摘要：
目的 探索聚乙二醇干扰素(PEG-IFNα-2a)初治的HBeAg阳性慢性乙型肝炎(CHB)患者的效果和疗效预测因素.方法 回顾性研究2011年1月-2015年6月于安徽医科大学第二附属医院肝病科就诊的PEG-IFNα-2a初治的HBeAg阳性CHB患者111例.随访基线及治疗后12、24、48周时血清HBsAg定量、HBeAg定量、HBV DNA定量、ALT水平.治疗48周时,111例患者中出现HBeAg血清学转换者35例(48周转换组),未转换者76例(48周末转换组).服从正态分布的计量资料组间比较采用独立样本t检验;非正态分布的计量资料组间比较采用Mann-Whitney U检验.计数资料组间比较采用x2检验.受试者工作特征曲线(ROC曲线)评价各指标预测治疗终点疗效的效能,通过比较ROC曲线下面积(AUC)评估各指标预测价值.二分类logistic 回归分析模型评估各自变量对HBeAg血清学转换影响大小.结果 治疗前2组患者的HBeAg水平比较差异有统计学意义(t=-3.361,P＜0.05);治疗12周时HBsAg定量(t=-3.225)、HBsAg下降情况(Z=-2.202)、HBeAg定量(Z=-5.025)、HBeAg下降情况(Z=-3.569)、HBV DNA定量(Z=-3.261)、HBV DNA下降情况(t=2.202)2组间比较差异均有统计学意义(P值均＜0.05);治疗24周时HBsAg定量(t=-3.222)、HBsAg下降情况(Z=-1.860)、HBeAg定量(Z=-5.951)、HBeAg下降情况(t=5.514)、HBV DNA定量(Z=-2.311)、ALT水平(Z=-2.234)2组间比较差异均有统计学意义(P值均＜0.05).24周HBeAg定量预测价值较高(AUC=0.88,P＜0.001),当截断值为0.18 log10 S/CO时,其灵敏度、特异度、阳性预测值、阴性预测值分别为94.03％、64.52％、85.10％、83.30％.此外12周HBeAg定量(AUC=0.81)和24周HBeAg下降情况(AUC=0.80)也有较好的预测价值.基线HBeAg ＜2.91 log10 S/CO[比值比(OR)=10.086,95％可信区间(95％ CI):1.64 ～61.93,P=0.013]、24周ALT＜1.45倍正常值上限(OR=5.228,95％CI:1.27 ～21.45,P=0.022)和24周HBeAg下降＞1.5 log10 S/CO(OR=5.780,95％ CI:1.38～24.25,P=0.016)为48周HBeAg血清学转换的独立预测因素.结论 基线HBeAg水平,治疗12周时HBsAg、HBeAg、HBV DNA水平及下降情况,治疗24周时HBsAg、HBeAg水平及下降情况以及同期HBV DNA、ALT水平对48周HBeAg血清学转换均有预测价值.%Objective To investigate the clinical effect of pegylated interferon α-2a (PEG-IFNα-2a) in the treatment of previously untreated HBeAg-positive chronic hepatitis B (CHB) patients and related predictive factors.Methods A retrospective analysis was performed for 111 previously untreated HBeAg-positive CHB patients who were treated with PEG-IFNα-2a in Department of Hepatology in the Second Affiliated Hospital of Anhui Medical University from January 2011 to June 2015.The patients were followed up for serum HBsAg quantitation,HBeAg quantitation,HBV DNA quantitation,and alanine aminotransferase (ALT) level at baseline and at weeks 12,24,and 48 of treatment.At week 48 of treatment,of all 111 patients,35 achieved HBeAg seroconversion (48-week seroconversion group) and 76did not achieve such seroconversion (48-week non-seroconversion group).The independent samples t-test was used for comparison of normally distributed continuous data between groups,and the Mann-Whitney U test was used for non-normally distributed continuous data between groups;the chi-square test was used for comparison of categorical data between groups.The receiver operating characteristic (ROC) curve was used to evaluate the efficiency of related indices in predicting treatment outcomes,and the area under the ROC curve (AUC) was compared to evaluate the predictive value of each index.The dichotomous logistic regression model was used to evaluate the influence of independent variables on HBeAg seroconversion.Results There was a significant difference in HBeAg level between the two groups before treatment (t =-3.361,P ＜ 0.05).At week 12 of treatment,there were significant differences between the two groups in HBsAg quantitation (t =-3.225,P ＜ 0.05),reduction in HBsAg (Z =-2.202,P ＜ 0.05),HBeAg quantitation (Z =-5.025,P ＜ 0.05),reduction in HBeAg (Z =-3.569,P ＜ 0.05),HBV DNA quantitation (Z =-3.261,P ＜ 0.05),and reduction in HBV DNA (t =2.202,P ＜ 0.05).At week 24 of treatment,there were significant differences between the two groups in HBsAg quantitation (t =-3.222,P ＜ 0.05),reduction in HBsAg (Z =-1.860,P ＜ 0.05),HBeAg quantitation (Z =-5.951,P ＜ 0.05),reduction in HBeAg (t =5.514,P ＜ 0.05),HBV DNA quantitation (Z =-2.311,P ＜ 0.05),and ALT level (Z =-2.234,P ＜ 0.05).HBeAg quantitation at week 24 had a high predictive value (AUC =0.88,P ＜ 0.001),with a sensitivity of 94.03％,a specificity of 64.52％,a positive predictive value of 85.10％,and a negative predictive value of 83.30％ at a cut-off value of 0.18 log10 S/CO.In addition,HBeAg quantitation at week 12 and reduction in HBeAg at week 24 had a good predictive value (AUC =0.81 and 0.80,respectively).Baseline HBeAg ＜ 2.91 log10S/CO (odds ratio [OR] =10.086,95 ％ confidence interval [CI]:1.64-61.93,P =0.013),ALT ＜ 1.45 x upper limit of normal (ULN) at week 24 (OR =5.228,95％ CI:1.27-21.45,P =0.022),and reduction in HBeAg ＞ 1.5 log10 S/CO at week 24 (OR =5.780,95％ CI:1.38-24.25,P =0.016) were independent predictive factors for HBeAg seroconversion at week 48.Conclusion Baseline HBeAg level,HBsAg/HBeAg/HBV DNA levels and reductions at week 12 of treatment,HBsAg/HBeAg levels and reductions at week 24 of treatment,and HBV DNA and ALT levels at the same time points have a certain value in predicting HBeAg seroconversion at week 48.
