联合聚乙二醇干扰素-α对恩替卡韦经治HBeAg阳性慢性乙型肝炎患者的疗效和预测因素  

Peginterferon treatment added on to entecavir in HBeAg positive chronic Hepatitis B patients:efficacy and predictive factors

作　　者：陈璐[1] 郭斯敏[1] 庄焱[1] 赵钢德[1] 周惠娟[1] 郭清[1] 杨菁[1] 蔡伟[1] 王晖[1] 谢青[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院感染科,200025

出　　处：《肝脏》2015年第6期434-437,共4页Chinese Hepatology

基　　金：国家自然科学基金资助项目(81171569);上海市科委优秀学术带头人项目(12XD1403600);国家"十二五"科技重大专项(2012ZX10002007-002-004;2012ZX10002004-003;2012ZX10002003-003-012;2013ZX10002001-001-004);上海市领军人才资助项目;国家临床重点专科建设项目(感染病学)

摘　　要：目的：探讨恩替卡韦（ETV）治疗HBeAg阳性慢性乙型肝炎患者获得病毒学应答后，加用聚乙二醇干扰素（Peg‐IFNα）的疗效和预测因素。方法 HBeAg阳性慢性乙型肝炎患者经过 ETV治疗6个月以上获得病毒学应答者84例，分成继续ET V单药治疗组45例和ET V基础上加用Peg‐IFNα联合治疗组39例，分别继续治疗24～48周。检测基线和治疗期间血清HBV DNA载量、HBV血清学标志物、肝功能指标。以 HBsAg下降幅度和 HBsAg≤150 IU／mL为主要疗效评价指标，以 HBeAg清除和HBeAg血清学转换为次要疗效评价指标，同时分析基线HBsAg水平对Peg‐IFN疗效的影响。组间差异采用Fisher检验。结果联合治疗组治疗结束时患者 HBsAg下降幅度明显大于ET V单药组（单药组为0．24 lg IU／mL ，联合治疗组为0．61 lg IU／mL ，P＝0．0007），且HBsAg≤150 IU／mL患者的比例也明显多于单药组（单药组为11．1％，联合治疗组为30．8％，P＝0．0315）。两组的 HBeAg清除和 HBeAg血清学转换相比较均差异无统计学意义。基线 HBsAg≤1500 IU／mL的患者，在加用Peg‐IFN治疗结束时 HBsAg≤150 IU／mL、HBeAg清除的患者比例均明显高于基线HBsAg＞1500 IU／mL的患者（HBsAg≤150 IU／mL ：66．7％比14．8％， P＝0．0024；HBeAg清除：58．3％比22．2％，P＝0．0272）。结论联合Peg‐INFα对已经获得病毒学应答的ETV经治患者可以获得更高的 HBsAg下降以及HBsAg≤150 IU／mL的概率，基线HBsAg≤1500 IU／mL患者加用Peg‐IFN能够获得更好的免疫控制。Objective To investigate the efficacy of peginterferon （Peg‐IFN） in chronic HBV patients who had been treated with entecavir （ETV） for more than 6 months and achieved viral response without HBeAg loss .Methods CHB patients who maintained viral response without HBeAg loss after ETV treatment were randomly divided into two groups . One group continued to be treated with ETV alone ,while the other group was subjected to ETV in combination with Peg‐IFN for 24 to 48 weeks .Serum levels of HBV DNA ,HBV serological markers ,peripheral polymorphonuclear leukocytes and platelet counts ,liver and renal functions were measured at baseline and during the treatment .The decrease amplitude of HBsAg and HBsAg≤150 IU/ml were the primary endpoints ,and HBeAg clearance and seroconversion were the secondary endpoints .We also analyzed the effect of baseline HBsAg levels on the Peg‐IFN add‐on efficacy .Inter‐group differences were compared using Fisher＆#39;s Test .Results 84 patients were enrolled and analyzed .Higher decrease amplitude of HBsAg was observed in peginterferon add‐on patients than ETV‐alone treated patients （ 0 .61 lg IU/mL vs 0 .24 lg IU/mL ,P=0 . 0007） .And there are more patients achieving HBsAg ≤ 150 IU/mL at the end of treatment in Peg‐IFN add‐on group comparing to the ETV‐alone treated ones （30 .8% vs 11 .1% , P=0 .0315） .No statistic differences in HBeAg loss and HBeAg seroconversion were observed between the two groups .Moreover ,patients with baseline HBsAg ≤1500 IU/mL＆amp;nbsp;achieved more HBeAg loss and HBsAg≤150 IU/mL at the end of Peg‐IFN added‐on treatment （HBsAg≤150 IU/mL ：66 . 7% vs 14 .8% ,P=0 .0024 ;HBeAg clearance：58 .3% vs 22 .2% ,P=0 .0272） .Conclusion Peginterferon added on to entecavir could get higher HBsAg decrease and more patients with HBsAg≤150 IU/mL in those who had been treated with ETV for more than 6 months and got viral response .Patients with baseline HBsAg ≤ 1500 IU/mL could achieve more HBsAg≤150 IU/mL and HBeAg lo

关 键 词：肝炎  乙型  慢性 聚乙二醇干扰素 核苷类药物 乙型肝炎表面抗原 乙型肝炎E抗原 

分 类 号：R512.62[医药卫生—内科学]