安全性研究：丙氨酸氨基转移酶的截断值设定得过高，无法可靠检测儿科慢性肝病。
SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease.
机构信息
Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics University of California, San Diego School of Medicine, San Diego, California 92103-8450, USA.
出版信息
Gastroenterology. 2010 Apr;138(4):1357-64, 1364.e1-2. doi: 10.1053/j.gastro.2009.12.052. Epub 2010 Jan 11.
BACKGROUND & AIMS: The appropriate alanine aminotransferase (ALT) threshold value to use for diagnosis of chronic liver disease in children is unknown. We sought to develop gender-specific, biology-based, pediatric ALT thresholds.
METHODS
The Screening ALT for Elevation in Today's Youth (SAFETY) study collected observational data from acute care children's hospitals, the National Health and Nutrition Examination Survey (NHANES, 1999-2006), overweight children with and without non-alcoholic fatty liver disease (NAFLD), and children with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. The study compared the sensitivity and specificity of ALT thresholds currently used by children's hospitals vs study-derived, gender-specific, biology-based, ALT thresholds for detecting children with NAFLD, HCV, or HBV.
RESULTS
The median upper limit of ALT at children's hospitals was 53 U/L (range, 30-90 U/L). The 95th percentile levels for ALT in healthy weight, metabolically normal, liver disease-free, NHANES pediatric participants were 25.8 U/L (boys) and 22.1 U/L (girls). The concordance statistics of these NHANES-derived thresholds for liver disease detection were 0.85 (95% confidence interval [CI]: 0.74-0.96) in boys and 0.91 (95% CI: 0.83-0.99) in girls for NAFLD, 0.80 (95% CI: 0.70-0.91) in boys and 0.79 (95% CI: 0.69-0.89) in girls for HBV, and 0.86 (95% CI: 0.77-0.95) in boys and 0.84 (95% CI: 0.75-0.93) in girls for HCV. Using current children's hospitals ALT thresholds, the median sensitivity for detection of NAFLD, HBV, and HCV ranged from 32% to 48%; median specificity was 92% (boys) and 96% (girls). Using NHANES-derived thresholds, the sensitivities were 72% (boys) and 82% (girls); specificities were 79% (boys) and 85% (girls).
CONCLUSIONS
The upper limit of ALT used in children's hospitals varies widely and is set too high to reliably detect chronic liver disease. Biology-based thresholds provide higher sensitivity and only slightly less specificity. Clinical guidelines for use of screening ALT and exclusion criteria for clinical trials should be modified.
背景与目的
用于诊断儿童慢性肝病的合适丙氨酸氨基转移酶（ALT）阈值尚不清楚。我们旨在制定基于性别、生物学的儿科 ALT 阈值。
方法
筛查 ALT 用于今日青少年的升高（SAFETY）研究从急症儿童医院、国家健康和营养检查调查（NHANES，1999-2006 年）、有或无非酒精性脂肪性肝病（NAFLD）的超重儿童以及慢性乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）感染儿童中收集观察性数据。该研究比较了目前儿童医院使用的 ALT 阈值与基于研究的、基于性别的、基于生物学的 ALT 阈值，以检测患有 NAFLD、HCV 或 HBV 的儿童的敏感性和特异性。
结果
儿童医院 ALT 的中位数上限为 53 U/L（范围，30-90 U/L）。健康体重、代谢正常、无肝病的 NHANES 儿科参与者的 ALT 第 95 百分位水平分别为 25.8 U/L（男孩）和 22.1 U/L（女孩）。这些 NHANES 衍生的用于检测肝病的阈值的一致性统计数据在男孩中为 0.85（95%置信区间[CI]：0.74-0.96），在女孩中为 0.91（95% CI：0.83-0.99），在男孩中为 0.80（95% CI：0.70-0.91），在女孩中为 0.79（95% CI：0.69-0.89），在男孩中为 0.86（95% CI：0.77-0.95），在女孩中为 0.84（95% CI：0.75-0.93）。使用当前儿童医院的 ALT 阈值，NAFLD、HBV 和 HCV 的中位检测敏感性范围为 32%至 48%；中位特异性为 92%（男孩）和 96%（女孩）。使用 NHANES 衍生的阈值，敏感性分别为 72%（男孩）和 82%（女孩）；特异性分别为 79%（男孩）和 85%（女孩）。
结论
儿童医院使用的 ALT 上限差异很大，设定得过高，无法可靠地检测慢性肝病。基于生物学的阈值提供了更高的敏感性，特异性仅略有降低。应修改用于筛查 ALT 的临床指南和临床试验的排除标准。
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