Platelets in liver disease, cancer and regeneration

Abstract

Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.

Identifying factors affecting the pharmacokinetics of voriconazole in patients with liver dysfunction: A population pharmacokinetic approach

“…38,39 Multiple factors can contribute to the development of thrombocytopaenia, including decreased production of thrombopoietin (TPO) by damaged hepatocytes, 38,40 increased destruction of PLT with splenomegaly 41 and suppression of PLT production in bone marrow due to alcohol abuse or viral infection. 42,43 Furthermore, PLT count is a strong independent predictor of long-term mortality on the liver transplantation waiting list. 44 Meanwhile, PLT count was also identified as an independent predictor of liver fibrosis or cirrhosis.…”

Platelets and Platelet‐Derived Extracellular Vesicles in Liver Physiology and Disease

“…Platelets play a role in carcinogenesis. After contact with epithelial cancer cells or by secretion of cytokines, platelets facilitate the epithelial‐mesenchymal transition, a cardinal step in the metastatic process . Moreover, platelets are able to protect free cancer cells from shear stress and natural killer cells during their circulation in the blood .…”

“…After contact with epithelial cancer cells or by secretion of cytokines, platelets facilitate the epithelial-mesenchymal transition, a cardinal step in the metastatic process. (77,98) Moreover, platelets are able to protect free cancer cells from shear stress and natural killer cells during their circulation in the blood. (77,(99)(100)(101) They allow their extravascular migration (mainly through their releasate) (77,102) and facilitate metastases implantation and proliferation.…”

“…(77,98) Moreover, platelets are able to protect free cancer cells from shear stress and natural killer cells during their circulation in the blood. (77,(99)(100)(101) They allow their extravascular migration (mainly through their releasate) (77,102) and facilitate metastases implantation and proliferation. (77) Platelets were also suggested to be implicated in hepatocellular carcinoma (HCC) growth and migration.…”

Organ Preservation into the 2020s: The Era of Dynamic Intervention

“…For example, the translational studies of regeneration and repair after I/R suggest the participation of platelets in liver recovery after partial hepatectomy. The repairing effect of platelets could possibly be explained by contact or even uptake of cells by hepatocytes [60] and the release of insulin-like growth factor-1 (IGF-1), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and serotonin from platelets, which together can promote hepatocyte proliferation [61]. Yet, further research is required to fully clarify the platelet regenerative potential following organ I/R.…”