南方医科大学学报

南方医科大学学报 ›› 2013, Vol. 33 ›› Issue (12): 1823-.

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拉米夫定与阿德福韦酯联合治疗应答不佳的慢性乙型肝炎患者的抗病毒治疗

黎明，吴锦瑜，徐冠军，张琴，陈志勇，刘珍花   

  • 出版日期:2013-12-20 发布日期:2013-12-20

Therapeutic effect of antiviral regimens for chronic hepatitis B refractory to lamivudine
plus adefovir

  • Online:2013-12-20 Published:2013-12-20

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摘要： 目的观察重组人干扰素α-2b（INFα-2b）单药治疗及恩替卡韦（ETV）与阿德福韦酯（ADV）联合治疗拉米夫定（LAM）与
ADV联合治疗应答不佳的慢性乙型肝炎患者的疗效和安全性。方法选择我院2008年6月~2011年1月LAM与ADV联合治疗
应答不佳的慢性乙型肝炎患者161例，随机分为A、B两组，A组给予INFα-2b 5×106，每周3次；B组ETV（0.5 mg，1次/d）与ADV
（10 mg，1 次/d）联合应用。所有病例治疗48 周为观察终点。采用化学发光法定量检测HBsAg和HBeAg，采用实时荧光定量
PCR检测HBV DNA水平，采用PCR产物直接测序法检测病毒耐药基因。组间比较采用配对t检验，率的比较采用χ2检验。结
果治疗48 周，A组与B 组患者血清HBV DNA水平中位数均明显下降，下降幅度分别为2.06±1.15log10 拷贝/ml 与1.77±
1.28log10 拷贝/ml；A组与B组血清病毒学应答率、血清学应答率、生化学应答率分别为：48.15%（39/81）与53.75%（43/80）、
61.70%（50/81）与53.75%（43/80）、49.38%（40/81）与60.00%（48/80），两组间差异均无统计学意义（P>0.05）；基因耐药变异率分
别为30.95%（13/42）与64.86%（24/37），差异有统计学意义（P<0.05）。结论LAM联合ADV治疗应答不佳的慢性乙型肝炎患者，
选择改用INF或改用ETV与ADV联合治疗，均能获得较好的临床疗效。若患者无干扰素禁忌证，尽可能选择干扰素治疗。

Abstract: Objective To compare the efficacy and safety of recombinant human interferon α-2b (INFα-2b) monotherapy and
combined therapy with entecavir (ETV) plus adefovir dipivoxil (ADV) in chronic hepatitis B patients with poor response to
combined therapy with lamivudine and ADV. Methods A total of 161 patients with chronic hepatitis B refractory to to
combined therapy with lamivudine (LAM) and ADV were randomized to receive INFα-2b monotherapy (5×106, three times a
week) (group A) or combined therapy with entecavir (0.5 mg/day) plus adefovir (10 mg/day) (group B). Serum levels of
HBsAg, HBeAg and HBV viral load were analyzed at 48 weeks using chemiluminescence assay and by real-time PCR as
appropriate. The drug resistance genes in HBV was tested by direct DNA sequencing. Results At 48 weeks of treatment, HBV
DNA decreased significantly in groups A and B to 2.06±1.15log10 copies/ml and 1.77±1.28log10 copies/ml, respectively. The
rates of viral response, serological response, and biochemical response in groups A and B were 48.15% (39/81) vs 53.75% (43/
80), 61.70% (50/81) vs 53.75% (43/80), and 49.38% (40/81) vs 60.00% (48/80), showing no significant differences between the two
groups (P>0.05). The drug resistance gene mutation rate was significanty higher in group B (64.86%, 24/37) than in group A
(30.95%, 13/42, P<0.05). Conclusions Chronic hepatitis B patients refractory to lamivudine combined with ADV have a good
response to INFα-2b monotherapy and combined therapy with entecavir and ADV , and interferon treatment is preferred to
reduce potential drug resistance gene mutations.