Juneja Deven, Nasa Prashant, Jain Ravi
Institute of Critical Care Medicine, Max Super Specialty Hospital, New Delhi 110017, India.
Critical Care Medicine, NMC Specialty Hospital, Dubai 7832, United Arab Emirates.
World J Hepatol. 2023 Jun 27;15(6):841-849. doi: 10.4254/wjh.v15.i6.841.
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.
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.
A systematic search was conducted on multiple databases including PubMed, Science Direct, , 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.
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 ( = 20, 74.1%). The mean time to onset of DILI was 40.6 d. The most common symptoms were jaundice ( = 15, 55.6%), malaise ( = 9, 33.3%), and vomiting ( = 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.
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.
药物性肝损伤（DILI）可由任何处方药引起，是新上市药物撤市的重要原因。直接口服抗凝剂（DOACs）是最近引入并越来越多地用于各种临床情况的非维生素K拮抗剂。一项对29项随机对照试验和152116名患者的荟萃分析报告称，DOACs不会增加DILI的风险。然而，在排除这些研究中已有肝病患者的情况下，预测个体患者发生DILI的风险因素具有挑战性。
通过对近期病例报告和病例系列进行系统评价和荟萃总结，确定继发于DOACs的DILI患者的风险因素和结局。
在多个数据库中进行系统检索，包括PubMed、Science Direct和谷歌学术。检索词包括“急性肝衰竭”或“慢加急性肝衰竭”或“急性化学和药物性肝损伤”或“慢性化学和药物性肝损伤”以及“Xa因子抑制剂”或“达比加群”或“利伐沙班”或“阿哌沙班”或“贝曲沙班”或“依度沙班”或“奥米沙班”。结果筛选出英文发表的关于成年患者的文献。仅纳入报告继发于DOACs的DILI病例的病例报告和病例研究。提取有关人口统计学、合并症、用药史、实验室检查、影像学、组织学、治疗和结局的数据。
分析共纳入15项研究（13例病例报告和2例病例系列），包括27例继发于DOACs的DILI患者。利伐沙班是最常涉及的DOAC（n = 20，74.1%）。DILI的平均发病时间为40.6天。最常见的症状是黄疸（n = 15，55.6%）、不适（n = 9，33.3%）和呕吐（n = 9，33.3%）。实验室检查显示肝酶和胆红素水平升高。影像学研究和肝活检显示急性肝炎和胆汁淤积性损伤的特征。大多数患者预后良好，只有1例患者（3.7%）因肝衰竭死亡。
DOACs越来越多地用于各种临床情况，继发于DOACs的DILI是一种罕见但可能严重的并发症。迅速识别并停用致病药物对于DILI的管理至关重要。大多数继发于DOACs的DILI患者预后良好，但一小部分患者可能进展为肝衰竭和死亡。需要进一步研究，包括上市后基于人群的研究，以更好地了解继发于DOACs的DILI的发病率和风险因素。
