013, the first guidelines for the diagnosis and management of DILI, were offered by the Practice Parameters Committee of the American College of Gastroenterology, and along with the identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have come to define the current state of the art, however, gaps in our knowledge still undoubtedly remain.

Keywords: Acute liver failure; Drug-induced liver injury; Hepatoxicity; Acetaminophen toxicity; Cholestatic injury; Liver biopsy; Pharmacoepidemiology; Herbal-induced liver injury; Hy’s law

Core tip: Drug-induced liver injury has gained a great amount of interest in the past decade, raising the question of whether we know everything. Various global registries have been established and the first guidelines for diagnosis and management have come to define the state of the art. The identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have amplified our understanding of the impact of drug-induced liver injury, however gaps in our knowledge still remain.