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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2017; 23(18): 3228-3239
Published online May 14, 2017. doi: 10.3748/wjg.v23.i18.3228
Platelets in liver disease, cancer and regeneration
Tomohiro Kurokawa, Nobuhiro Ohkohchi
Tomohiro Kurokawa, Nobuhiro Ohkohchi, Department of Surgery, Division of Gastroenterological and Hepatobiliary Surgery, and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
Author contributions: Kurokawa T and Ohkohchi N made equal contribution to all aspects of the study and its presentation.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Nobuhiro Ohkohchi, Professor, Department of Surgery, Division of Gastroenterological and Hepatobiliary Surgery, and Organ Transplantation, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. nokochi3@md.tsukuba.ac.jp
Telephone: +81-29-8533221 Fax: +81-29-8533221
Received: October 8, 2016
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
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.

Keywords: Platelet, Liver cirrhosis, Liver regeneration, Cancer, Thrombopoietin, Thrombopoietin agonist, Eltrombopag

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.