Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause
Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause
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DOI：
10.1542/peds.2006-0069
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发表时间：
2006-09-01
期刊：
影响因子：
8
通讯作者：
Squires, Robert H.
中科院分区：
文献类型：
--
作者：
James, Laura P.;Alonso, Estella M.;Squires, Robert H.
客观的。对乙酰氨基酚半胱氨酸蛋白加合物被广泛认为与对乙酰氨基酚介导的实验动物肝损伤相关。本研究的目的是使用一种新的检测方法来检测急性肝衰竭儿童中的对乙酰氨基酚半胱氨酸蛋白加合物，以确定对乙酰氨基酚毒性在不明原因急性肝衰竭中的作用。使用高效液相色谱法和电化学检测技术测定了急性肝衰竭儿童血清样本中的对乙酰氨基酚半胱氨酸蛋白加合物。为了进行比较，还测量了具有明确对乙酰氨基酚毒性的儿童和患有已知其他急性肝衰竭原因的儿童的样本中的对乙酰氨基酚半胱氨酸蛋白加合物。分析实验室对患者的诊断不知情。 结果。对乙酰氨基酚半胱氨酸蛋白加合物在对乙酰氨基酚毒性引起的急性肝衰竭儿童样本中检出率为 90%，在不明原因急性肝衰竭儿童样本中检出率为 12.5%，在其他原因引起的急性肝衰竭儿童样本中检出率为 9.6%。来自不明原因亚组的加合物阳性患者的血清天冬氨酸转氨酶和丙氨酸转氨酶水平较高，而胆红素水平较低。加合物阳性患者的移植率也较低，自发缓解率较高。结论。一小部分但显着比例的不明原因急性肝衰竭儿童对乙酰氨基酚半胱氨酸蛋白加合物检测呈阳性，强烈表明对乙酰氨基酚毒性是急性肝衰竭的原因。检测对乙酰氨基酚半胱氨酸蛋白加合物的测定可以帮助诊断儿童与对乙酰氨基酚相关的肝损伤。
OBJECTIVE. Acetaminophen cysteine protein adducts are a widely recognized correlate of acetaminophen-mediated hepatic injury in laboratory animals. The objective of this study was to use a new assay for the detection of acetaminophen cysteine protein adducts in children with acute liver failure to determine the role of acetaminophen toxicity in acute liver failure of unknown cause.METHODS. Serum samples from children with acute liver failure were measured for acetaminophen cysteine protein adducts using high-performance liquid chromatography with electrochemical detection. For comparison, samples from children with well-characterized acetaminophen toxicity and children with known other causes of acute liver failure also were measured for acetaminophen cysteine protein adducts. The analytical laboratory was blinded to patient diagnoses.RESULTS. Acetaminophen cysteine protein adduct was detected in 90% of samples from children with acute liver failure that was attributed to acetaminophen toxicity, 12.5% of samples from children with acute liver failure of indeterminate cause, and 9.6% of samples from children with acute liver failure that was attributed to other causes. Adduct-positive patients from the indeterminate cause subgroup had higher levels of serum aspartate aminotransferase and alanine aminotransferase and lower levels of bilirubin. Adduct-positive patients also had lower rates of transplantation and higher rates of spontaneous remission.CONCLUSIONS. A small but significant percentage of children with acute liver failure of indeterminate cause tested positive for acetaminophen cysteine protein adducts, strongly suggesting acetaminophen toxicity as the cause of acute liver failure. An assay for the detection of acetaminophen cysteine protein adducts can aid the diagnosis of acetaminophen-related liver injury in children.