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

Maaike Biewenga, Monique K van der Kooij, Michel W J M Wouters, Maureen J B Aarts, Franchette W P J van den Berkmortel, Jan Willem B de Groot, Marye J Boers-Sonderen, Geke A P Hospers, Djura Piersma, Rozemarijn S van Rijn, Karijn P M Suijkerbuijk, Albert J Ten Tije, Astrid A M van der Veldt, Gerard Vreugdenhil, John B A G Haanen, Alfons J M van der Eertwegh, Bart van Hoek, Ellen Kapiteijn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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

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