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World J Gastroenterol. Aug 28, 2021; 27(32): 5376-5391
Published online Aug 28, 2021. doi: 10.3748/wjg.v27.i32.5376
Immune checkpoint inhibitor-related hepatotoxicity: A review
Devika Remash, David S Prince, Catriona McKenzie, Simone I Strasser, Steven Kao, Ken Liu
Devika Remash, David S Prince, Catriona McKenzie, Simone I Strasser, Ken Liu, AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney 2050, NSW, Australia
Catriona McKenzie, Simone I Strasser, Steven Kao, Ken Liu, Sydney Medical School, University of Sydney, Sydney 2006, NSW, Australia
Catriona McKenzie, Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney 2050, NSW, Australia
Catriona McKenzie, New South Wales Health Pathology, New South Wales Health, Sydney 2050, NSW, Australia
Steven Kao, Medical Oncology, Chris O’Brien Lifehouse, Sydney 2050, NSW, Australia
Author contributions: McKenzie C, Kao S, Strasser SI and Liu K were involved in the conception of the review, and critically revised the article; Remash D, Prince DS and Liu K performed the literature review, and drafted the article; all authors have read and approved the final version.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
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: Ken Liu, BSc, FRACP, MBBS, Consultant Physician-Scientist, Senior Lecturer, Staff Physician, AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney 2050, NSW, Australia. ken.liu@health.nsw.gov.au
Received: March 31, 2021
Peer-review started: March 31, 2021
First decision: June 23, 2021
Revised: June 28, 2021
Accepted: August 3, 2021
Article in press: August 3, 2021
Published online: August 28, 2021
Processing time: 146 Days and 12.4 Hours
Abstract

The application of immune checkpoint inhibitors (ICI) in advanced cancer has been a major development in the last decade. The indications for ICIs are constantly expanding into new territory across different cancers, disease stages and lines of therapy. With this increased use, adverse events including immune checkpoint inhibitor-related hepatotoxicity (ICH) have emerged as an important clinical problem. This along with the introduction of ICI as first- and second-line treatments for advanced hepatocellular carcinoma makes ICH very relevant to gastroenterologists and hepatologists. The incidence of ICH varies between 1%-20% depending on the number, type and dose of ICI received. Investigation and management generally involve excluding differential diagnoses and following a stepwise escalation of withholding or ceasing ICI, corticosteroid treatment and adding other immunosuppressive agents depending on the severity of toxicity. The majority of patients with ICH recover and some may even safely recommence ICI therapy. Guideline recommendations are largely based on evidence derived from retrospective case series which highlights a priority for future research.

Keywords: Immunotherapy, Immune checkpoint inhibitors, Hepatitis, Adverse drug event, Drug-induced liver injury, Immunosuppression

Core Tip: Immune checkpoint inhibitor (ICI)-related hepatotoxicity (ICH) is an increasingly encountered clinical problem for gastroenterologists. Although the diagnosis should be suspected in patients receiving ICI with liver function test derangements, a thorough history, examination and targeted liver investigations including cross-sectional imaging should be performed to exclude differential diagnoses. Once ICH is confirmed, its severity should be graded which then guides management. Management of ICH follows a stepwise approach beginning with cessation of ICI, followed by corticosteroids and other immunosuppressants with close monitoring after each step. The decision to recommence ICI after recovery is made on a case-by-case basis.