Review
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 27, 2020; 12(4): 125-136
Published online Apr 27, 2020. doi: 10.4254/wjh.v12.i4.125
Liver injury induced by paracetamol and challenges associated with intentional and unintentional use
Laura Rotundo, Nikolaos Pyrsopoulos
Laura Rotundo, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
Nikolaos Pyrsopoulos, Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
Author contributions: All authors designed the study, drafted and revised the manuscript; Pyrsopoulos N supervised the study.
Conflict-of-interest statement: Dr. Pyrsopoulos reports grants from Allergan, grants from Bayer, grants from Beigene, grants from Bristol Myers, grants from Confirm, grants from Conatus, grants from Intercept, grants from Mallinckrodt, grants from Novartis, grants from Resusix, grants from Saro, grants from Valeant, grants from Gilead, grants from Exelixis, grants from Hologic, grants from Shire, grants from Genfit, grants from Prometheus, outside the submitted work. Dr. Rotundo certifies that she has no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Nikolaos Pyrsopoulos, MD, PhD, Professor, Department of Gastroenterology and Hepatology, Rutgers-New Jersey Medical School, University Hospital, 185 South Orange Avenue, MSB H-538, Newark, NJ 07103, United States. pyrsopni@njms.rutgers.edu
Received: October 11, 2019
Peer-review started: October 11, 2019
First decision: November 2, 2019
Revised: December 26, 2019
Accepted: February 17, 2020
Article in press: February 17, 2020
Published online: April 27, 2020
Processing time: 194 Days and 14.8 Hours
Abstract

Drug induced liver injury (DILI) is a common cause of acute liver injury. Paracetamol, also known as acetaminophen, is a widely used anti-pyretic that has long been established to cause liver toxicity once above therapeutic levels. Hepatotoxicity from paracetamol overdose, whether intentional or non-intentional, is the most common cause of DILI in the United States and remains a global issue. Given the increased prevalence of combination medications in the form of pain relievers and antihistamines, paracetamol can be difficult to identify and remains a significant cause of acute hepatotoxicity, as evidenced by its contribution to over half of all acute liver failure cases in the United States. This is especially concerning given that, when co-ingested with other medications, the rise in serum paracetamol levels may be delayed past the 4-hour post-ingestion mark that is currently used to determine patients that require medical therapy. This review serves to describe the clinical and pathophysiologic features of hepatotoxicity secondary to paracetamol and provide an update on current available knowledge and treatment options.

Keywords: Paracetamol; Drug-induced liver injury; Hepatotoxicity; Acute liver failure

Core tip: Paracetamol is a widely used anti-pyretic that has long been established to cause liver toxicity once above therapeutic levels. Given the increased prevalence of combination medications in the form of pain relievers and antihistamines, paracetamol can be difficult to identify and remains a significant cause of acute hepatotoxicity globally. This is especially concerning given that, when co-ingested with other medications, the rise in serum paracetamol levels may be delayed and alter medical management. This review serves to describe the clinical and pathophysiologic features of hepatotoxicity secondary to paracetamol and provide an update on current available knowledge and treatment options.