推进药物性肝损伤研究的新框架。前瞻性欧洲 DILI 注册研究。
A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry.
机构信息
Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
Department of Gastroenterology, Landspitali University Hospital Reykjavik, Reykjavík, Iceland.
出版信息
Liver Int. 2023 Jan;43(1):115-126. doi: 10.1111/liv.15378. Epub 2022 Aug 15.
BACKGROUND & AIMS: No multi-national prospective study of drug-induced liver injury (DILI) has originated in Europe. The design of a prospective European DILI registry, clinical features and short-term outcomes of the cases and controls is reported.
METHODS
Patients with suspected DILI were prospectively enrolled in the United Kingdom, Spain, Germany, Switzerland, Portugal and Iceland, 2016-2021. DILI cases or non-DILI acute liver injury controls following causality assessment were enrolled.
RESULTS
Of 446 adjudicated patients, 246 DILI patients and 100 had acute liver injury due to other aetiologies, mostly autoimmune hepatitis (n = 42) and viral hepatitis (n = 34). DILI patients (mean age 56 years), 57% women, 60% with jaundice and 3.6% had pre-existing liver disease. DILI cases and non-DILI acute liver injury controls had similar demographics, clinical features and outcomes. A single agent was implicated in 199 (81%) DILI cases. Amoxicillin-clavulanate, flucloxacillin, atorvastatin, nivolumab/ipilimumab, infliximab and nitrofurantoin were the most commonly implicated drugs. Multiple conventional medications were implicated in 37 (15%) and 18 cases were caused by herbal and dietary supplements. The most common single causative drug classes were antibacterials (40%) and antineoplastic/immunomodulating agents (27%). Overall, 13 (5.3%) had drug-induced autoimmune-like hepatitis due to nitrofurantoin, methyldopa, infliximab, methylprednisolone and minocycline. Only six (2.4%) DILI patients died (50% had liver-related death), and another six received liver transplantation.
CONCLUSIONS
In this first multi-national European prospective DILI Registry study, antibacterials were the most commonly implicated medications, whereas antineoplastic and immunomodulating agents accounted for higher proportion of DILI than previously described. This European initiative provides an important opportunity to advance the study on DILI.
背景与目的
目前尚无源自欧洲的多国药物性肝损伤（DILI）前瞻性研究。本文报告了一项前瞻性欧洲 DILI 登记研究的设计、病例和对照组的临床特征及短期结局。
方法
2016 年至 2021 年，英国、西班牙、德国、瑞士、葡萄牙和冰岛前瞻性纳入疑似 DILI 患者。经因果关系评估后纳入 DILI 病例或非 DILI 急性肝损伤对照组。
结果
446 例经裁决的患者中，246 例为 DILI 患者，100 例为其他病因导致的急性肝损伤，主要为自身免疫性肝炎（n=42）和病毒性肝炎（n=34）。DILI 患者（平均年龄 56 岁），57%为女性，60%有黄疸，3.6%有既往肝脏疾病。DILI 病例和非 DILI 急性肝损伤对照组的人口统计学、临床特征和结局相似。199 例（81%）DILI 患者与单一药物相关。最常与 DILI 相关的药物依次为阿莫西林克拉维酸钾、氟氯西林、阿托伐他汀、纳武利尤单抗/伊匹单抗、英夫利昔单抗和呋喃妥因。37 例（15%）与多种常规药物相关，18 例与草药和膳食补充剂相关。最常见的单一药物类别为抗菌药物（40%）和抗肿瘤/免疫调节药物（27%）。总体而言，有 13 例（5.3%）因呋喃妥因、甲基多巴、英夫利昔单抗、甲泼尼龙和米诺环素导致药物诱导的自身免疫性肝炎样肝损伤。仅 6 例（2.4%）DILI 患者死亡（50%与肝脏相关），另有 6 例接受了肝移植。
结论
在这项首个多国家欧洲前瞻性 DILI 登记研究中，抗菌药物是最常涉及的药物，而抗肿瘤和免疫调节药物导致的 DILI 比例高于此前描述。这一欧洲举措为推进 DILI 研究提供了重要机会。
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