Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Department of Transfusion Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Hepatol Int. 2022 Oct;16(5):1127-1136. doi: 10.1007/s12072-022-10314-x. Epub 2022 Mar 23.
Liver transplant, the definitive treatment of decompensated cirrhosis (DC), is constrained by donor shortage and long-term complications. Granulocyte colony-stimulating factor (G-CSF) has been explored as an alternative option in open-label studies. This double-blind, randomized, placebo-controlled trial was designed to elucidate the efficacy of G-CSF in DC.
Seventy patients were randomized to either G-CSF plus standard medical therapy (group A, n = 35) or placebo plus standard medical therapy (group B, n = 35). Primary outcome was 12-month overall survival in patients who received at least one cycle of intervention. Secondary outcomes were mobilization of CD34+ cells at day 6, improvement in Child-Turcotte-Pugh (CTP), and model for end-stage liver disease (MELD), liver stiffness measurement, quality of life, nutrition, hepatic decompensation, infection, hospitalization, and acute kidney injury.
Survival in group A was higher than that in Group B although the difference was not statistically significant (87.9% vs 66.7%; p = 0.053). CD34+ cells at day 6 were significantly higher in group A as compared to baseline (p < 0.001). Ascites control (p = 0.03) and CTP score improvement (p = 0.02) were better in group A at 12-months. Encephalopathy episodes (p = 0.005), infections (p = 0.005) were fewer in group A than group B at 12 months. Other secondary outcomes did not improve post-therapy. There were no treatment-related discontinuations or severe adverse events.
G-CSF therapy is safe. The improvement in survival at 12 months is not statistically significant. Better control of ascites, improvement of CTP score, fewer encephalopathy episodes and decreased rate of infections were observed with G-CSF therapy (NCT03911037). Trials Registration NCT03911037.
肝移植是治疗失代偿性肝硬化(DC)的明确方法,但受到供体短缺和长期并发症的限制。粒细胞集落刺激因子(G-CSF)已在开放标签研究中被探索为替代方案。本双盲、随机、安慰剂对照试验旨在阐明 G-CSF 在 DC 中的疗效。
70 名患者被随机分为 G-CSF 加标准药物治疗组(A 组,n=35)或安慰剂加标准药物治疗组(B 组,n=35)。主要结局是接受至少一个周期干预的患者在 12 个月时的总体生存率。次要结局为第 6 天 CD34+细胞的动员、Child-Turcotte-Pugh(CTP)和终末期肝病模型(MELD)评分的改善、肝硬度测量、生活质量、营养状况、肝失代偿、感染、住院和急性肾损伤。
A 组的生存率高于 B 组,但差异无统计学意义(87.9%比 66.7%;p=0.053)。与基线相比,第 6 天 A 组的 CD34+细胞明显更高(p<0.001)。12 个月时,A 组腹水控制(p=0.03)和 CTP 评分改善(p=0.02)更好。12 个月时,A 组脑病发作(p=0.005)和感染(p=0.005)较少。其他次要结局治疗后无改善。无治疗相关停药或严重不良事件。
G-CSF 治疗是安全的。12 个月时的生存率改善无统计学意义。与 G-CSF 治疗相比,腹水控制更好,CTP 评分改善,脑病发作减少,感染发生率降低(NCT03911037)。试验注册 NCT03911037。