HBeAg早期下降对聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎的疗效预测  

Quantifiable changes in HBeAg expression predict therapeutic efficacy of peg-interferon alfa-2a in patients with HBeAg-pos^e chronic hepatitis B

作　　者：纪永健[1] 李菲菲[1] 任万华[1] 主余华[1] 秦成勇[1] 

机构地区：[1]山东大学附属省立医院感染性疾病科,济南250021

出　　处：《中华肝脏病杂志》2013年第5期335-339,共5页Chinese Journal of Hepatology

基　　金：山东省科技攻关课题（2010GSF10271）

摘　　要：目的观察24周HBeAg下降对聚乙二醇干扰素α-2a单药治疗HBeAg阳性巨陛乙型肝炎48周疗效的预测作用及与肝组织HBVcccDNA的关系，探讨I临床实用的疗效预测指标。方法96例HBeAg阳性慢陛乙型肝炎患者应用聚乙二醇干扰素α-2a治疗24周时，按HBeAg下降水平将患者分为4组：下降〉2log10S／CO为A组，下降1～2log10S／CO为B组，下降〈1log10S／CO为C组，C组患者随机分至C1组和C2组，A、B、C1组继续单药治疗，C2组加用拉米夫定联合治疗，治疗48周时进行疗效评估；每组取1／3的患者行肝穿刺检测肝组织HBVcccDNA水平，分析HBeAg早期下降与48周疗效及肝组织HBVcccDNA的关系。A、B、C1组间多重比较采用Nemenyi法，C1、C2两组间比较采用Mann-WhimeyU检验，组间HBVDNA检测不到率和HBeAg／抗一HBe转换率的比较采用X2检验。结果（1）治疗48周时，血清HBVDNA自基线下降值（中位数）：A组为5．8log10拷贝／ml，B组为3．8log10拷贝／ml，C1组为2．8log10拷贝／ml，C2组为5．7log10拷贝／ml，A组下降幅度高于B组和C1组（X2值分别为9．06和23．45，P值均〈0．05），C2组下降幅度高于C1组（U=44．0，P〈0．01）。血清HBeAg定量较基线下降值（中位数）：A组为2．7log10S／CO，B组为1．9log10S／CO，C1组为0．9log10S／CO，C2组为1．610g10s／CO，A组下降值大于B组和C1组（X2值分别为10．58和43．32，P值均〈0．05），B组下降值大于C1组（X2=10．82，P〈0．05），C2组下降值也大于C1组（U=109．0，P〈0．01）。（2）治疗48周时，A、B、C1、C2组HBVDNA检测不到率分别为87．5％、34．5％、17．40％、85．0％，A组高于B组和C1组（X2值分别为15．203和23．186，P值均〈0．01），C2组高于C1组（X2=19．570，P〈0．01）}HBeAg血清学转换率分别为75．0％、24．1％、13．0％、25．0％，A组高于B组和C1组（X2值分别为13．632和18．240，P值均〈0．01）。（3）48周时，A�Objective To investigate whether quantifiable changes in serum levels of hepatitis Be antigen （HBeAg） in response to 24 weeks of pegylated-interferon alfa-2a （Peg-IFN-a 2a） treatment are predictive of therapeutic efficacy at 48 weeks of treatment in HBeAg-positive chronic hepatitis B （CHB） patients and to investigate the efficacy of using an individualized antiviral treatment strategy. Methods Ninety-six HBeAg-positive CHB patients with detectable HBeAg at week 24 of Peg-IFN-a 2a treatment were categorized according to the quantitative change in HBeAg （vs, pre-treatment baseline）： group A, HBeAg decline 〉 2 log; group B, HBeAg decline between 1-2 log; group C, HBeAg decline 〈 1 log, which was then randomly divided into two sub-groups： C1 and C2. Group A, B, and C1 patients continued the original therapy for an additional 24 weeks, while group C2 patients were supplemented with lamivudine （3TC ＋ Peg- IFN-a 2a） for the additional 24 weeks of treatment. All patients underwent liver biopsy at the end of treatment （week 48）, and HBV covalently-closed circular （ccc）DNA was quantified as a measure of therapeutic efficacy. A, B, and C1 between-group multiple comparisons were made by the Nemenyi test; C1 and C2 between- group comparison was made：by the Mann-Whitney U test. The significance of between-group differences in decreased HBV cccDNA vs. HBeAg/anti-HBe seroconversion was made by the Chi-squared test. Results At week 48, the mean decrease of serum HBV cccDNA in each group was： A, 5.8 log10 copy/ml; B, 3.8 log10 copy/ml; C1, 2.8 log10 copy/ml; C2, 5.7 log10 copy/ml. Statistically significant differences were observed for group A vs. B and C1 （P 〈 0.01） and C1 vs. C2 （P 〈 0.01）; however, the difference between group B and C1 did not reach statistical significance （P = 0.19）. The mean decrease of HBeAg in each group was： A, 2.7 log10 S/CO; B, 1.9 log10 S/CO; C1, 0.9 log10 S/CO; C2, 1.6 log10 S/CO. Statistically significant differences were observed for group

关 键 词：肝炎 乙型 慢性 聚乙烯二醇类 干扰素Α-2A 肝炎E抗原 乙型 

分 类 号：R512.62[医药卫生—内科学]