Plasma exchange as potential treatment of severe immune checkpoint inhibitor-induced hepatitis
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background & Aims: Immune checkpoint inhibitors (ICIs) improve cancer survival but can cause severe immune-related hepatitis. Standard therapy with corticosteroids and second-line agents such as mycophenolate mofetil fails in some cases. Therapeutic plasma exchange (TPE) has been suggested as rescue therapy, but supporting evidence is limited. Methods: We retrospectively analyzed French multicenter data (March 2021-April 2025) on patients with grade 4 ICI-induced hepatitis refractory to corticosteroids ± other immunosuppressants who underwent TPE. Results: Thirteen patients (median age 63 years; 54% male) were included. Eleven had acute hepatitis, including seven with acute liver injury, and two had steroid-refractory cholestatic hepatitis. TPE was initiated a median of 28 days after hepatitis onset (median MELD score 21) and administered in 2-8 sessions. Liver function improved in eight patients (61.5%), allowing resumption of anticancer therapy without ICI rechallenge in five. Three patients with cirrhosis and hepatocellular carcinoma died of liver failure, and three died from other causes. TPE-related adverse events were mild to moderate. Conclusion: TPE is feasible, safe, and may be effective for severe steroid- and immunosuppressant-refractory ICI-induced hepatitis. Early initiation could improve outcomes; prospective studies are needed to clarify optimal timing and patient selection. Impact and implications: Severe immune checkpoint inhibitor-induced hepatitis represents a rare but life-threatening complication for which therapeutic options are limited once corticosteroids and immunosuppressants fail. Our study provides the first multicenter evidence suggesting that therapeutic plasma exchange (TPE) is a feasible and safe approach that may improve hepatic outcomes in this setting. These findings are particularly relevant for oncologists, hepatologists, and intensivists facing refractory immune checkpoint inhibitor-induced liver injury, as TPE could offer a bridge to recovery when liver transplantation is not feasible. Early consideration of TPE, alongside careful patient selection, could optimize outcomes, although larger prospective studies are required to confirm efficacy and define the best timing and indications.
Source: JHEP Reports
Authors: Lucy Meunier, Clement Monet, Antonio Saviano, Marwin Farrugia, François Villeret, Fanny Lebossé, Marion Khaldi, Olivier Moranne, Christine Chambon, Philippe Ichai, Astrid Laurent-Bellue, Ariane Laparra, Rodolphe Anty, Simona Tripon, Mialy Randrianarisoa, Alexandre Maria, Lina Hountondji, Eleonora De Martin
Institutions: Inserm, Hôpital Saint Eloi, Centre National de la Recherche Scientifique, Université de Montpellier, Physiologie et Médecine Expérimentale du Coeur et des Muscles, Centre Hospitalier Universitaire de Montpellier, Hôpitaux Universitaires de Strasbourg, Université Côte d'Azur, Hôpital l'Archet, Lyon 1 Université, Hospices Civils de Lyon, Pathobiologie et thérapie des maladies du foie, Centre Hospitalier Universitaire de Nantes, Nantes Université, Hôpital Edouard Herriot, Université Paris-Saclay, Assistance Publique – Hôpitaux de Paris, Hôpital Paul-Brousse, Bicêtre Hospital, Institut Gustave Roussy, Fondation Gustave Roussy, Institute for Regenerative Medicine & Biotherapy
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,110
OpenAlex ID: W4416443952