Comparison of seven bile acids in intrahepatic cholestasis by HPLC-MS/MS at different gestational stages and the clinical significance
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摘要: 目的 比较妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)孕妇、肝功异常孕妇和正常孕妇胆汁酸谱中7种胆汁酸亚型在不同孕周的血清水平差异及其与妊娠结局的关系,探讨血清胆汁酸亚型分析在临床应用中的价值。 方法 回顾性分析2018年9月—2019年2月于杭州市妇产科医院常规产检并分娩的ICP孕妇84例、单纯肝功异常孕妇20例和正常孕妇30例,于9~13+6周、15~20+6周及28~40周采集空腹静脉血,应用高效液相色谱串联质谱法(HPLC-MS/MS)检测血清中胆酸(CA)、鹅脱氧胆酸(CDCA)、石胆酸(LCA)、熊脱氧胆酸(UDCA)、甘氨胆酸(GCA)、牛磺胆酸(TCA)、甘氨鹅脱氧胆酸(GCDCA)水平;分析与相应妊娠结局间的关系。 结果 孕早、中、晚期ICP孕妇均有多种胆汁酸亚型水平显著高于正常孕妇组和肝功异常孕妇组,以GCA和TCA为主;ICP组胆汁酸谱随孕周升高趋势明显,7种胆汁酸亚型在3个妊娠阶段均有显著差异;GCA与分娩孕周负相关,GCA、LCA、GCDCA与新生儿体重负相关,其他胆汁酸与临床结局无显著相关性。 结论 3组病例的胆汁酸谱随孕周变化规律不同;CA/CDCA比值有望作为区分ICP和单纯肝功异常的指标;LCA、GCA和GCDCA升高可能与不良预后有关,HPLC-MS/MS法检测的7种胆汁酸可用于ICP临床诊断及疗效评估。
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关键词:
- 妊娠期肝内胆汁淤积症 /
- 胆汁酸谱 /
- 高效液相色谱串联质谱法
Abstract: Objective To compare the serum levels of seven bile acid subtypes at different gestational stages among pregnant women with intrahepatic cholestasis of pregnancy(ICP), pregnant women with abnormal liver function and normal pregnant women as well as the relationship between bile acid serum level with pregnancy outcomes so as to investigate value of bile acids analysis in clinical application. Methods A retrospective analysis of totally 84 ICP cases, 20 abnormal liver function cases and 30 normal cases underwent routine check-up and delivery in our hospital was collected from September 2018 to February 2019. At 9-13+6 weeks, 15-20+6 weeks and 28-40 weeks respectively, the venous serum samples of each case were collected and determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to come to measure the serum level of cholic acid (CA), chenodeoxycholic (CDCA) acid, glycocholic acid (GCA), taurocholic acid (TCA), glycochenodeoxycholic acid (GCDCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA). The relationship with the corresponding pregnancy outcomes was analyzed. Results The levels of bile acid subtypes in ICP pregnant women in early, middle and late gestational stages were significantly higher than those in normal pregnant women and pregnant women with abnormal liver function, mainly GCA and TCA. The bile acids serum levels in ICP group significantly increased with the gestational week increasing. The seven bile acid subtypes varied differently in the three gestational stages. GCA level was negatively related to the gestational age of childbirth. The levels of GCA, LCA and GCDCA were negatively related to the weight of the newborn, and other bile acids were not significantly related to clinical outcomes. Conclusion The bile acid profiles of three groups vary with gestational weeks. The CA/CDCA ratio is expected to be an indicator to distinguish ICP pregnancy women from abnormal liver function ones. The increase of LCA, GCA, and GCDCA may be related to poor prognosis. Detecting seven bile acids by HPLC-MS/MS can be used for clinical diagnosis and therapeutic effect evaluation of ICP.
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