Immune checkpoint inhibitors (ICIs) have reshaped cancer therapy. ICIs enhance T cell activation through various mechanisms and may help reverse the exhausted phenotype of tumour-infiltrating lymphocytes. However, disrupting the key role that checkpoint molecules play in immune homeostasis may result in autoimmune complications. A broad range of immune-related adverse events (irAEs) involve almost every organ but mostly affect the skin, digestive system, lung, endocrine glands, nervous system, kidney, blood cells, and musculoskeletal system. They are usually manageable but can be life-threatening. The incidence of irAEs is not very different in patients with hepatocellular carcinoma (HCC) compared to other tumour types, although there is a trend towards a higher incidence of hepatic irAEs. HCC usually develops on a background of cirrhosis with associated systemic manifestations. Extrahepatic organ dysfunction in cirrhosis may cause signs and symptoms that overlap with irAEs or increase their severity. Available guidelines for the management of irAEs have not specifically considered the assessment of toxicities in the context of patients with liver cancer and cirrhosis. This review addresses the toxicity profile of ICIs in patients with HCC, focusing on the challenges that the underlying liver disease poses to their diagnosis and management. Challenges include late recognition, inadequate work-up and delayed treatment, overdiagnosis and inappropriate interruption of ICIs, complications caused by immunosuppressive therapy, and increased cost. A specific algorithm for the management of hepatic irAEs is provided.

中文翻译：

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肝细胞癌免疫检查点抑制剂毒性的诊断和处理

免疫检查点抑制剂 (ICI) 重塑了癌症治疗。ICI 通过各种机制增强 T 细胞活化，并可能有助于逆转肿瘤浸润淋巴细胞的衰竭表型。然而，破坏检查点分子在免疫稳态中的关键作用可能会导致自身免疫并发症。范围广泛的免疫相关不良事件 (irAE) 几乎涉及每个器官，但主要影响皮肤、消化系统、肺、内分泌腺、神经系统、肾脏、血细胞和肌肉骨骼系统。它们通常是可控的，但可能危及生命。与其他肿瘤类型相比，肝细胞癌 (HCC) 患者的 irAE 发生率没有太大差异，尽管肝 irAE 的发生率有更高的趋势。HCC 通常在具有相关全身表现的肝硬化背景下发展。肝硬化的肝外器官功能障碍可能会导致与 irAE 重叠的体征和症状或增加其严重程度。现有的 irAE 管理指南并未专门考虑对肝癌和肝硬化患者的毒性评估。本综述讨论了 ICIs 在 HCC 患者中的毒性特征，重点关注潜在肝病对其诊断和管理带来的挑战。挑战包括识别晚、检查不充分和治疗延迟、过度诊断和 ICI 的不当中断、免疫抑制治疗引起的并发症以及成本增加。提供了管理肝脏 irAE 的特定算法。