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利用对乙酰氨基酚-半胱氨酸加合物证实对乙酰氨基酚在不明原因急性肝衰竭中的致病作用。

Confirming the Causative Role of Acetaminophen in Indeterminate Acute Liver Failure Using Acetaminophen-Cysteine Adducts.

作者信息

Frey Sean M, Wiegand Timothy J, Green Jody L, Heard Kennon J, Wilkins Diana G, Gorodetsky Rachel M, Dart Richard C

机构信息

Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.

出版信息

J Med Toxicol. 2015 Jun;11(2):218-22. doi: 10.1007/s13181-015-0476-x.

Abstract

INTRODUCTION

Acetaminophen-cysteine adducts (APAP-CYS) are a serum biomarker of acetaminophen exposure, formed when the oxidative metabolite of acetaminophen binds to cysteine residues of hepatic proteins. APAP-CYS adducts become elevated in cases of acute liver failure following acetaminophen overdose and have been proposed as a diagnostic tool to identify acetaminophen-induced acute liver failure when standard testing is inconclusive.

CASE REPORT

A 26-year-old female with history of unexplained, severe hepatitis presented with a second episode of severe hepatitis including coagulopathy and transaminase levels >10,000 U/L. The patient reported ingesting "only a couple" of acetaminophen tablets several days prior to her presentation. An acetaminophen concentration of 14 mcg/mL at presentation aroused suspicion that acetaminophen might have caused the patient's liver failure, despite her adamant denial of overdose. APAP-CYS adduct levels measured from serum obtained 4 days after her presentation and in two consecutive serum samples are reported alongside previously reported APAP-CYS levels.

DISCUSSION

The patient's APAP-CYS adduct levels were consistent with those seen in acute liver injury due to acetaminophen toxicity, even up to 1 week following presentation, and allowed for confirmation of acetaminophen toxicity as the cause of the her hepatitis. Overall, this case demonstrates the real-time application of APAP-CYS adducts as a biomarker to diagnose acetaminophen toxicity in patients with indeterminate acute liver failure.

摘要

引言

对乙酰氨基酚-半胱氨酸加合物(APAP-CYS)是对乙酰氨基酚暴露的血清生物标志物,由对乙酰氨基酚的氧化代谢产物与肝脏蛋白质的半胱氨酸残基结合形成。在对乙酰氨基酚过量导致急性肝衰竭的情况下,APAP-CYS加合物水平会升高,并且在标准检测结果不确定时,已被提议作为识别对乙酰氨基酚诱导的急性肝衰竭的诊断工具。

病例报告

一名有不明原因严重肝炎病史的26岁女性出现了第二次严重肝炎发作,包括凝血功能障碍和转氨酶水平>10,000 U/L。患者报告在就诊前几天仅服用了“几片”对乙酰氨基酚片。就诊时对乙酰氨基酚浓度为14 mcg/mL,尽管患者坚称未过量服用,但这引起了怀疑,即对乙酰氨基酚可能导致了患者的肝衰竭。报告了在她就诊4天后获得的血清以及两个连续血清样本中测得的APAP-CYS加合物水平,同时列出了先前报告的APAP-CYS水平。

讨论

患者的APAP-CYS加合物水平与对乙酰氨基酚毒性导致的急性肝损伤所见一致,甚至在就诊后长达1周时也是如此,从而确认了对乙酰氨基酚毒性是她肝炎的病因。总体而言,该病例证明了APAP-CYS加合物作为生物标志物在诊断急性肝衰竭病因不明患者的对乙酰氨基酚毒性方面的实时应用。

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Acetaminophen protein adducts: a review.对乙酰氨基酚蛋白加合物:综述
Clin Toxicol (Phila). 2009 Jan;47(1):2-7. doi: 10.1080/15563650801941831.

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