Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
Clin Chim Acta. 2017 Dec;475:28-35. doi: 10.1016/j.cca.2017.10.005. Epub 2017 Oct 4.
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is characterized by conjugated hyperbilirubinemia and increased plasma bile acid concentrations. However, the underlying mechanisms remain unclear. We established a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneously quantifying plasma bile acids and examined bile acid profiles in NICCD infants.
We measured 15 bile acids within 15min and found a wide linear range for individual bile acids.
The within-run and run-to-run CV of all bile acids was 1.2-10.9% and 3.1-10.8%, respectively, with a mean recovery of 90.5-112.6%. Compared to infants with citrullinemia without mutations in SLC25A13 (non-NICCD), NICCD infants showed increased plasma total bile acid concentrations (mean: 201 vs. 42μM, p<0.001), with a distinct bile acid profile characterized by increased conjugated primary bile acid concentrations. The calculated ratios, including primary/secondary bile acid (714 vs. 235, p<0.05) and conjugated/free bile acid (371 vs. 125, p<0.05) ratios, were higher in NICCD infants. The area under receiver operating characteristic curve for conjugated/free bile acid ratio to identify infants with NICCD was 0.871 (95% confidence interval, 0.713-1.0).
Together, our findings indicated plasma bile acid profile as a potential noninvasive diagnostic biomarker for NICCD.
由于 citrin 缺乏引起的新生儿肝内胆汁淤积症（NICCD）的特征是结合胆红素升高和血浆胆汁酸浓度增加。然而，其潜在机制尚不清楚。我们建立了一种液相色谱串联质谱（LC-MS/MS）方法，用于同时定量检测血浆胆汁酸，并检查 NICCD 婴儿的胆汁酸谱。
我们在 15 分钟内测量了 15 种胆汁酸，发现每个胆汁酸的线性范围都很广。
所有胆汁酸的批内和批间 CV 分别为 1.2-10.9%和 3.1-10.8%，平均回收率为 90.5-112.6%。与 SLC25A13 无突变的 citrullinemia 婴儿（非-NICCD）相比，NICCD 婴儿的血浆总胆汁酸浓度升高（均值：201 与 42μM，p<0.001），胆汁酸谱特征为结合型初级胆汁酸浓度增加。计算的比值，包括初级/次级胆汁酸（714 与 235，p<0.05）和结合/游离胆汁酸（371 与 125，p<0.05）比值，在 NICCD 婴儿中更高。用于识别 NICCD 婴儿的结合/游离胆汁酸比值的受试者工作特征曲线下面积为 0.871（95%置信区间，0.713-1.0）。
综上所述，我们的研究结果表明，血浆胆汁酸谱可能是 NICCD 的一种潜在非侵入性诊断生物标志物。
