Analysis of reported adverse liver reactions associated with drugs used to treat patients with coronavirus disease 2019

Abstract Hepatic injury has been documented in patients with coronavirus disease 2019 (COVID-19). However, pharmacotherapy can frequently impact liver alterations, given the known hepatotoxic potential of drugs not effective to treat COVID-19. The objective of the present study was to evaluate reports of suspected liver reactions to drugs used for treating COVID-19, compare their use for other indications among patients with COVID-19, and assess possible interactions between them. We obtained reports on drugs used to treat COVID-19 (tocilizumab, remdesivir, hydroxychloroquine, and/or lopinavir/ritonavir), registered on June 30, 2020, from the Food and Drug Administration Adverse Event Reporting System (FAERS) Public Dashboard. We then analyzed the risk of developing liver events with these drugs by calculating the reported odds ratios (ROR). We identified 662, 744, and 1381 reports related to tocilizumab, lopinavir/ ritonavir, and hydroxychloroquine use, respectively. The RORs (95% confidence intervals) were 6.32 (5.28-7.56), 6.12 (5.22-7.17), and 9.07 (8.00-10.29), respectively, demonstrating an increased risk of liver events among patients with COVID-19 when compared with uninfected patients. The elevated risk of reporting adverse liver events in patients with COVID-19 who receive these drugs, alone or in combination, highlights the need for careful drug selection and efforts to reduce drug combinations without notable benefits. Similar to any other condition, the use of drugs without established efficacy should be avoided.

摘要 新型冠状病毒肺炎（Coronavirus Disease 2019, COVID-19）患者中已有肝损伤的相关报道。然而，鉴于部分对新型冠状病毒肺炎无效的药物具有明确肝毒性潜力，药物治疗往往会对肝脏状态产生影响。本研究旨在评估新型冠状病毒肺炎治疗药物引发疑似肝不良反应的相关报道，对比此类药物在新型冠状病毒肺炎患者中的其他适应证使用情况，并评估药物间潜在的相互作用。本研究从美国食品药品监督管理局不良事件报告系统（Food and Drug Administration Adverse Event Reporting System, FAERS）公共查询面板于2020年6月30日收录的报告中，提取了用于新型冠状病毒肺炎治疗的药物：托珠单抗（tocilizumab）、瑞德西韦（remdesivir）、羟氯喹（hydroxychloroquine）以及/或洛匹那韦/利托那韦（lopinavir/ritonavir）的相关数据。随后，通过计算报告比值比（reported odds ratios, ROR），分析了此类药物引发肝脏不良事件的风险。本研究分别纳入了与托珠单抗、洛匹那韦/利托那韦、羟氯喹使用相关的报告662份、744份及1381份。三类药物对应的报告比值比（95%置信区间）分别为6.32（5.28~7.56）、6.12（5.22~7.17）及9.07（8.00~10.29），结果显示，相较于未感染新型冠状病毒的人群，新型冠状病毒肺炎患者使用此类药物时发生肝脏不良事件的风险显著升高。新型冠状病毒肺炎患者单独或联合使用此类药物时，报告肝脏不良事件的风险升高，这提示临床需谨慎选择药物，并尽量减少无明确获益的联合用药方案。与其他疾病诊疗原则一致，应避免使用疗效未明确的药物。