背景:药物性肝损伤(DILI)可由任何处方药引起,并且是新上市药物停药的重要原因。直接作用的口服抗凝剂(DOAC)是最近引入的基于非维生素K的拮抗剂,并且越来越多地用于各种临床病症。对29项随机对照试验和152116例患者进行的荟萃分析报告,DOAC患者的DILI风险没有增加。然而,在这些研究中排除已有肝病患者的个体患者中,预测DILI的危险因素具有挑战性.
目的:通过近期病例报告和系列的系统评价和荟萃总结,确定DOAC继发DILI患者的危险因素和结局。
方法:对包括PubMed在内的多个数据库进行了系统搜索,科学直接,参考引文分析,谷歌学者。搜索条件包括\"急性肝衰竭\"或\"急性慢性肝衰竭\"或\"急性化学和药物诱导的肝损伤\"或\"慢性化学和药物诱导的肝损伤\"和\"因子Xa抑制剂\"或\"达比加群\"或\"利伐沙班\"或\"阿哌沙班\"\"结果被过滤为以英语和成人患者发表的文献。仅包括报告DOAC继发DILI病例的病例报告和案例研究。人口统计数据,合并症,用药史,实验室调查,成像,组织学,管理,并提取结果。
结果:共15项研究(13例病例报告和2例病例系列)纳入分析,包括27例发生DOAC继发DILI的患者。利伐沙班是最常见的DOAC(n=20,74.1%)。DILI的平均发病时间为40.6d。最常见的症状是黄疸(n=15,55.6%),萎靡不振(n=9,33.3%),呕吐(n=9,33.3%)。实验室调查显示肝酶和胆红素水平升高。影像学检查和肝活检显示了急性肝炎和胆汁淤积性损伤的特征。大多数患者都有良好的结果,只有1例(3.7%)因肝功能衰竭死亡。
结论:DOAC越来越多地用于各种临床病症,DOAC继发的DILI是一种罕见但潜在严重的并发症。及时识别和停止犯罪药物对于DILI的管理至关重要。大多数DOAC继发的DILI患者具有良好的结果,但一小部分可能进展为肝功能衰竭和死亡。进一步研究,包括上市后基于人口的研究,需要更好地了解DOAC继发DILI的发生率和危险因素。
BACKGROUND: Drug-induced liver injury (DILI) can be caused by any prescribed drug and is a significant reason for the withdrawal of newly launched drugs. Direct-acting oral anticoagulants (DOACs) are non-vitamin K-based antagonists recently introduced and increasingly used for various clinical conditions. A meta-analysis of 29 randomised controlled trials and 152116 patients reported no increased risk of DILI with DOACs. However, it is challenging to predict the risk factors for DILI in individual patients with exclusion of patients with pre-existing liver disease from these studies.
OBJECTIVE: To determine the risk factors and outcomes of patients who developed DILI secondary to DOACs by systematic review and meta-summary of recent case reports and series.
METHODS: A systematic search was conducted on multiple databases including PubMed, Science Direct, Reference Citation Analysis, and Google Scholar. The search terms included \"Acute Liver Failure\" OR \"Acute-On-Chronic Liver Failure\" OR \"Acute Chemical and Drug Induced Liver Injury\" OR \"Chronic Chemical and Drug Induced Liver Injury\" AND \"Factor Xa Inhibitors\" OR \"Dabigatran\" OR \"Rivaroxaban\" OR \"apixaban\" OR \"betrixaban\" OR \"edoxaban\" OR \"Otamixaban\". The results were filtered for literature published in English and on adult patients. Only case reports and case studies reporting cases of DILI secondary to DOACs were included. Data on demographics, comorbidities, medication history, laboratory investigations, imaging, histology, management, and outcomes were extracted.
RESULTS: A total of 15 studies (13 case reports and 2 case series) were included in the analysis, comprising 27 patients who developed DILI secondary to DOACs. Rivaroxaban was the most commonly implicated DOAC (n = 20, 74.1%). The mean time to onset of DILI was 40.6 d. The most common symptoms were jaundice (n = 15, 55.6%), malaise (n = 9, 33.3%), and vomiting (n = 9, 33.3%). Laboratory investigations showed elevated liver enzymes and bilirubin levels. Imaging studies and liver biopsies revealed features of acute hepatitis and cholestatic injury. Most patients had a favourable outcome, and only 1 patient (3.7%) died due to liver failure.
CONCLUSIONS: DOACs are increasingly used for various clinical conditions, and DILI secondary to DOACs is a rare but potentially serious complication. Prompt identification and cessation of the offending drug are crucial for the management of DILI. Most patients with DILI secondary to DOACs have a favourable outcome, but a small proportion may progress to liver failure and death. Further research, including post-marketing population-based studies, is needed to better understand the incidence and risk factors for DILI secondary to DOACs.