Severe alcoholic hepatitis (SAH) is often a progressive disease with high mortality and limited steroid responsiveness. Management options of steroid nonresponsive SAH (day 7 Lille score > 0.45) are limited. We assessed the efficacy and safety of granulocyte colony‐stimulating factor (G‐CSF) in steroid nonresponders. A randomized, double‐blind, single‐center trial (NCT01820208) was conducted between March 2013 and June 2016 in patients with histologically proven SAH, nonresponsive to 40 mg/day of prednisolone were randomized to G‐CSF (12 doses, 300 μg each in 28 days) or placebo. Responders were continued with prednisolone. Of the 430 patients with SAH, 132 received steroid therapy. Of these, 33 (25%) were nonresponders and were randomized to G‐CSF or placebo (14 in each group after exclusions). The baseline characteristics of both groups were comparable. The 28‐day mortality was comparable between the groups (21.4%, G‐CSF; 28.6%, placebo; P = 0.69). At 90 days, in the G‐CSF but not in the placebo group, the Model for End‐Stage Liver Disease reduced from 24.6 ± 3.9 to 19.4 ± 3.7 (P = 0.002) and Maddrey’s discriminant function from 74.8 ± 22.8 to 57.4 ± 31 (P = 0.26). Infections were less common (28% versus 71%; P < 0.001) with lower 90‐day mortality (35.7% versus 71.4%; P = 0.04) in the G‐CSF than in the placebo group. On Cox regression analysis, receiving G‐CSF (hazard ratio, 0.37; SD, 0.14‐0.98; P = 0.04), and high baseline serum creatinine (hazard ratio, 4.12; SD, 1.7‐10.3; P = 0.002) predicted day‐90 outcomes in steroid nonresponsive SAH. Patients tolerated G‐CSF without any major adverse events. Conclusion: Approximately one‐quarter of patients with SAH do not respond to corticosteroid therapy. Administration of G‐CSF is safe and helps to reduce the disease severity and 90‐day mortality in these patients.

中文翻译：

---

g-csf 治疗类固醇无反应性重度酒精性肝炎的疗效：一项双盲随机对照试验

严重酒精性肝炎 (SAH) 通常是一种进行性疾病，死亡率高，类固醇反应有限。类固醇无反应性 SAH（第 7 天里尔评分 > 0.45）的管理选择是有限的。我们评估了粒细胞集落刺激因子 (G-CSF) 在类固醇无反应者中的有效性和安全性。2013 年 3 月至 2016 年 6 月期间，在组织学证实的 SAH 患者中进行了一项随机、双盲、单中心试验 (NCT01820208)，将泼尼松龙 40 毫克/天无反应的患者随机分配至 G-CSF（12 剂，每次 300 微克）在 28 天内）或安慰剂。应答者继续使用泼尼松龙。在 430 名 SAH 患者中，132 名接受了类固醇治疗。其中，33 人 (25%) 为无反应者，随机分配至 G-CSF 或安慰剂组（排除后每组 14 人）。两组的基线特征具有可比性。两组之间的 28 天死亡率具有可比性（21.4%，G-CSF；28.6%，安慰剂；P = 0.69）。90 天时，在 G-CSF 而非安慰剂组中，终末期肝病模型从 24.6 ± 3.9 降至 19.4 ± 3.7 (P = 0.002)，Maddrey 判别函数从 74.8 ± 22.8 降至 57.4 ± 31 (P = 0.26)。与安慰剂组相比，G-CSF 感染较少见（28% 对 71%；P < 0.001），90 天死亡率（35.7% 对 71.4%；P = 0.04）较低。在 Cox 回归分析中，接受 G-CSF（风险比，0.37；SD，0.14-0.98；P = 0.04）和高基线血清肌酐（风险比，4.12；SD，1.7-10.3；P = 0.002）预测天数-类固醇无反应性 SAH 的 90 项结果。患者耐受 G-CSF，无任何重大不良事件。结论：大约四分之一的 SAH 患者对皮质类固醇治疗没有反应。G-CSF 的给药是安全的，有助于降低这些患者的疾病严重程度和 90 天死亡率。