There is a link between liver injury and a tendency toward excessive clotting in patients with COVID-19, and the organ’s own blood vessels could be responsible, new research shows.
The effect of IL-6 on the liver sinusoidal endothelial cells lining the liver blood vessels creates a prothrombotic environment that includes the release of factor VIII, said investigator Matthew McConnell, MD, from the Yale University, New Haven, Conn.
Dr. McConnell presented the results at the virtual annual meeting of the American Association for the Study of Liver Diseases.
These associations offer insights into why COVID-19 patients with underlying liver disease can experience “devastating complications” related to improper blood vessel function in the organ, he added.
For their study, Dr. McConnell and colleagues analyzed data on ALT and hypercoagulability from 68 adults treated at the Yale–New Haven Hospital. The liver and coagulation tests were administered within 5 days of each other.
The team set the ALT cutoff for liver injury at three times the upper limit of normal. Patients with two or more parameters indicating excessive clotting were considered to have a hypercoagulable profile, which Dr. McConnell called “a signature clinical finding of COVID-19 infection.”
Patients with high levels of ALT also experienced elevations in clotting-related factors, such as fibrinogen levels and the activity of factor VIII and factor II. Furthermore, liver injury was significantly associated with hypercoagulability (P < .05).
Because COVID-19 is linked to the proinflammatory IL-6, the investigators examined how this cytokine and its receptor affect human liver sinusoidal cells. Cells exposed to IL-6 and its receptor pumped out factor VIII at levels that were significantly higher than in unexposed cells (P < .01). Exposed cells also produced significantly more von Willebrand factor (P < .05), another prothrombotic molecule, and showed increased expression of genes that induce the expression of factor VIII.There is utility in the findings beyond COVID-19, said Dr. McConnell. They provide “insights into complications of critical illness, in general, in the liver blood vessels” of patients with underlying liver disease.
Dr. McConnell has no conflicts.
For the latest clinical guidance, education, research, and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.
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