2025 Hepatoxicity SIG: Mechanisms and consequences of coagulation activity in acute and chronic liver injury-Mechanisms and consequences of coagulation activity in acute and chronic liver injury

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Video Summary

In June's Hepatotoxicity Special Interest Group Seminar, Dr. Lauren Poole from Rutgers Robert Wood Johnson Medical School presented her research on the role of blood coagulation factors in liver injury. Her work focuses on the coagulation cascade's involvement in acute and chronic liver injury and its potential as a therapeutic target. Dr. Poole discussed the liver disease background, highlighting its diverse etiologies and significant global health burden, including increased mortality associated with advanced stages like cirrhosis. Despite new therapeutic strategies, an effective universal treatment remains elusive, necessitating further research into disease-driving pathways.<br /><br />Dr. Poole introduced the coagulation cascade, explaining how intrinsic and extrinsic pathways lead to blood clot formation. She highlighted evidence suggesting the coagulation cascade's pathological role in liver disease progression, posing a potential therapeutic target for mitigation. However, she acknowledged the challenge due to liver disease patients' rebalanced hemostatic system, often leading to a hypercoagulable state despite impaired hepatic synthesis of clotting factors.<br /><br />Her studies, utilizing experimental liver injury models in mice, aimed to elucidate mechanisms of coagulation activation, revealing that tissue factor, particularly from hepatic non-parenchymal cells, is crucial in driving coagulation activation post-injury, not hepatocyte tissue factor as previously thought. Despite blocking coagulation activation, tissue factor deficiency did not significantly affect fibrosis development, suggesting it might play a more nuanced role.<br /><br />The seminar concluded with discussions on tissue factor's potential as a therapeutic target to manage thrombotic risks in liver disease, underscoring the need to identify and modulate tissue factor expression mechanisms to develop safer therapies. Continued research is necessary to further comprehend these dynamics and translate findings into clinical applications.

Keywords

Hepatotoxicity

blood coagulation

liver injury

coagulation cascade

therapeutic target

liver disease

tissue factor

hypercoagulable state

fibrosis

thrombotic risks