Bessone F, Bjornsson ES. Checkpoint inhibitor-induced hepatotoxicity: Role of liver biopsy and management approach. World J Hepatol 2022; 14(7): 1269-1276 [PMID: 36158917 DOI: 10.4254/wjh.v14.i7.1269]
Corresponding Author of This Article
Fernando Bessone, MD, Full Professor, Department of Gastroenterology and Hepatology, Facultad de Ciencias Médicas, Hospital Provincial del Centenario, University of Rosario School of Medicine, Urquiza 3101, Rosario 2000, Santa Fe, Argentina. bessonefernando@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Editorial
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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/
World J Hepatol. Jul 27, 2022; 14(7): 1269-1276 Published online Jul 27, 2022. doi: 10.4254/wjh.v14.i7.1269
Checkpoint inhibitor-induced hepatotoxicity: Role of liver biopsy and management approach
Fernando Bessone, Einar Stefan Bjornsson
Fernando Bessone, Department of Gastroenterology and Hepatology, Facultad de Ciencias Médicas, Hospital Provincial del Centenario, University of Rosario School of Medicine, Rosario 2000, Santa Fe, Argentina
Einar Stefan Bjornsson, Department of Gastroenterology, Natl Univ Hosp Iceland, Sect Gastroenterol & Hepatol, Dept Internal Med, Hringbraut 11D, IS-101 Reykjavik, Iceland
Einar Stefan Bjornsson, Landspitali University Hospital and Faculty of Medicine, University of Iceland, Reykjavik Postal code 101, State of Reykjavik, Iceland
Author contributions: Bessone F and Bjornsson ES contributed to this paper; Bessone F designed the overall concept and outline of the manuscript; Bjornsson ES contributed to the discussion and design of the manuscript; They both contributed to the writing, and editing the manuscript and review of literature.
Conflict-of-interest statement: All 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: Fernando Bessone, MD, Full Professor, Department of Gastroenterology and Hepatology, Facultad de Ciencias Médicas, Hospital Provincial del Centenario, University of Rosario School of Medicine, Urquiza 3101, Rosario 2000, Santa Fe, Argentina. bessonefernando@gmail.com
Received: February 3, 2022 Peer-review started: February 3, 2022 First decision: April 8, 2022 Revised: April 13, 2022 Accepted: June 13, 2022 Article in press: June 13, 2022 Published online: July 27, 2022 Processing time: 173 Days and 17.4 Hours
Abstract
Immunological checkpoint inhibitors (ICIs) have revolutionized therapy of many different malignanices. Concomitant immune-mediated adverse effects are common and can affect many organs such as the skin, lungs, gastrointestinal and endocrine organs as well as the liver. Liver injury has been reported in 3%-8% of patients with grade III-IV hepatitis in retrospective studies. The liver injury is characterized by hepatocellular injury resembling autoimmune hepatitis biochemically but not immunologically as patients with ICI induced hepatoxicity rarely have auto-antibodies or IgG elevation. The role for liver biopsy (LB) in patients with suspected liver injury due to ICIs is controversial and it is not clear whether results of a LB will change clinical management. LB can be helpful when there is diagnostic uncertainty and pre-existing liver disease is suspected. Although there are no distinctive histological features, the finding of granulomas and endothelitis may suggest a specific type of hepatitis induced by ICIs. The natural history of hepatotoxicity of ICI therapy is not well known. Recent studies have demonstrated that 33%-50% of patients improve spontaneously with discontinuation of ICIs. In patients with jaundice and/or coagulopathy corticosteroids are used. The high doses of corticosteroids with 1-2 mg/kg/d of methylprednisolone recommended by the oncological societies are controversial. Recently it has shown that initial treatment with 1 mg/kg/d provided similar liver tests improvement which was also associated with a reduced risk of steroid-induced adverse effects in comparison with higher-dose regimens. Secondary immunosuppression mostly with mycophenolate mofetil has been reported to be helpful.
Core Tip: Liver injury associated with immunological checkpoint inhibitors (ICIs) has been reported in 3%-8% of patients with grade III-IV hepatitis in retrospective studies. Although there are no distinctive histological features, the finding of granulomas and endothelitis may suggest a specific type of hepatitis induced by ICIs. Recent studies have demonstrated that 33-50% of patients improve spontaneously with discontinuation of ICIs. The high doses of corticosteroids with 1-2 mg/kg/d of methylprednisolone recommended by the oncological societies are controversial. Patients with ICI induced hepatoxicity without jaundice and/or coagulopathy should be monitored.
