Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, United Kingdom.
Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
Semin Liver Dis. 2021 Aug;41(3):298-307. doi: 10.1055/s-0041-1723034. Epub 2021 May 15.
Patients with acute-on-chronic liver failure (ACLF) have a devastating prognosis and therapeutic options are limited. Granulocyte-colony stimulating factor (G-CSF) mobilizes immune and stem cells and possess immune-modulatory and proregenerative capacities. In this review, we aim to define the current evidence for the treatment with G-CSF in end-stage liver disease. Several smaller clinical trials in patients with different severity grades of end-stage liver disease have shown that G-CSF improves survival and reduces the rate of complications. Adequately powered multicenter European trials could not confirm these beneficial effects. In mouse models of ACLF, G-CSF increased the toll-like receptor (TLR)-mediated inflammatory response which led to an increase in mortality. Adding a TLR4 signaling inhibitor allowed G-CSF to unfold its proregenerative properties in these ACLF models. These data suggest that G-CSF requires a noninflammatory environment to exert its protective properties.
伴有慢加急性肝衰竭（ACLF）的患者预后极差，治疗选择有限。粒细胞集落刺激因子（G-CSF）可动员免疫和干细胞，并具有免疫调节和促再生能力。在这篇综述中，我们旨在确定 G-CSF 治疗终末期肝病的现有证据。几项较小的临床试验显示，G-CSF 可改善不同严重程度终末期肝病患者的生存率并降低并发症发生率。但规模更大的、多中心的欧洲临床试验未能证实这些有益作用。在 ACLF 小鼠模型中，G-CSF 增加了 Toll 样受体（TLR）介导的炎症反应，导致死亡率增加。添加 TLR4 信号抑制剂可使 G-CSF 在这些 ACLF 模型中发挥其促再生特性。这些数据表明，G-CSF 需要非炎症环境才能发挥其保护特性。
