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内质网氨肽酶ERAP2致病突变rs1363907在阿莫西林克拉维酸诱导的肝损伤中的作用:一例特殊病例报告。

The role of endoplasmic reticulum aminopeptidase ERAP2 pathogenic mutation rs1363907 in amoxicillin clavulanate-induced liver injury: a special case report.

作者信息

Zhan Yan, Liao Jin-Mao, Ye Ling, Zhang Long, Zhang Zheng, Yin Ji-Ye

机构信息

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.

Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China.

出版信息

Front Pharmacol. 2025 May 21;16:1564124. doi: 10.3389/fphar.2025.1564124. eCollection 2025.

Abstract

Idiosyncratic hepatotoxicity is a type of drug-induced liver injury (DILI) that is unpredictable and clinically severe, and amoxicillin clavulanate (AC) is the most implicated drug in DILI worldwide. The clinical manifestations of amoxicillin clavulanate-induced liver injury (AC-DILI) are fatigue and jaundice, which some allergic features may accompany, but autoimmune phenomena are uncommon. Here, we describe a special case report of a patient with AC-DILI accompanied by autoimmune phenomena for the first time. The patient was a middle-aged Chinese woman who developed liver damage after taking AC for a period of time, with a RUCAM score of 6. The patient tested positive for antinuclear antibodies and had elevated levels of IgG. Human leukocyte antigen (HLA)-targeted sequencing results showed that the patient did not carry known AC-DILI-related HLA polymorphisms, but Sanger sequencing suggested that the patient had the ERAP2 rs1363907 mutation, which may be a pathogenic factor of AC-DILI in the patient. The patient's progress notes, disease diagnosis, and treatment are summarized, and the role of ERAP2 pathogenic mutation rs1363907 in AC-DILI is discussed.

摘要

特异质性肝毒性是一种不可预测且临床严重的药物性肝损伤(DILI)类型,而阿莫西林克拉维酸(AC)是全球范围内DILI中最常涉及的药物。阿莫西林克拉维酸所致肝损伤(AC-DILI)的临床表现为疲劳和黄疸,可能伴有一些过敏特征,但自身免疫现象并不常见。在此,我们首次描述了一例伴有自身免疫现象的AC-DILI患者的特殊病例报告。该患者为一名中年中国女性,服用AC一段时间后出现肝损伤,RUCAM评分为6分。患者抗核抗体检测呈阳性,IgG水平升高。人类白细胞抗原(HLA)靶向测序结果显示,该患者未携带已知的与AC-DILI相关的HLA多态性,但桑格测序表明该患者存在ERAP2 rs1363907突变,这可能是该患者AC-DILI的致病因素。总结了该患者的病程记录、疾病诊断和治疗情况,并讨论了ERAP2致病突变rs1363907在AC-DILI中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0ea/12133467/5bf851595ac9/fphar-16-1564124-g001.jpg

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