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免疫检查点抑制剂与肝脏:权衡治疗益处与不良事件

Immune checkpoint inhibitors and the liver: balancing therapeutic benefit and adverse events.

作者信息

De Martin Eleonora, Fulgenzi Claudia A M, Celsa Ciro, Laurent-Bellue Astrid, Torkpour Aria, Lombardi Pasquale, D'Alessio Antonio, Pinato David J

机构信息

Centre Hepatobiliaire, Paul Brousse Hospital, Villejuif, France

Paris-Saclay University, Faculty of Medicine, Le Kremlin-Bicetre, France.

出版信息

Gut. 2025 Jun 6;74(7):1165-1177. doi: 10.1136/gutjnl-2024-332125.

Abstract

Immune checkpoint inhibitors (ICI) have led to breakthrough improvements in the management of malignancy including hepatocellular (HCC) and biliary tract cancer, improving decades-old standards of care and increasing patient survival. In both liver tumour types, which commonly arise in the context of liver inflammation and underlying functional impairment, the lack of validated predictors of response underscores the need to balance predicted gains in survival with risk of treatment-related hepatoxicity and decompensation of underlying chronic liver disease.In addition, the liver is implicated in the toxicity associated with ICI therapy for non-liver cancers, which exhibits a high degree of variability in presentation and severity. An accurate assessment is mandatory for the diagnosis and management of ICI-induced liver injury.In this Recent Advances article, we provide an overview of the mechanisms of efficacy and toxicity of anticancer immunotherapy in liver tumours and liver toxicity in extrahepatic malignancies.We compare and contrast characteristics, management strategies and outcomes from immune-related liver injury in patients with chronic hepatitis/cirrhosis or with an underlying healthy liver and discuss the latest findings on how toxicity and decompensation may impact the outlook of patients with liver tumours and extrahepatic malignancies offering insights into the future directions of clinical research and practice in the field.

摘要

免疫检查点抑制剂(ICI)已在包括肝细胞癌(HCC)和胆管癌在内的恶性肿瘤治疗方面带来了突破性进展,改善了数十年的治疗标准并提高了患者生存率。在这两种通常在肝脏炎症和潜在功能损害背景下发生的肝脏肿瘤类型中,缺乏经过验证的反应预测指标凸显了在平衡预测的生存获益与治疗相关肝毒性风险以及潜在慢性肝病失代偿之间的必要性。此外,肝脏还与ICI治疗非肝癌的毒性有关,其表现和严重程度具有高度变异性。准确评估对于ICI诱导的肝损伤的诊断和管理至关重要。在这篇《最新进展》文章中,我们概述了抗癌免疫疗法在肝脏肿瘤中的疗效和毒性机制以及肝外恶性肿瘤中的肝脏毒性。我们比较并对比了慢性肝炎/肝硬化患者或肝脏健康患者免疫相关肝损伤的特征、管理策略和结果,并讨论了毒性和失代偿如何影响肝脏肿瘤和肝外恶性肿瘤患者预后的最新发现,为该领域临床研究和实践的未来方向提供见解。

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