TY - JOUR
T1 - Clinical course of liver injury induced by immune checkpoint inhibitors in patients with advanced malignancies
AU - Ito, Takanori
AU - Ishigami, Masatoshi
AU - Yamamoto, Takafumi
AU - Mizuno, Kazuyuki
AU - Yamamoto, Kenta
AU - Imai, Norihiro
AU - Ishizu, Yoji
AU - Honda, Takashi
AU - Kawashima, Hiroki
AU - Yasuda, Satoshi
AU - Toyoda, Hidenori
AU - Yokota, Kenji
AU - Hase, Tetsunari
AU - Nishio, Naoki
AU - Maeda, Osamu
AU - Kato, Masashi
AU - Hashimoto, Naozumi
AU - Hibi, Hideharu
AU - Kodera, Yasuhiro
AU - Sone, Michihiko
AU - Ando, Yuichi
AU - Akiyama, Masashi
AU - Shimoyama, Yoshie
AU - Fujishiro, Mitsuhiro
N1 - Publisher Copyright:
© 2021, Asian Pacific Association for the Study of the Liver.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
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U2 - 10.1007/s12072-021-10238-y
DO - 10.1007/s12072-021-10238-y
M3 - Article
C2 - 34373964
AN - SCOPUS:85112080064
SN - 1936-0533
VL - 15
SP - 1278
EP - 1287
JO - Hepatology International
JF - Hepatology International
IS - 5
ER -