血清NLR、sVCAM-1和IGFBP-3水平与妊娠期肝内胆汁淤积症病情程度和疾病预后的相关性

Correlation of serum NLR,sVCAM-1 and IGFBP-3 levels with the severity and prognosis of intrahepatic cholestasis during pregnancy

目的探讨血清中性粒细胞/淋巴细胞比值(NLR)、可溶性血管细胞黏附因子-1(sVCAM-1)和胰岛素样生长因子结合蛋白3(IGFBP-3)水平检测在妊娠期肝内胆汁淤积症(ICP)病情和预后评估的价值。方法将2019年1月-2021年12月南通大学附属海安医院收治的83例ICP孕妇列入观察组,根据血清总胆汁酸(TBA)水平分为轻度亚组(n=34)、中度亚组(n=30)和重度亚组(n=19),根据妊娠结局分为良好亚组(n=65)和不良亚组(n=18);选择同期产检和分娩的健康产妇35名列入对照组。检测比较观察组和对照组、观察组中不同病情严重程度和不同妊娠结局亚组的NLR、sVCAM-1和IGFBP-3水平,Pearson分析NLR、sVCAM-1和IGFBP-3水平与血清ALT、TBil水平以及胎儿生长受限(FGR)和术后出血量的相关性,绘制ROC分析单独和联合检测NLR、sVCAM-1和IGFBP-3水平对ICP病情和预后的评估效能。结果观察组的NLR和sVCAM-1分别为(3.76±0.85)和(769.50±69.53)pg/L,高于对照组的(1.82±0.49)和(423.29±48.37)pg/L,观察组的IGFBP-3为(4.38±0.72)μg/L,低于对照组的(5.73±0.96)μg/L,差异有统计学意义(t=9.528、15.947、11.852,均P<0.05)。观察组重度亚组的NLR和sVCAM-1分别为(4.86±1.02)和(952.41±89.76)pg/L,高于中度和轻度亚组的(3.90±0.85)、(734.65±67.53)pg/L和(2.71±0.69)、(564.52±55.49)pg/L;重度亚组的IGFBP-3为(2.36±0.42)μg/L,低于中度和轻度亚组的(2.93±0.54)μg/L和(3.58±0.67)μg/L,差异有统计学意义(Z=23.924、36.571、17.862,均P<0.05)。观察组妊娠结局不良亚组的NLR和sVCAM-1分别为(4.95±1.05)和(971.46±92.35)pg/L,高于良好亚组的(3.67±0.78)和(698.75±63.24)pg/L,不良亚组的IGFBP-3为(2.24±0.39)μg/L,低于良好亚组的(3.12±0.58)μg/L,差异有统计学意义(t=8.207、7.853、7.426,均P<0.05)。Pearson分析显示,观察组的NLR和sVCAM-1与ALT、TBil和术后出血量呈正相关,与FGR呈负相关;IGFBP-3与FGR呈正相关,与ALT、TBil和术后出血量呈负相关(P<0.01)。ROC显示,NLR、sVCAM-1和IGFBP-3水平单独及联合检测评估ICP的AUC分别为0.691、0.638、0.725和0.914,联合检测的敏感度和特异度均高于任一单项检测,差异有统计学意义(P<0.01)。结论血清NLR、sVCAM-1和IGFBP-3水平联合检测对ICP患者的病情程度和预后评估的临床价值较高。

Objective To investigate the value of serum neutrophil/lymphocyte ratio(NLR),soluble vascular cell adhesion factor-1(sVCAM-1)and insulin-like growth factor binding protein 3(IGFBP-3)in the diagnosis and prognosis of intrahepatic cholestasis during pregnancy(ICP).Methods A total of 83 pregnant women with ICP admitted from January 2019 to December 2021 were included in the observation group.They were divided into mild subgroup(n=34),moderate subgroup(n=30)and severe subgroup(n=19)according to serum TBA level.Based on pregnancy outcomes,they were further classified into good outcome subgroup(n=65)and poor outcome subgroup(n=18).Meanwhile,35 healthy pregnant women who underwent prenatal checkups and delivery during the same period were included in the control group.The levels of NLR,SVCAM-1 and IGFBP-3 were compared between the observation group and the control group,as well as among the subsets of the observation group categorized by disease severity and different pregnancy outcomes.Pearson analysis was used to examine the correlation of NLR,sVCAM-1 and IGFBP-3 levels with serum ALT,TBil levels,fetal growth restriction(FGR)and postoperative blood loss.ROC curves were constructed to assess the diagnostic and prognostic efficacy of individual and combined measurements of NLR,sVCAM-1 and IGFBP-3 levels for ICP.Results The NLR and sVCAM-1 levels in the observation group were 3.76±0.85 and 769.50±69.53 pg/L respectively,which were significantly higher than those in the control group(1.82±0.49 and 423.29±48.37 pg/L respectively).Additionally,the IGFBP-3 level in the observation group was 4.38±0.72μg/L.The differences were statistically significant(t=9.528,15.947,11.852,all P<0.05).The NLR and sVCAM-1 levels in the severe subgroup were 4.86±1.025 and 952.41±89.76 pg/L respectively,higher than those in both the moderate(3.90±0.85 and 734.65±67.53 pg/L)and mild subgroups(2.71±0.69 and 564.52±55.49 pg/L respectively).The IGFBP-3 level in the severe subgroup was 2.36±0.42μg/L,lower than those in the moderate and mild subgroups(2.93±0.54μg/L and 3.58±0.67μg/L respectively),the differences were statistically significant(F=23.924,36.571,17.862,all P<0.05).The NLR and SVCAM-1 levels of the poor outcome subgroup were 4.95±1.05 and 971.46±92.35 pg/L respectively,which were higher than those of the good outcome subgroup(3.67±0.78 and 698.75±63.24 pg/L respectively).Moreover,the IGFBP-3 level in the poor outcome subgroup was 2.24±0.39μg/L,significantly lower than the 3.12±0.58μg/L observed in the good outcome subgroup,the differences were statistically significant(t=8.207,7.853,7.426,all P<0.05).Pearson analysis showed that in the observation group,NLR and sVCAM-1 were positively correlated with ALT,TBIL,and postoperative blood loss,and negatively correlated with FGR.IGFBP-3 was positively correlated with FGR,but negatively correlated with ALT,TBIL and postoperative blood loss(P<0.01).ROC curve revealed that the AUC values for the evaluation of ICP using NLR,sVCAM-1 and IGFBP-3 levels individually and in combination were 0.691,0.638,0.725 and 0.914,respectively.The sensitivity and specificity of combined detection were both higher than any single test,and the difference was statistically significant(P<0.01).Conclusion The combined detection of serum NLR,sVCAM-1 and IGFBP-3 levels has high clinical value in evaluating the severity and prognosis of ICP patients.