Researchers from the American University of Yale and the Papa Giovanni XXIII hospital in Bergamo have shown “for the first time in the world” how the pandemic coronavirus attacks the liver. This was announced by the Bergamo Asst, reporting the results of a work published in the ‘Journal of Hepatology’. The pathological process at the origin of the liver damage associated with serious and fatal forms of Covid-19 is “an alteration of the vascularization due to the excessive production of interleukin IL-6, a cytokine that regulates the body’s immune response”. The protein thus confirms a possible anti-Covid therapeutic target. Analyzes conducted on an animal model in the laboratories of the US university have reproduced the entire process for the first time – they report from the territorial social health company – confirming the key role of IL-6 and the mechanism of action described by the scholars of the ‘ Papa Giovanni ‘analyzing data and radiographs of 43 patients who died in Bergamo from Covid in the spring of 2020. “This is at the time of the first study ever published on an animal model involving the largest numerical sample of human tissues from patients who died from infection with Covid-19 “, underline the experts. The Sars-Cov-2 virus – they explain based on the observed results – induces the endothelial cells of the blood vessels that supply the liver to produce a protein called interleukin IL-6 which, in situations normal, it has a regulating function of immune processes. However, when its production is unregulated and excessive, IL-6 can lead to abnormal inflammatory states. In the case of Covid-19, this so-called ‘cytokine storm’ leads to the inflammatory state (endotheliopathy) and blood clotting inside the hepatic vessels. Department of Laboratory Medicine Andrea Gianatti and his fellow anatomopathologist Aurelio Sonzogni, recall a note. The biochemical and humoral data of the selected patients were analyzed and evaluated by Maria Grazia Alessio, Giulia Previtali and Michela Seghezzi of Laboratory Medicine, clinical chemical analysis of Pope John. The radiological investigations carried out at the time of hospitalization by the Radiology Unit of Pope John are also fundamental. The director Sandro Sironi, professor at the University of Milano-Bicocca at the post Graduate School in Diagnostic Radiology, together with the radiologists Clarissa Valle and Pietro Bonaffini, are among the authors who collaborated on the study. “The markers of endothelial cell and platelet activation (factor VIII, fibrinolytic enzymes, D-dimer, von Willebrand-Vwf factor antigen) indicated a link between liver damage, coagulopathy and endotheliopathy – says Sonzogni dell ‘Pathological anatomy of Asst Papa Giovanni XXIII – The cytokine IL-6, through a process called’ trans-signaling ‘, causes an increase in anticoagulants (factor VIII, Vwf) and inflammatory agents. It also generates an increase in platelets in the cells of the endothelium. We detected the inhibitory action of the natural inhibitor gp130, of the drug ruxolitinib that was administered in some of these patients, and of particular antibodies (Stat1 / 3 siRna). We transmitted this succession of data and this model to colleagues at Yale, who tested it in the laboratory, obtaining confirmation of what we hypothesized “. One of the largest clinical studies to have evaluated the relationship between liver damage and Sars-CoV-2 – highlighted by the Bergamo hospital – had found that, out of 2,273 patients, 45% had mild liver damage, 21% moderate and 6.4% severe. Patients with acute liver injury were at increased risk of ICU admission (69%), intubation (65%), renal replacement therapy (33%), and mortality (42%). The role of endothelial cell inflammation had already been hypothesized, but in the case of the liver it had never been demonstrated on tissue. Furthermore, previous research has so far focused mainly on coagulopathy, i.e. on the increase in thrombotic and microvascular complications generated by the inflammatory response of the immune system and resulting from the cytokine storm induced by Sars-CoV-2. Now the Italy-USA study returns to emphasize the role of endotheliopathy as the main cause of liver damage compared to coagulopathy, precisely because it would be the cause of the latter. This conclusion suggests that early identification of endotheliopathy and therapeutic strategies to reduce its inflammatory acceleration could improve the treatment of severe Covid-19. The new work also confirms that IL-6 may more generally be a potential target for targeted therapy of the disease, also because the damage is ubiquitous, that is, widespread in the body and not limited to the lung alone. “From Pope John comes once again a contribution to the collective effort of the international scientific community to know and thus effectively fight this disease – comments Fabio Pezzoli, medical director of Asst Papa Giovanni XXIII – I thank our professionals for their scientific rigor and the seriousness with which they are facing the challenge represented by this new virus “.
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