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Clinical Characteristics and Adverse Impact of Hepatotoxicity due to Immune Checkpoint Inhibitors.

免疫检查点抑制剂肝毒性的临床特点和不良影响。

  • 影响因子:4.03
  • DOI:10.14309/ajg.0000000000000398
  • 作者列表:"Miller ED","Abu-Sbeih H","Styskel B","Nogueras Gonzalez GM","Blechacz B","Naing A","Chalasani N
  • 发表时间:2020-02-01
Abstract

INTRODUCTION:We conducted this study to characterize the incidence, clinical features, treatment, and outcomes of immune checkpoint inhibitor (ICI) hepatotoxicity. METHODS:Patients who received ICIs (with either single-agent or combination regimens) from January 1, 2010, to March 31, 2018, were identified. Hepatotoxicity was defined as alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN), in the absence of an alternate cause, and categorized as grade 3 (ALT 5-20× ULN) or grade 4 (ALT >20× ULN), according to Common Terminology Criteria for Adverse Events 4.03. RESULTS:Among 5,762 patients, 100 (2%) developed hepatotoxicity, occurring in a higher proportion of recipients of combination therapy (9.2%) compared with monotherapy (up to 1.7%, P < 0.001). ICIs were discontinued permanently in 69 and temporarily in 31 patients. Sixty-seven patients received steroids, 10 of whom (14%) had recurrent hepatotoxicity after the steroid taper. Thirty-one patients resumed ICIs after ALT improvement, 8 of whom (26%) developed recurrent hepatotoxicity. Characteristics of liver injury, response to steroids, and outcomes were similar between 38 individuals with and 62 without possible pre-existing liver disease. The severity and outcome of hepatotoxicity due to combination therapy were not significantly different from monotherapy. There were 36 deaths. Two had liver failure at the time of death, both with progression of liver metastases and grade 3 hepatotoxicity. DISCUSSION:Clinically significant ICI-related hepatotoxicity was uncommon but led to permanent ICI discontinuation in the majority. ICIs were restarted in a sizable proportion of patients, most of whom did not experience recurrent hepatotoxicity.

摘要

简介: 我们进行这项研究是为了描述免疫检查点抑制剂 (ICI) 肝毒性的发生率、临床特征、治疗和结局。 方法: 确定 2010 年 1 月 1 日至 20 18 年 3 月 31 日接受ICIs (单药或联合方案) 的患者。肝毒性定义为丙氨酸氨基转移酶 (ALT)> 正常上限 (ULN) 的 5 倍,在没有替代原因的情况下,并根据不良事件通用术语标准 4.03 分为 3 级 (ALT 5-20 × ULN) 或 4 级 (ALT >20 × ULN)。 结果: 在 5,762 例患者中,100 例 (2%) 发生肝毒性,与单药治疗相比,联合治疗的接受者比例较高 (9.2%) (高达 1.7%,P <0.001)。69 例患者永久停用ICIs,31 例患者暂时停用ICIs。67 例患者接受类固醇治疗,其中 10 例 (14%) 在类固醇减量后出现复发性肝毒性。31 例患者在ALT改善后恢复ICIs,其中 8 例 (26%) 发生复发性肝毒性。肝损伤的特征,对类固醇的反应和结果在 38 和 62 个体之间相似,没有可能存在的肝脏疾病。联合治疗所致肝毒性的严重程度和结局与单药治疗无显著差异。有 36 人死亡。2 例在死亡时出现肝衰竭,均伴有肝转移进展和 3 级肝毒性。 讨论: 临床显著的ICI相关肝毒性不常见,但导致大多数患者永久停用ICI。相当比例的患者重新启动了ICIs,其中大多数患者没有出现复发性肝毒性。

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皮肤肿瘤方向

皮肤肿瘤是发生在皮肤的细胞增生性疾病,是一种常见病。发生于皮内或皮下组织的新生物,种类很多,临床上分良性肿瘤和恶性肿瘤。恶性肿瘤可以不断增殖,引起转移,威胁生命,称为皮肤癌。

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