聚乙二醇干扰素-α-2a治疗24周应答不佳的乙型肝炎e抗原阳性的慢性乙型肝炎患者优化治疗分析  

Optimized strategy peginterferon-α-2a therapy for hepatits B e antigen positive chronic hepatitis B patients with suboptimal response at 24 weeks

作　　者：梁雪松[1] 李成忠[1] 尹伟[1] 范文瀚[1] 刘亚允[1] 薛建亚[1] 万谟彬[1] 

机构地区：[1]上海长海医院感染科,200433

出　　处：《中华传染病杂志》2014年第5期280-284,共5页Chinese Journal of Infectious Diseases

摘　　要：目的 评价聚乙二醇干扰素-α-2a（peg-IFN-α-2a）治疗24周应答不佳的HBeAg阳性CHB患者优化治疗策略的疗效和安全性.方法 本研究为开放、单中心、前瞻性临床观察研究.2009年1月至2011年12月上海长海医院感染科收治经peg-IFN-α-2a治疗24周应答不佳的HBeAg阳性CHB患者,根据病毒学指标结合患者意愿将24周干扰素应答不佳CHB患者分别纳入转换替比夫定（LdT）组和peg-IFN-α-2a联合阿德福韦酯（ADV）组.所有患者于优化治疗后12、24和48周接受HBV病毒学、血清学标志物和不良反应监测.治疗前、后和不同治疗组间比较采用x^2检验,连续资料分析应用Kruskall-Wallis检验和Mann-Whitney检验.结果 经干扰素治疗的HBeAg阳性CHB患者193例,其中有67例应答不佳患者纳入本研究：peg-IFN-α-2a联合ADV组45例,转换LdT治疗组22例.67例患者优化治疗48周后HBeAg血清学转换率为25.3％,HBeAg阴转率为26.8％,HBV DNA＜1×10^3拷贝/mL检测下限率为73.1％,ALT复常率为83.5％.优化治疗12、24和48周时,转换LdT组较联合ADV组获得较好的HBV DNA抑制效率（P值分别为0.00、0.00和0.01）,但两组48周时HBVDNA阴转率比较差异无统计学意义（x^2=0.01,P=0.89）.两种优化策略均未见明显不可耐受不良反应发生.结论 24周干扰素应答不佳HBeAg阳性CHB实施优化治疗48周可获得较高HBeAg血清学转换率;转换LdT策略较联合ADV策略具有更佳的HBV DNA抑制效率;两种优化策略耐受性均较好.Objective To investigate the efficacy and safety of different optimal therapy strategies for hepatits B e antigen （HBeAg） positive chronic hepatitis B （CHB） patients with suboptimal response to peginterferon-α-2a （peg-IFN-α-2a） at 24 weeks.Methods This open-label,single-center and prospective clinical observational study was conducted in Department of Infectious Diseases at Shanghai Changhai Hospital between January 2009 and December 2011.The cases of HBeAg-positive CHB with suboptimal response to peg-IFN-α-2a at week 24 were enrolled.Based on virological markers and patient preference,patients were treated with either peg-IFN-α-2a add-on adefovir dipivoxil （ADV） or switch-to telbivudine （LdT）.Hepatitis B virus （HBV） virological and serological data were collected at week 12,24 and 48 after the initiation of optimal therapy.Adverse reactions were also monitored.Therapeutic efficacy was compared between two groups of patients before and after treatment by x^2 test.Kruskall Wallis test and Mann-Whitney test were used for analysis of continuous variables.Results Among 193 HBeAg positive CHB patients treated with interferon,67 had suboptimal response and were enrolled.Forty five cases received peg IFN-α-2a add-on ADV treatment and 22 cases received switch-to LdT treatment.After 48 weeks of optimized therapy,the total tBeAg seroconversion rate was 25.3 %.The rates of HBeAg loss,HBV DNA negative and alanine aminotransferase normalization were 26.8%,73.1% and 83.5%,respectively.The peg-IFN-α-2a switch-to LdT strategy had better HBV DNA inhibition efficiency compared with the peg-IFN-α-2a add-on ADV strategy at week 12,24 and 48 （P=0.00,0.00 and 0.01,respectively）.However,there was no significant difference of HBV DNA negative rate between two groups at week 48 （x^2 =0.01,P=0.89）.The obviously intolerable adverse reaction was not reported in two optimized strategy groups.Conclusions The 48-week optimized treatment for HBeAg positive CHB with suboptimal response to peg-IFN-α-2a at w

关 键 词：肝炎e抗原 乙型 聚乙烯二醇类 干扰素-α-2a 肝炎 乙型 慢性 优化治疗 

分 类 号：R512.62[医药卫生—内科学]