核苷(酸)类似物序贯派格宾治疗慢性乙型肝炎实现功能性治愈的预测因素  

Predictive factors for functional cure after sequential therapy with nucleos (t) ide analogues and pegylated interferon alfa-2b in treatment of chronic hepatitis B

作　　者：臧海洋 李伟娜[3] 刘守胜 周永 辛永宁[2] ZANG Haiyang;LI Weina;LIU Shousheng;ZHOU Yong;XIN Yongning(School of Clinical Medicine,Weifang Medicine University,Weifang,Shandong 261000,China;Department of Infectious Diseases,Qingdao Municipal Hospital,Qingdao,Shandong 266011,China;Second Department of Gastroenterology,Qingdao Municipal Hospital,Qingdao,Shandong 266011,China;Clinical Research Center,Qingdao Municipal Hospital,Qingdao,Shandong 266011,China;Second Department of Gastroenterology,Qingdao Sixth People’s Hospital,Qingdao,Shandong 266011,China)

机构地区：[1]潍坊医学院临床医学院,山东潍坊261000 [2]青岛市市立医院感染性疾病科,山东青岛266011 [3]青岛市市立医院消化内二科,山东青岛266011 [4]青岛市市立医院临床研究中心,山东青岛266011 [5]青岛市第六人民医院消化内二科,山东青岛266011

出　　处：《临床肝胆病杂志》2023年第2期299-306,共8页Journal of Clinical Hepatology

基　　金：国家自然科学基金(32171277)。

摘　　要：目的 探究长期核苷(酸)类似物(NUC)抗病毒治疗后序贯派格宾(聚乙二醇干扰素α-2b)治疗的慢性乙型肝炎(CHB)患者实现功能性治愈的独立预测因素。方法 以青岛市多家医院2018年—2021年收治的CHB患者共162例为研究对象,所有患者均应用派格宾治疗至少48周,且在派格宾治疗前经过了1年及以上的NUC治疗。根据派格宾治疗48周时是否实现HBsAg阴转将入组患者分为功能性治愈组(79例)和未治愈组(82例),比较两组患者相关临床指标的差异。定量资料两组间比较采用两独立样本t检验和Mann-Whitney U秩和检验;定性资料两组间比较采用χ~2检验。相关性分析采用Spearman检验。单因素和多因素Logistic回归分析实现功能性治愈的独立预测因素。绘制相关变量的受试者工作特征曲线(ROC曲线),以曲线下面积(AUC)评估变量的预测准确度。结果 功能性治愈组患者的基线HBsAg显著低于未治愈组[21.63(3.33~157.60)IU/mL vs 794.70(336.10~1 185.34)IU/mL,Z=-8.869,P<0.001],派格宾治疗12周的HBsAg显著低于未治愈组[1.34(0.04~16.59)IU/mL vs 567.11(226.09~1 047.86)IU/mL,Z=-9.847,P<0.001],派格宾治疗24周的HBsAg显著低于未治愈组[0.01(0.00~0.34)IU/mL vs 304.79(89.24~772.23)IU/mL,Z=-10.474,P<0.001],派格宾治疗12周的HBsAg下降程度显著高于未治愈组[89.6%(57.5%~99.4%) vs 21.8%(2.0%~40.9%),Z=-7.926,P<0.001],派格宾治疗24周的HBsAg下降程度显著高于未治愈组[99.9%(99.0%~100.0%) vs 44.1%(20.6%~73.8%),Z=-9.593,P<0.05],基线HBeAg阳性率显著低于未治愈组(8.9%vs 25.3%,χ~2=7.652,P=0.006),基线HBV DNA>1000 IU/mL的比例显著低于未治愈组(0 vs 8.4%,χ~2=5.073,P=0.024),基线总胆红素显著低于未治愈组[12.60(10.12~15.93)μmol/L vs 15.50(11.80~24.10)μmol/L,Z=-3.611,P<0.001],治疗12周的AST显著高于未治愈组[47.00(34.00~68.00)U/L vs 41.00(30.00~56.50)U/L,Z=-2.031,P=0.042],治疗12周AST>2倍正常值上限比例显著高于未治愈组(16.5%vs 4.8%,χ~2=5.835,P=0.Objective To investigate the independent predictive factors for functional cure after long-term nucleos(t)ide analogue(NUC) antiviral therapy followed by pegylated interferon α-2b therapy in chronic hepatitis B(CHB) patients.Methods A total of 162 CHB patients who were admitted to several hospitals in Qingdao,China,from 2018 to 2021 were enrolled as subjects,and all patients received pegylated interferon α-2b for at least 48 weeks after NUC therapy for one year or longer.According to whether HBsAg clearance was achieved at week 48 of pegylated interferon α-2b treatment,the patients were divided into functional cure group with 79 patients and non-cure group with 83 patients,and related clinical indices were compared between the two groups.The two-independent-samples t test and the Mann-Whitney U rank sum test were used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.The Spearman correlation analysis was performed,and the univariate and multivariate logistic regression analyses were used to investigate the independent predictive factors for functional cure.The receiver operating characteristic(ROC) curve was plotted for related variables,and the area under the ROC curve(AUC) was used to evaluate the prediction accuracy of the variables.Results Compared with the non-cure group,the functional cure group had a significantly lower HBsAg level at baseline [21.63(3.33-157.60) IU/mL vs 794.70(336.10-1 185.34) IU/mL,Z=-8.869,P1000 IU/mL(0 vs 8.4%,χ~2=5.073,P=0.024),a significantly lower level of total bilirubin at baseline [12.60(10.12-15.93) μmol/L vs 15.50(11.80-24.10) μmol/L,Z=-3.611,P2×upper limit of normal(16.5% vs 4.8%,χ~2=5.835,P=0.016).The multivariate logistic regression analysis showed that baseline HBsAg(odds ratio [OR]=0.996,95% confidence interval [CI]:0.995-0.997,P<0.001),HBsAg at week 12 of pegylated interferon α-2b treatment(OR=0.990,95%CI:0.986-0.994,P<0.001),HBsAg at week 24 of pegylated interferon α-2b t

关 键 词：乙型肝炎 慢性 抗病毒药 聚乙二醇干扰素Α-2B 乙型肝炎表面抗原 

分 类 号：R512.62[医药卫生—内科学]