Coagulopathy of COVID-19 correlates with liver injury

The coagulopathy of COVID-19 driven by endothelial Factor VIII correlated with liver injury, according to a presenter at The Liver Meeting Digital Experience.

“Our study illuminates a mechanism of injury in COVID-19 that was previously unknown,” Matthew McConnell, MD, from the department of internal medicine/digestive diseases at Yale School of Medicine, said during his presentation. “Our study therefore provides a first step toward understanding how patients will be affected long-term after suffering from this liver injury. Our study centers around the global coagulopathy of COVID-19 and defines a mechanism for increased coagulation and factor levels that may be future targets for treatment.”

At Yale New Haven Hospital, McConnell and colleagues measured coagulation parameters and liver tests in 68 patients with PCR-confirmed COVID-19. They assessed liver tests 5 days prior and 5 days after coagulation paraments and recorded peak values if no liver tests were gathered within the time window.

Investigators cultured the primary human liver sinusoidal endothelial cells (LSEC) with interleukin 6 (IL-6) and soluble IL-6 receptor (sIL-6R) for the in vitro studies to mimic IL-6 trans signaling thought to occur in COVID-19.

The study comprised three cohorts based on ALT three times over the upper limit of normal or ALT three times under the upper limit of normal.

Results showed a higher percentage of patients with ALT three times over the upper limit of normal also had a hypercoagulable TEG profile (P < .05). In the plasma of patients with ALT three times the upper limit of normal, investigators saw an elevation of factor VIII, fibrinogen and factor II (P < .05).

“We focused on determining whether the liver sinusoidal endothelial cells may be stimulated by the inflammatory markers of COVID-19 to adopt a hyper coagulable phenotype by producing excessive Factor VIII,” he said. “Because the complex of the IL-6 and sIL-6R has gained increasing importance as a pathologic inflammatory signal for endothelial cells in COVID-19, we treated sinusoidal endothelial cells with this complex and found significantly elevated gene expression of Factor VIII and its stabilizing protein factor.”

McConnell and colleagues also found the IL-6/IL-6R complex induced activation of STAT1 (P < .01) transcription factors that are known to induce Factor VIII expression.