John Libbey Eurotext

Hépato-Gastro & Oncologie Digestive


Liver toxicity of immune checkpoint inhibitors Volume 28, issue 8, Octobre 2021


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1 Hôpital Paul Brousse, Centre Hépato-Biliaire, Hépatologie et transplantation hépatique, 12 avenue Paul Vaillant Couturier, 94800 Villejuif
2 Unité INSERM 1193
3 FHU Hepatinov
* Correspondance

Immune checkpoint inhibitors (ICI) represent a revolution in oncological management with an increased survival rate for patients affected by different cancers. The downside of ICI are the immune-related adverse events (irAEs). The management of immune mediated hepatitis is challenging due to its heterogeneous presentation. The diagnosis is based on the exclusion of other causes of acute hepatitis. Liver biopsy can help in confirming the diagnosis and it is indicated in most severe cases. The evaluation of severity is overestimated by the oncological classification Common Terminology Criteria for Adverse Events (CTCAE) and the management by an hepatologist is paramount as the introduction of immunosuppressive agents is based on the severity of liver injury. The spectrum of severity is also heterogeneous and goes from a mild elevation of liver tests to severe/fulminant hepatitis. The management consist in stopping the immunotherapy and for the most severe cases in the administration of corticosteroids. Spontaneous improvement has been reported and the introduction of corticosteroids should be individualized. Patients resistant to high doses of corticosteroids need the add of a second immunosuppressive molecule such as mycophenolate mofetil. The reintroduction of ICIs in a patient with previous immune mediated hepatitis may be possible, but the risk/benefit ratio should be considered, as the risk factors for hepatitis recurrence are currently unclear. The management of these patients requires a balance between efficacy, toxicity and specific treatments therefore it needs a multidisciplinary approach. The incidence of immune-related liver toxicity will continue to rise based on the increasing use of ICIs for most cancers, mandating improved understanding and management of this complication.