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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HBVDNA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rtN236T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)明显高于治疗组的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。
Objective To investigate the curative effect of lamivudine combined with adefovir dipivoxil in the treatment of chronic hepatitis B and to detect its effect on the drug resistance mutation of HBV by reverse dot blot hybridization. Methods 156 patients with chronic hepatitis B were randomly divided into two groups: control group, 70 cases treated with lamivudine, 86 cases treated with lamivudine combined with adefovir dipivoxil treatment. The HBV-DNA load and HBeAg of two groups before and 48 weeks after treatment were detected by real-time fluorescent quantitative PCR and ELISA. HBV resistance of the two groups after 48 weeks of treatment was detected by PCR-reverse dot blot hybridization (PCR-RDB) Gene mutation. Results After 48 weeks of treatment, the HBVDNA load of the control group and the treatment group were significantly decreased (P <0.05), and the HBV-DNA load of the treatment group was significantly lower than that of the control group (P <0.05). After 48 weeks of treatment, HBeAg negative conversion rate was 54.9% in the treatment group, which was significantly higher than that in the control group (15.0%, P <0.05). 44 cases in the control group showed no resistance mutation, 6 cases were rtL180M mutation in 25 cases of lamivudine resistance mutation, 11 cases were rtM204V / I mutation and 8 cases were rtL180M + rtM204V / I mutation in combination. Adefovir dipivoxil rtN236T resistance 1 case of mutation. There were no mutations in 77 cases in the treatment group, 1 case of rtL180M mutation, 2 cases of rtM204V / I mutation and 2 cases of rtL180M + rtM204V / I mutation in 5 cases of lamivudine-resistant mutations, adefovir dipivoxil-resistant mutations 1 case of rtN236T mutation; 3 cases of mixed mutations of rtN236T + rtM204V / I with lamivudine and adefovir dipivoxil. The rate of drug-resistant mutation in the control group was 37.1% (26/70), significantly higher than that in the treatment group (10.5%, 9/86) (P <0.05). Conclusions Lamivudine combined with adefovir dipivoxil is effective in the treatment of chronic hepatitis B and plays a role in reducing the mutation of HBV resistance gene.