Mishra Ajay Kumar, Shasthry Saggere Muralikrishna, Vijayaraghavan Rajan, Kumar Guresh, Sarin Shiv K
Department of Hepatology, ILBS, New Delhi, India.
Department of Clinical Research, ILBS, New Delhi, India .
Am J Gastroenterol. 2025 May 1;120(5):1087-1097. doi: 10.14309/ajg.0000000000003038. Epub 2024 Aug 20.
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.
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).
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.
Addition of GCSF to prednisolone improves steroid responsiveness and 90-day survival with fewer infections and new onset complications in patients with SAH.
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。
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。
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。
在泼尼松龙中添加GCSF可提高类固醇反应性和90天生存率，且SAH患者的感染和新发并发症更少。
