Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
Liver Int. 2023 Jun;43(6):1298-1306. doi: 10.1111/liv.15534. Epub 2023 Mar 8.
Patients with cirrhosis and treatment non-responsive spontaneous bacterial peritonitis (SBP) have high mortality. We aimed to investigate whether GM-CSF can improve SBP response rates.
In this open-label RCT, 131 cirrhosis patients with difficult-to-treat SBP (DTT SBP) were randomized to receive meropenem alone (1 g IV thrice daily for 5 days) (MERO Group, n = 66) or in combination with GM-CSF (1.5 mcg/Kg daily IV till resolution or till 5d) (MEROGM Group, n = 65). The primary end-point was SBP early-response (reduction in absolute neutrophil count (ANC) by >25% after 48 h). Secondary end-points included SBP resolution at day 5.
Patients in MEROGM group in comparison to MERO group had higher SBP early-response (60% vs. 31.8%; p = .001) and SBP resolution rates (55.4% vs. 24.2%; p = .0003). Patients in the combination arm also had better resolution of pneumonia {8/17 (47.05%) vs. 2/19 (10.5%), p = .02} and lower incidence of new-onset AKI (15.4% vs. 31.8%, p = .02), HE (18.5% vs. 34.8%, p = .04) and infections (21.5% vs. 37.9%, p = .05). In comparison to MERO group, 7-day survival was higher in MEROGM group (89.2% vs. 78.7%, p = .03), though the 28-day survival was comparable (78.4% vs. 71.2%; p = .66). None of the patients developed treatment-related severe adverse effects requiring discontinuation of therapy.
The addition of GM-CSF to meropenem significantly improves response rates in DTT SBP patients within 48 h. Early use of GMCSF modulates host immune response, and enhances antibiotic response with higher SBP resolution. The use of GMCSF needs to be considered in combating difficult SBP in cirrhosis patients.
肝硬化伴治疗无应答自发性细菌性腹膜炎（SBP）患者死亡率较高。我们旨在研究 GM-CSF 是否能提高 SBP 应答率。
在这项开放标签 RCT 中，131 例肝硬化伴难治性 SBP（DTT SBP）患者被随机分为接受美罗培南单药治疗（1 g 静脉滴注，每日 3 次，连用 5 天）（MERO 组，n=66）或联合 GM-CSF 治疗（1.5 mcg/Kg 静脉滴注，直至缓解或连用 5 天）（MEROGM 组，n=65）。主要终点为 SBP 早期应答（48 小时后绝对中性粒细胞计数（ANC）下降>25%）。次要终点包括第 5 天 SBP 缓解。
与 MERO 组相比，MEROGM 组 SBP 早期应答率（60%比 31.8%；p=0.001）和 SBP 缓解率（55.4%比 24.2%；p=0.0003）更高。联合治疗组的肺炎缓解率也更高（8/17 [47.05%]比 2/19 [10.5%]，p=0.02），新发急性肾损伤（AKI）发生率更低（15.4%比 31.8%，p=0.02）、肝性脑病（HE）发生率更低（18.5%比 34.8%，p=0.04）和感染发生率更低（21.5%比 37.9%，p=0.05）。与 MERO 组相比，MEROGM 组 7 天生存率更高（89.2%比 78.7%，p=0.03），但 28 天生存率无差异（78.4%比 71.2%；p=0.66）。没有患者因治疗相关严重不良反应而停止治疗。
在 DTT SBP 患者中，GM-CSF 联合美罗培南可显著提高 48 小时内的应答率。GMCSF 的早期使用可调节宿主免疫反应，增强抗生素反应，提高 SBP 缓解率。在肝硬化患者中，应考虑使用 GM-CSF 来治疗难治性 SBP。
