胆道闭锁患儿胆管上皮细胞维生素D受体表达水平与临床预后的相关性研究

The correlation between the expression levels of vitamin D receptor in bile duct epithelial cells and the prognosis of biliary atresia

目的探索胆道闭锁(biliary atresia,BA)患儿胆管上皮细胞中维生素D受体(vitamin D receptor,VDR)的表达情况,并研究VDR表达水平与临床病理预后的相关性。方法选取2017年1月至2020年12月在西安交通大学第二附属医院小儿外科接受Kasai手术的48例有明确病理结果的BA患儿为研究对象。免疫组织化学法检测胆管上皮细胞VDR表达情况,Masson染色法观察肝组织纤维化程度。根据VDR表达水平将48例BA患儿分为VDR显著低表达组(30例)和正常/高表达组(18例)。收集所有患儿Kasai手术前1周内的实验室检查结果及肝脏剪切波弹性成像(shear wave elastography,SWE)数据。后期随访BA患儿Kasai手术与肝移植手术间隔时间为0~60个月,随访其难治性胆管炎发生率及自体肝中位生存时间。结果BA患儿肝纤维化程度与SWE值呈负相关(r=-0.805,P<0.01)。VDR显著低表达组和VDR正常/高表达组比较,VDR显著低表达组SWE值[(20.57±1.28)kPa vs.(18.02±1.41)kPa,P<0.05]、肝损伤的血生化指标[ALT(215.8±24.7)U/L vs.(182.6±21.2)U/L,P=0.021;AST(165.4±22.3)U/L vs.(139.6±21.4)U/L,P=0.014]、Kasai术后难治性胆管炎发生频率(60.00%vs.22.22%,P=0.037)更高,自体肝中位生存时间(27.00月vs.36.00月,P=0.032)更短。结论BA患儿胆管上皮细胞VDR表达显著降低可能是BA预后不良的标志。

ObjectiveTo investigate the expression of vitamin D receptor(VDR)in biliary epithelial cells of children with biliary atresia(BA)and explore the correlation between VDR epression levels and clinical pathological prognosis.MethodsA total of 48 BA patients who underwent Kasai surgery in the Pediatric Surgery Department of the Second Affiliated Hospital of Xi′an Jiaotong University from January 2017 to December 2020 with confirmed pathological results were selected as the study subjects.Immunohistochemistry was used to determine the expression of VDR in biliary epithelial cells,and Masson staining was used to determine the degree of liver tissue fibrosis.Based on the VDR expression levels,the 48 BA patients were divided into the significantly low VDR expression group(30 cases)and the normal/high expression group(18 cases).Laboratory testing results within 1 week before Kasai surgery and liver shear wave elastography(SWE)data were collected for all patients.Follow-up was conducted for a period of 0 to 60 months after Kasai surgery or liver transplantation,meanwhile,the occurrence of refractory cholangitis and auto-liver survival time were collected.ResultsThere was a negative correlation between the degree of liver fibrosis and SWE value in children with BA(r=-0.805,P<0.01).In comparison between the two groups,the significantly low VDR expression group had higher SWE values[(20.57±1.28)kPa vs.(18.02±1.41)kPa,P<0.05],higher liver injury biochemical indicators[ALT(215.8±24.7)U/L vs.(182.6±21.2)U/L,P=0.021;AST(165.4±22.3)U/L vs.(139.6±21.4)U/L,P=0.014],a higher frequency of post-Kasai surgery refractory cholangitis(60.00%vs.22.22%,P=0.037),and a shorter median autologous liver survival time(27.00 months vs.36.00 months,P=0.032)than those in the normal/high expression group.ConclusionThe significant decrease in VDR expression in biliary epithelial cells may serve as an indicator of poor prognosis in BA.