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粒细胞集落刺激因子(G-CSF)用于治疗严重酒精性肝炎患者:一项真实世界经验。

G-CSF-In Patients With Severe Alcohol-Associated Hepatitis: A Real-World Experience.

作者信息

Singh Ritu Raj, Chhabra Puneet, Dhillon Sonu

机构信息

University of Illinois College of Medicine, Peoria, Illinois, USA.

Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

出版信息

Liver Int. 2025 Apr;45(4):e16137. doi: 10.1111/liv.16137. Epub 2024 Oct 28.

Abstract

BACKGROUND AND AIMS

Severe alcohol-associated hepatitis (SAH) is associated with high short-term mortality, and failure of response to corticosteroids is associated with a mortality of ~70%-80% within 6 months. Granulocyte colony-stimulating factor (G-CSF) has been studied in steroid non-responders; however, the data are limited.

METHODS

This is a multicentre retrospective cohort study. The study period was from January 2016 to November 2023. SAH was defined as alcohol-associated hepatitis (ICD-10-CM codes) with serum bilirubin ≥ 5.0 mg/dL and INR ≥ 1.5. Other aetiologies of acute hepatitis and biliary obstruction were excluded. The primary outcome was 90-day median overall survival in SAH patients treated with G-CSF compared with standard medical therapy (SMT) or corticosteroids. Propensity score (1:1) matching was performed to control confounding variables.

RESULTS

Among 20 132 patients with SAH, 10800 (53.65%) were treated with corticosteroids and 224 (1.11%) G-CSF. The G-CSF group was younger (45.5 vs. 48.4) White (79.91% vs. 72.40%); however, there was no age or gender difference between G-CSF and corticosteroid groups. Whites and patients with more comorbidities received G-CSF more frequently than SMT or corticosteroids. After propensity score matching, 90-day overall survival was better in patients who received G-CSF (88.31% vs. 62.36%, p < 0.01) compared with SMT or corticosteroids (88.31% vs. 74.39%, p < 0.01). Patients on G-CSF had better 6-month transplant-free survival compared with SMT (83.53% vs. 55.36%, p < 0.001) or corticosteroids (82.89% vs. 60.21%, p < 0.001). Gastrointestinal bleeding was less common in G-CSF group compared with corticosteroids (5.02% vs. 10.50%, p < 0.001).

CONCLUSIONS

A small minority of patients with severe alcohol-associated hepatitis receive G-CSF. G-CSF improves 90-day overall survival in patients with severe alcohol-associated hepatitis and is non-inferior to corticosteroids.

摘要

背景与目的

严重酒精性肝炎(SAH)与短期高死亡率相关,对皮质类固醇治疗无反应者的6个月内死亡率约为70%-80%。已对粒细胞集落刺激因子(G-CSF)在对类固醇无反应者中进行了研究;然而,数据有限。

方法

这是一项多中心回顾性队列研究。研究期间为2016年1月至2023年11月。SAH定义为伴有血清胆红素≥5.0mg/dL和国际标准化比值(INR)≥1.5的酒精性肝炎(ICD-10-CM编码)。排除急性肝炎和胆道梗阻的其他病因。主要结局是与标准药物治疗(SMT)或皮质类固醇相比,接受G-CSF治疗的SAH患者的90天中位总生存率。进行倾向评分(1:1)匹配以控制混杂变量。

结果

在20132例SAH患者中,10800例(53.65%)接受了皮质类固醇治疗,224例(1.11%)接受了G-CSF治疗。G-CSF组患者更年轻(45.5岁对48.4岁),白人比例更高(79.91%对72.40%);然而,G-CSF组与皮质类固醇组之间在年龄或性别上无差异。与SMT或皮质类固醇相比,白人以及合并症更多的患者更频繁地接受G-CSF治疗。倾向评分匹配后,接受G-CSF治疗的患者90天总生存率更高(88.31%对62.36%,p<0.01),而SMT或皮质类固醇组为(88.31%对74.39%,p<0.01)。与SMT(83.53%对55.36%,p<0.001)或皮质类固醇(82.89%对60.21%,p<0.001)相比,接受G-CSF治疗的患者6个月无移植生存率更高。与皮质类固醇组相比,G-CSF组胃肠道出血较少见(5.02%对10.50%,p<0.001)。

结论

一小部分严重酒精性肝炎患者接受G-CSF治疗。G-CSF可提高严重酒精性肝炎患者的90天总生存率,且不劣于皮质类固醇。

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