目的分析正常妊娠、妊娠期肝内胆汁淤积症（ICP）及无症状高胆汁酸血症（AHP）孕妇血清中的胆汁酸组分，评估血清胆汁酸谱在ICP和AHP诊断中的应用价值。
方法收集2022年6月至2023年5月于徐州市妇幼保健院产前检查的122例孕妇的临床资料，其中正常妊娠组54例，ICP组28例，AHP组40例。采用超高效液相色谱-串联质谱技术检测各组孕妇血清中15种胆汁酸水平，包括胆酸（CA）、鹅脱氧胆酸（CDCA）、脱氧胆酸（DCA）、石胆酸（LCA）、熊脱氧胆酸（UDCA）、甘氨胆酸（GCA）、甘氨鹅脱氧胆酸（GCDCA）、甘氨脱氧胆酸（GDCA）、甘氨石胆酸（GLCA）、甘氨熊脱氧胆酸（GUDCA）、牛磺胆酸（TCA）、牛磺鹅脱氧胆酸（TCDCA）、牛磺脱氧胆酸（TDCA）、牛磺石胆酸（TLCA）和牛磺熊脱氧胆酸（TUDCA）。应用主成分分析（PCA）和正交偏最小二乘法判别分析（OPLS-DA）模型筛选差异胆汁酸，受试者工作特征（ROC）曲线分析组间差异胆汁酸及其联合指标的诊断效能。
结果（1）与正常妊娠组比较，ICP组孕妇血清中LCA、GCA、GCDCA、GDCA、GLCA、UDCA、TCA、TCDCA、TDCA、TLCA、GUDCA及TUDCA水平的差异均有统计学意义（ P均 <0.05），AHP组孕妇血清中LCA、DCA、GCA、GCDCA、GDCA、GLCA、TCA、TCDCA、TDCA、TLCA、GUDCA及TUDCA水平的差异均有统计学意义（ P均 <0.05）；与ICP组比较，AHP组孕妇血清中CDCA、DCA、UDCA、TDCA、GUDCA及TUDCA水平的差异均有统计学意义（ P均 <0.05）。（2）OPLS-DA模型中，ICP组与AHP组之间的差异胆汁酸为TUDCA、TCA、UDCA、GUDCA和GCA，其变量投影重要性（VIP）值分别为1.489、1.345、1.344、1.184和1.111；AHP组与正常妊娠组之间的差异胆汁酸为TCA、GCDCA、GCA、TDCA、GDCA和TCDCA，其VIP值分别为1.236、1.229、1.197、1.145、1.139和1.138。（3）ROC曲线分析结果显示，TUDCA、TCA、UDCA、GUDCA和GCA组成的联合指标对于ICP与AHP鉴别诊断的曲线下面积（AUC）为0.860，敏感度和特异度分别为67.9%、95.0%；TCA、GCDCA、GCA、TDCA、GDCA和TCDCA组成的联合指标诊断AHP的AUC为0.964，敏感度和特异度分别为95.0%、93.1%。
结论正常妊娠、ICP及AHP孕妇的血清胆汁酸谱有差异，血清胆汁酸谱对ICP与AHP的鉴别诊断及AHP的诊断具有潜在应用价值。
ObjectiveTo analyze serum bile acid profiles in pregnant women with normal pregnancy, intrahepatic cholestasis of pregnancy (ICP) and asymptomatic hypercholanemia of pregnancy (AHP), and to evaluate the application value of serum bile acid profiles in the diagnosis of ICP and AHP.
MethodsThe clinical data of 122 pregnant women who underwent prenatal examination in Xuzhou Maternal and Child Health Care Hospital from June 2022 to May 2023 were collected, including 54 cases of normal pregnancy group, 28 cases of ICP group and 40 cases of AHP group. Ultraperformance liquid chromatography-tandem mass spectrometry was used to measure the levels of 15 serum bile acids in each group, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), glycolcholic acid (GCA), glycochenodeoxycholic acid (GCDCA), glycodeoxycholic acid (GDCA), glycolithocholic acid (GLCA), glycoursodeoxycholic acid (GUDCA), taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA), taurodeoxycholic acid (TDCA), taurolithocholic acid (TLCA) and tauroursodeoxycholic acid (TUDCA). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to screen differential bile acids. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of differential bile acids and combined indicators between groups.
Results(1) Compared with normal pregnancy group, the serum levels of LCA, GCA, GCDCA, GDCA, GLCA, UDCA, TCA, TCDCA, TDCA, TLCA, GUDCA and TUDCA in ICP group were significantly different (all P<0.05), while the levels of LCA, DCA, GCA, GCDCA, GDCA, GLCA, TCA, TCDCA, TDCA, TLCA, GUDCA and TUDCA in AHP group were significantly different (all P<0.05). Compared with ICP group, the serum levels of CDCA, DCA, UDCA, TDCA, GUDCA and TUDCA in AHP group were significantly different (all P<0.05). (2) In the OPLS-DA model, the differential bile acids between ICP group and AHP group were TUDCA, TCA, UDCA, GUDCA and GCA, and their variable importance in projection (VIP) were 1.489, 1.345, 1.344, 1.184 and 1.111, respectively. TCA, GCDCA, GCA, TDCA, GDCA and TCDCA were the differentially expressed bile acids between AHP group and normal pregnancy group, and their VIP values were 1.236, 1.229, 1.197, 1.145, 1.139 and 1.138, respectively. (3) ROC analysis showed that the area under the curve (AUC) of TUDCA, TCA, UDCA, GUDCA and GCA in the differential diagnosis of ICP and AHP was 0.860, and the sensitivity and specificity were 67.9% and 95.0%, respectively. The AUC of TCA, GCDCA, GCA, TDCA, GDCA and TCDCA in the diagnosis of AHP was 0.964, and the sensitivity and specificity were 95.0% and 93.1%, respectively.
ConclusionsThere are differences in serum bile acid profiles among normal pregnant women, ICP and AHP. The serum bile acid profiles of pregnant women have potential application value in the differential diagnosis of ICP and AHP and the diagnosis of AHP.
National Health Insurance Information Platform，MR-32-23-018429
缑灵山,尹馨,刘杰,等. 妊娠期肝内胆汁淤积症及无症状妊娠期高胆汁酸血症孕妇血清胆汁酸谱的特征及其诊断价值[J]. 中华妇产科杂志,2024,59(04)：270-278.
DOI:10.3760/cma.j.cn112141-20231004-00126版权归中华医学会所有。
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缑灵山：设计实验、收集和统计分析数据、论文撰写；尹馨：实验操作、数据整理、论文修改和定稿；刘杰：参与选题、样本采集、数据解读、论文修改；索峰：实验操作、数据分析、论文修改；吴昕雨、王真真、王巧莲、董步连：临床资料收集、数据解释、论文修改；顾茂胜：课题指导、论文修改；刘道彦：设计实验、样本和资料采集、数据整理分析、论文撰写和修改、经费支持
国家全民健康保障信心平台，MR-32-23-018429
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