Clinical course of liver injury induced by immune checkpoint inhibitors in patients with advanced malignancies

Takanori Ito, Masatoshi Ishigami, Takafumi Yamamoto, Kazuyuki Mizuno, Kenta Yamamoto, Norihiro Imai, Yoji Ishizu, Takashi Honda, Hiroki Kawashima, Satoshi Yasuda, Hidenori Toyoda, Kenji Yokota, Tetsunari Hase, Naoki Nishio, Osamu Maeda, Masashi Kato, Naozumi Hashimoto, Hideharu Hibi, Yasuhiro Kodera, Michihiko SoneYuichi Ando, Masashi Akiyama, Yoshie Shimoyama, Mitsuhiro Fujishiro

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


Background: The clinical course of liver injury induced by immune checkpoint inhibitors (ICIs) varies among individuals, and there were few reports on the therapeutic effects of corticosteroids based on the patterns of liver injury. Methods: We evaluated the characteristics and clinical course of immune-related liver injury in 1214 patients treated with ICIs for advanced malignancies except for hepatocellular carcinoma between August 2014 and May 2021. Results: During the follow-up period (median, 252 days), 58 patients (4.8%) had an immune-related liver injury (≥ Grade 3). The liver-injury patterns were hepatocellular (n = 26, 44.8%), mixed (n = 11, 19.0%), or cholestatic (n = 21, 36.2%), and the median time to onset of liver injury was 39, 81, and 53 days, respectively; the hepatocellular pattern occurred earlier than the other types (p = 0.047). Corticosteroids were administered to 30 (51.7%) patients; while liver injury was improved in almost all patients with the hepatocellular pattern (n = 13/14, 92.9%), that failed to show improvement in over half of the patients with the non-hepatocellular patterns, and three patients with mixed patterns needed secondary immunosuppression with mycophenolate mofetil. Liver biopsies performed in 13 patients mainly showed lobular injury, endothelialitis, and spotty necrosis with infiltration of T cells positive for CD3 and CD8, but not CD4 or CD20. Conclusion: The incidence pattern and therapeutic response to corticosteroids in immune-related liver injury differ according to the injury type. Although corticosteroids were effective for the hepatocellular pattern, an additional strategy for refractory non-hepatocellular patterns is needed.

Original languageEnglish
Pages (from-to)1278-1287
Number of pages10
JournalHepatology International
Issue number5
Publication statusPublished - 10-2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hepatology


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