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

• Published in: Hepatology international 2021-10, Vol.15 (5), p.1278-1287
• Main Authors: Ito, Takanori, Ishigami, Masatoshi, Yamamoto, Takafumi, Mizuno, Kazuyuki, Yamamoto, Kenta, Imai, Norihiro, Ishizu, Yoji, Honda, Takashi, Kawashima, Hiroki, Yasuda, Satoshi, Toyoda, Hidenori, Yokota, Kenji, Hase, Tetsunari, Nishio, Naoki, Maeda, Osamu, Kato, Masashi, Hashimoto, Naozumi, Hibi, Hideharu, Kodera, Yasuhiro, Sone, Michihiko, Ando, Yuichi, Akiyama, Masashi, Shimoyama, Yoshie, Fujishiro, Mitsuhiro
• Format: Article
• Language: English
• Subjects: Biopsy; CD20 antigen; CD3 antigen; CD4 antigen; CD8 antigen; Colorectal Surgery; Corticoids; Corticosteroids; Hepatocellular carcinoma; Hepatology; Immune checkpoint inhibitors; Immunosuppression; Inhibitors; Injuries; Liver; Liver cancer; Lymphocytes; Lymphocytes T; Medicine; Medicine & Public Health; Mycophenolate mofetil; Mycophenolic acid; Necrosis; Original Article; Patients; Steroids; Surgery
• ISSN: 1936-0533; 1936-0541
• DOI: 10.1007/s12072-021-10238-y

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.