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免疫检查点抑制剂致晚期胆道癌患者肝损伤的临床特征。

Clinical characteristics of liver injury induced by immune checkpoint inhibitors in patients with advanced biliary tract carcinoma.

机构信息

Department of Medical Oncology, Peking University First Hospital, No.8, Xishiku Street, Beijing, 100034, China.

Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, No.8, Xishiku Street, Beijing, 100034, China.

出版信息

Invest New Drugs. 2023 Oct;41(5):719-726. doi: 10.1007/s10637-023-01391-2. Epub 2023 Aug 17.

Abstract

Immune-related liver injuries are closely associated with the liver's fundamental state. Patients with advanced biliary tract carcinoma (BTC) have poor liver function. We evaluated the clinical data of immune-related liver injury in patients with advanced BTC and gastric cancer (GC) during immune checkpoint inhibitor (ICI) treatment between February 2019 and July 2022 at Peking University First Hospital. Twenty-five patients with advanced BTC were identified. Fifteen patients (60%) experienced immune-related liver injury during ICI treatment. We also evaluated the clinical status of patients with GC in another group receiving immunotherapy. The results demonstrated that the incidence of immune-related liver injury was higher in patients with BTC than in GC cancer (p=0.040). Multivariate analysis suggested that the type of malignant tumor and baseline liver function status were high-risk factors for grade 2 and higher immune-related liver injuries. Two patients were diagnosed with immune-related cholangitis. Both biliary enzymes can be decreased to a certain degree by corticosteroid and ursodeoxycholic acid (UDCA) therapy but are difficult to reduce to normal levels. Liver function normalized, and symptoms improved after local treatment for cholestasis (stent implantation or PTBD). We observed a higher incidence of immune-related liver injury after ICI treatment in patients with advanced BTC. Effect of baseline liver function on the incidence of liver injury associated with immunotherapy. Interventional therapy provides rapid relief from cholestasis and is an indispensable and effective approach to the treatment of immune-related cholangitis.

摘要

免疫相关肝损伤与肝脏的基本状态密切相关。晚期胆道癌(BTC)患者肝功能较差。我们评估了 2019 年 2 月至 2022 年 7 月期间在北京大学第一医院接受免疫检查点抑制剂(ICI)治疗的晚期 BTC 和胃癌(GC)患者的免疫相关肝损伤的临床数据。确定了 25 例晚期 BTC 患者。15 名患者(60%)在 ICI 治疗期间发生免疫相关肝损伤。我们还评估了另一组接受免疫治疗的 GC 患者的临床状况。结果表明,BTC 患者的免疫相关肝损伤发生率高于 GC 癌症(p=0.040)。多变量分析表明,恶性肿瘤类型和基线肝功能状态是 2 级及以上免疫相关肝损伤的高危因素。两名患者被诊断为免疫相关性胆管炎。皮质类固醇和熊去氧胆酸(UDCA)治疗均可使胆汁酶在一定程度上降低,但难以降低至正常水平。局部治疗(支架植入或 PTBD)后,胆汁淤积的肝功能正常,症状改善。我们观察到晚期 BTC 患者接受 ICI 治疗后免疫相关肝损伤的发生率更高。基线肝功能对免疫治疗相关肝损伤发生率的影响。介入治疗可迅速缓解胆汁淤积,是治疗免疫相关性胆管炎不可或缺的有效方法。

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