检查点抑制剂（CPI）导致药物引起的肝损伤（DILI）案例不断增加。我们的目标是确定检查点抑制剂引起的肝损伤（ChILI）的发生率和相关危险因素。在2011年至2021年间，对接受CPI治疗的所有黑色素瘤和肾癌患者在三级中心进行了处方事件监测。使用已验证的DILI的定义、分级和因果关系评估方法来确定ChILI的病例。我们使用多因素 Logistic 回归模型评估了CPI 未曾接受机构治疗的患者与 ChILI 相关的危险因素。两个其他三级中心中的疑似 ChILI 连续患者进行了裁决，并结合进行病例特征化和 ChILI 的结局。在十年时间内共有 432 名接受 CPI 治疗的患者中，有 38 例（8.8%）发生了 ChILI，其总发生率为每 1000 人月 11.5 例（95% CI 8.2-15.8）。ChILI 的概率在联合治疗中最高（32%），超过治疗 135 天后没有新事件发生。危险因素分析显示，联合治疗、女性性别、较高的碱性转移酶基线水平和较低的碱性磷酸酶基线水平与 ChILI 的风险较高相关。总共，三个中心的 99 例患者被裁决出患有 ChILI。尽管常见术语不良事件分类准则(classified)将 20 例患者(20.2%)评定为 '危及生命'的 4 级肝炎，ChILI 的严重程度在 45 例（45.5%）中评为轻度，其余 54 例（54.5%）评为中度。ChILI 的真实世界风险高于以往报道。在接受双重CPI治疗的患者中，此风险在治疗4.5个月后显著降低。由于常见术语不良事件分类准则过高估计了其临床严重性，应修订ChILI的病例定义、评估和管理，以协调护理。 使用处方事件监测在 10 年期间，基于建立的药物诱发肝损伤 (DILI) 的病例定义，检查点抑制剂引起的肝损伤 (ChILI) 的发生率为每 1000 人月 11.5 例。正式的因果关系评估发现，在疑似 ChILI 的患者中，19% 的患者存在其他原因，强调临床医生系统评估的重要性，以减少不必要的免疫抑制。在联合治疗方案接受治疗 4.5 个月后，监测的强度可以降低，因为此后新发 ChILI 的风险很低。目前的常见术语不良事件分类准则(CTCAE)过高评估了 ChILI 的临床严重性，因此导致可避免的住院。©2023 作者们。

Checkpoint inhibitors (CPI) account for increasing numbers of drug-induced liver injury (DILI) cases. We aimed to determine the incidence rate and risk factors associated with checkpoint inhibitor-induced liver injury (ChILI).Prescription event monitoring was performed on all melanoma and renal cancer patients who received CPI at a tertiary centre between 2011 and 2021. ChILI cases were identified using the definitions, grading, and causality assessment methods validated for DILI. We assessed risk factors associated with ChILI in CPI-naive patients using multivariable logistic regression model. Consecutive patients with suspected ChILI from two other tertiary centres were adjudicated and combined for case characterisation and outcomes of ChILI.Out of 432 patients who received CPI over 10 years, ChILI occurred in 38 (8.8%) with an overall incidence rate of 11.5 per 1,000 person-months (95% CI 8.2-15.8). Probability of ChILI was highest in combination therapy (32%) and no new events occurred beyond 135 days of treatment. Risk factor analysis showed that combination therapy, female sex, higher baseline alanine transferase level and lower baseline alkaline phosphatase level were independently associated with higher risk of ChILI. In total, 99 patients were adjudicated to have ChILI from three centres. Although Common Terminology Criteria for Adverse Events classified 20 patients (20.2%) to have 'life-threatening' grade 4 hepatitis, ChILI severity was graded as mild in 45 (45.5%) and moderate in the remaining 54 (54.5%) cases.The real-world risk of ChILI is higher than previously reported. Among patients receiving dual CPI, this risk falls markedly after 4.5 months. As Common Terminology Criteria for Adverse Events overestimates its clinical severity, case-definition, evaluation and management of ChILI should be revised to harmonise care.Using prescription event monitoring over a 10-year period, the incidence rate of checkpoint inhibitor induced liver injury (ChILI) based on established case definitions for drug-induced liver injury (DILI) is 11.5 per 1,000 person-months. Formal causality assessment identified an alternative cause in 19% of patients with suspected ChILI highlighting the importance of systematic evaluation by clinicians to minimise unnecessary immunosuppression. Intensity of monitoring in patients receiving combination therapy regime after 4.5 months of therapy can be reduced as the risk of new onset ChILI beyond this point is minimal. Current Common Terminology Criteria for Adverse Events (CTCAE) grading overestimates clinical severity of ChILI and hence contributes to avoidable hospitalisation.© 2023 The Authors.