拉米夫定联合阿德福韦酯治疗乙型肝炎的疗效及对HBV耐药基因突变的影响

目的探讨拉米夫定联合阿德福韦酯治疗慢性乙型肝炎的疗效,并利用反向点杂交技术检测其对HBV基因耐药突变的影响。方法156例慢性乙型肝炎患者随机分为2组：对照组70例采用拉米夫定治疗,治疗组86例采用拉米夫定联合阿德福韦酯治疗。采用实时荧光定量PCR和ELISA检测2组治疗前和治疗后48周的HBV-DNA载量和HBeAg并采用PCR-反向点杂交技术（PCR-RDB）检测2组治疗48周后的HBV耐药基因突变情况。结果对照组及治疗组在经过48周治疗后HBV-DNA载量较治疗前都明显下降（P 〈0. 05）,治疗组HBV-DNA载量明显低于对照组（P〈0.05）。治疗组经过48周治疗后HBeAg的阴转率为54.9%，明显高于对照组15.0% （P 〈0.05）。对照组44例未出现耐药突变,25例拉米夫定耐药突变中rtL180M突变6例,rtM204V/I突变11例，rtL180M ＋ rtM204V/I混合突变8例;阿德福韦酯HN236T耐药突变1例。治疗组77例未出现耐药突变;5例拉米夫定耐药突变中rtL180M突变1例，rtM204V/I突变2例，rtL180M ＋ rtM204V/I混合突变2例;阿德福韦酯耐药突变中rtN236T突变1例；拉米夫定和阿德福韦酯交叉耐药rtN236T ＋ rtM204V/I混合突变3例。对照组耐药突变率为37. 1%（26/70）明显髙于治疗组的10.5%（9/86）（P〈0.05）。结论拉米夫定联合阿德福韦酯对治疗慢性乙型肝炎方面有效并在减少HBV耐药基因突变方面具有一定的作用。

The curative effect and drug-resistance genic mutation of lamivudine combined with adefovir dipivoxil in the treatment of chronic hepatitis B

Objective To explore the curative effect of Lamivudine combined with adefovir dipivoxil in the treatment of chronichepatitis B,and detect drug-resistance mutation of HBV using RDB hybridization assay. Methods A total of 156 patients with chronichepatitis B were randomly divided to two groups,70 cases of control group were treated by Lamivudine,86 cases of treatment group weretreated by Lamivudine combined with adefovir dipivoxil. The detection of HBV-DNA load and HBeAg by real-time fluorescence quantita-tive PCR and ELISA before and after treatment of chronic hepatitis B for 48 weeks in two groups, and drug-resistance genic mutation ofHBV Using PCR- reverse dot blot hybridization assay （ PCR-RDB） after treatment of chronic hepatitis B for 48 weeks. Results TheHBV-DNA load of the control and treatment the group were obviously decreased after treatment for 48 weeks than before treatment byLamivudine or adefovir dipivoxil （P 〈 0. 05 ） . The HBV-DNA load of the treatment group was lower than the control group （P 〈 0. 05 ）.
The HBeAg negative conversion rate of the treatment group （54. 9% ） was significantly higher than the control group （ 15. 0% ） after treat-ment for 48 weeks （P 〈 0. 05）. There were 44 cases without drug-resistance genic mutation, 25 cases with lamivudine-resistance muta-tions T and 1 case with adefovir dipivoxil-resistance in the control group. The main types of lamivudine-resistance mutations were rtL180M（6）,rtM204V/I（ 11）, rtL180M ＋ rtM204V/I（8）,the type of lamivudine-resistance mutations were rtN236T（ 1 ） . There were 77 caseswithout drug resistance mutation,5 cases with lamivudine-resistance mutations,1 case with adefovir dipivoxil-resistance,and 3 cases withlamivudine and adefovir dipivoxil cross resistance in the treatment group. The main types of lamivudine-resistance mutations were rtL180M（1 ）,rtM204V/I（2）,rtL180M ＋ rtM204V/I（2） . The type of adefovir dipivoxil-resistance mutations was rtN236T（ 1 ）,the types of lami-vudine and adefovir dipivoxil cross resistance were rtN236T ＋ rtM204V/I （ 3 ） . The drug-resistance mutation rate of the control group（37. 1 % ） was significantly higher than the treatment group （10.5%）（P〈0.05）. Conclusion Lamivudine combined with adefovir dipivoxil can effectively treat the chronic hepatitis B and decrease the rate of drug-resistance genic mutation of hepatitis B virus.