FGF19在妊娠期肝内胆汁淤积症患者血清中的表达水平及相关因素分析

Serum FGF19 levels in patients with intrahepatic cholestasis of pregnancy and its relative factors

目的:探讨成纤维细胞生长因子19(fibroblast growth factor 19,FGF19)在妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)患者血清中的表达水平,并分析其相关因素。方法:采用前瞻性研究方法收集2021年1月至2022年1月在中山大学附属第三医院产检并住院分娩的25例ICP患者及25例健康孕妇的空腹血清,使用酶联免疫吸附法测定FGF19浓度,全自动生化分析仪检测肝功能指标,同时登记并随访研究对象的临床资料及妊娠结局。采用t检验、Wilcoxon秩和检验、χ^(2)检验、Spearman相关等进行统计分析,比较两组血清FGF19水平的差异,分析其相关影响因素。结果:ICP患者的血清FGF19水平的平均值为116.43 pg/ml,中位数为87.17 pg/ml,明显低于对照组的234.93 pg/ml和176.67 pg/ml,两组间差异具有统计学意义(P<0.05)。ICP患者血清FGF19水平与总胆汁酸浓度呈负相关(r=-0.472,P=0.017),而健康孕妇两个指标间无相关(P>0.05)。血清FGF19水平与ALT、AST、TBil、入组孕周、年龄、孕前BMI、入院BMI均无相关。与健康孕妇比较,ICP患者的血清AST水平较高、孕前BMI较低、分娩孕周更早,两组间差异有统计学意义(P<0.05)。结论:ICP患者血清FGF19水平下降,且与总胆汁酸浓度呈负相关,今后ICP的研究方向可关注FGF19因子上下游通路的激活状态。

Objective In this study,we aimed to investigate the serum FGF19 levels in intrahepatic cholestasis of pregnancy(ICP)and its relative factors.Methods This prospective clinical study was conducted at the Department of Obstetrics,the Third Affiliated Hospital of Sun Yat-sen University.25 women whose pregnancies were complicated with ICP and 25 healthy pregnant women without ICP were recruited for the study group.The fasting blood samples for the FGF19 analyses were prospectively collected.The serum FGF19 concentrations were measured using an enzyme-linked immunosorbent assay,and the serological indicators including ALT,AST,TBA,and TBil were detected by an automatic biochemical analyzer.The patient characteristics,including maternal age,gestational age at the time of diagnosis and delivery,body mass index(BMI),and perinatal outcome were followed up and recorded.Student′s text,Wilcoxon rank sum test,Chi-square test and the Spearman′s rank coefficient of correlation were used for statistical analysis.The differences in serum FGF19 levels between the two groups were compared and the relative factors were analyzed.Results The mean and median levels of maternal serum FGF19 in the ICP cases were 116.43 pg/ml and 87.17 pg/ml,which were significantly lower than in the control group(234.93 pg/ml and 176.67 pg/ml)(P<0.05).A significantly negative correlation was between maternal serum FGF19 levels and maternal serum total bile acid levels in ICP patients(r=-0.472,P=0.017),but there was no correlation between the two indexes in healthy pregnant women(P>0.05).There was no correlation between serum FGF19 levels and serum ALT concentrations,serum AST concentrations,serum TBil concentrations,maternal age,gestational age of at the time of diagnosis,or BMI.Compared with healthy pregnant women,the ICP cases have higher serum AST levels,lower preconception BMI and earlier delivery(P<0.05).Conclusions The serum FGF19 levels decreased in ICP patients and were negatively correlated with the serum total bile acid concentrations.FGF19 may be used as an auxiliary diagnostic factor for ICP.