Kawano Miki, Yano Yoshihiko, Yamamoto Atsushi, Yasutomi Eiichiro, Inoue Yuta, Kitadai Jun, Yoshida Ryutaro, Matsuura Takanori, Shiomi Yuuki, Ueda Yoshihide, Kodama Yuzo
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Department of Gastroenterology, Hyogo Prefectural Kakogawa Medical Center, Kakogawa 675-8555, Japan.
Diagnostics (Basel). 2024 Apr 14;14(8):815. doi: 10.3390/diagnostics14080815.
Immune checkpoint inhibitor (ICI)-induced liver injury (LI) is a common adverse event, but the clinical characteristics based on the classification of hepatocellular injury and cholestatic types are not fully evaluated. This study aims to analyze risk factors and histological findings in relation to the classification of ICI-induced LI. In total, 254 ICI-induced LI patients among 1086 treated with ICIs between September 2014 and March 2022 were classified according to the diagnostic criteria for drug-induced LI (DILI), and their risk factors and outcomes were evaluated. Kaplan-Meier analyses showed that overall survival in patients with hepatocellular-injury-type LI was significantly longer than others ( < 0.05). Regarding pre-treatment factors, the lymphocyte count was significantly higher in patients with ICI-induced LI, especially in hepatocellular-injury-type LI. Gamma glutamyl transferase (γGTP) and alkaline phosphatase (ALP) were also significantly lower in patients with ICI-induced LI ( < 0.05). Multivariate analyses revealed that malignant melanoma, high lymphocyte count, and low ALP levels were extracted as factors contributing to hepatocellular-injury-type LI. The histological findings among 37 patients diagnosed as ICI-induced LI via liver biopsy also revealed that the spotty/focal necrosis was significantly frequent in hepatocellular-injury-type LI, whereas ductular reactions were frequently observed in cholestatic-type LI. It is suggested that the histological inflammation pattern in patients with LI is closely correlated with the type of DILI.
免疫检查点抑制剂（ICI）引起的肝损伤（LI）是一种常见的不良事件，但基于肝细胞损伤和胆汁淤积类型分类的临床特征尚未得到充分评估。本研究旨在分析与ICI诱导的LI分类相关的危险因素和组织学表现。2014年9月至2022年3月期间接受ICI治疗的1086例患者中，共有254例ICI诱导的LI患者根据药物性肝损伤（DILI）的诊断标准进行分类，并评估其危险因素和预后。Kaplan-Meier分析显示，肝细胞损伤型LI患者的总生存期明显长于其他患者（<0.05）。关于治疗前因素，ICI诱导的LI患者，尤其是肝细胞损伤型LI患者的淋巴细胞计数显著更高。ICI诱导的LI患者的γ-谷氨酰转移酶（γGTP）和碱性磷酸酶（ALP）也显著更低（<0.05）。多变量分析显示，恶性黑色素瘤、高淋巴细胞计数和低ALP水平被确定为导致肝细胞损伤型LI的因素。通过肝活检诊断为ICI诱导的LI的37例患者的组织学表现还显示，肝细胞损伤型LI中斑点状/局灶性坏死明显更常见，而胆汁淤积型LI中则经常观察到小胆管反应。提示LI患者的组织学炎症模式与DILI类型密切相关。
