■已提出将粒细胞集落刺激因子(G-CSF)治疗作为重度酒精性肝炎(AH)患者的治疗选择。这项研究的目的是合成有关G-CSF在AH中功效的可用证据。
■这是一项评估90天死亡风险和感染风险的随机对照试验的荟萃分析。
■纳入了7项研究。在总共396名患者中,336有AH,197例患者接受G-CSF治疗,199人接受安慰剂或己酮可可碱。在总体荟萃分析中,G-CSF治疗与90天死亡风险降低相关(比值比[OR]0.28;95%CI0.09-0.88;p=0.03)。研究之间存在高度异质性(p<0.001;I2=80%)。在亚洲进行了五项研究,在欧洲进行了两项研究。在亚洲进行的研究的亚组分析中,G-CSF与死亡风险降低相关(OR0.15;95%CI0.08-0.28;p<0.001;异质性:p=0.5,I2=0%)。在欧洲研究中,与对照组相比,G-CSF倾向于增加死亡率,尽管差异不显著(OR1.89;95%CI0.90-3.98;p=0.09;异质性:p=0.8,I2=0%)。在亚洲研究中,G-CSF患者的感染发生率低于对照组(OR0.12;95%CI0.06-0.23;p<0.001;异质性:p=0.7,I2=0%),而在欧洲研究中,该发生率无统计学差异(OR0.92;95%CI0.50-1.68;p=0.78;异质性:p=0.5,I2=0%).在敏感性分析中,不包括AH以外的慢性急性肝衰竭(ACLF)患者的研究,不太严重的AH患者,或对皮质类固醇无反应的患者,结果与总体分析相似,死亡率和感染的发生。
■粒细胞集落刺激因子治疗可改善重症AH患者的预后。然而,由于在亚洲和欧洲研究之间相互矛盾的结果引起的整体分析中观察到的高度异质性,G-CSF目前不能推荐用于AH,尤其是在欧洲。这些差异是否可以通过种族差异或患者选择和疾病严重程度的差异来解释,目前尚不清楚。
■这项荟萃分析的主要发现是,与未接受该疗法的对照组相比,使用粒细胞集落刺激因子(G-CSF)可使酒精性肝炎(AH)患者在3个月时的死亡率降低70%以上。然而,由于在亚洲和欧洲研究之间相互矛盾的结果引起的整体分析中观察到的高度异质性,G-CSF目前不能推荐用于AH患者,尤其是在欧洲。这些差异是否可以通过种族差异或患者选择和疾病严重程度的差异来解释,目前尚不清楚。
UNASSIGNED: Granulocyte colony-stimulating factor (G-CSF) treatment has been proposed as a therapeutic option for patients with severe alcoholic hepatitis (AH). The aim of this study was to synthesise available evidence on the efficacy of G-CSF in AH.
UNASSIGNED: This is a meta-analysis of randomised controlled trials evaluating the risk of death at 90 days and the risk of infection.
UNASSIGNED: Seven studies were included. Of a total of 396 patients, 336 had AH, 197 patients were treated with G-CSF, and 199 received placebo or pentoxifylline. In overall meta-analysis, G-CSF therapy was associated with a reduced risk of death at 90 days (odds ratio [OR] 0.28; 95% CI 0.09-0.88; p = 0.03). There was high heterogeneity between studies (p <0.001; I 2 = 80%). Five studies were performed in Asia and 2 in Europe. In the subgroup analysis of studies performed in Asia, G-CSF was associated with a reduced risk of death (OR 0.15; 95% CI 0.08-0.28; p <0.001; heterogeneity: p = 0.5, I 2 = 0%). In European studies, G-CSF tended to increase mortality compared with controls, although the difference was not significant (OR 1.89; 95% CI 0.90-3.98; p = 0.09; heterogeneity: p = 0.8, I 2 = 0%). In Asian studies, occurrence of infection was less frequent in G-CSF patients than in controls (OR 0.12; 95% CI 0.06-0.23; p <0.001; heterogeneity: p = 0.7, I 2 = 0%), whilst in European studies, this occurrence was not statistically different (OR 0.92; 95% CI 0.50-1.68; p = 0.78; heterogeneity: p = 0.5, I 2 = 0%). In sensitivity analyses, excluding studies that included patients with acute-on-chronic liver failure (ACLF) other than AH, patients with less severe AH, or patients with non-response to corticosteroids, results were similar to those of overall analyses, both for mortality and occurrence of infection.
UNASSIGNED: Granulocyte colony-stimulating factor therapy may improve the prognosis of patients with severe AH. However, owing to the high heterogeneity observed in the overall analysis caused by conflicting results between the Asian and European studies, G-CSF cannot currently be recommended for AH, particularly in Europe. Whether these differences can be explained by ethnic differences or disparities in patient selection and disease severity remains unclear.
UNASSIGNED: The main finding of this meta-analysis is that the use of granulocyte colony-stimulating factor (G-CSF) is associated with a mortality reduction of more than 70% at 3 months amongst patients with alcoholic hepatitis (AH) compared with controls who did not receive this therapy. However, owing to the high heterogeneity observed in the overall analysis caused by conflicting results between the Asian and European studies, G-CSF cannot currently be recommended for patients with AH, particularly in Europe. Whether these differences can be explained by ethnic differences or disparities in patient selection and disease severity remains unclear.