药物性肝损伤：对提交至西班牙登记处的10年间461例病例的分析。

Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period.

作者信息

Andrade Raúl J, Lucena M Isabel, Fernández M Carmen, Pelaez Gloria, Pachkoria Ketevan, García-Ruiz Elena, García-Muñoz Beatriz, González-Grande Rocio, Pizarro Angeles, Durán José Antonio, Jiménez Manuel, Rodrigo Luis, Romero-Gomez Manuel, Navarro José María, Planas Ramón, Costa Joan, Borras Africa, Soler Aina, Salmerón Javier, Martin-Vivaldi Rafael

机构信息

Unidad de Hepatología y Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Coordinating Centre, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain.

出版信息

Gastroenterology. 2005 Aug;129(2):512-21. doi: 10.1016/j.gastro.2005.05.006.

DOI:10.1016/j.gastro.2005.05.006

PMID:16083708

Abstract

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 nonjaundiced patients (P < .04). Factors associated with the development of fulminant hepatic failure were female sex (OR = 25; 95% CI: 4.1-151; P < .0001), hepatocellular damage (OR = 7.9; 95% CI: 1.6-37; P < .009), and higher baseline plasma bilirubin value (OR = 1.15; 95% CI: 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.

摘要

背景与目的

由于缺乏用于检测确诊病例的系统性方案，药物性肝损伤（DILI）易感性因素的认识进展及预后可预测性受到阻碍。

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来识别所有DILI疑似病例。根据肝细胞性、胆汁淤积性和混合性实验室标准以及可用时的组织学标准对肝损伤进行特征描述。因果关系评估的进一步评估由中心进行。

结果

从1994年4月至2004年8月，提交的570例病例中有461例（涉及505种药物）被认为与DILI有关。抗感染药物组是最常被归咎的，阿莫西林 - 克拉维酸占整个系列的12.8%。肝细胞损伤模式最为常见（58%），与年龄呈负相关（P <.0001），且预后最差（Cox回归，P <.034）。实际上，如果患者就诊时出现黄疸，该组肝移植和死亡的发生率为11.7%，而无黄疸患者的相应数字为3.8%（P <.04）。与暴发性肝衰竭发生相关的因素为女性（OR = 25；95% CI：4.1 - 151；P <.0001）、肝细胞损伤（OR = 7.9；95% CI：1.6 - 37；P <.009）以及更高的基线血浆胆红素值（OR = 1.15；95% CI：1.09 - 1.22；P <.0001）。