5PSQ-178急性托珠单抗治疗与SARS-CoV-2感染患者的肝毒性

L. Cantarelli, F. G. Nicolás, J. G. Garcia, Gj Nazco Casariego
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The following variables were collected: age, sex, posology scheme of TCZ, admission to the intensive care unit (ICU), need for orotracheal intubation (OTI) and death during the hospital stay. The hepatic profile was analysed for levels of hepatic transaminases (GOT/AST and GPT/ALT) and total bilirubin (TOT BL) pre and post completion of treatment with TCZ. Alteration of liver parameters was classified as mild (1–3 × upper limit of normality (UPN)), moderate (3–5 × UPN) and severe (≥5 × UPN). Results During the study period, 44 patients with SARS-CoV-2 infection were treated with TCZ (65.9% men (n=29); mean age 62.3 years (31–82)). The posology scheme of TCZ used was the following: single dose (68.2%, n=30), double dose (18.2%, n=8) and triple dose (11.6%, n=6). Two patients (4.5%) received a 50% reduced dose because of previous liver failure. During admission, 56.8% (n=25) of patients required a stay in the ICU. 36.4% (n=16) needed OTI. 9.1% (n=4) died during admission. Liver profile analysis showed that 72.7% of patients (n=32) presented with normal levels of GPT/ALT and GOT/AST before treatment. 59.1% (n=26) presented with normal levels of BL TOT and 4.5% (n=2) had high levels. In 34.1% (n=15) there were no data. After treatment with TCZ, 86.3% (n=38) developed hepatotoxicity. Elevation of GPT/ALT was observed: mild (42.1%), moderate (28.9%) and severe (28.9%); elevation of GOT/AST: mild (44.7%), moderate (31.6%) and severe (13.2%). 42.9% (n=12) presented with high levels of BL TOT after receiving TCZ. Conclusion and relevance The study showed how a high proportion of patients with SARS-CoV-2 infection developed severe liver toxicity after the use of the drug. However, future studies will be needed to clarify the involvement of SARS-CoV-2 itself in the development of hepatotoxicity. 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引用次数: 0

摘要

背景和重要性Tocilizumab (TCZ)已被提出用于缓解与SARS-CoV-2相关的细胞因子风暴综合征。然而,这种药物的急性管理已被证明在肝脏水平上引起严重的不良反应,包括急性肝衰竭。目的与目的评价急性使用TCZ对SARS-CoV-2感染患者的肝毒性。材料与方法对所有临床怀疑/诊断为SARS-CoV-2感染并接受过TCZ治疗的患者进行了为期2个月的回顾性单中心研究(2020年3月至4月)。收集以下变量:年龄、性别、TCZ的病理学方案、入住重症监护病房(ICU)、是否需要口气管插管(OTI)和住院期间死亡。分析治疗前后肝脏转氨酶(GOT/AST和GPT/ALT)和总胆红素(TOT BL)水平。肝脏参数改变分为轻度(1-3 ×正常上限)、中度(3-5 ×正常上限)和重度(≥5 ×正常上限)。结果在研究期间,有44例SARS-CoV-2感染患者接受了TCZ治疗,其中男性占65.9% (n=29);平均年龄62.3岁(31-82岁)。TCZ采用单次给药(68.2%,n=30)、两次给药(18.2%,n=8)、三次给药(11.6%,n=6)。两名患者(4.5%)因既往肝功能衰竭而减少了50%的剂量。入院期间,56.8% (n=25)的患者需要在ICU住院。36.4% (n=16)需要OTI治疗。9.1% (n=4)在入院期间死亡。肝谱分析显示,72.7%的患者(n=32)在治疗前GPT/ALT和GOT/AST水平正常。59.1% (n=26)呈正常水平,4.5% (n=2)呈高水平。34.1% (n=15)患者无资料。经TCZ治疗后,86.3% (n=38)发生肝毒性。GPT/ALT升高:轻度(42.1%)、中度(28.9%)、重度(28.9%);GOT/AST升高:轻度(44.7%)、中度(31.6%)和重度(13.2%)。42.9% (n=12)患者在接受TCZ治疗后出现高水平的BL TOT。结论及相关性本研究显示,高比例的SARS-CoV-2感染患者在使用该药后出现严重的肝毒性。然而,未来的研究将需要澄清SARS-CoV-2本身在肝毒性发展中的作用。参考文献和/或致谢利益冲突无利益冲突
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5PSQ-178 Hepatotoxicity associated with acute tocilizumab treatment in patients with SARS-CoV-2 infection
Background and importance Tocilizumab (TCZ) has been proposed to mitigate the cytokine storm syndrome associated with SARS-CoV-2. However, acute administration of this drug has been shown to cause serious adverse effects at the level of the liver, including acute liver failure. Aim and objectives To evaluate the liver toxicity profile associated with the acute use of TCZ in patients with SARS-CoV-2 infection. Material and methods A retrospective single centre study, lasting 2 months (March to April 2020), was conducted in all patients with a clinical suspicion/diagnosis confirmed of SARS-CoV-2 infection and who had received treatment with TCZ. The following variables were collected: age, sex, posology scheme of TCZ, admission to the intensive care unit (ICU), need for orotracheal intubation (OTI) and death during the hospital stay. The hepatic profile was analysed for levels of hepatic transaminases (GOT/AST and GPT/ALT) and total bilirubin (TOT BL) pre and post completion of treatment with TCZ. Alteration of liver parameters was classified as mild (1–3 × upper limit of normality (UPN)), moderate (3–5 × UPN) and severe (≥5 × UPN). Results During the study period, 44 patients with SARS-CoV-2 infection were treated with TCZ (65.9% men (n=29); mean age 62.3 years (31–82)). The posology scheme of TCZ used was the following: single dose (68.2%, n=30), double dose (18.2%, n=8) and triple dose (11.6%, n=6). Two patients (4.5%) received a 50% reduced dose because of previous liver failure. During admission, 56.8% (n=25) of patients required a stay in the ICU. 36.4% (n=16) needed OTI. 9.1% (n=4) died during admission. Liver profile analysis showed that 72.7% of patients (n=32) presented with normal levels of GPT/ALT and GOT/AST before treatment. 59.1% (n=26) presented with normal levels of BL TOT and 4.5% (n=2) had high levels. In 34.1% (n=15) there were no data. After treatment with TCZ, 86.3% (n=38) developed hepatotoxicity. Elevation of GPT/ALT was observed: mild (42.1%), moderate (28.9%) and severe (28.9%); elevation of GOT/AST: mild (44.7%), moderate (31.6%) and severe (13.2%). 42.9% (n=12) presented with high levels of BL TOT after receiving TCZ. Conclusion and relevance The study showed how a high proportion of patients with SARS-CoV-2 infection developed severe liver toxicity after the use of the drug. However, future studies will be needed to clarify the involvement of SARS-CoV-2 itself in the development of hepatotoxicity. References and/or acknowledgements Conflict of interest No conflict of interest
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