G-CSF 治疗失代偿期肝病：一把双刃剑？

StephenW

社论
    开放存取
    发布时间：2022 年 9 月 2 日

G-CSF 治疗失代偿期肝病：一把双刃剑？

    科尼利厄斯·恩格尔曼和托马斯·伯格

Hepatology International 第 16 卷，第 979–982 页（2022 年）引用这篇文章

    297 次访问

    指标详情

粒细胞集落刺激因子 (G-CSF) 具有再生和免疫调节特性，因此对晚期肝病患者来说是一种有吸引力的治疗方法。几乎没有任何物质在终末期肝病中提供了与 G-CSF 类似的显着结果，因此它已经被认为是这些患者可能的标准疗法。 Garg 等人于 2012 年发表。在一项针对总共 47 名患者的小型单中心试验中显示，给予 G-CSF 的剂量为 5 µg/kg s.c.在 26 天内进行 12 次注射可将慢加急性肝衰竭 (ACLF) 患者的 60 天生存率从约 30% 提高到近 70% [1]。治疗成功归因于免疫细胞功能的改善、感染并发症的减少以及肝脏中 CD34+ 干细胞数量的增加，这可能有助于其从损伤中恢复。在急性酒精性肝炎 [2, 3] 或失代偿期肝硬化 [4, 5] 患者的进一步研究中研究 G-CSF 的效果时，显示出相当的存活率改善。在严重急性酒精性肝炎中，当患者接受 G-CSF（剂量为 10 µg/kg/天）治疗时，90 天死亡率从标准护理后的 70% 以上下降至约 20%中心试验和两项研究中的 G-CSF 治疗导致严重感染减少 [2, 3]。即使在不显示 ACLF 特征的失代偿期肝硬化中，G-CSF 的短期治疗已在几项随机试验中证明了其改善患者生存率的潜力 [4, 5]。其中，两项研究特别值得一提，因为它们招收了大量患者。普拉贾帕蒂等人。共有 253 名患者随机接受短期高剂量 G-CSF 治疗（300 µg，每天两次，为期 5 天）或标准药物治疗。给予 G-CSF 后 79% 的累积 6 个月生存率显着高于标准药物治疗后的 68% (p = 0.025)，后者因严重感染导致更多死亡 [5]。德等人。试图通过对失代偿期肝硬化患者应用长期 G-CSF 治疗，以 5 天为周期，每 3 个月给予一次，共 12 个月，以最大限度地提高治疗效果。 G-CSF 显着改善了病程，12 个月生存率提高了 74%，而对照组为 42% (p < 0.001)，感染发作次数减少 [4]。

StephenW

Editorial
    Open Access
    Published: 02 September 2022

G-CSF treatment in decompensated liver disease: a double-edged sword?

    Cornelius Engelmann & Thomas Berg

Hepatology International volume 16, pages 979–982 (2022)Cite this article

    297 Accesses

    Metrics details

Granulocyte colony-stimulating factor (G-CSF) exhibits regenerative and immunomodulatory properties, therefore, representing an attractive therapeutic approach for patients with advanced liver disease. There was almost no substance that has provided similarly remarkable results in end-stage liver disease as G-CSF, and consequently it was already considered a possible standard therapy for these patients. Published in 2012, Garg et al. showed in a small single-center trial with in total of 47 patients that the administration of G-CSF with a dose of 5 µg/kg s.c. and 12 injections over a period of 26 days improved the 60-day survival of patients with acute-on-chronic liver failure (ACLF) from about 30% to almost 70% [1]. The treatment success was attributed to an improved immune cell function, fewer infectious complications as well as higher numbers of CD34+ stem cells in the liver potentially facilitating its recovery from injury. A comparable improvement in survival was shown when the effect of G-CSF was investigated in further studies either in patients with acute alcoholic hepatitis [2, 3] or with decompensated cirrhosis [4, 5]. In severe acute alcoholic hepatitis, the 90-day mortality rate declined from more than 70% after standard of care to about 20% when patients were treated with G-CSF (with a dose of 10 µg/kg/day) in two randomised single-center trials and in both studies G-CSF therapy resulted in fewer severe infections [2, 3]. Even in decompensated cirrhosis that does not show features of ACLF, short-term therapy with G-CSF has demonstrated its potential on improving patients’ survival in several randomised trials [4, 5]. Among them, two studies are especially worth mentioning as they enrolled a high number of patients. Prajapati et al. randomized in total of 253 patients to receive either a short term, high-dose G-CSF therapy (300 µg twice daily over a period of 5 days) or standard medical therapy. The cumulative 6-month survival of 79% when G-CSF was given was significantly higher than 68% (p = 0.025) after standard medical therapy with more deaths caused by a severe infection in the latter group [5]. De et al. tried to maximise the therapeutic effect by applying long-term G-CSF therapy given every 3 months in 5 days cycles for a total of 12 months to patients with decompensated liver cirrhosis. G-CSF improved substantially the disease course with an increased 12-month survival of 74% compared to 42% in the control group (p < 0.001) and fewer episodes of infections [4].

StephenW

https://link.springer.com/conten ... 072-022-10379-8.pdf