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本文引用的文献

1
Liver Injury in Critically Ill and Non-critically Ill COVID-19 Patients: A Multicenter, Retrospective, Observational Study.重症和非重症COVID-19患者的肝损伤:一项多中心、回顾性、观察性研究。
Front Med (Lausanne). 2020 Jun 23;7:347. doi: 10.3389/fmed.2020.00347. eCollection 2020.
2
Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19.托珠单抗治疗 COVID-19 机械通气患者。
Clin Infect Dis. 2021 Jul 15;73(2):e445-e454. doi: 10.1093/cid/ciaa954.
3
Serious adverse events with tocilizumab: Pharmacovigilance as an aid to prioritize monitoring in COVID-19.托珠单抗的严重不良事件:药物警戒作为 COVID-19 监测重点的辅助手段。
Br J Clin Pharmacol. 2021 Mar;87(3):1533-1540. doi: 10.1111/bcp.14459. Epub 2020 Jul 26.
4
Interleukin-6 as prognosticator in patients with COVID-19.白细胞介素-6作为新型冠状病毒肺炎患者的预后指标
J Infect. 2020 Sep;81(3):452-482. doi: 10.1016/j.jinf.2020.06.008. Epub 2020 Jun 8.
5
Efficacy and safety of tocilizumab in severe COVID-19 patients: a single-centre retrospective cohort study.托珠单抗治疗重症 COVID-19 患者的疗效和安全性:一项单中心回顾性队列研究。
Eur J Intern Med. 2020 Jun;76:43-49. doi: 10.1016/j.ejim.2020.05.021. Epub 2020 May 22.
6
First case of drug-induced liver injury associated with the use of tocilizumab in a patient with COVID-19.首例 COVID-19 患者使用托珠单抗致药物性肝损伤。
Liver Int. 2020 Aug;40(8):1901-1905. doi: 10.1111/liv.14516. Epub 2020 Jun 1.
7
Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy.意大利米兰托珠单抗超适应证治疗严重急性呼吸综合征冠状病毒 2 型肺炎。
Eur J Intern Med. 2020 Jun;76:36-42. doi: 10.1016/j.ejim.2020.05.011. Epub 2020 May 21.
8
Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19.IL-6 和 CRP 水平升高可预测 COVID-19 患者需要机械通气。
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9
Use of subcutaneous tocilizumab in patients with COVID-19 pneumonia.皮下注射托珠单抗在新冠肺炎肺炎患者中的应用。
J Med Virol. 2021 Jan;93(1):32-34. doi: 10.1002/jmv.26016. Epub 2020 Sep 30.
10
Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia.低剂量托珠单抗对 COVID-19 相关肺炎患者死亡率的影响。
Eur J Intern Med. 2020 Jun;76:31-35. doi: 10.1016/j.ejim.2020.05.009. Epub 2020 May 13.

托珠单抗与新冠病毒肺炎患者的肝损伤

Tocilizumab and liver injury in patients with COVID-19.

作者信息

Serviddio Gaetano, Villani Rosanna, Stallone Giovanni, Scioscia Giulia, Foschino-Barbaro Maria Pia, Lacedonia Donato

机构信息

C.U.R.E. (University Centre for Liver Disease Research and Treatment), Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto 1, Foggia, 71122, Italy.

C.U.R.E. (University Centre for Liver Disease Research and Treatment), Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

出版信息

Therap Adv Gastroenterol. 2020 Oct 7;13:1756284820959183. doi: 10.1177/1756284820959183. eCollection 2020.

DOI:10.1177/1756284820959183
PMID:33101458
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7545299/
Abstract

Current mortality rate in patients with COVID-19 disease is about 2%, whereas 5% of patients require admission to the intensive care unit. It is assumed that interleukin (IL)-6 may be involved in the pathogenesis of severe COVID-19 infections; therefore, in the absence of a specific antiviral therapy, some authors have suggested that tocilizumab - a drug used to block the signal transduction pathway of IL-6 - could have beneficial effects in the management of severe COVID-19 disease. However, mild-to-moderate elevation in transaminases and drug-induced liver injury have been observed in patients treated with tocilizumab. We present seven cases of patients with elevated liver enzymes [up to five times the upper limit of normal (ULN)] at baseline who received tocilizumab for life-threatening COVID-19 disease. All patients had no history of liver or pulmonary disease and were admitted for acute hypoxemic respiratory failure, dyspnea and fever due to COVID-19 bilateral pneumonia. IL-6 was available in six patients, and was significantly increased particularly in those with severe impairment of lung function. All patients received tocilizumab (8 mg/kg/day) for two consecutive days because of lack of improvement after hydroxychloroquine, azithromycin and lopinavir/ritonavir treatment. After tocilizumab administration, clinical condition rapidly improved and liver function test normalized within 3 weeks of treatment. Tocilizumab may be effective for the treatment of severe COVID-19 disease, even in patients with elevated liver function tests. Further studies are needed to evaluate the impact of tocilizumab use on liver function tests in patients with pre-existing chronic liver disease.

摘要

新型冠状病毒肺炎(COVID-19)患者目前的死亡率约为2%,而5%的患者需要入住重症监护病房。据推测,白细胞介素(IL)-6可能参与了重症COVID-19感染的发病机制;因此,在缺乏特异性抗病毒治疗的情况下,一些作者建议,托珠单抗——一种用于阻断IL-6信号转导途径的药物——可能对重症COVID-19疾病的治疗有益。然而,在接受托珠单抗治疗的患者中观察到转氨酶轻度至中度升高以及药物性肝损伤。我们报告了7例基线时肝酶升高[高达正常上限(ULN)的5倍]的患者,他们因危及生命的COVID-19疾病接受了托珠单抗治疗。所有患者均无肝脏或肺部疾病史,因COVID-19双侧肺炎导致急性低氧性呼吸衰竭、呼吸困难和发热而入院。6例患者检测了IL-6,其水平显著升高,尤其是在肺功能严重受损的患者中。由于在使用羟氯喹、阿奇霉素和洛匹那韦/利托那韦治疗后病情无改善,所有患者连续两天接受托珠单抗治疗(8mg/kg/天)。给予托珠单抗后,临床状况迅速改善,肝功能检查在治疗3周内恢复正常。托珠单抗可能对重症COVID-19疾病有效,即使是肝功能检查结果升高的患者。需要进一步研究来评估托珠单抗的使用对已有慢性肝病患者肝功能检查的影响。