Kurokawa Tomohiro, Ohkohchi Nobuhiro
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.
World J Gastroenterol. 2017 May 14;23(18):3228-3239. doi: 10.3748/wjg.v23.i18.3228.
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.
尽管多年来病毒性肝炎的治疗方法不断发展，但由此导致的肝硬化仍无法完全治愈。血小板含有止血所需的蛋白质，以及器官发育、组织再生和修复所需的多种生长因子。血小板减少症在慢性肝病（CLD）和肝硬化患者中经常出现，可能是由于血小板生成素产生减少以及脾功能亢进导致血小板破坏加速所致；然而，血小板减少症与肝病发病机制之间的关系以及血小板在CLD中的作用仍知之甚少。在本文中，我们根据本实验室进行的研究以及其他研究人员的最新进展报告，总结并讨论了血小板改善肝纤维化和加速肝再生的实验证据。此外，我们根据这些研究结果阐述了我们目前的观点。血小板通过使肝星状细胞失活来改善肝纤维化，从而减少胶原蛋白的产生。血小板在肝脏中的再生作用涉及对肝细胞的直接作用、与肝窦内皮细胞的协同作用以及与库普弗细胞的协作作用。基于这些观察结果，我们确定了血小板输注对改善CLD和肝硬化患者肝功能的几个指标的直接作用。然而，与我们之前的临床研究结果不同，接受艾曲泊帕治疗6个月的CLD患者肝功能的较小增量变化是由于从异质人群中选择患者所致。我们强调了目前关于血小板在CLD和癌症中的作用的知识，并预期基于血小板的临床治疗在治疗肝病方面的新应用。
