Immune Checkpoint Inhibitor-Induced Hepatic Injury: A Clinicopathologic Review.
Immune Checkpoint Inhibitor-Induced Hepatic Injury: A Clinicopathologic Review.
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DOI：
10.14218/jctp.2022.00017
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发表时间：
2022-09
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尽管免疫检查点抑制剂（ICI）是免疫肿瘤学的一个革命性里程碑，但由于T细胞活化增强和免疫失调，可能会发生免疫相关不良事件（irAE）。irAE最早可在数天内发生，据报告最晚可达26周。它们可以影响身体中的任何器官系统，最常见的是腔胃肠道、肝脏、皮肤、内分泌系统和肺。irAE的机制很复杂，尚未完全了解。已经提出了自身耐受性的破坏，其由于T细胞的增强的活化和浸润或自身抗体的产生而导致自身抗原反应性，以及非特异性自身炎症机制。关于ICI诱导的肝损伤的临床和病理特征的数据有限。本文综述了ICI诱导的肝损伤的临床和常见的组织病理学特征和模式，鉴别诊断和临床处理。现有数据表明，ICI诱导的肝损伤的组织病理学结果通常是非特异性的，并与其他具有挑战性的鉴别诊断重叠。因此，充分了解ICI诱导的肝损伤的组织病理学谱及其鉴别诊断，结合血清学检测结果、临床相关性以及与临床团队的沟通，是做出准确和及时诊断的必要条件。
Although immune checkpoint inhibitors (ICIs) have been a revolutionary milestone in immuno-oncology, immune-related adverse events (irAEs) may occur due to enhanced T cell activation and immune dysregulation. The irAEs can occur as early as within days to reportedly as late as up to 26 weeks. They may affect any organ system in the body, most commonly the luminal gastrointestinal tract, liver, skin, endocrine system, and lungs. The mechanisms of irAEs are complex and have not been fully understood. A breach of self-tolerance, which leads to autoantigen reactivity due to the enhanced activation and infiltration of T cells or the production of autoantibodies, and a non-specific autoinflammatory mechanism have been proposed. Limited data is available on the clinical and pathologic features of ICI-induced liver injury. This review presents an overview of the clinical and common histopathologic features and patterns of ICI-induced liver injury, the differential diagnoses, and the clinical management. Available data suggest that the histopathologic findings of ICI-induced hepatic injury are often non-specific and overlap with other challenging differential diagnoses. Therefore, a good knowledge of the histopathologic spectrum of ICI-induced hepatic injury and their differential diagnoses combined with the serological test results, clinical correlation, and communication with the clinical team is necessary to make an accurate and timely diagnosis.