INTRODUCTION Severe alcohol-associated hepatitis (SAH) carries high 1-month mortality. Corticosteroids provide a modest 28-day but not 90-day survival benefit, due to development of infections and organ failures. Granulocyte colony-stimulating factor (GCSF) has shown promise in patients with SAH by its immunomodulatory and regenerative capabilities. We studied the safety and efficacy of combination (GCSF + prednisolone, GPred) therapy in management of steroid-eligible patients with SAH. METHODS Steroid eligible patients with SAH (discriminant function scores 32-90) were randomized to receive prednisolone (GrA, n = 42), GPred (GrB, n = 42), or GCSF alone (GrC, n = 42). GCSF was given as 150-300 mcg/d for 7 days followed by every third day for a maximum of 12 doses in 1 month. Prednisolone 40 mg/d was given for 7 days and continued for 28 days in responders (Lille score <0.45). RESULTS Baseline characteristics of patient groups were comparable. On intention-to-treat analysis, the primary endpoint of 90-day survival was achieved in 64.3% (27/42) in prednisolone, 88.1% (37/42) in GPred, and 78.6%(33/42) in GCSF groups, respectively ( P = 0.03, prednisolone vs GPred). The 28-day survival was not different between the groups (85.7%, 95.2%, and 85.7%, respectively [ P = 0.27]). The GPred group had more responders by day 7 (71.4% vs 92.9% vs 76.2%, P = 0.037) and had greater reduction in discriminant function (-7.33 ± 4.78, -24.59 ± 3.7, -14.59 ± 3.41, P = 0.011) and MELDNa (-1.69 ± 1.26, -7.02 ± 1.24, -3.05 ± 0.83, P = 0.002) by day 90. The prednisolone-only group had higher incidence of new infections (35.7%, 19%, 7.1%, respectively, P < 0.002). Acute kidney injury (33.3%, 7.1%, 11.9%, P = 0.002), hepatic encephalopathy (35.7%, 9.5%, 26.2%, P = <0.001), and rehospitalizations (59.5%, 14.3%, 30.9%, P =<0.01) were lower in the GPred group. CONCLUSION Addition of GCSF to prednisolone improves steroid responsiveness and 90-day survival with fewer infections and new onset complications in patients with SAH.

中文翻译：

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粒细胞集落刺激因子可改善符合类固醇条件的严重酒精相关性肝炎的泼尼松龙反应性和 90 天生存率：GPreAH 研究 一项随机试验。


引言 重度酒精相关性肝炎 （SAH） 的 1 个月死亡率很高。由于感染和器官衰竭的发展，皮质类固醇提供适度的 28 天生存获益，但不是 90 天。粒细胞集落刺激因子 （GCSF） 通过其免疫调节和再生能力在 SAH 患者中显示出前景。我们研究了联合 （GCSF + 泼尼松龙，GPred） 治疗符合类固醇条件的 SAH 患者治疗的安全性和有效性。方法 符合类固醇条件的 SAH 患者 （判别功能评分 32-90） 随机接受泼尼松龙 （GrA， n = 42） 、 GPred （GrB， n = 42） 或单独接受 GCSF （GrC， n = 42）。GCSF 以 150-300 mcg/d 给药 7 天，然后每 3 天给药一次，在 1 个月内最多 12 剂。反应者给予泼尼松龙 40 mg/d 7 天，持续 28 天 （Lille 评分 <0.45）。结果 患者组的基线特征具有可比性。在意向治疗分析中，泼尼松龙组达到 90 天生存率的主要终点分别为 64.3% （27/42）、GPred 和 78.6%（33/42） （P = 0.03，泼尼松龙 vs GPred）。两组之间的 28 天生存率没有差异 （分别为 85.7% 、 95.2% 和 85.7% [ P = 0.27]）。到第 7 天 （71.4% vs 92.9% vs 76.2%，P = 0.037） 时，GPred 组有更多的反应者 （-7.33 vs 92.9% vs 76.2%，P = 0.037），判别函数 （-7.33 ± 4.78， -24.59 ± 3.7， -14.59 ± 3.41， P = 0.011） 和 MELDNa （-1.69 ± 1.26， -7.02 ± 1.24， -3.05 ± 0.83， P = 0.002） 降低幅度更大。单用泼尼松龙组新发感染发生率较高 （分别为 35.7% 、 19% 、 7.1%，P < 0.002）。急性肾损伤 （33.3%， 7.1%， 11.9%， P = 0.002）， 肝性脑病 （35.7%， 9.5%， 26.2%， P = <0.001） 和再住院 （59.5% 、 14.3% 、 30.9% 、 P =<0.01） 在 GPred 组中较低。结论 在泼尼松龙中加入 GCSF 可提高类固醇反应性和 90 天生存率，减少 SAH 患者的感染和新发并发症。