Retreatment With Immune Checkpoint Inhibitors After a Severe Immune-Related Hepatitis: Results From a Prospective Multicenter Study

M. Riveiro-Barciela, A. Barreira-Díaz, A. Callejo-Pérez, E. Muñoz-Couselo, N. Díaz-Mejía, Á. Díaz-González, M.-C. Londoño, M.-T. Salcedo, M. Buti

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17 Citations (Scopus)


Background & aims: Liver injury related to immunotherapy is a relatively frequent immune-related adverse event that requires permanent discontinuation of immune checkpoint inhibitors (ICIs) in severe cases. We present the outcome of a cohort of patients who were retreated with immunotherapy after resolution of severe immune-related hepatitis.
Methods: We performed a prospective, multicenter, noninterventional study that included all consecutive patients with cancer and previous grade 3 or 4 immune-related hepatitis who were retreated with ICIs in 3 academic hospitals.
Results: Twenty-three patients who developed severe immune-related hepatitis were included: 20 of 23 (87.0%) received a single ICI and 3 of 23 (13.0%) received anti-programmed cell death protein-1 plus an anti-cytotoxic T-lymphocyte-associated antigen. The most frequent cancers were lung cell and urinary tract (7 and 6 cases, respectively). Immunotherapy was discontinued in all cases. Nineteen patients (82.6%) also received corticoids. Patients mainly were retreated with the same ICI (18 of 23; 78.3%) after a median time of 10 weeks (range, 1-54 wk) from the severe immune-related hepatitis. Fifteen patients (65.2%) did not have recurrence of the immune-related hepatitis after retreatment. Among the 8 (34.8%) subjects with recurrence, 5 of 8 were grade 3 and 3 of 8 were grade 4. Six (75%) had either an underlying autoimmune disease or antinuclear antibodies ≥1/80 (75% vs 26.7%; P = .037). None of the patients with previously grade 4 hepatitis had a recurrence, and those patients who had a recurrence tended to present with a better oncological prognosis. Overall, 19 (82.6%) subjects required permanent discontinuation of ICIs, with cancer progression the main reason for discontinuation (9 of 19; 47.8%).
Conclusions: Retreatment with ICIs is a feasible option after a severe immune-related hepatitis, even with the same ICIs, without recurrence of the liver injury retreatment in up to 65% of patients.
Original languageEnglish
Pages (from-to)732-740
Number of pages9
JournalClinical Gastroenterology and Hepatology
Issue number3
Publication statusPublished - Mar 2023


  • Hepatotoxicity
  • Immune checkpoint inhibitors
  • Immune-Related Hepatitis
  • Immunotherapy


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