Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, China.
Br J Clin Pharmacol. 2024 Nov;90(11):2870-2882. doi: 10.1111/bcp.16184. Epub 2024 Jul 23.
Programmed cell death receptor (ligand)-1 inhibitors (PD-(L)1), as the preferred immunotherapy, have been widely used in the Chinese mainland and drug-induced liver injury (DILI) has been reported. The study aimed to investigate the clinical features or risk factors for immunotherapy-related DILI.
Patients who received PD-(L)1 inhibitors from January 2020 to July 2021 were retrospectively reviewed. The likelihood of DILI was adjudicated by the Roussel-Uclaf causality assessment.
A total of 1175 patients were included in the study and 89 patients (7.6%) developed DILI, of which 12 (13.5%) progressed to acute liver failure (ALF) and three (3.4%) died. Among the DILI population, 56 (62.9%) had a cholestatic pattern and exhibited a prolonged treatment course and duration for resolution compared to the hepatocellular and mixed patterns. Hepatocellular carcinoma (HCC), hepatitis B virus (HBV) and abnormal baseline of alkaline phosphatase (ALP) had increased risks of DILI by 2.1-fold (95% confidence interval [CI], 1.231-3.621), 1.9-fold [95% CI, 1.123-3.325] and 2.1-fold [95% CI, 1.317-3.508], respectively. The model for end-stage liver disease (MELD) score had a c-statistic of 0.894 (95% CI, 0.778-1.000) with a sensitivity of 67% and a specificity of 95% for poor outcomes. COX analysis showed that the MELD ≥ 18 was predictive of immunotherapy-related ALF or death.
PD-(L)1 inhibitor-related liver injury manifests primarily as a cholestatic pattern, on which corticosteroid treatment has minimal effect compared to hepatocellular and mixed patterns. MELD score ≥ 18 at the time of liver injury performed best in the prediction of ALF or death in immune checkpoint inhibitor (ICI)-related DILI.
程序性细胞死亡受体（配体）-1 抑制剂（PD-（L）1）作为首选的免疫疗法，已在中国内地广泛应用，并已报告了药物性肝损伤（DILI）。本研究旨在探讨免疫治疗相关 DILI 的临床特征或危险因素。
回顾性分析 2020 年 1 月至 2021 年 7 月接受 PD-（L）1 抑制剂治疗的患者。采用 Roussel-Uclaf 因果关系评估法判断 DILI 的可能性。
共纳入 1175 例患者，89 例（7.6%）发生 DILI，其中 12 例（13.5%）进展为急性肝衰竭（ALF），3 例（3.4%）死亡。在 DILI 人群中，56 例（62.9%）表现为胆汁淤积模式，与肝细胞和混合模式相比，其治疗过程延长，恢复时间延长。肝细胞癌（HCC）、乙型肝炎病毒（HBV）和碱性磷酸酶（ALP）基线异常使 DILI 的风险分别增加 2.1 倍（95%可信区间[CI]：1.231-3.621）、1.9 倍（95%CI：1.123-3.325）和 2.1 倍（95%CI：1.317-3.508）。终末期肝病模型（MELD）评分的 C 统计量为 0.894（95%CI：0.778-1.000），其对不良结局的敏感性为 67%，特异性为 95%。COX 分析显示，MELD≥18 与免疫治疗相关的 ALF 或死亡相关。
PD-（L）1 抑制剂相关肝损伤主要表现为胆汁淤积模式，与肝细胞和混合模式相比，皮质类固醇治疗效果较差。在预测免疫检查点抑制剂（ICI）相关 DILI 的 ALF 或死亡方面，肝损伤时 MELD 评分≥18 表现最佳。
