血清可溶性甘露糖受体在慢性乙型肝炎患者中的表达及诊断肝纤维化的价值

Diagnostic value of serum soluble mannose receptor for hepatic fibrosis in patients with chronic hepatitis B

目的探讨血清可溶性甘露糖受体(sMR)在慢性乙型肝炎(CHB)肝纤维化中的表达及预测价值。方法选取2016年11月至2018年10月在浙江省台州医院感染科住院行肝穿刺活检的CHB患者50例,其中男28例,女22例。根据肝纤维化分期分为无纤维化组(S0)15例,轻度纤维化组(S1~2)20例,中重度纤维化组(S3~4)15例。另选取20名健康体检者作为对照,其中男12名,女8名。应用酶联免疫吸附试验(ELISA)检测各组肝纤维化血清标志物透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原N端肽(PⅢP)、Ⅳ型胶原(CIV)和sMR的表达水平。采用单因素方差分析、Spearman秩相关及受试者工作特征曲线(Receiver operating characteristic,ROC)对数据进行分析。结果S3~4组患者血清中的sMR、HA、LN、CIV和PⅢP水平均高于S0组(t=10.20、4.69、8.94、2.35和4.34,P值<0.05)和S1~2组(t=5.77、4.23、7.88、2.71和3.43,P值均<0.05),且S1~2组患者血清中的sMR水平高于S0组(t=6.23,P<0.05)。Spearman秩相关分析显示,血清sMR与肝组织纤维化程度呈正相关(r=0.860,P<0.01)。ROC曲线分析发现,sMR>228.69 ng/mL时可以预测有无肝纤维化发生,sMR的特异度和敏感度为93.3%和88.6%,诊断效能分别优于HA、LN、CIV和PⅢP(Z=3.179、3.467、5.241和3.567,P值均<0.05)。sMR>345.80 ng/mL可以预测有无中重度肝纤维化发生,其诊断的特异度和敏感度为85.7%和86.7%,诊断效能分别优于HA、CIV和PⅢP(Z=2.253、2.475和2.092,P值均<0.05)。结论sMR与肝纤维化进展有关,有望成为无创性评估肝纤维化的新型血清学标志物。

Objective To assess the diagnostic value of serum soluble mannose receptor(sMR)for hepatic fibrosis in patients with chronic hepatitis B(CHB).Methods Fifty patients with CHB undergoing liver biopsy in the Department of Infectious Diseases,Taizhou Hospital of Zhejiang Province from November 2016 to October 2018 were enrolled,including 28 males and 22 females.According to the stage of liver fibrosis,there were 15 cases without fibrosis(S0 group),12 cases of mild fibrosis(S1-2 group),and 15 cases of moderate-severe fibrosis(S3-4 group).Twenty healthy subjects(12 males and 8 females)were recruited as controls.Enzyme linked immunosorbent assay(ELISA)was used to detect the serum hyaluronic acid(HA),laminin(LN),procollagen typeⅢN-terminal peptide(PⅢP),collagen type IV(CIV)and sMR in all groups.One-way ANOVA,Spearman correlation analysis and receiver operating characteristic(ROC)curve were used to analyze the data.Results The serum levels of sMR,HA,LN,CIV and PⅢP in S3-4 group were significantly higher than those in S0 group(t=10.20,4.69,8.94,2.35 and 4.34,respectively;all P<0.05)and S1-2 group(t=5.77,4.23,7.88,2.71 and 3.43,respectively;all P<0.05);and serum sMR level in S1-2 group was higher than that in S0 group(t=6.23,P<0.05).Spearman rank correlation demonstrated that serum sMR level was positively correlated with the degree of liver fibrosis(r=0.860,P<0.01).ROC curve analysis showed that when 228.69 ng/mL was taken as cut-off value of sMR,its specificity and sensitivity for diagnosis of hepatic fibrosis were 93.3%and 88.6%,respectively.The diagnostic efficacy of sMR was significantly better than that of HA,LN,CIV and PⅢP(Z=3.179,3.467,5.241 and 3.567,respectively;all P<0.05).When 345.80 ng/mL was taken as cut-off value of sMR,the specificity and sensitivity for diagnosis of moderate to severe hepatic fibrosis were 85.7%and 86.7%,respectively;and its diagnostic efficacy was better than that of HA,CIV and PⅢP(Z=2.253,2.475 and 2.092,all P<0.05).Conclusion Serum sMR level is associated with the progression of liver fibrosis,it may be used as a new serological marker for non-invasive assessment of liver fibrosis.