Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure.
Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure.
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DOI：
10.1002/hep.24060
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发表时间：
2011-02
期刊：
影响因子：
13.5
通讯作者：
Lee, William M.
中科院分区：
文献类型：
--
作者：
Khandelwal, Niraj;James, Laura P.;Sanders, Corron;Larson, Anne M.;Lee, William M.
尽管进行了广泛的调查，但14%的急性肝衰竭患者的肝损伤原因仍然未知（不确定）。在一项初步研究中，使用一种新的检测方法，在36例不确定患者中的7例（19%）中检测到高度特异性的对乙酰氨基酚-半胱氨酸加合物。为了扩展这些观察结果，使用类似但更有效和更灵敏的加合物测定法分析了急性肝衰竭研究组登记处招募的110名患有不确定急性肝衰竭的受试者的血清。作为阳性对照，评估了另外199例已知或推测为对乙酰氨基酚诱导的肝衰竭患者加合物的存在和数量。比较两组的临床、实验室和结局数据。根据已知治疗暴露和对乙酰氨基酚过量的既往数据，血清中的加合物浓度≥ 1.0 nmol/mL表明对乙酰氨基酚过量。在110例不确定病例中，18%的测定值≥ 1.0，中位水平为9.2 nmol/mL; 94.5%的阳性对照（已知APAP）病例的测定值≥ 1.0 nmol/mL。无论初始诊断如何，加合物水平升高的受试者均表现出与对乙酰氨基酚过量相关的临床特征和超急性生化损伤模式：女性占优势、转氨酶水平极高和胆红素水平低。这些数据证实并扩展了先前的观察结果，即在不确定的急性肝衰竭受试者中，未识别或不确定的对乙酰氨基酚毒性的患病率较高（18%）。N-乙酰半胱氨酸的使用在该组中是有限的，可能是因为缺乏对乙酰氨基酚毒性的特异性诊断。
Despite extensive investigation, the cause of liver injury in 14% of acute liver failure patients remains unknown (indeterminate). In a pilot study, using a novel assay, highly specific acetaminophen-cysteine adducts were detected in 7 of 36 (19%) indeterminate patients. To extend these observations, sera from 110 subjects enrolled in the Acute Liver Failure Study Group registry with indeterminate acute liver failure were analyzed using a similar but more efficient and sensitive adduct assay. As positive controls, an additional 199 patients with known or presumed acetaminophen-induced liver failure were assessed for the presence and quantity of adducts. Clinical, laboratory and outcome data were compared for the two groups. Based on previous data from known therapeutic exposures and acetaminophen overdoses, an adduct concentration of ≥1.0 nmol/mL serum indicated a definite acetaminophen overdose. Among the 110 indeterminate cases, 18% had assay values ≥1.0, with a median level of 9.2 nmol/mL; 94.5 % of the positive control (known APAP) cases had values ≥1.0 nmol/mL. Regardless of initial diagnosis, subjects with elevated adduct levels demonstrated the clinical profile and hyperacute biochemical injury pattern associated with acetaminophen overdose: predominance of female gender, very high aminotransferase levels and low bilirubin levels. These data confirm and extend previous observations regarding the high (18%) prevalence of unrecognized or uncertain acetaminophen toxicity among subjects with indeterminate acute liver failure. N-acetylcysteine use was limited in this group, presumably because of the lack of a specific diagnosis of acetaminophen toxicity.
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