Real world data of liver injury induced by immune checkpoint inhibitors in Japanese patients with advanced malignancies

• Published in: Journal of gastroenterology 2020-06, Vol.55 (6), p.653-661
• Main Authors: Mizuno, Kazuyuki, Ito, Takanori, Ishigami, Masatoshi, Ishizu, Yoji, Kuzuya, Teiji, Honda, Takashi, Kawashima, Hiroki, Inukai, Yosuke, Toyoda, Hidenori, Yokota, Kenji, Hase, Tetsunari, Maeda, Osamu, Kiyoi, Hitoshi, Nagino, Masato, Hibi, Hideharu, Kodera, Yasuhiro, Fujimoto, Yasushi, Sone, Michihiko, Gotoh, Momokazu, Ando, Yuichi, Akiyama, Masashi, Hasegawa, Yoshinori, Fujishiro, Mitsuhiro
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Bile; Bile ducts; Biliary Tract; Cancer; Care and treatment; Cholangitis; Colorectal Surgery; Complications and side effects; CTLA-4 protein; Cytotoxicity; Fever; Gastroenterology; Hepatology; Immune checkpoint inhibitors; Ipilimumab; Liver; Lymphocytes T; Medicine; Medicine & Public Health; Monoclonal antibodies; Multivariate analysis; Original Article—Liver; Pancreas; Risk factors; Surgical Oncology
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-020-01677-9

Background Liver injury induced by immune checkpoint inhibitors (ICIs) is an immune-related adverse event (irAE) whose incidence has increased with the broader use of ICIs in clinical practice. However, the incidental risk factors of immune-related liver injury are unknown. We investigated the clinical characteristics of immune-related liver injury. Methods A total of 546 patients treated with ICIs for advanced malignancies between September 2014 and February 2019 were included retrospectively. Factors associated with immune-related liver injury were determined. Results Immune-related liver injury (≥ Grade 3) occurred in 29 (5.3%) patients (Grade 3, n  = 20; Grade 4, n  = 8; Grade 5, n  = 1) during the follow-up period (median 153 days). The patterns of liver injuries were hepatocellular, n  = 6 (20.7%); cholestatic, n  = 17 (58.6%); and mixed, n  = 6 (20.7%). The median period between the initial administration of ICIs and the incidence of irAEs was 52 days. Of 29 patients with immune-related liver injury (≥ Grade 3), four showed immune-related cholangitis with non-obstructive dilation of the bile ducts. Factors that were significantly associated with the incidence of immune-related liver injury in multivariate analysis were use of ipilimumab, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agent [hazard ratio [HR] 4.22, 95% confidence interval (CI) 1.65–10.80, P  = 0.003], and fever over 38 °C within 24 h of initial ICI administration (HR 6.21, 95% CI 2.68–14.40, P