Drug-induced liver injury:: An analysis of 461 incidences submitted to the Spanish Registry over a 10-year period
Drug-induced liver injury:: An analysis of 461 incidences submitted to the Spanish Registry over a 10-year period
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DOI：
10.1053/j.gastro.2005.05.006
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发表时间：
2005-08-01
期刊：
影响因子：
29.4
通讯作者：
Martin-Vivaldi, R
中科院分区：
文献类型：
--
作者：
Andrade, RJ;Lucena, MI;Martin-Vivaldi, R
背景和目标：药物性肝损伤（DILI）易感因素的认识和结果的可预测性的进展受到缺乏系统的程序来检测真正的情况。方法：1994年在西班牙建立了一个合作网络，通过前瞻性结构化报告表识别所有DILI疑似病例。根据肝细胞、胆汁淤积和混合实验室标准以及组织学标准（如适用）对肝损伤进行表征。集中进行了因果关系评估的进一步评价。结果：自1994年4月至2004年8月，在提交的570例病例中，有461例被认为与DILI有关，涉及505种药物。抗感染药物组最常见，阿莫西林-克拉维酸占12.8%。肝细胞损害最常见（58%），与年龄呈负相关（P <0.0001），预后最差（考克斯回归，P <0.034）。事实上，如果患者在就诊时有黄疸，肝移植和死亡的发生率为11.7%，而在无黄疸的患者中相应的数字为3.8%（P <0.04）。与暴发性肝功能衰竭发生相关的因素是女性（OR = 25; 95% CI：4.1-151; P < .0001），肝细胞损伤（OR = 7.9; 95% CI：1.6-37; P <0.009）和基线血浆胆红素值较高（OR = 1.15; 95% CI：1.09-1.22; P <0.0001）。结论：药物性肝细胞性黄疸患者有11.7%的机会进展至死亡或移植。阿莫西林-克拉维汀是与DILI相关的最常见药物。
Background & Aims: Progress in the understanding of susceptibility factors to drug-induced liver injury (DILI) and outcome predictability are hampered by the lack of systematic programs to detect bona fide cases. Methods: A cooperative network was created in 1994 in Spain to identify all suspicions of DILI following a prospective structured report form. The liver damage was characterized according to hepatocellular, cholestatic, and mixed laboratory criteria and to histologic criteria when available. Further evaluation of causality assessment was centrally performed. Results: Since April 1994 to August 2004, 461 out of 570 submitted cases, involving 505 drugs, were deemed to be related to DILI. The antiinfective group of drugs was the more frequently incriminated, amoxicillin-clavulanate accounting for the 12.8% of the whole series. The hepatocellular pattern of damage was the most common (58%), was inversely correlated with age (P < .0001), and had the worst outcome (Cox regression, P < .034). Indeed, the incidence of liver transplantation and death in this group was 11.7% if patients had jaundice at presentation, whereas the corresponding figure was 3.8% in non-jaundiced patients (P < .04). Factors associated with the development of fulminant hepatic failure were female sex (OR = 25; 95% Cl: 4.1-151; P < .0001), hepatocellular damage (OR = 7.9; 95% Cl: 1.6-37; P < .009), and higher baseline plasma bilirubin value (OR = 1.15; 95% Cl: 1.09-1.22; P < .0001). Conclusions: Patients with drug-induced hepatocellular jaundice have 11.7% chance of progressing to death or transplantation. Amoxicillin-clavulanate stands out as the most common drug related to DILI.