胆汁酸谱在诊断妊娠期肝内胆汁淤积症和高胆汁酸血症中的价值
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江苏省卫生健康委医学科研项目(K2019015)


The value of bile acid profile in diagnosis of intrahepatic cholestasis of pregnancy and asymptomatic hypercholanemia of pregnancy
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    摘要:

    目的:探讨胆汁酸谱在诊断妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)和无症状高胆汁酸血症(asymptomatic hypercholanemia of pregnancy,AHP)中的价值。方法:选取正常妊娠者100例、ICP患者60例、AHP患者30例,采用高效液相色谱串联质谱(high performance liquid chromatography tandem mass spectrometry,HPLC-MS/MS)分析各组胆汁酸含量,并通过建立正交偏最小二乘判别分析(orthogonal projections to latent structures,OPLS-DA)模型,寻找ICP组和AHP组差异性的胆汁酸。利用受试者工作特征(receiver operating characteristic,ROC)曲线分析两者差异性胆汁酸以及联合指标的诊断效能。结果:15种胆汁酸中,除鹅脱氧胆酸(chenodeoxycholic acid,CDCA)外,其余胆汁酸的含量在3组间差异均有统计学意义(P<0.05);通过OPLS-DA模型找到ICP组和AHP组差异性的胆汁酸为牛磺结合型胆酸(taurocholic acid,TCA)、牛磺结合型鹅脱氧胆酸(taurochenodeoxycholic acid,TCDCA)、甘氨结合型胆酸(glycocholic acid,GCA)、甘氨结合型鹅脱氧胆酸(glycohenodeoxycholic acid,GCDCA)、牛磺结合型熊脱氧胆酸(tauroursodeoxycholic acid,TUDCA)。ROC结果显示,TCA的诊断效能最高,曲线下面积(area under curve,AUC)为0.808,联合TCA、TCDCA、GCA、GCDCA、TUDCA诊断ICP的效能更高,AUC为0.967,灵敏度为90.6%,特异度为98.0%。结论:ICP和AHP的胆汁酸谱有差异,利用OPLS-DA模型找到的差异性胆汁酸可以作为两者鉴别诊断的一种重要方法。

    Abstract:

    Objective:This study aims to investigate the value of bile acid profile in diagnosis of intrahepatic cholestasis of pregnancy(ICP)and asymptomatic hypercholanemia of pregnancy(AHP). Methods:Total 100 cases of normal pregnancy,60 cases of ICP and 30 cases of AHP were selected. The content of bile acid in each group was analyzed by high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS). In addition,the orthogonal projections to latent structures(OPLS-DA)model was developed to explore the differences of bile acids between the ICP and AHP groups. The diagnostic effiency of the differential bile acids and the combined indicators was analyzed by receiver operating characteristic(ROC) curves. Results:Except for chenodeoxycholic acid(CDCA),the contents of 15 kinds of bile acids among the three groups were statistically significant(P < 0.05). According to the OPLS-DA model,the differential bile acids in ICP group and AHP group were taurocholic acid(TCA),taurochenodeoxycholic acid(TCDCA),glycocholic acid(GCA),glycohenodeoxycholic acid(GCDCA),tauroursodeoxycholic acid(TUDCA). ROC results showed that TCA had the highest diagnostic efficiency with area under curve(AUC) of 0.808. The combination of TCA,TCDCA,GCDCA and TUDCA was more effective in the diagnosis of ICP. The AUC was 0.967,the sensitivity was 90.6%,and the specificity was 98.0%. Conclusion:There are differences in bile acid profile between ICP and AHP. The differential bile acids found by OPLS-DA model can be used as an important method for differential diagnosis between ICP and AHP.

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孙 宁,钟天鹰,陈亚军,陈 辰,陈 晨.胆汁酸谱在诊断妊娠期肝内胆汁淤积症和高胆汁酸血症中的价值[J].南京医科大学学报(自然科学版),2021,(6):856-861

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  • 收稿日期:2020-09-07
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  • 在线发布日期: 2021-06-26
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