Abenavoli Ludovico, Aquila Isabella, Sacco Matteo Antonio, Scarlata Giuseppe Guido Maria, Procopio Anna Caterina, Boccuto Luigi, Scarpellini Emidio, Greco Marta, Foti Daniela Patrizia, Ricci Pietrantonio, Luzza Francesco
Department of Health Sciences, University "Magna Græcia", Viale Europa, 88100 Catanzaro, Italy.
Institute of Legal Medicine, Department of Medical and Surgical Sciences, University "Magna Graecia", Viale Europa, 88100 Catanzaro, Italy.
Diseases. 2023 Oct 13;11(4):141. doi: 10.3390/diseases11040141.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated an unprecedented challenge for healthcare systems worldwide. Currently, the scientific community wonders if liver injury in patients suffering from severe forms is a direct consequence of the virus or secondary manifestations of systemic inflammation. The liver plays an essential role in the development of the inflammatory storm typical of this disease, and its involvement is associated with worse clinical outcomes and a higher risk of morbidity and mortality from Coronavirus disease 2019 (COVID-19).
Ten patients suffering from severe COVID-19 disease who died between January 2020 and December 2021 were included in the present analysis. These subjects underwent a post mortem examination with a focused evaluation of the hepatic injury. Also, several laboratory parameters have been evaluated, with a primary focus on prothrombin time, partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers to detect coagulative changes.
The main cause of death was represented by pulmonary thromboembolism events (50%). The analysis of coagulation laboratory parameters and liver biomarkers revealed a statistically significant rise in aPTT and ALP, and a decrease in albumin, when comparing the blood value at admission and death. We also found high levels of D-dimers in most of the subjects at the time of hospitalization. Interestingly, the post mortem analysis of the liver showed ample morphologic variability, with several disease features. In detail, the liver histology revealed the following: the presence of a variable degree of micro- and macrovacuolar steatosis, inflammation (also, hepato-cholangitis), and variable fibrosis. Of mention, we were also able to detect organized fibrinous material.
Our results indicate that in subjects with a severe form of COVID-19, liver disease is related to changes in coagulative and fibrinolytic pathways. In particular, we noted low fibrinogen levels and high D-dimer levels with histological liver findings. Our data suggest that fibrinogen and D-dimers may be used as prognostic markers to detect the severity of liver disease in patients with COVID-19. Finally, we underline the crucial role of coagulation balance in subjects with severe forms of COVID-19.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行给全球医疗系统带来了前所未有的挑战。目前，科学界想知道重症患者的肝损伤是病毒的直接后果还是全身炎症的继发表现。肝脏在这种疾病典型的炎症风暴发展中起着至关重要的作用，其受累与更差的临床结果以及2019冠状病毒病（COVID-19）更高的发病和死亡风险相关。
本分析纳入了2020年1月至2021年12月期间死亡的10例重症COVID-19患者。这些受试者接受了尸检，并重点评估了肝损伤。此外，还评估了几个实验室参数，主要关注凝血酶原时间、部分凝血活酶时间、纤维蛋白原、抗凝血酶III和D-二聚体以检测凝血变化。
主要死亡原因是肺血栓栓塞事件（50%）。比较入院时和死亡时的血液值，凝血实验室参数和肝脏生物标志物分析显示活化部分凝血活酶时间（aPTT）和碱性磷酸酶（ALP）有统计学意义的升高，白蛋白降低。我们还发现大多数受试者在住院时D-二聚体水平较高。有趣的是，肝脏的尸检分析显示出丰富的形态学变异性，有几种疾病特征。详细而言，肝脏组织学显示如下：存在不同程度的微泡和大泡性脂肪变性、炎症（也有肝内胆管炎）以及不同程度的纤维化。值得一提的是，我们还能够检测到有组织的纤维蛋白物质。
我们的结果表明，在重症COVID-19患者中，肝脏疾病与凝血和纤维蛋白溶解途径的变化有关。特别是，我们注意到纤维蛋白原水平低和D-二聚体水平高以及肝脏组织学发现。我们的数据表明，纤维蛋白原和D-二聚体可用作预测标志物，以检测COVID-19患者肝脏疾病的严重程度。最后，我们强调凝血平衡在重症COVID-19患者中的关键作用。
