Department of Medicine II, Liver Centre Munich, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany,
Department of Medicine II, Liver Centre Munich, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany.
Dig Dis. 2021;39(3):275-282. doi: 10.1159/000511635. Epub 2020 Sep 17.
A proportion of patients with drug-induced liver injury (DILI) present with autoantibodies, which has led to the current concept of autoimmune-like DILI. However, no standardized definition exists and the clinical relevance has not been studied in detail yet.
143 patients with DILI enrolled in a prospective study were analyzed. DILI diagnosis was based on the monocyte-derived hepatocyte-like cell test and supported by Roussel Uclaf Causality Assessment Method (RUCAM) and expert adjudication. Testing for antinuclear antibodies (ANA) and antimitochondrial antibodies (AMA) was performed using immunofluorescence. ANA titers ≥1:100 were considered positive and ≥1:400 clinically relevant; AMA positivity was considered at titers ≥1:100.
67% exhibited ANA ≥1:100 and 29% ANA ≥1:400; 10% were AMA positive. There was no significant correlation between the ANA titers and the causative drug, while AMA positive patients had taken nonsteroidal anti-inflammatory drugs more frequently. No difference was seen regarding clinical characteristics or laboratory parameters in patients with ANA ≥1:400, while patients with positive AMA presented with higher aminotransferases, bilirubin, and international normalized ratio. Significantly higher proportions of patients with ANA ≥1:400 or AMA positivity exhibited elevated immunoglobulin G levels. AMA positivity but not elevated ANA titers correlated with a higher proportion of Hy's law positivity.
A closer look in a causality proven DILI cohort provided no evidence that presence of ANA titers is specific for DILI by a certain medication. AMA rather than ANA positivity was related to a more pronounced liver injury.
一部分药物性肝损伤（DILI）患者存在自身抗体，这导致了目前自身免疫样 DILI 的概念。然而，目前尚无标准化的定义，其临床相关性也尚未详细研究。
分析了一项前瞻性研究中纳入的 143 例 DILI 患者。DILI 诊断基于单核细胞衍生的肝细胞样细胞试验，并通过 Roussel Uclaf 因果关系评估方法（RUCAM）和专家裁决得到支持。使用免疫荧光法检测抗核抗体（ANA）和抗线粒体抗体（AMA）。ANA 滴度≥1:100 被认为阳性，≥1:400 为临床相关；AMA 阳性的滴度≥1:100。
67%的患者 ANA ≥1:100，29%的患者 ANA ≥1:400；10%的患者 AMA 阳性。ANA 滴度与致病药物之间无显著相关性，而 AMA 阳性患者更常服用非甾体抗炎药。ANA ≥1:400 的患者在临床特征或实验室参数方面无差异，而 AMA 阳性的患者转氨酶、胆红素和国际标准化比值更高。ANA ≥1:400 或 AMA 阳性的患者显著更高比例的免疫球蛋白 G 水平升高。AMA 阳性而非 ANA 滴度升高与更高比例的 Hy's 法则阳性相关。
在因果关系明确的 DILI 队列中进行更仔细的观察并未提供证据表明 ANA 滴度的存在是特定药物引起 DILI 的特异性标志物。与更明显的肝损伤相关的是 AMA 阳性而非 ANA 阳性。
