Department of pharmacy, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
College of Pharmacy, Changsha Medical University, Changsha, Hunan, China.
Immunopharmacol Immunotoxicol. 2024 Dec;46(6):757-762. doi: 10.1080/08923973.2024.2402338. Epub 2024 Sep 17.
Cholangitis is an uncommon and severe adverse reaction of nivolumab with unclear clinical features. The purpose of this study was to investigate the clinicopathological features, imaging, and treatment of nivolumab-induced cholangitis.
Case reports, case series, and clinical studies of nivolumab-induced cholangitis were retrospectively analyzed by searching Chinese and English databases from January 1, 2017 to December 31, 2023.
Thirty-eight patients entered the study. The median number of cycles of cholangitis onset was seven cycles after administration (range 1, 28) and the median time was 11 days (range 78, 390). Abdominal pain (42.1%) and fever (18.4%) were the most important initial symptoms. Some patients (15.8%) showed elevated liver enzymes without any clinical symptoms. The median alkaline phosphatase level was 1721 IU/L (range 126, 9118), and the median γ-glutamyltranspeptidase level was 829 IU/L (range 104, 3442). Anti-nuclear antibodies, anti-mitochondrial antibodies, and IgG4 typically show negative results. Imaging shows extrahepatic bile duct and intrahepatic bile duct dilation, hypertrophy, and stenosis. Liver biopsy and biliary tract biopsy mainly found CD8 inflammatory cell infiltration. Systemic steroids (84.2%) and ursodeoxycholic acid (UDCA) (34.2%) were administered, and 24 patients (63.2%) had poor to moderate response to steroids. Thirty-one patients (81.6%) improved and seven patients (18.4%) did not improve.
Clinicians must remain vigilant for patients experiencing cholestasis while on nivolumab and should assess for cholangitis and carry out appropriate imaging tests. Considering the excellent efficacy of UCDA in cholangitis, steroids combined with UDCA may be a viable treatment option in cases where steroids are ineffective for cholangitis.
胆管炎是纳武利尤单抗的一种罕见且严重的不良反应，其临床特征尚不明确。本研究旨在探讨纳武利尤单抗诱导胆管炎的临床病理特征、影像学表现和治疗方法。
通过检索 2017 年 1 月 1 日至 2023 年 12 月 31 日的中、英文数据库，回顾性分析了纳武利尤单抗诱导胆管炎的病例报告、病例系列和临床研究。
共纳入 38 例患者。胆管炎发病的中位周期数为纳武利尤单抗给药后 7 个周期（范围 128 个周期），中位时间为 11 天（范围 78390 天）。腹痛（42.1%）和发热（18.4%）是最重要的初始症状。部分患者（15.8%）表现为肝酶升高但无任何临床症状。中位碱性磷酸酶水平为 1721IU/L（范围 1269118IU/L），中位γ-谷氨酰转肽酶水平为 829IU/L（范围 1043442IU/L）。抗核抗体、抗线粒体抗体和 IgG4 通常为阴性。影像学表现为肝外胆管和肝内胆管扩张、肥厚和狭窄。肝活检和胆管活检主要发现 CD8 炎性细胞浸润。系统性类固醇（84.2%）和熊去氧胆酸（UDCA）（34.2%）治疗，24 例患者（63.2%）对类固醇反应差或中等。31 例患者（81.6%）改善，7 例患者（18.4%）无改善。
临床医生在使用纳武利尤单抗时必须对发生胆汁淤积的患者保持警惕，并评估胆管炎并进行适当的影像学检查。鉴于 UDCA 在胆管炎中的良好疗效，对于类固醇治疗胆管炎无效的患者，类固醇联合 UDCA 可能是一种可行的治疗选择。
