Edmond Atallah
Incidence, risk factors and outcomes of checkpoint inhibitor-induced liver injury: A 10-year real-world retrospective cohort study
Atallah, Edmond; Welsh, Sarah J; O'Carrigan, Brent; Oshaughnessy, Ana; Dolapo, Igboin; Kerr, Andrew S; Kucharczak, Joanna; Lee, Colin; Crooks, Colin; Hicks, Amy; Chimakurthi, Chenchu Ramu; Rao, Ankit; Franks, Hester; Patel, Poulam M.; Aithal, Guruprasad P.
Authors
Sarah J Welsh
Brent O'Carrigan
Ana Oshaughnessy
Igboin Dolapo
Andrew S Kerr
Joanna Kucharczak
Colin Lee
Dr COLIN CROOKS Colin.Crooks@nottingham.ac.uk
Clinical Associate Professor
Amy Hicks
Chenchu Ramu Chimakurthi
Ankit Rao
HESTER FRANKS HESTER.FRANKS@NOTTINGHAM.AC.UK
Clinical Associate Professor/ anne Mclaren Fellowship
POULAM PATEL POULAM.PATEL@NOTTINGHAM.AC.UK
Professor of Clinical Oncology
GURUPRASAD AITHAL Guru.Aithal@nottingham.ac.uk
Professor of Hepatology
Contributors
KHANH NGUYEN
Other
Abstract
Background & Aims: Checkpoint inhibitors (CPI) account for increasing numbers of drug-induced liver injury (DILI) cases. We aimed to determine the incidence rate and risk factors associated with checkpoint inhibitor-induced liver injury (ChILI). Methods: Prescription event monitoring was performed on all melanoma and renal cancer patients who received CPI at a tertiary centre between 2011 and 2021. ChILI cases were identified using the definitions, grading, and causality assessment methods validated for DILI. We assessed risk factors associated with ChILI in CPI-naive patients using multivariable logistic regression model. Consecutive patients with suspected ChILI from two other tertiary centres were adjudicated and combined for case characterisation and outcomes of ChILI. Results: Out of 432 patients who received CPI over 10 years, ChILI occurred in 38 (8.8%) with an overall incidence rate of 11.5 per 1,000 person-months (95% CI 8.2–15.8). Probability of ChILI was highest in combination therapy (32%) and no new events occurred beyond 135 days of treatment. Risk factor analysis showed that combination therapy, female sex, higher baseline alanine transferase level and lower baseline alkaline phosphatase level were independently associated with higher risk of ChILI. In total, 99 patients were adjudicated to have ChILI from three centres. Although Common Terminology Criteria for Adverse Events classified 20 patients (20.2%) to have ‘life-threatening’ grade 4 hepatitis, ChILI severity was graded as mild in 45 (45.5%) and moderate in the remaining 54 (54.5%) cases. Conclusions: The real-world risk of ChILI is higher than previously reported. Among patients receiving dual CPI, this risk falls markedly after 4.5 months. As Common Terminology Criteria for Adverse Events overestimates its clinical severity, case-definition, evaluation and management of ChILI should be revised to harmonise care. Impact and implications: Using prescription event monitoring over a 10-year period, the incidence rate of checkpoint inhibitor induced liver injury (ChILI) based on established case definitions for drug-induced liver injury (DILI) is 11.5 per 1,000 person-months. Formal causality assessment identified an alternative cause in 19% of patients with suspected ChILI highlighting the importance of systematic evaluation by clinicians to minimise unnecessary immunosuppression. Intensity of monitoring in patients receiving combination therapy regime after 4.5 months of therapy can be reduced as the risk of new onset ChILI beyond this point is minimal. Current Common Terminology Criteria for Adverse Events (CTCAE) grading overestimates clinical severity of ChILI and hence contributes to avoidable hospitalisation.
Citation
Atallah, E., Welsh, S. J., O'Carrigan, B., Oshaughnessy, A., Dolapo, I., Kerr, A. S., …Aithal, G. P. (2023). Incidence, risk factors and outcomes of checkpoint inhibitor-induced liver injury: A 10-year real-world retrospective cohort study. JHEP Reports, 5(10), Article 100851. https://doi.org/10.1016/j.jhepr.2023.100851
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 6, 2023 |
Online Publication Date | Sep 11, 2023 |
Publication Date | 2023-10 |
Deposit Date | Jul 6, 2023 |
Publicly Available Date | Jul 12, 2023 |
Journal | JHEP Reports |
Electronic ISSN | 2589-5559 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 5 |
Issue | 10 |
Article Number | 100851 |
DOI | https://doi.org/10.1016/j.jhepr.2023.100851 |
Keywords | Checkpoint inhibitors, immunotherapy, immune-mediated hepatitis, hepatotoxicity, drug-induced liver injury, incidence rate, risk factors |
Public URL | https://nottingham-repository.worktribe.com/output/22722199 |
Publisher URL | https://www.sciencedirect.com/science/article/pii/S2589555923001829 |
Files
Incidence, risk factors and outcomes of checkpoint inhibitor-induced liver injury
(827 Kb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search