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Immune checkpoint inhibitors induced liver injury: an observational study
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Edité par CCSD -
International audience. Introduction: Liver toxicity associated with immune checkpoint inhibitors (ICI), such as PD-1, PD-L1 and CTLA-4 inhibitors, is frequent. International guidelines recommend pausing immunotherapy and administering corticosteroids, regardless of the hepatitis phenotype. The aim of our study was to describe the different phenotypes of ICI-induced hepatitis and to assess their evolution.Material and methods: We analyzed the patients with immune-mediated hepatitis due to ICI presented to the « ToxImmun » multidisciplinary meeting in Montpellier between December 2018 and October 2021. Data regarding cancer, hepatitis phenotype, hepatitis management, and ICI rechallenge were collected at diagnosis, week 1, 2 and 4, and once a week until hepatitis recovery.Results: Among 389 patients with immune-related Adverse Events (irAE), hepatitis accounted for 14.7% (n = 57), and 52 were included. Median age was 66 (range 23–87) and 52.8% were men (n = 28). PD-1 inhibitors were the most represented ICI (n = 48, 92.3%), alone (n = 31, 59.6%), or with CTLA-4 inhibitor (n = 17, 32.7%). Hepatitis phenotype was cholestatic in 40.4% (n = 21), hepatocellular in 30.8% (n = 16), and mixed in 28.8% (n = 15). Hepatitis were predominantly grade 3, according to the CTCAE system (71.2%, n = 37). No case of severe acute hepatitis was reported. Liver biopsy was performed in 38.5% (n = 20). Biliary stenosis occurred in 6 patients (28.6%). An extra-hepatic irAE was reported in 46.2% (n = 24). Most patients were treated with corticosteroids (76.9%, n = 40) and ursodeoxycholic acid (UDCA) (32.7%, n = 17). ICI was resumed in 46.2% (n = 24), 70.8% received the same ICI (n = 17) and 95.8% received a single ICI (n = 23). The rate of hepatitis recurrence after treatment reintroduction was 37.5% (n = 9). Ten patients died (19.2%), unrelated to ICI.Discussion/Conclusion: The frequency of ICI-related hepatitis was about 15% in our study which is consistent with the literature. Future research should study the hepatitis management, particularly in the case of cholestatic pattern, by specifying the place of UDCA.
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