Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital.
Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital.
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DOI：
10.1002/hep.26294
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发表时间：
2013-08
期刊：
影响因子：
13.5
通讯作者：
Park, B. Kevin
中科院分区：
文献类型：
--
作者：
Antoine, Daniel J.;Dear, James W.;Lewis, Philip Starkey;Platt, Vivien;Coyle, Judy;Masson, Moyra;Thanacoody, Ruben H.;Gray, Alasdair J.;Webb, David J.;Moggs, Jonathan G.;Bateman, D. Nicholas;Goldring, Christopher E.;Park, B. Kevin
醋氨酚过量是住院的常见原因，也是西方世界最常见的肝毒性原因。及早识别将有助于患者的个体化治疗策略。我们研究了一组新的生物标记物(具有增强的肝脏表达或与毒性机制有关)在目前使用的标记物在正常范围内的情况下首次出现在医院时识别对乙酰氨基酚诱导的急性肝损伤(ALI)患者的潜力。在首次入院的患者(n=129)的血浆样本中，我们检测了microRNA-122(miR-122；高肝脏特异性)、高迁移率族蛋白-1(HMGB1；坏死的标志)、全长和caspase裂解的角蛋白-18(K18；坏死和凋亡的标志)以及谷氨酸脱氢酶(GLDH；线粒体功能障碍的标志)。受试者特征曲线分析和阳性/阴性预测值用于比较肝损伤与丙氨酸氨基转移酶(ALT)和国际标准化比率(INR)的敏感性。在所有患者中，首次发病时的生物标志物与ALT峰值或INR显著相关。在ALT或INR正常的患者中，miR-122、HMGB1和坏死K18以高度的准确性识别肝损伤的发展(n=15)或不发生(n=84)，并且显著优于ALT、INR和血浆对乙酰氨基酚浓度来预测随后的ALI(n=11)，而在服药过量后8小时内出现ALI的患者中没有ALI(n=52)。结论：血浆miR-122、HMGB1和坏死灶K18的升高证实了对乙酰氨基酚过量用药后不久入院的患者和ALT在正常范围内的患者随后发生ALI。这种生物标志物小组的应用可以提高临床决策的速度，无论是在ALI的治疗中，还是在设计/执行患者个性化的治疗策略方面都是如此。
Acetaminophen overdose is a common reason for hospital admission and the most frequent cause of hepatotoxicity in the Western world. Early identification would facilitate patient-individualized treatment strategies. We investigated the potential of a panel of novel biomarkers (with enhanced liver expression or linked to the mechanisms of toxicity) to identify patients with acetaminophen-induced acute liver injury (ALI) at first presentation to the hospital when currently used markers are within the normal range. In the first hospital presentation plasma sample from patients (n = 129), we measured microRNA-122 (miR-122; high liver specificity), high mobility group box-1 (HMGB1; marker of necrosis), full-length and caspase-cleaved keratin-18 (K18; markers of necrosis and apoptosis), and glutamate dehydrogenase (GLDH; marker of mitochondrial dysfunction). Receiver operator characteristic curve analysis and positive/negative predictive values were used to compare sensitivity to report liver injury versus alanine transaminase (ALT) and International Normalized Ratio (INR). In all patients, biomarkers at first presentation significantly correlated with peak ALT or INR. In patients presenting with normal ALT or INR, miR-122, HMGB1, and necrosis K18 identified the development of liver injury (n = 15) or not (n = 84) with a high degree of accuracy and significantly outperformed ALT, INR, and plasma acetaminophen concentration for the prediction of subsequent ALI (n = 11) compared with no ALI (n = 52) in patients presenting within 8 hours of overdose. Conclusion: Elevations in plasma miR-122, HMGB1, and necrosis K18 identified subsequent ALI development in patients on admission to the hospital, soon after acetaminophen overdose, and in patients with ALTs in the normal range. The application of such a biomarker panel could improve the speed of clinical decision-making, both in the treatment of ALI and the design/execution of patient-individualized treatment strategies.
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影响因子：
25.7
作者：
Antoine, Daniel J.;Jenkins, Rosalind E.;Dear, James W.;Williams, Dominic P.;McGill, Mitchell R.;Sharpe, Matthew R.;Craig, Darren G.;Simpson, Kenneth J.;Jaeschke, Hartmut;Park, B. Kevin
通讯作者：
Park, B. Kevin
影响因子：
5.9
作者：
Jaeschke H;McGill MR;Ramachandran A
通讯作者：
Ramachandran A
影响因子：
3.3
作者：
Waring, W. Stephen;Stephen, Alexandra F.;Pettie, Janice M.
通讯作者：
Pettie, Janice M.
DOI：
10.1073/pnas.0813371106
发表时间：
2009-03-17
影响因子：
11.1
作者：
Wang, Kai;Zhang, Shile;Galas, David J.
通讯作者：
Galas, David J.
影响因子：
105.7
作者：
MANT, TGK;TEMPOWSKI, JH;TALBOT, JCC
通讯作者：
TALBOT, JCC