联合聚乙二醇干扰素-α治疗核苷(酸)类似物经治的血清HBsAg低水平的慢性乙型肝炎患者疗效研究  

Study on the efficacy of combined pegylated interferon-αtherapy in chronic hepatitis B patients with low levels of serum HBsAg treated with nucleos(t)ide analogs

作　　者：朱圣涛 谢琴秀[1] ZHU Sheng-tao;XIE Qin-xiu(Department of Infectious Diseases,the First Affiliated Hospital of Anhui Medical University,Hefei Anhui,230000,China)

机构地区：[1]安徽医科大学第一附属医院,安徽合肥230000 [2]安徽省公共卫生临床中心

出　　处：《中西医结合肝病杂志》2023年第12期1061-1064,1068,共5页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

摘　　要：目的:评估核苷(酸)类似物(NAs)经治的慢性乙型肝炎(CHB)血清HBsAg低水平患者接受聚乙二醇干扰素-α(PEG-IFN-α)联合治疗的疗效,并对影响临床疗效的因素进行分析。方法:选取2018年1月至2020年12月收治的NAs经治且血清HBsAg<1500 IU/ml的CHB患者106例,均在原NAs治疗的基础上联合PEG-IFN-α治疗48周。采用实时荧光定量PCR法检测血清HBV DNA,采用化学发光法检测血清HBV标记物。采用Listic回归分析影响疗效的因素,应用受试者工作特征曲线(ROC)计算评价指标的曲线下面积(AUC)。结果:治疗48周时患者HBsAg清除率为39.6%。HBsAg清除组患者的平均年龄和基线HBsAg水平分别为(37.5±8.7)岁和(1.5±1.1)lg IU/ml,均显著低于未清除组(41.3±9.2)岁和(2.4±0.6)lg IU/ml(P<0.05)。多因素Logistic回归分析显示基线HBsAg水平和治疗24周HBsAg下降幅度为治疗48周时HBsAg清除的独立预测因素,而患者治疗前的年龄、性别、BMI、NAs经治时间、乙型肝炎家族史、HBeAg状态、HBV DNA水平与治疗48周时HBsAg清除无显著相关性。经ROC曲线分析,基线HBsAg水平、治疗24周时HBsAg下降幅度对治疗48周时HBsAg清除有预测价值;以血清HBsAg基线水平小于129.1 IU/ml为截断点,其预测的AUC为0.754,敏感度为66.7%,特异度为76.6%;以HBsAg 24周下降幅度>80.1%为截断点,其预测的AUC为0.943,敏感度为97.6%,特异度为81.2%。基线HBsAg水平≤129.1 IU/ml,并在治疗24周时HBsAg下降幅度≥80.06%的患者HBsAg清除率高达93.33%。结论:NAs经治的CHB患者联合PEG-IFN-α治疗可实现更高的HBsAg清除率,基线时HBsAg水平低和治疗时HBsAg下降幅度大是CHB患者治疗48周时获得HBsAg清除的较好预测因素。Objective:Evaluate the efficacy of nucleos(t)ide analogs(NAs)treatment in patients with chronic hepatitis B(CHB)with low serum HBsAg levels,and analyze the factors influencing the therapeutic effect of combination therapy with pegylated interferon-α(PEG-IFN-α).Methods:A total of 106 CHB patients treated with NAs and serum HBsAg<1500 IU/ml were enrolled in our hospital between January 2018 and December 2020,were given the original NAs therapy combined with PEG-IFN-αfor 48 weeks.Serum HBV DNA loads was detected by real-time quantitative polymerase chain reaction,and serum HBV markers were detected by chemiluminescence.Logistic regression was used to analyze the influencing factors,and receiver operating characteristic curves(ROC curves)were used to evaluate its predictive value.Results:The HBsAg clearance rate was 39.6%at 48 weeks.The age and baseline HBsAg level in the HBsAg clearance group were(37.5±8.7)years and(1.5±1.1)lg IU/ml,respectively,which were significantly lower than those in the non-cleared group(41.3±9.2)years and(2.4±0.6)lg IU/ml(P<0.05).Multivariate logistic regression analysis showed that baseline HBsAg levels and HBsAg decline from baseline to week 24 were independent predictors of HBsAg clearance at 48 weeks.There was no significant correlation between age,sex,BMI,NAs treatment time,family history of hepatitis B,HBeAg status and HBV DNA level before treatment and HBsAg clearance at 48 weeks.According to ROC curve analysis,HBsAg baseline concentration and the percentage decrease in HBsAg at week 24 had predictive value for HBsAg clearance.The AUC,sensitivity and specificity were 0.754,66.7%and 76.6%,respectively,when the HBsAg baseline was less than 129.1 IU/mL.The AUC,sensitivity and specificity were 0.943,97.6%and 81.2%,respectively,when the decrease of HBsAg was greater than 80.1%at week 24.Patients with baseline HBsAg levels less than 129.1 IU/mL had clearance rates as high as 93.33%when HBsAg levels decreased by more than 80.06%at week 24.Conclusion:The combination of PEG-IFN-αtherap

关 键 词：慢性乙型肝炎 聚乙二醇干扰素-α 乙型肝炎表面抗原清除 乙型肝炎表面抗原血清转换 

分 类 号：R512.6[医药卫生—内科学]