血清胆汁酸代谢轮廓分析 用于妊娠期肝内胆汁淤积症的早期诊断

Early diagnosis of intrahepatic cholestasis of pregnancy based on metabolic profiling analysis of serum bile acids

摘要:

目的：探讨血清胆汁酸代谢轮廓分析在妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy，ICP）的早期诊断中的应用价值。方法：应用超高效液相色谱-三重四级杆-飞行时间质谱法对50例健康孕妇、51例ICP孕妇、14例早期ICP孕妇和21例妊娠肝功能紊乱孕妇血清中的27种已知胆汁酸和29种鉴定胆汁酸进行检测。采用偏最小二乘判别分析建立ICP的诊断模型，应用受试者工作特征曲线和Logistic回归筛选成分胆汁酸作为ICP早期诊断标志物。结果：与正常孕妇比，早期ICP孕妇的牛磺胆酸（taurocholic acid，TCA）、甘氨胆酸（glycolcholic acid，GCA）、甘氨结合型三羟基胆汁酸-3（Gtri-3）、甘氨结合型三羟基胆汁酸-5（Gtri-5）等多种血清成分胆汁酸明显升高（P<0.05），而妊娠肝功能紊乱孕妇未见明显改变（P > 0.05）。ICP诊断模型对早期ICP的预测灵敏度为85.7%，特异性为95.2%。鉴定的胆汁酸Gtri-3和牛磺结合型三羟基胆汁酸-2作为联合标志物，对ICP的早期诊断具有较高效能，灵敏度为92.9%，特异性为90.5%。结论：血清胆汁酸代谢轮廓分析是一种较特异、灵敏的ICP早期诊断方法。

Abstract:

Objective：To investigate the value of metabolic profiling analysis of serum bile acids in the early diagnosis of intrahepatic cholestasis of pregnancy（ICP）. Methods：Ultra-performance liquid chromatography-triple quadrupole time-of-flight mass spectrome－try was used to measure the serum levels of 27 known bile acids and 29 identified bile acids in 50 healthy pregnant women，51 pa－tients with ICP，14 patients with early-stage ICP，and 21 pregnant women with liver dysfunction. A partial least squares-discriminant analysis was used to establish a diagnostic model of ICP，and the receiver operating characteristic（ROC） curve and logistic regression analysis were used to screen out the bile acids as the markers for the early diagnosis of ICP. Results：Compared with the normal pregnant women，the pregnant women with early-stage ICP had significant increases in the serum levels of taurocholic acid，glyco－cholic acid，glycine-conjugated bile acid with three hydroxyl-3（Gtri-3），and glycine-conjugated bile acid with three hydroxyl-5（Gtri-5，P<0.05），while no significant changes were observed in the pregnant women with liver dysfunction. The ICP diagnostic model had a sensitivity of 85.7% and a specificity of 95.2% in the diagnosis of early-stage ICP. Gtri-3 and taurine-conjugated bile acid with three hydroxyl-2（Ttri-2） were selected as the markers for the early diagnosis of ICP，with a sensitivity of 92.9% and a speci－ficity of 90.5%. Conclusion：The metabolic profiling analysis of serum bile acids is a highly specific and sensitive method for the early diagnosis of ICP.