Abstract：
GCSF may improve the prognosis of severe liver disease by promoting liver regeneration and immune restoration. Our Aim was to investigate its controversial efficacy in decompensated cirrhosis, acute alcoholic hepatitis (AAH), or acute-on-chronic liver failure (ACLF) through meta-analysis.
Meta-analysis of proportions (random effect model) including 19 RCTs (1287 patients from 16 Asian and 3 European studies including 487 ACLF, 231 AAH and 569 cirrhotic patients) evaluating survival at day-28, day-90, 6 months, one year, and/or occurrence of sepsis as major outcomes.
In patients with decompensated cirrhosis, G-CSF administration was associated with a reduction in the weight-adjusted risk of mortality of 9% at day-90 (OR=0.33; 95%CI: 0.18-0.58; p = 0.0002), 16% at 6 months (OR=0.31; 95%CI: 0.15-0.62; p = 0.0009), 26% at one year (OR=0.21; 95%CI:0.12-0.38, p<0.0001) and a weight-adjusted 28% risk reduction for sepsis (OR=0.28; 95%CI: 0.16-0.49; p<0.0001). Only Asian studies were positive. In AAH, G-CSF was associated with an 18% reduction in weight-adjusted mortality risk at day-28 (OR=0.31; 95%CI:0.11-0.83, p = 0.021), 32% at day-90 (OR=0.20; 95%CI:0.09-0.46, p<0.0001) and a weight-adjusted 42% risk reduction for sepsis (OR=0.17; 95%CI: 0.08-0.38; p<0.0001). Only Asian studies, in which corticosteroids were not given systematically in case of severe AAH, were positive. In patients with ACLF, the results on mortality at day-28 were heterogeneous, and GCSF had no beneficial effect on sepsis or survival at day-90.
G-CSF may be effective in patients with decompensated cirrhosis or AAH by reducing the occurrence of sepsis and mortality. Further meta-analyses of individual data, or new, powerful and methodologically flawless therapeutic trials, are warranted to confirm these results, which harbor wide divergences between Asian and European RCTs.
Meta-analysis of proportions (random effect model) including 19 RCTs (1287 patients from 16 Asian and 3 European studies including 487 ACLF, 231 AAH and 569 cirrhotic patients) evaluating survival at day-28, day-90, 6 months, one year, and/or occurrence of sepsis as major outcomes.
In patients with decompensated cirrhosis, G-CSF administration was associated with a reduction in the weight-adjusted risk of mortality of 9% at day-90 (OR=0.33; 95%CI: 0.18-0.58; p = 0.0002), 16% at 6 months (OR=0.31; 95%CI: 0.15-0.62; p = 0.0009), 26% at one year (OR=0.21; 95%CI:0.12-0.38, p<0.0001) and a weight-adjusted 28% risk reduction for sepsis (OR=0.28; 95%CI: 0.16-0.49; p<0.0001). Only Asian studies were positive. In AAH, G-CSF was associated with an 18% reduction in weight-adjusted mortality risk at day-28 (OR=0.31; 95%CI:0.11-0.83, p = 0.021), 32% at day-90 (OR=0.20; 95%CI:0.09-0.46, p<0.0001) and a weight-adjusted 42% risk reduction for sepsis (OR=0.17; 95%CI: 0.08-0.38; p<0.0001). Only Asian studies, in which corticosteroids were not given systematically in case of severe AAH, were positive. In patients with ACLF, the results on mortality at day-28 were heterogeneous, and GCSF had no beneficial effect on sepsis or survival at day-90.
G-CSF may be effective in patients with decompensated cirrhosis or AAH by reducing the occurrence of sepsis and mortality. Further meta-analyses of individual data, or new, powerful and methodologically flawless therapeutic trials, are warranted to confirm these results, which harbor wide divergences between Asian and European RCTs.
摘要：
背景：GCSF可能通过促进肝脏再生和免疫恢复来改善严重肝病的预后。我们的目的是调查其在失代偿期肝硬化中的有争议的疗效，急性酒精性肝炎（AAH），或慢性急性肝衰竭（ACLF）通过荟萃分析。
方法：包括19项RCT的比例（随机效应模型）的荟萃分析（来自16项亚洲和3项欧洲研究的1287例患者，包括487项ACLF，231AAH和569例肝硬化患者）评估第28天，第90天，6个月的生存率，一年,和/或以败血症为主要结果。
结果：在失代偿期肝硬化患者中，G-CSF给药与90天体重调整后死亡风险降低9%相关(OR=0.33;95CI:0.18-0.58;p=0.0002),6个月时为16％（OR=0.31；95CI：0.15-0.62；p=0.0009），1年为26%(OR=0.21;95CI:0.12-0.38,p<0.0001),体重调整后脓毒症风险降低28%(OR=0.28;95CI:0.16-0.49;p<0.0001)。只有亚洲研究是积极的。在AAH,G-CSF与第28天体重调整后的死亡风险降低18%相关(OR=0.31;95CI:0.11-0.83,p=0.021),90天时32%(OR=0.20;95CI:0.09-0.46,p<0.0001),体重调整后脓毒症风险降低42%(OR=0.17;95CI:0.08-0.38;p<0.0001)。只有亚洲研究，在严重AAH的情况下，没有系统地给予皮质类固醇，是积极的。在ACLF患者中，第28天死亡率的结果是异质的，GCSF在第90天对脓毒症或存活没有有益作用。
结论：G-CSF可有效降低失代偿期肝硬化或AAH患者败血症的发生率和死亡率。个人数据的进一步荟萃分析，或新的，强大且方法完美的治疗试验，有必要确认这些结果，亚洲和欧洲RCT之间存在很大差异。
方法：包括19项RCT的比例（随机效应模型）的荟萃分析（来自16项亚洲和3项欧洲研究的1287例患者，包括487项ACLF，231AAH和569例肝硬化患者）评估第28天，第90天，6个月的生存率，一年,和/或以败血症为主要结果。
结果：在失代偿期肝硬化患者中，G-CSF给药与90天体重调整后死亡风险降低9%相关(OR=0.33;95CI:0.18-0.58;p=0.0002),6个月时为16％（OR=0.31；95CI：0.15-0.62；p=0.0009），1年为26%(OR=0.21;95CI:0.12-0.38,p<0.0001),体重调整后脓毒症风险降低28%(OR=0.28;95CI:0.16-0.49;p<0.0001)。只有亚洲研究是积极的。在AAH,G-CSF与第28天体重调整后的死亡风险降低18%相关(OR=0.31;95CI:0.11-0.83,p=0.021),90天时32%(OR=0.20;95CI:0.09-0.46,p<0.0001),体重调整后脓毒症风险降低42%(OR=0.17;95CI:0.08-0.38;p<0.0001)。只有亚洲研究，在严重AAH的情况下，没有系统地给予皮质类固醇，是积极的。在ACLF患者中，第28天死亡率的结果是异质的，GCSF在第90天对脓毒症或存活没有有益作用。
结论：G-CSF可有效降低失代偿期肝硬化或AAH患者败血症的发生率和死亡率。个人数据的进一步荟萃分析，或新的，强大且方法完美的治疗试验，有必要确认这些结果，亚洲和欧洲RCT之间存在很大差异。
