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美国药物性急性肝衰竭肝移植的结局:器官共享联合网络数据库分析

Outcome of liver transplantation for drug-induced acute liver failure in the United States: analysis of the United Network for Organ Sharing database.

作者信息

Mindikoglu Ayse L, Magder Laurence S, Regev Arie

机构信息

Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201-1595, USA.

出版信息

Liver Transpl. 2009 Jul;15(7):719-29. doi: 10.1002/lt.21692.

Abstract

Acute liver failure (ALF) is an uncommon but potentially lethal drug-related adverse effect that often leads to liver transplantation (LT) or death. A retrospective cohort study was performed with the United Network for Organ Sharing Standard Transplant Analysis and Research files. Recipients who underwent LT for drug-induced acute liver failure (DIALF) from 1987 through 2006 were analyzed. A total of 661 patients transplanted for DIALF were included in the analysis. The 4 leading implicated drug groups were acetaminophen (n = 265; 40%), antituberculosis drugs (n = 50; 8%), antiepileptics (n = 46; 7%), and antibiotics (n = 39; 6%). One-year estimated survival probabilities were 76%, 82%, 52%, 82%, and 79% for acetaminophen, antituberculosis drugs, antiepileptics, antibiotics, and others, respectively. The lower rate of survival among those exposed to antiepileptics was observed mainly in children. Of the 22 patients less than 18 years old who had ALF due to antiepileptics, 73% died within the first year. The difference in overall survival between acetaminophen-related and non-acetaminophen-related ALF was not statistically significant. Patients with acetaminophen-related ALF required dialysis prior to LT at a significantly higher rate than all other drug groups (27% versus 3%-10%, P < 0.0001). According to Cox proportional hazards regression analysis, the independent pretransplant predictors of death after LT were being on life support, DIALF due to antiepileptic drugs at age less than 18, and elevated serum creatinine. In conclusion, the leading drug groups causing LT due to DIALF in the United States were acetaminophen, antituberculosis drugs, antiepileptics, and antibiotics. Children who had ALF due to antiepileptics had a substantially higher risk of death after LT in comparison with other drugs. Patients transplanted for acetaminophen-related ALF required dialysis at a significantly higher rate. Being on life support, DIALF due to antiepileptics (at age less than 18), and elevated serum creatinine were independent pretransplant predictors of poor survival after LT for DIALF.

摘要

急性肝衰竭(ALF)是一种罕见但可能致命的药物相关不良反应,常导致肝移植(LT)或死亡。我们利用器官共享联合网络的标准移植分析和研究文件进行了一项回顾性队列研究。对1987年至2006年因药物性急性肝衰竭(DIALF)接受肝移植的受者进行了分析。共有661例因DIALF接受移植的患者纳入分析。4个主要相关药物组分别为对乙酰氨基酚(n = 265;40%)、抗结核药物(n = 50;8%)、抗癫痫药物(n = 46;7%)和抗生素(n = 39;6%)。对乙酰氨基酚、抗结核药物、抗癫痫药物、抗生素及其他药物导致的DIALF患者1年估计生存概率分别为76%、82%、52%、82%和79%。抗癫痫药物导致的DIALF患者生存率较低主要见于儿童。在22例因抗癫痫药物导致ALF的18岁以下患者中,73%在第一年内死亡。对乙酰氨基酚相关和非对乙酰氨基酚相关ALF患者的总体生存率差异无统计学意义。与所有其他药物组相比,对乙酰氨基酚相关ALF患者在肝移植前需要透析的比例显著更高(27%对3%-10%,P < 0.0001)。根据Cox比例风险回归分析,肝移植后死亡的独立移植前预测因素为接受生命支持、18岁以下因抗癫痫药物导致的DIALF以及血清肌酐升高。总之,在美国,导致因DIALF进行肝移植的主要药物组为对乙酰氨基酚、抗结核药物、抗癫痫药物和抗生素。与其他药物相比,因抗癫痫药物导致ALF的儿童肝移植后死亡风险显著更高。对乙酰氨基酚相关ALF患者接受肝移植时需要透析的比例显著更高。接受生命支持、18岁以下因抗癫痫药物导致的DIALF以及血清肌酐升高是因DIALF进行肝移植后生存不良的独立移植前预测因素。

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