粒细胞集落刺激因子可改善符合使用类固醇治疗条件的严重酒精性肝炎患者对泼尼松龙的反应及90天生存率：GPreAH研究（一项随机试验）

Granulocyte Colony-Stimulating Factor Improves Prednisolone Responsiveness and 90-Day Survival in Steroid-Eligible Severe Alcohol-Associated Hepatitis: The GPreAH Study a Randomized Trial.

作者信息

Mishra Ajay Kumar, Shasthry Saggere Muralikrishna, Vijayaraghavan Rajan, Kumar Guresh, Sarin Shiv K

机构信息

Department of Hepatology, ILBS, New Delhi, India.

Department of Clinical Research, ILBS, New Delhi, India .

出版信息

Am J Gastroenterol. 2025 May 1;120(5):1087-1097. doi: 10.14309/ajg.0000000000003038. Epub 2024 Aug 20.

DOI:10.14309/ajg.0000000000003038

PMID:39162744

Abstract

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.

摘要

引言

严重酒精性肝炎（SAH）的1个月死亡率很高。由于感染和器官衰竭的发生，皮质类固醇可提供适度的28天生存获益，但无法提供90天生存获益。粒细胞集落刺激因子（GCSF）凭借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）治疗对符合使用类固醇治疗条件的SAH患者的安全性和疗效。

方法

符合使用类固醇治疗条件的SAH患者（判别函数评分32 - 90）被随机分为接受泼尼松龙（A组，n = 42）、GPred（B组，n = 42）或单独使用GCSF（C组，n = 42）。GCSF以150 - 300 mcg/d的剂量给药7天，之后每三天给药一次，1个月内最多给药12剂。泼尼松龙40 mg/d给药7天，对有反应者（ Lille评分<0.45）持续给药28天。

结果

各患者组的基线特征具有可比性。在意向性分析中，泼尼松龙组、GPred组和GCSF组90天生存这一主要终点的实现率分别为64.3%（27/42）、88.1%（37/42）和78.6%（33/42）（P = 0.03，泼尼松龙组与GPred组比较）。各组间28天生存率无差异（分别为85.7%、95.2%和85.7% [P = 0.27]）。到第7天时，GPred组有更多有反应者（分别为71.4%、92.9%和76.2%，P = 0.037），到第90天时判别函数下降幅度更大（-7.33 ± 4.78、-24.59 ± 3.7、-14.59 ± 3.41，P = 0.011），终末期肝病模型钠评分（MELDNa）下降幅度也更大（-1.69 ± 1.26、-7.02 ± 1.24、-3.05 ± 0.83，P = 0.002）。仅使用泼尼松龙的组新感染发生率更高（分别为35.7%、19%、7.1%，P < 0.002）。GPred组急性肾损伤（分别为33.3%、7.1%、11.9%，P = 0.002）、肝性脑病（分别为35.7%、9.5%、26.2%，P = <0.001）和再次住院率（分别为59.5%、14.3%、30.9%，P =<0.01）更低。