Platelets as Modulators of Liver Diseases

Abstract

Platelets are key players in thrombosis and hemostasis. Alterations in platelet count and function are common in liver disease, and may contribute to bleeding or thrombotic complications in liver diseases and during liver surgery. In addition to their hemostatic function, platelets may modulate liver diseases by mechanisms that are incompletely understood. Here, we present clinical evidence for a role of platelets in the progression of chronic and acute liver diseases, including cirrhosis, acute liver failure, and hepatocellular carcinoma. We also present clinical evidence that platelets promote liver regeneration following partial liver resection. Subsequently, we summarize studies in experimental animal models that support these clinical observations, and also highlight studies that are in contrast with clinical observations. The combined results of clinical and experimental studies suggest that platelets may be a therapeutic target in the treatment of liver injury and repair, but the gaps in our understanding of mechanisms involved in platelet-mediated modulation of liver diseases call for caution in clinical application of these findings.

Pemafibrate Dramatically Ameliorated the Values of Liver Function Tests and Fibrosis Marker in Patients with Non-Alcoholic Fatty Liver Disease

“…Platelets, another factor of APRI, are reported as an active participant in the process of liver inflammation. 30 Platelets exert potent inflammatory effects and play a central part in the progression from simple steatosis to NASH. 31 Excessive platelet consumption is one of the mechanisms of thrombocytopenia in chronic liver disease.…”

Thioacetamide-induced liver damage and thrombocytopenia is associated with induction of antiplatelet autoantibody in mice

“…Thrombocytopenia has been demonstrated to be related to the degree of liver damage in both clinical cases and animal models 47–49 . Because the liver is the major organ expressing TPO, discovering thrombocytopenia in patients with chronic liver diseases would be expected 1–5 .…”

“…Despite severe hepatic dysfunction, serum TPO level was normal and not associated with platelet count in acute liver failure in one study 50 , suggesting that additional pathological factors are more critical. Because coagulation pathways have been demonstrated to be activated during acute liver injury and antiplatelet therapy has decreased liver injury and mortality 48,49,51 , the activation of platelet-related coagulation pathways are likely to be part of the pathophysiology. As the mechanism remains elusive, various candidate pathogenic factors may be involved 5 .…”

<p>Dihydrodiosgenin inhibits endothelial cell-derived factor VIII and platelet-mediated hepatocellular carcinoma metastasis</p>

“…It is worth noting that platelets might also contribute to the development of HCC 14–16. Lisman and Luyendyk demonstrated that platelets played an important role in HCC growth and metastasis 17. Meanwhile, platelet lysate has been found to stimulate proliferation of four different HCCs 18.…”