早期血清前S1抗原(PreS1)对干扰素α治疗的HBeAg阳性慢性乙型肝炎儿童HBsAg阴转的预测价值  

Value of serum PreS1 in early prediction of HBsAg clearance after IFN-αtreatment in children with HBeAg-positive chronic hepatitis B

作　　者：樊佩瑶 王福川 高银杰 徐志强 董漪 闫建国 曹丽丽 冯丹妮 钟彦伟 张敏[1,2] FAN Peiyao;WANG Fuchuan;GAO Yinjie;XU Zhiqiang;DONG Yi;YAN Jianguo;CAO Lili;FENG Danni;ZHONG Yanwei;ZHANG Min(Peking University 302 Clinical Medical School,Beijing 100191,China;Department of Liver Diseases,The Fifth Medical Center of Chinese PLA General Hospital,Beijing 100039,China)

机构地区：[1]北京大学三〇二临床医学院,北京100191 [2]解放军总医院第五医学中心肝病学部,北京100039

出　　处：《临床肝胆病杂志》2023年第8期1825-1831,共7页Journal of Clinical Hepatology

基　　金：国家科技重大专项(2018ZX10301404);北京市科技计划项目(Z201100005520048);首都临床诊疗技术研究及转化应用项目(Z201100005520048)。

摘　　要：目的探讨血清前S1抗原(PreS1)水平作为预测干扰素α(IFN-α)治疗48周的HBeAg阳性慢性乙型肝炎(CHB)儿童HBsAg转阴指标的价值。方法纳入2016年6月—2020年1月接受IFN-α治疗48周的88例1~16岁HBeAg阳性CHB患儿,每3个月评估患儿的HBsAg定量(qHBsAg)、HBV DNA定量、ALT等,并采用磁微粒化学发光免疫分析法(双抗体夹心法)检测PreS1水平。根据IFN-α治疗48周终点时HBsAg是否转阴分为转阴组(n=17)和未转阴组(n=71)。计量资料的两组间比较采用Mann-Whitney U检验,计数资料的两组间比较采用χ^(2)检验或Fisher精确检验。用Spearman秩相关检验评估PreS1水平和其他生物标志物之间的关系。用受试者工作特征曲线下面积(AUC)评估不同标志物对IFN-α治疗48周终点HBsAg转阴的预测价值。结果PreS1水平与血清qHBsAg、HBV DNA水平呈正相关(r值分别为0.912、0.535,P值均<0.05)。基线时,PreS1/qHBsAg比值(AUC=0.694)较PreS1水平(AUC=0.530)和qHBsAg水平(AUC=0.514)具有较好的48周HBsAg转阴预测价值。治疗12周的PreS1水平(AUC=0.867,P<0.001)和PreS1/qHBsAg比值下降量(AUC=0.800,P=0.002)均对48周终点时HBsAg转阴有很好的预测作用。治疗24周的PreS1水平、qHBsAg水平和HBV DNA均可有效预测第48周的HBsAg转阴,AUC分别为0.917、0.949和0.762(P值均<0.001)。结论治疗12周时血清PreS1水平和PreS1/qHBsAg比值下降量是预测IFN-α治疗期间CHB患儿HBsAg转阴的候选标志物。Objective To investigate the value of PreS1 level in predicting HBsAg clearance in children with HBeAg-positive chronic hepatitis B(CHB)after 48 weeks of IFN-αtreatment.Methods A total of 88 children with HBeAg-positive CHB,aged 1-16 years,who received 48 weeks of IFN-αtreatment from June 2016 to January 2020 were enrolled.HBsAg quantification(qHBsAg),HBV DNA quantification,and alanine aminotransferase were measured every three months,and magnetic particle chemiluminescence immunoassay(double-antibody sandwich)was used to measure the level of PreS1.Acc ording to whether HBsAg clearance was achieved at the end of IFN-αtreatment for 48 weeks,the 88 children were divided into HBsAg clearance group with 17 children and non-HBsAg clearance group with 71 children.The Mann-Whitney U test was used for comparison of quantitative data between the two groups,and the chi-square test or the Fisher’s exact test was used for comparison of qualitative data between the two groups.The Spearman rank correlation test was used to evaluate the correlation of PreS1 level with other biomarkers,and the area under the ROC curve(AUC)was used to investigate the value of different markers in predicting HBsAg clearance at the end of 48-week IFN-αtreatment.Results PreS1 level was positively correlated with the serum levels of qHBsAg and HBV DNA(r=0.912 and 0.535,both P<0.05),and baseline PreS1/qHBsAg ratio(AUC=0.694)had a better value than PreS1 level(AUC=0.530)and qHBsAg level(AUC=0.514)in predicting HBsAg clearance at week 48.PreS1 level(AUC=0.867,P<0.001)and the reduction in PreS1/qHBsAg ratio(AUC=0.800,P=0.002)at week 12 of treatment had a good value in predicting HBsAg clearance at week 48.PreS1 level,qHBsAg level,and HBV DNA at week 24 of treatment could effectively predict HBsAg clearance at week 48,with AUCs of 0.917,0.949,and 0.762,respectively(all P<0.001).Conclusion Serum PreS1 level and the reduction in PreS1/qHBsAg ratio at week 12 of treatment can be used as candidate markers for predicting HBsAg clearance in children with

关 键 词：PRES1 生物标记 乙型肝炎 慢性 儿童 干扰素Α 

分 类 号：R725.1[医药卫生—儿科]