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与非法使用合成代谢雄激素类固醇相关的肝毒性的独特表型。

Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids.

作者信息

Robles-Diaz M, Gonzalez-Jimenez A, Medina-Caliz I, Stephens C, García-Cortes M, García-Muñoz B, Ortega-Alonso A, Blanco-Reina E, Gonzalez-Grande R, Jimenez-Perez M, Rendón P, Navarro J M, Gines P, Prieto M, Garcia-Eliz M, Bessone F, Brahm J R, Paraná R, Lucena M I, Andrade R J

机构信息

Servicio de Farmacología Clínica and Unidad de Gestión Clínica (UGC) de Gastroenterología y Hepatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga (UMA), Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.

出版信息

Aliment Pharmacol Ther. 2015 Jan;41(1):116-25. doi: 10.1111/apt.13023. Epub 2014 Nov 13.

Abstract

BACKGROUND

We have observed an increase in hepatotoxicity (DILI) reporting related to the use of anabolic androgenic steroids (AAS) for bodybuilding.

AIM

To characterise phenotype presentation, outcome and severity of AAS DILI.

METHODS

Data on 25 cases of AAS DILI reported to the Spanish (20) and Latin-American (5) DILI Registries were collated and compared with previously published cases.

RESULTS

AAS DILI increased from representing less than 1% of the total cases in the Spanish DILI Registry in the period 2001-2009 to 8% in 2010-2013. Young men (mean age 32 years), requiring hospitalisation, hepatocellular injury and jaundice were predominating features among the AAS cases. AAS DILI caused significantly higher bilirubin values independent of type of damage when compared to other drug classes (P = 0.001). Furthermore, the cholestatic AAS cases presented significantly higher mean peak bilirubin (P = 0.029) and serum creatinine values (P = 0.0002), compared to the hepatocellular cases. In a logistic regression model, the interaction between peak bilirubin values and cholestatic damage was associated with the development of AAS-induced acute kidney impairment (AKI) [OR 1.26 (95% CI: 1.035-1.526); P = 0.021], with 21.5 ×ULN being the best bilirubin cut-off point for predicting AKI risk (AUCROC 0.92). No fatalities occurred.

CONCLUSIONS

Illicit recreational AAS use is a growing cause of reported DILI that can lead to severe hepatic and renal injury. AAS DILI is associated with a distinct phenotype, characterised by considerable bilirubin elevations independent of type of damage. Although hepatocellular injury predominates, acute kidney injury develops in cholestatic cases with pronounced jaundice.

摘要

背景

我们观察到与使用合成代谢雄激素类固醇(AAS)进行健美相关的肝毒性(药物性肝损伤,DILI)报告有所增加。

目的

描述AAS所致DILI的表型表现、结局及严重程度。

方法

整理了向西班牙(20例)和拉丁美洲(5例)DILI登记处报告的25例AAS所致DILI的数据,并与先前发表的病例进行比较。

结果

AAS所致DILI在西班牙DILI登记处占总病例数的比例从2001 - 2009年的不到1%增至2010 - 2013年的8%。年轻男性(平均年龄32岁)、需要住院治疗、肝细胞损伤和黄疸是AAS病例的主要特征。与其他药物类别相比,AAS所致DILI导致的胆红素值显著更高(P = 0.001)。此外,与肝细胞型病例相比,胆汁淤积型AAS病例的平均胆红素峰值(P = 0.029)和血清肌酐值(P = 0.0002)显著更高。在逻辑回归模型中胆红素峰值与胆汁淤积性损伤之间的相互作用与AAS诱导的急性肾损伤(AKI)的发生相关[比值比1.26(95%可信区间:1.035 - 1.526);P = 0.021],21.5倍正常上限值是预测AKI风险的最佳胆红素临界值(曲线下面积0.92)。无死亡病例。

结论

非法使用娱乐性AAS是报告的DILI的一个日益增多的原因,可导致严重的肝和肾损伤。AAS所致DILI与一种独特的表型相关,其特征是无论损伤类型如何胆红素均显著升高。虽然肝细胞损伤占主导,但在黄疸明显的胆汁淤积型病例中会发生急性肾损伤。

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