聚乙二醇干扰素α-2a初治HBeAg阳性慢性乙型肝炎患者的效果及预测因素分析

娄鑫; 郜玉峰; 叶珺; 王殷秋; 管子姝; 邹桂舟

doi:10.3969/j.issn.1001-5256.2018.05.014

聚乙二醇干扰素α-2a初治HBeAg阳性慢性乙型肝炎患者的效果及预测因素分析

DOI: 10.3969/j.issn.1001-5256.2018.05.014

安徽医科大学第二附属医院肝病科

基金项目:

安徽省自然科学基金(1608085MH164)；

详细信息

中图分类号: R512.62
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出版历程
- 收稿日期: 2017-11-06
- 出版日期: 2018-05-20

Clinical effect of pegylated interferon α-2a in treatment of previously untreated HBeAg-positive chronic hepatitis B patients and related predictive factors

Department of Hepatology, The Second Affiliated Hospital of Anhui Medical University

Research funding:

摘要

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HBs Ag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周未转换组）。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χ2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HBs Ag定量（t=-3.225）、HBs Ag下降情况（Z=-2....
- 肝炎,乙型,慢性 /
- 聚乙烯二醇类 /
- 干扰素类 /
- 肝炎e抗原,乙型 /
- 治疗结果
Abstract: Objective To investigate the clinical effect of pegylated interferon α-2 a ( PEG-IFNα-2 a) 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-2 a 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 HBs Ag quantitation, HBeAg quantitation, HBV DNA quantitation, and alanine aminotransferase ( ALT) level at baseline and at weeks 12, 24, and48 of treatment. At week 48 of treatment, of all 111 patients, 35 achieved HBeAg seroconversion ( 48-week seroconversion group) and 76 did 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 HBs Ag quantitation ( t =-3. 225, P < 0. 05) , reduction in HBs Ag ( 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 HBs Ag quantitation ( t =-3. 222, P < 0. 05) , reduction in HBs Ag ( 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 of85. 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 log10 S/CO ( odds ratio [OR]= 10. 086, 95% confidence interval [CI]: 1. 64-61. 93, P = 0. 013) , ALT < 1. 45 × 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, HBs Ag/HBeAg/HBV DNA levels and reductions at week 12 of treatment, HBs Ag/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.
- hepatitis B, chronic /
- polyethylene glycols /
- interferons /
- hepatitis B e antigens /
- treatment outcome

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参考文献(12)

[1] Chinese Society of Hepatology, Chinese Society of Infectious Diseases, Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B (2010 version) [J].J Clin Hepatol, 2011, 27 (1) :I-XVI. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.慢性乙型肝炎防治指南 (2010年版) [J].临床肝胆病杂志, 2011, 27 (1) :I-XVI.

[2]WANG YJ, YANG L, ZUO JP.Recent developments in antivirals against hepatitis B virus[J].Virus Res, 2016, 213 (1) :205-213.

[3]KIM V, ABREU RM, NAKAGAWA DM, et al.Pegylated interferon alfa for chronic hepatitis B:systematic review and meta-analysis[J].J Viral Hepat, 2016, 23 (3) :154-169.

[4]ALIMUJIANG MLAS, BULIBULI MNF, GULIJIAZIYILA, et al.Effect of different therapeutic regimen in the treatment of HBe Agpositive chronic hepatitis B and the influence on the serum IFN-γand IL-10[J].China Med Herald, 2017, 14 (5) :137-140. (in Chinese) 阿力木江·毛拉艾沙, 布力布力·马那甫, 古丽加孜依拉, 等.不同用药方案治疗HBe Ag阳性慢性乙型肝炎的效果及对血清IFN-γ、IL-10的影响[J].中国医药导报, 2017, 14 (5) :137-140.

[5]PENG H, WEI F, LIU JY, et al.Response-guided therapy of regimens based on PEG-interferon for chronic hepatitis B using on-treatment hepatitis B surface antigen quantification:a meta-analysis[J].Hepatol Int, 2015, 9 (4) :543-557.

[6]PIRATVISUTH T, MARCELLIN P, POPESCU M, et al.Hepatitis B surface antigen:association with sustained response to peginterferon alfa-2a in hepatitis B e antigen-positive patients[J].Hepatol Int, 2013, 7 (2) :429-436

[7]WANG YC, YANG SS, SU CW, et al.Predictors of response to pegylated interferon in chronic hepatitis B:a real-world hospitalbased analysis[J].Sci Rep, 2016, 6:29605.

[8]ZHANG HY, ZHOU P, GONG ZJ.Predictive value of HBs Ag quantification in pegylated interferon therapy for chronic hepatitis B[J].J Clin Hepatol, 2016, 32 (5) :977-980. (in Chinese) 张海月, 周培, 龚作炯.HBs Ag定量检测对聚乙二醇干扰素治疗慢性乙型肝炎效果的预测价值[J].临床肝胆病杂志, 2016, 32 (5) :977-980.

[9]ZHANG N, YAN XB, HAO JG, et al.Changes and clinical significance of quantitative hepatitis B surface antigen in patients with chronic hepatitis B receiving interferon therapy[J/CD].Chin J Exp Clin Infect Dis:Electronic Edition, 2016, 10 (2) :146-150. (in Chinese) 张楠, 颜学兵, 郝俊贵, 等.HBs Ag定量在慢性乙型肝炎患者干扰素抗病毒治疗中的变化及临床意义[J/CD].中华实验和临床感染病杂志:电子版, 2016, 10 (2) :146-150.

[10]SONNEVELD MJ, RIJCKBORST V, BOUCHER CA, et al.Prediction of sustained response to peginterferon alfa-2b for hepatitis B e antigen-positive chronic hepatitis B using on-treatment hepatitis B surface antigen decline[J].Hepatology, 2010, 52 (4) :1251-1257.

[11]YANG S, XING H, WANG Y, et al.HBs Ag and HBe Ag in the prediction of a clinical response to peginterferonα-2b therapy in Chinese HBe Ag-positive patients[J].Virol J, 2016, 13 (1) :180-188.

[12]LIN ZH, WANG BB, LIN XF, et al.Clinical efficacy and influencing factors of IFN-αtreatment on chronic hepatitis B[J].Chin J Biochem Pharmaceut, 2014, 34 (2) :99-100.

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