Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Madrid, Spain; Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.
Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Madrid, Spain.
Gastroenterol Hepatol. 2023 May;46(5):350-359. doi: 10.1016/j.gastrohep.2022.09.007. Epub 2022 Sep 27.
A dysfunctional immune response is key to the pathogenesis of acute-on-chronic liver failure (ACLF). It has been suggested that treatment with granulocyte colony-stimulating factor (G-CSF) increases survival in patients with ACLF by improving immune cell dysfunction and promoting liver regeneration. The aim of the study is to evaluate the survival benefit associated with G-CSF administration compared with standard medical therapy (SMT) in ACLF.
Systematic review and meta-analysis of randomized controlled trials. The primary outcome was survival at 60-90 days. We searched Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to August 2021. Manual searches of reference lists in relevant articles and conference proceedings were also included. The revised Cochrane risk-of-bias tool was used for quality and risk of bias assessment. Two independent investigators extracted the data, and disagreements were solved by a third collaborator.
The initial search identified 142 studies. Four randomized controlled trials were selected for quantitative analysis including 310 patients (154 G-CSF and 156 SMT). Significant heterogeneity was observed (I=74%, Chi=11.57, p=0.009). G-CSF administration did not improve survival in patients with ACLF (random-effects model, risk ratio=0.64 [95% CI 0.39, 1.07]). However, when considering only the results from the studies performed in Asia, a significant decrease on mortality was observed (risk ratio=0.53 [95% CI 0.35, 0.81]). Severity scores (MELD and Child) and CD34+ peripheral cells mobilization did not significantly improve with G-CSF.
In a systematic review and meta-analysis, G-CSF administration did not significantly improve overall survival compared to SMT in patients with ACLF. The beneficial effects observed in Asian studies, as opposed to the European region, suggest that specific populations may benefit from further research aiming to identify certain subgroups with favourable outcomes when using G-CSF.
免疫功能紊乱是导致慢加急性肝衰竭（ACLF）发病机制的关键。有研究表明，粒细胞集落刺激因子（G-CSF）治疗通过改善免疫细胞功能障碍和促进肝再生，可提高 ACLF 患者的生存率。本研究旨在评估与标准药物治疗（SMT）相比，G-CSF 给药在 ACLF 中的生存获益。
系统评价和随机对照试验的荟萃分析。主要结局为 60-90 天的生存率。我们从 Ovid Medline、EMBASE 和 Cochrane 对照试验中心注册库中检索了从建库到 2021 年 8 月的文献。还包括相关文章和会议论文集的参考文献列表的手工检索。使用修订后的 Cochrane 偏倚风险工具进行质量和偏倚风险评估。两名独立的研究者提取数据，如有分歧则由第三位合作者解决。
初步检索确定了 142 项研究。四项随机对照试验被选入定量分析，共纳入 310 例患者（G-CSF 组 154 例，SMT 组 156 例）。观察到显著的异质性（I=74%，Chi=11.57，p=0.009）。G-CSF 治疗并未改善 ACLF 患者的生存率（随机效应模型，风险比=0.64[95%CI 0.39，1.07]）。然而，当仅考虑在亚洲进行的研究结果时，死亡率显著下降（风险比=0.53[95%CI 0.35，0.81]）。G-CSF 并未显著改善严重程度评分（MELD 和 Child）和 CD34+外周细胞动员。
在系统评价和荟萃分析中，与 SMT 相比，G-CSF 治疗并未显著提高 ACLF 患者的总体生存率。在亚洲研究中观察到的有益效果，与欧洲地区相反，表明特定人群可能受益于进一步的研究，旨在确定使用 G-CSF 时具有良好结局的特定亚组。
