丙戊酸致罕见特异性肝毒性1例报告

Malek Michael Bouhairie
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摘要

丙戊酸引起的肝毒性是众所周知的副作用,经常需要定期监测血清药物水平。丙戊酸引起的肝毒性通常发生在超治疗药物水平。偶尔会引起特异性反应,尽管血清丙戊酸水平正常,但仍可能发生肝损伤,主要发生在慢性使用者中。我们在此确定一个不寻常的病例急性特异性丙戊酸诱导肝毒性。我们报告一例65岁男性血脂异常和癫痫发作史,丙戊酸治疗,表现为精神状态改变和嗜睡。患者的家庭药物仅包括每日10毫克的泽尼和一个月前开始使用的丙戊酸盐。在演讲时,他是清醒的,有方向感,但昏昏欲睡。实验室检测显示肝细胞损伤伴转氨酶水平升高、直接高胆红素血症和凝血功能障碍。氨水平正常,丙戊酸水平在治疗范围内。腹部计算机断层扫描与静脉造影剂和MRCP结果无关。特异性丙戊酸盐毒性是在排除所有其他可能的病因并在停药后临床和实验室迅速改善后诊断出来的。根据患者的临床情况,诊断为丙戊酸盐引起的肝毒性。本病例强调了在症状无法解释的情况下识别、诊断和处理丙戊酸盐毒性的重要性。我们需要进一步的尝试和更多的研究,以提高肝脏不良反应的检测,获得可靠的信息,发现新的生物标志物或工具,早期预测DILI,以及获得准确的流行病学,药物安全性和发病机制的信息,以改善管理,提高生存率。
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Case Report of A Rare Idiosyncratic Hepatotoxicity Induced by Valproic Acid
Valproate induced hepatotoxicity is a well-known side effect, which frequently required periodic monitoring of serum drug level. Hepatotoxicity caused by valproate typically occurs at supratherapeutic drug levels. Once in a while, an idiosyncratic reaction is elicited, liver injury might occur despite normal serum valproate level mainly in chronic users. We hereby identify an unusual case of acute idiosyncratic valproate induced hepatotoxicity. We report a case of a 65 years old male with dyslipidemia and history of seizure, on valproic acid therapy, presented with altered mental status and drowsiness. The patient’s home medications include only zenil 10 mg daily and valproate which was started one month ago. At presentation, He was awake, oriented, but lethargic. Laboratory testing reveals hepatocellular injury with elevated transaminase levels, direct hyperbilirubinemia and coagulopathy. The ammonia level was normal and valproate level was within the therapeutic range. Abdomen computed tomography with IV contrast and MRCP results were irrelevant. Idiosyncratic valproate toxicity was diagnosed after exclusion of all other possible etiologies and after a rapid clinical and laboratory improvement once the drug was discontinued. Based on the patient’s clinical context the diagnosis of valproate induced hepatotoxicity was confirmed. This case emphasizes the importance of identifying, diagnosing, and managing valproate toxicity when no alternative clarification for their symptoms. We need further attempts and more researches to improve the detection of adverse hepatic reactions and to obtain reliable information about the discovery of new biomarkers or tools for early prediction of DILI, as well as to obtain accurate information on epidemiology, drug safety, and pathogenesis in order to improve management for better survival.
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