Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan.
J Gastroenterol Hepatol. 2020 Oct;35(10):1782-1788. doi: 10.1111/jgh.15041. Epub 2020 Mar 31.
Immune checkpoint inhibitors (ICI) have revolutionized anti-malignancy therapy and thus have been increasingly used. Although ICI may cause immune-related adverse events (irAE) in various organs, including the liver, the prevalence and predictive factors of irAE have not been clarified.
In this retrospective study, consecutive patients who had malignancies and were treated with ICI without other chemotherapeutic agents at Hokkaido University Hospital between 2014 and 2019 were screened. Patients were excluded if they were < 20 years old and had insufficient clinical data.
Of the 233 patients screened, 202 patients met the inclusion criteria and were included in the analysis. The patients were aged 25-92 years, and 60.9% were male. The patients received nivolumab (n = 137), pembrolizumab (n = 45), ipilimumab (n = 17), atezolizumab (n = 2), and avelumab (n = 1). The prevalence of any grade and grade ≥ 3 irAE hepatitis was 8.4% (17/202) and 4.0% (8/202), respectively. irAE hepatitis occurred at a median duration of 42 days in any grade and 36 days in grade ≥ 3 after ICI initiation. The clinical course of grade ≥ 3 irAE hepatitis was generally favorable; however, 50% required corticosteroid treatment and two patients required additional mycophenolate mofetil. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis.
Grade ≥ 3 irAE hepatitis was observed in 4.0% of the patients who were treated with ICI. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis.
免疫检查点抑制剂（ICI）彻底改变了抗肿瘤治疗方法，因此越来越多地被应用。尽管 ICI 可能会导致包括肝脏在内的各种器官的免疫相关不良反应（irAE），但 irAE 的发生率和预测因素尚未明确。
在这项回顾性研究中，筛选了 2014 年至 2019 年在北海道大学医院接受 ICI 治疗且未接受其他化疗药物治疗的连续恶性肿瘤患者。如果患者年龄<20 岁且临床数据不足，则将其排除在外。
在筛选出的 233 名患者中，有 202 名符合纳入标准并被纳入分析。患者年龄为 25-92 岁，60.9%为男性。患者接受了纳武利尤单抗（n=137）、帕博利珠单抗（n=45）、伊匹单抗（n=17）、阿特珠单抗（n=2）和avelumab（n=1）治疗。任何级别和≥3 级 irAE 肝炎的发生率分别为 8.4%（17/202）和 4.0%（8/202）。ICI 开始后，任何级别 irAE 肝炎的中位发病时间为 42 天，≥3 级为 36 天。≥3 级 irAE 肝炎的临床病程通常较好；然而，50%需要皮质类固醇治疗，有 2 名患者需要加用霉酚酸酯。女性和 ICI 治疗史与≥3 级 irAE 肝炎的发生率显著相关。
接受 ICI 治疗的患者中有 4.0%发生≥3 级 irAE 肝炎。女性和 ICI 治疗史与≥3 级 irAE 肝炎的发生率显著相关。
