Liver Injury Linked to COVID-19-Related Coagulopathy

Emily Willingham

November 17, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

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.

Cells that line the liver's blood vessels produce high levels of factor VIII, a coagulation factor, when they are exposed to interleukin (IL)-6, an inflammatory molecule associated with COVID-19.

These findings "center the liver in global coagulopathy of COVID-19 and define a mechanism for increased coagulation factor levels that may be treatment targets," said investigator Matthew McConnell, MD, from the Yale University School of Medicine in New Haven, Connecticut.

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 McConnell, who presented the results at The Liver Meeting 2020.

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, McConnell and his colleagues analyzed data on alanine aminotransferase (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 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.

As we learn more about COVID-19, we find that it is as much a coagulatory as a respiratory disease.

"As we learn more about COVID-19, we find that it is as much a coagulatory as a respiratory disease," said Tien Dong, MD, PhD, from UCLA Health in Los Angeles, who was not involved in the study.

These findings are in line with a lot of other COVID-19-related research that suggests a link between hepatocyte injury and clotting disorders, he added.

One important factor is existing liver disease, said Dong. "If you have COVID-19 on top of that, you're probably at risk of developing acute liver injury from the infection itself."

That said, it's still a good idea to check liver function in patients with COVID-19 and no known liver disease, he advised. Staying on top of these measures will keep the odds of long-term problems "a lot lower."

There is utility in the findings beyond COVID-19, said McConnell. They provide "insights into complications of critical illness, in general, in the liver blood vessels" of patients with underlying liver disease.

McConnell and Dong have disclosed no relevant financial relationships.

The Liver Meeting Digital Experience 2020: American Association for the Study of Liver Diseases (AASLD): Abstract 106. Presented November 15, 2020.

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