Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients

M. Biewenga, M.K. van der Kooij, M.W.J.M. Wouters, M.J.B. Aarts, F.W.P.J. van den Berkmortel, J.W.B. de Groot, M.J. Boers-Sonderen, G.A.P. Hospers, D. Piersma, R.S. van Rijn, K.P.M. Suijkerbuijk, A.J. ten Tije, A.A.M. van der Veldt, G. Vreugdenhil, J.B.A.G. Haanen, A.J.M. van der Eertwegh, B. van Hoek, E. Kapiteijn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background Checkpoint inhibitor-induced hepatitis is an immune-related adverse event of programmed cell death protein 1 (PD-1) inhibition, cytotoxic T-lymphocyte associated 4 (CTLA-4) inhibition or the combination of both. Aim of this study was to assess whether checkpoint inhibitor-induced hepatitis is related to liver metastasis and outcome in a real-world nationwide cohort. Methods Data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR) was used to analyze incidence, risk factors of checkpoint inhibitor-induced grade 3-4 hepatitis and outcome. Results 2561 advanced cutaneous melanoma patients received 3111 treatments with checkpoint inhibitors between May 2012 and January 2019. Severe hepatitis occurred in 30/1620 (1.8%) patients treated with PD-1 inhibitors, in 29/1105 (2.6%) patients treated with ipilimumab and in 80/386 (20.7%) patients treated with combination therapy. Patients with hepatitis had a similar prevalence of liver metastasis compared to patients without hepatitis (32% vs. 27%; p = 0.58 for PD-1 inhibitors; 42% vs. 29%; p = 0.16 for ipilimumab; 38% vs. 43%; p = 0.50 for combination therapy). There was no difference in median progression free and overall survival between patients with and without hepatitis (6.0 months vs. 5.4 months progression-free survival; p = 0.61; 17.0 vs. 16.2 months overall survival; p = 0.44). Conclusion Incidence of hepatitis in a real-world cohort is 1.8% for PD-1 inhibitor, 2.6% for ipilimumab and 20.7% for combination therapy. Checkpoint inhibitor-induced hepatitis had no relation with liver metastasis and had no negative effect on the outcome.
Original languageEnglish
Pages (from-to)510-519
Number of pages10
JournalHepatology International
Issue number2
Early online date25 Feb 2021
Publication statusPublished - Apr 2021


  • ctla-4 inhibitor
  • drug-induced hepatitis
  • immune-related adverse events
  • ipilimumab
  • liver metastasis
  • nivolumab
  • overall survival
  • pd-1 inhibitor
  • progression-free survival
  • risk factors
  • Immune-related adverse events
  • Ipilimumab
  • PD-1 inhibitor
  • Risk factors
  • CTLA-4 inhibitor
  • Nivolumab
  • Progression-Free Survival
  • Overall survival
  • Drug-induced Hepatitis
  • Liver metastasis

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