Hepatic immune-mediatedadverseeffects of immune checkpoint inhibitors: analysis of real-life experience

• Autor(a) principal: Silva, Joana
• Data de Publicação: 2021
• Outros Autores: Falcão, Daniela, Cardoso, Cláudia, Pires, Ana Luísa, Araújo, António, Castro-Poças, Fernando
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.16/2897
• topic: Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Hepatotoxicity; Immune-related adverse event; Immunotherapy; cancer

Introduction and objectives: Immune Checkpoint Inhibitors (ICI) have shifted the paradigm of cancer therapy treatment. Despite their efficacy, ICIs may induce immune-related adverse events (irAE), which can affect various organs, namely the liver. This study intends to perform a comprehensive clinical description of the hepatic irAEs associated with ICI in a Portuguese population of a tertiary hospital centre. Materials and methods: A retrospective analysis of patients who developed immune-mediated liver injury (IMLI), among a cohort of patients treated with ICIs between March 15th of 2015 and December 15th of 2019 in a tertiary hospital. We used both Common Terminology Criteria for Adverse Events (CTCAE) and Drug-Induced Liver Injury Network (DILIN) criteria to define liver injury. Results: Among 151 patients, eight (5.3%) patients developed liver injury grade ≥3, of which five had hepatic metastasis. As such, only 3 cases were classified as IMLI. All IMLI presented with cholestasis pattern; the median duration from ICI initiation to IMLI was 84 days and/or 4 ICI cycles; one patient registered IMLI one month after nivolumab suspension; all were treated with steroids and one was successfully submitted to ICI re-challenge; a favourable outcome was seen in all patients; the median time to hepatic biochemistries normalization was 150 days. Among 10 patients with previous hepatic conditions, only one developed liver injury grade 2. Conclusions: Clinically significant ICI-related hepatotoxicity was uncommon; Immune-mediated liver injury may present a cholestatic pattern predominance. There was a low rate of liver injury of any kind in patients with previous hepatic disease while on ICI.