Time to use the right classification to predict the severity of checkpoint inhibitor-induced liver injury, as assessed for causality using the updated RUCAM.

Autor:	Hountondji L; Hepatology and Liver Transplantation Unit, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France., Faure S; Hepatology and Liver Transplantation Unit, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France., Palassin P; Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, France., Viel PWD; Department of Medical Oncology, Montpellier Cancer Institute, Montpellier University Hospital, Montpellier, France.; Internal Medicine, Beziers Hospital, Béziers, France., Dupuy M; Hepatology and Liver Transplantation Unit, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France.; Department of Oncology, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France., Larrey D; Hepatology and Liver Transplantation Unit, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France.; REFHEPS, Montpellier, France., Lamoureux A; Department of Dermatology, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France., Coustal C; Internal Medicine & Immuno-Oncology (MedI2O), Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France., Pureur D; Department of Oncology, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France., Lesage C; Department of Dermatology, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France., Assenat É; Hepatology and Liver Transplantation Unit, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France.; Department of Oncology, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France.; Montpellier University, Montpellier, France., Rivière B; Department of Pathology, Montpellier University Hospital, University of Montpellier, Montpellier, France., Faillie JL; Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, Montpellier University Hospital, Montpellier, France.; Montpellier University, Montpellier, France., Quantin X; Department of Medical Oncology, Montpellier Cancer Institute, Montpellier University Hospital, Montpellier, France., Pageaux GP; Hepatology and Liver Transplantation Unit, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France.; Montpellier University, Montpellier, France., Maria ATJ; Internal Medicine & Immuno-Oncology (MedI2O), Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France.; Montpellier University, Montpellier, France.; Internal Medicine & Immuno-Oncology (MedI2O), Institute for Regenerative Medicine and Biotherapy (IRMB), Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France., Meunier L; Hepatology and Liver Transplantation Unit, Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France.; REFHEPS, Montpellier, France.; Internal Medicine & Immuno-Oncology (MedI2O), Institute for Regenerative Medicine and Biotherapy (IRMB), Saint Eloi Hospital, Montpellier University Hospital, Montpellier, France.
Jazyk:	angličtina
Zdroj:	Alimentary pharmacology & therapeutics [Aliment Pharmacol Ther] 2024 Dec; Vol. 60 (11-12), pp. 1561-1572. Date of Electronic Publication: 2024 Sep 24.
DOI:	10.1111/apt.18276
Abstrakt:	Background and Aims: While immune checkpoint inhibitors (ICIs) are revolutionising cancer therapy, checkpoint inhibitor-induced liver injury is a significant immune-related side effect of this immunotherapy. This study focuses on the severity classifications and characteristics of patients with checkpoint inhibitor-induced hepatitis. Methods: A retrospective analysis of patients with severe Checkpoint Inhibitor-induced hepatitis grade 3 and 4 according to the recommended Common Terminology Criteria for Adverse Events (CTCAE) classification was conducted. Data on clinicobiological characteristics, treatment and outcomes were collected from 3 university hospitals, and causality was assessed by using the updated Roussel Uclaf Causality Assessment Method. The severity of hepatitis was assessed using the Model for End-stage Liver Disease score, the Drug-Induced Liver Injury Network, and the Drug-Induced Liver Injury International Expert Working Group classifications. Results: We retrospectively included 100 patients presenting various hepatitis patterns with a median time to onset of 20 days after checkpoint inhibitors. Severity grading varied significantly among the classifications used. A lower incidence of severe cases was observed when using the Drug-Induced Liver Injury classifications instead of the recommended CCTCAE classification, and this was correlated with outcomes. Conclusions: This retrospective study challenges the efficacy of the CTCAE classification in defining the severity of Checkpoint Inhibitor-induced hepatitis and suggests that the traditional hepatology-focused scores may be more relevant. The CTCAE classification is inconsistent and gives equal weight to jaundice and elevated transaminases, which leads to steroid overtreatment and limits the rechallenge of ICIs. (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)
Databáze:	MEDLINE
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