Published online May 14, 2017. doi: 10.3748/wjg.v23.i18.3228
Peer-review started: October 11, 2016
First decision: October 28, 2016
Revised: November 17, 2016
Accepted: March 15, 2017
Article in press: March 15, 2017
Published online: May 14, 2017
Processing time: 218 Days and 14.1 Hours
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.
Core tip: Platelets improve liver fibrosis and accelerate liver regeneration; therefore, patients with liver dysfunction due to chronic liver disease (CLD) and cirrhosis can benefit from platelet transfusion. However, administration of the thrombopoietin receptor agonist eltrombopag for 6 mo did not result in the improvement of liver function in patients with CLD despite its long-term safety and ability to maintain an increased platelet count. We believe that this difference is due to platelet aging. Therefore, we are pursuing novel strategies with thrombopoietin receptor agonists and desialylated formulations to treat liver diseases.