药物性自身免疫性肝炎:使用两种不同的经过验证的评分诊断算法进行可靠的因果关系评估。

Drug-Induced Autoimmune Hepatitis: Robust Causality Assessment Using Two Different Validated and Scoring Diagnostic Algorithms.

作者信息

Teschke Rolf, Eickhoff Axel, Danan Gaby

机构信息

Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, D-63450 Hanau, Germany.

Academic Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/Main, D-60629 Frankfurt am Main, Germany.

出版信息

Diagnostics (Basel). 2025 Jun 23;15(13):1588. doi: 10.3390/diagnostics15131588.

Abstract

Drug-induced autoimmune hepatitis (DIAIH) is a relatively new subtype of idiosyncratic drug-induced liver injury (iDILI), but the features of DIAIH have been variably described due to the inhomogeneity of assessed study cohorts. The aim of this analysis is to harmonize DIAIH cohorts by unifying causality assessments, which may help characterize the features of DIAIH. Methods: Published reports of DIAIH cases were evaluated for the causality assessment methods used to verify the diagnosis of DIAIH. This disorder consists of two parts, i.e., the iDILI part and the autoimmune (AIH) part, whereby each part needs a specific diagnostic algorithm. The validated and scoring Roussel Uclaf Causality Assessment (RUCAM) is privileged for assessing the iDILI part, and the validated, simplified AIH score is the perfect choice for evaluating the AIH part. The analysis of DIAIH publications revealed that 12/20 reports (60%) presented cases assessed by both the RUCAM and the simplified AIH score, providing 49 drugs and drug combinations as causative drugs in up to 25 cases of DIAIH. Serum alanine aminotransferase activities of up to 3489 UL and high titers of autoimmune parameters such as anti-nuclear antibodies, anti-smooth-muscle antibodies, and soluble liver antigen antibodies supported DIAIH diagnosis. In contrast, 4/20 reports (20%) applied only RUCAM, and 2/20 reports (10%) used only the simplified AIH score; these 6 reports therefore provided insufficient criteria for a valid DIAIH diagnosis. Moreover, 2/20 reports (10%) did not use any causality algorithm, providing elusive features of DIAIH. While DIAIH is clearly restricted to drugs as responsible agents, this term is erroneously used to refer to disease induced by non-drugs such as herbs, green tea, dimethoate (an organophosphate insecticide), dietary supplements, biologics, herbal remedies, different viruses, and bacteria, as well as vaccines. For diseases induced by these agents, a better term could be, for instance, non-drug-induced autoimmune hepatitis. Drug cessation and immunotherapy with corticosteroids and azathioprine comprise the treatment of choice. The characteristics of DIAIH can best be described if both the RUCAM and the simplified AIH score are used concomitantly.

摘要

药物性自身免疫性肝炎(DIAIH)是特异质性药物性肝损伤(iDILI)中一种相对较新的亚型,但由于评估研究队列的异质性,DIAIH的特征描述存在差异。本分析的目的是通过统一因果关系评估来协调DIAIH队列,这可能有助于刻画DIAIH的特征。方法:对已发表的DIAIH病例报告进行评估,以确定用于验证DIAIH诊断的因果关系评估方法。这种疾病由两部分组成,即iDILI部分和自身免疫(AIH)部分,因此每个部分都需要特定的诊断算法。经过验证的Roussel Uclaf因果关系评估(RUCAM)评分法在评估iDILI部分时具有优势,而经过验证的简化AIH评分法是评估AIH部分的理想选择。对DIAIH相关出版物的分析显示,20篇报告中有12篇(60%)呈现了同时采用RUCAM和简化AIH评分法评估的病例,在多达25例DIAIH病例中提供了49种药物及药物组合作为致病药物。血清丙氨酸氨基转移酶活性高达3489 UL,以及高滴度的自身免疫参数,如抗核抗体、抗平滑肌抗体和可溶性肝抗原抗体,支持DIAIH的诊断。相比之下,20篇报告中有4篇(20%)仅应用了RUCAM,2篇报告(10%)仅使用了简化AIH评分法;因此,这6篇报告提供的有效DIAIH诊断标准不足。此外。20篇报告中有2篇(10%)未使用任何因果关系算法,导致DIAIH的特征难以捉摸。虽然DIAIH明确局限于药物作为致病因素,但该术语被错误地用于指代由非药物因素引起的疾病,如草药、绿茶、乐果(一种有机磷杀虫剂)、膳食补充剂、生物制品、草药疗法、不同病毒和细菌以及疫苗。对于由这些因素引起的疾病,一个更好的术语可以是,例如,非药物性自身免疫性肝炎。停药以及使用皮质类固醇和硫唑嘌呤进行免疫治疗是首选的治疗方法。如果同时使用RUCAM和简化AIH评分法,就能最好地描述DIAIH的特征。

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