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己酮可可碱用于酒精性肝炎合并急性肾损伤并不能改善生存率:一项全球研究。

Pentoxifylline use in alcohol-associated hepatitis with acute kidney injury does not improve survival: a global study.

作者信息

Idalsoaga Francisco, Diaz Luis Antonio, Dunn Winston, Mehta Heer, Caldentey Vicente, Arnold Jorge, Ayares Gustavo, Sarin Shiv K, Maiwall Rakhi, Zhang Wei, Qian Steve, Simonetto Douglas, Singal Ashwani K, Elfeki Mohamed A, Khan Mohammad Qasim, Mortuza Rokhsana, Malhi Gurpreet, Islam Alvi Husni, Guizzetti Leonardo, Ramirez-Cadiz Carolina, Cabezas Joaquín, Echavarria Victor, Poca Maria, Cuyas Berta, Soriano German, Ventura Cots Meritxell, Higuera-De La Tijera María Fátima, Abraldes Juan G, Al-Karaghouli Mustafa, Skladaný Lubomir, Havaj Daniel Jan, Rincón Diego, Shah Vijay, Arrese Marco, Kamath Patrick S, Bataller Ramon, Arab Juan Pablo

机构信息

Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile.

Division of Gastroenterology and Hepatology, Western University and London Health Sciences Centre, London, Ontario, Canada.

出版信息

eGastroenterology. 2025 Apr 20;3(2):e100179. doi: 10.1136/egastro-2024-100179. eCollection 2025 Jan.

Abstract

BACKGROUND

Severe alcohol-associated hepatitis (sAH) is a life-threatening condition with high mortality, where corticosteroid use is the only treatment that has shown short-term benefits. Pentoxifylline, an anti-tumour necrosis factor-alpha agent, has been proposed for its potential to improve outcomes, especially in patients with acute kidney injury (AKI). We aimed to evaluate the impact of pentoxifylline on mortality in patients with sAH and AKI in a well-characterised global cohort.

METHODS

We conducted a retrospective, registry-based study including patients meeting the National Institute on Alcohol Abuse and Alcoholism clinical criteria for sAH and AKI. Mortality was the primary endpoint, with liver transplantation as a competing risk. Statistical analysis included Cox regression and Kaplan-Meier survival estimates.

RESULTS

We included 525 patients from 20 centres across eight countries. The median age was 48 years, with 26.1% females, and 76.9% had a history of cirrhosis. Multivariable Cox regression models showed that pentoxifylline use was not associated with survival (HR 1.20, 95% CI 0.85 to 1.69, p=0.291). Factors associated with mortality included age (HR 1.23, 95% CI 1.10 to 1.36, p<0.001), Model for End-Stage Liver Disease score at admission (HR 1.06, 95% CI 1.04 to 1.08, p<0.001) and renal replacement therapy use (HR 1.39, 95% CI 1.05 to 1.84, p=0.019). The main causes of death were multiple organ failure (42%), infections (10%), oesophageal varices bleeding (7%) and renal failure (6%).

CONCLUSION

Pentoxifylline showed no significant benefit on mortality in patients with sAH and AKI. Further studies are needed to refine treatment strategies for this high-risk group.

摘要

背景

严重酒精性肝炎(sAH)是一种危及生命的疾病,死亡率很高,使用皮质类固醇是唯一显示出短期益处的治疗方法。己酮可可碱是一种抗肿瘤坏死因子-α药物,因其有可能改善治疗结果而被提出,特别是在急性肾损伤(AKI)患者中。我们旨在评估己酮可可碱对一个特征明确的全球队列中sAH和AKI患者死亡率的影响。

方法

我们进行了一项基于登记处的回顾性研究,纳入符合美国国立酒精滥用与酒精中毒研究所sAH和AKI临床标准的患者。死亡率是主要终点,肝移植作为竞争风险。统计分析包括Cox回归和Kaplan-Meier生存估计。

结果

我们纳入了来自八个国家20个中心的525名患者。中位年龄为48岁,女性占26.1%,76.9%有肝硬化病史。多变量Cox回归模型显示,使用己酮可可碱与生存无关(风险比1.20,95%置信区间0.85至1.69,p=0.291)。与死亡率相关的因素包括年龄(风险比1.23,95%置信区间1.10至1.36,p<0.001)、入院时终末期肝病模型评分(风险比1.06,95%置信区间1.04至1.08,p<0.001)和使用肾脏替代治疗(风险比1.39,95%置信区间1.05至1.84,p=0.019)。主要死亡原因是多器官功能衰竭(42%)、感染('10%)、食管静脉曲张出血(7%)和肾衰竭(6%)。

结论

己酮可可碱对sAH和AKI患者的死亡率没有显著益处。需要进一步研究以完善针对这一高危群体的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc7f/12020771/cb13d82a60bd/egastro-3-2-g001.jpg

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