血清N-聚糖生物标志物预测抗病毒治疗慢性乙型肝炎患者肝纤维化改善的临床意义

Clinical significance of serum N-glycan markers for monitoring liver fibrosis regression in chronic hepatitis B patients receiving antiviral therapy

目的本研究旨在探究血清N-聚糖变化预测抗病毒治疗慢性乙型肝炎(乙肝)患者肝纤维化改善的可能性。方法本研究共纳入2013—2020年在全国33家医院招募的符合入组标准的128例慢性乙肝患者,全部患者均完成78周的抗病毒治疗和随访,在基线和78周均进行肝组织活检。采用Ishak评分系统评估患者肝组织纤维化程度。应用基于DNA测序仪的荧光糖电泳技术检测患者血清N-聚糖图谱。利用随机森林(random forest,RF)、支持向量机(support vector machine,SVM)和逻辑回归(logistics regression,LR)方法构建血清N-聚糖RF-R、SVM-R和LR-R模型,预测抗病毒治疗患者肝纤维化改善情况。结果经78周抗病毒治疗,89例(69.53%)慢性乙肝患者实现肝纤维化改善(Ishak评分至少下降1分),糖峰1~7变化值与肝纤维化改善显著相关。建模组中,血清N-聚糖RF-R、SVM-R和LR-R模型预测肝纤维化改善的受试者工作特征曲线下面积(area under receiver operating characteristic curve,AUROC)分别为0.97、0.97和0.69,与肝组织活检的符合率分别为89.77%、84.09%和69.32%。验证组中得到相似的结果。结论血清N-聚糖模型可作为监测抗病毒治疗慢性乙肝患者肝纤维化改善的潜在生物标志物。

Objective To investigate the role of serum N-glycan markers for monitoring liver fibrosis regression in chronic hepatitis B patients receiving antiviral therapy.Methods A total of 128 chronic hepatitis B patients recruited from 33 hospitals nationwide during 2013—2020 had received antiviral therapy of 78 weeks and been followed-up for every 3-month.All patients had undergone liver biopsy at baseline and 78-week,and the liver fibrosis stages were assessed using the Ishak scoring system.Serum N-glycan profiles were analyzed using DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis(DSA-FACE).Serum N-glycan RF-R,SVM-R and LR-R models were constructed by random forest(RF),support vector machine(SVM)and logistic regression(LR)analysis,to predict the regression of liver fibrosis in patients receiving antiviral therapy.Results After antiviral therapy of 78 weeks,89(69.53%)chronic hepatitis B patients achieved liver fibrosis regression(Ishak score decreased by at least 1 point).The changes of serum N-glycan peaks 1~7 were associated with liver fibrosis regression.In the training cohort,the diagnostic area under receiver operating characteristic curve(AUROC)of the serum N-glycan RF-R,SVM-R and LR-R models were 0.97,0.97 and 0.69,respectively,and the coincidence rate with liver biopsy were 89.77%,84.09%and 69.32%,respectively.Similar results had been observed in the validation group.Conclusions Serum N-glycan biomarkers may predict liver fibrosis regression for chronic hepatitis B patients receiving antiviral therapy.