Outcome and prognostic markers in severe drug-induced liver disease
Outcome and prognostic markers in severe drug-induced liver disease
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DOI：
10.1002/hep.20800
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发表时间：
2005-08-01
期刊：
影响因子：
13.5
通讯作者：
Olsson, R
中科院分区：
文献类型：
--
作者：
Björnsson, E;Olsson, R
据报道，高转氨酶（肝细胞损伤）和黄疸的组合导致不同药物的死亡率为10%至50%，这种现象称为“海氏法则”。然而，Hy规则从未得到验证，并且关于肝细胞和其他形式药物诱导性肝病结果的预测因素的数据有限。审查了瑞典药物不良反应咨询委员会（1970-2004）收到的所有疑似肝脏药物不良反应报告。分析胆红素水平为正常上限（ULN）2倍或以上的病例。共检索到784例病例-409例为肝细胞损伤，206例为胆汁淤积性损伤，169例为混合性肝损伤。死亡/移植率为9.2%，死亡/移植受者的胆红素（中位数18.7 × ULN [IQR 12.6-25];范围4.5-42）高于存活患者（中位数5：5 × ULN [IQR 3.3-9.51;范围2.0-38）（P < .0001）。胆汁淤积型和混合型死亡率分别为7.8%和2.4%。不同药物的肝细胞损伤死亡率从氟烷的40%（6/15）到红霉素的0%（0/32）不等，总计12.7%。使用logistic回归分析，发现年龄、天冬氨酸转氨酶（AST）和胆红素是肝细胞组死亡或肝移植的独立预测因素，而在胆汁淤积性/混合性肝损伤患者中，胆红素是唯一的独立预测因素。总之，肝细胞性黄疸的死亡率很高，但因药物不同而异。AST和胆红素水平是死亡或肝移植的最重要预测因素。
The combination of high aminotransferases (hepatocellular injury) and jaundice has been reported to lead to a mortality rate of 10 % to 50 % for different drugs, a phenomenon known as "Hy's rule." However, Hy's rule has never been validated, and limited data exist on predictors for outcome in hepatocellular and other forms of drug-induced liver disease. All reports of suspected hepatic adverse drug reactions received by the Swedish Adverse Drug Reactions Advisory Committee (1970-2004) were reviewed. Cases with bilirubin levels 2 or more times the upper limit of normal (ULN) were analyzed. A total of 784 cases were retrieved-409 with hepatocellular injury, 206 with cholestatic injury, and 169 with mixed liver injury. The mortality/transplantation rate was 9.2 %, and bilirubin (median 18.7 X ULN [IQR 12.6-25]; range 4.5-42) was higher (P < .0001) in the deceased/transplant recipients compared with the surviving patients (median 5:5 X ULN [IQR 3.3-9.51; range 2.0-38). A total of 7.8 % with cholestatic and 2.4 % with a mixed pattern died. The mortality rate in hepatocellular injury for different drugs varied from 40 % (6 of 15) for halothane to 0 % (0 of 32) for erythromycin, in total 12.7 %. Using logistic regression analysis, age, aspartate aminotransferase (AST) and bilirubin were found to independently predict death or liver transplantation in the hepatocellular group, whereas among patients with cholestatic/mixed liver injury, bilirubin was the only independent predictor. In conclusion, hepatocellular jaundice has a high but variable mortality rate, depending on the drug involved. The AST and bilirubin levels are the most important predictors of death or liver transplantation.