Department of Pathophysiology and TransplantationUniversità degli Studi di MilanoMilanItaly.
Department of Transfusion Medicine and HaematologyFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly.
Hepatol Commun. 2021 Nov;5(11):1824-1832. doi: 10.1002/hep4.1794. Epub 2021 Sep 14.
The changing epidemiology of liver disease, and modifications in the recommended analytical methodology call for a re-evaluation of the upper reference limits (URLs) of alanine aminotransferase (ALT) levels. Using the same approach consolidated 20 years ago to define the healthy population, we defined the URL for the newly recommended International Federation of Clinical Chemistry (IFCC) standardized test. In a cross-sectional study, we examined 21,296 apparently healthy blood donors (age 18-65 years) and calculated the sex-specific URL by the 95th percentile in individuals without risk factors for liver disease. These were tested for the ability to predict liver damage in a subset of 745 participants with dysmetabolism, in an independent cohort of 977 unselected donors, and in 899 patients with chronic liver disease. ALT levels were measured by the IFCC test. Male sex, body mass index, glucose, lipids, ferritin, hypertension, and younger age were independent ALT predictors (P < 0.001). Updated URLs were identified at 42/30 U/L in males/females, approximately 30% lower than those currently recommended by the IFCC. Due to improved sensitivity, they conferred the ability to detect steatosis and significant fibrosis in individuals with dysmetabolism (odds ratio [OR] = 2.31, range 1.40-3.80, P = 0.001; and OR = 3.35, range 1.19-9.42, P = 0.021; respectively), although with a limited accuracy, and significant fibrosis in unselected donors (OR = 2.32, 1.02-5.31, P = 0.045). Updated URLs had a moderate to high accuracy to discriminate liver conditions (area under the receiver operating characteristic curve = 0.81, range 0.78-0.91). Conclusion: Updated URLs by the IFCC method were lower than those calculated in initial studies, but higher than those in use with the recommended old, nonstandardized method, and were able to better predict liver disease. The limited awareness that different techniques are still in use should be regarded as a possible source of medical errors.
肝脏疾病的流行病学变化以及推荐分析方法的改变，要求重新评估丙氨酸氨基转移酶（ALT）水平的上限参考值（URL）。我们使用 20 年前用于定义健康人群的相同方法，定义了新推荐的国际临床化学联合会（IFCC）标准化检测的 URL。在一项横断面研究中，我们检查了 21296 名看似健康的献血者（年龄 18-65 岁），并通过无肝脏疾病风险因素的个体第 95 百分位数计算了性别特异性 URL。在一个独立的 745 名代谢异常参与者亚组、977 名未选择的献血者和 899 名慢性肝病患者中，我们测试了这些 URL 预测肝脏损伤的能力。ALT 水平通过 IFCC 检测进行测量。男性、体重指数、血糖、血脂、铁蛋白、高血压和年龄较小是 ALT 的独立预测因素（P<0.001）。男性和女性的更新 URL 分别为 42/30 U/L，比 IFCC 目前推荐的 URL 低约 30%。由于敏感性提高，它们能够在代谢异常的个体中检测到脂肪变性和显著纤维化（比值比[OR]为 2.31，范围为 1.40-3.80，P=0.001；和 OR 为 3.35，范围为 1.19-9.42，P=0.021），尽管准确性有限，并且在未选择的献血者中检测到显著纤维化（OR 为 2.32，1.02-5.31，P=0.045）。更新的 URL 对鉴别肝脏疾病具有中等至高的准确性（接受者操作特征曲线下面积=0.81，范围为 0.78-0.91）。结论：IFCC 方法的更新 URL 低于初始研究中计算的 URL，但高于使用推荐的旧非标准化方法的 URL，并且能够更好地预测肝脏疾病。应该将对不同技术仍在使用的有限认识视为可能导致医疗错误的一个因素。
