Plasma exchange as potential treatment of severe immune checkpoint inhibitor-induced hepatitis

TL;DR

This study suggests that plasma exchange may help treat severe liver damage caused by cancer immunotherapy when standard treatments fail.

Contribution

The first multicenter evidence supporting therapeutic plasma exchange for severe, treatment-resistant immune checkpoint inhibitor-induced hepatitis.

Findings

Liver function improved in 61.5% of patients after plasma exchange.

TPE allowed resumption of non-ICI anticancer therapy in some patients.

Non-responders had higher MELD scores and encephalopathy, suggesting the need for early selection.

Abstract

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.

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.

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.

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.

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.

Image 1

•This French multicenter cohort is the first systematic evaluation of TPE for severe ICI-induced hepatitis refractory to therapy.•Liver function improved or normalized in 61.5%, enabling resumption of non-ICI anticancer therapy in several patients.•Non-responders more often had encephalopathy and higher post-TPE MELD scores, highlighting the importance of early selection.•TPE may be a rescue option for non-transplant candidates, supporting prospective studies on timing and indications.

This French multicenter cohort is the first systematic evaluation of TPE for severe ICI-induced hepatitis refractory to therapy.

Liver function improved or normalized in 61.5%, enabling resumption of non-ICI anticancer therapy in several patients.

Non-responders more often had encephalopathy and higher post-TPE MELD scores, highlighting the importance of early selection.

TPE may be a rescue option for non-transplant candidates, supporting prospective studies on timing and indications.

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