恩替卡韦对核苷类药物经治慢性乙型病毒性肝炎患者的抗病毒疗效观察

Clinical efficacy of entecavir for patients with chronic hepatitis B resistant to combined administration of lamivudine and adefovir

目的观察联合应用恩替卡韦和阿德福韦对拉米夫定耐药后联合阿德福韦治疗效果欠佳慢性乙型病毒性肝炎患者(慢乙肝)的抗病毒疗效。方法 124例拉米夫定耐药后联合阿德福韦治疗效果欠佳者按治疗意愿分为研究组(70例)和对照组(54例),对照组按原方案继续治疗,研究组换为恩替卡韦和阿德福韦联合治疗。追溯患者在拉米夫定初始治疗时和出现耐药时HBV DNA载量和耐药位点,观察比较治疗12个月内2组HBV DNA、HBeAg的阴转率和抗-HBe的阳转率。结果2组患者在拉米夫定初始治疗时和出现耐药时HBV DNA载量和耐药位点分布比较差异均无统计学意义(P均>0.05)。治疗6、9、12个月时,研究组的HBV DNA阴转率分别为74%、100%和100%,均高于对照组同时点的HBV DNA阴转率(P均<0.05)。研究组治疗9、12个月时的HBe Ag阴转率分别为43%和49%,均高于对照组同时点的HBe Ag阴转率(P均<0.05)。2组在不同时点的抗-HBe阳转率比较差异均无统计学意义(P均>0.05)。结论对拉米夫定耐药后联合阿德福韦治疗效果欠佳的慢乙肝患者改用恩替卡韦和阿德福韦联合治疗可以获得更佳的抗病毒效果。

Objective To evaluate the efficacy and safety of entecavir combined with adefovir for patients with chronic hepatitis B（chronic HBV） who were resistant to combined administration of lamivudine and adefovir.Methods In total,124 chronic HBV patients who yielded poor response to lamivudine combined with adefovir were divided into study（n=70） and control groups（n=54）.In the control group,original treatment was delivered.In the study group,entecavir combined with adefovir was administered.HBV DNA viral load and resistance mutation site during lamivudine administration and upon drug resistance were retrospectively analyzed.The conversion rate of serum HBV DNA and HBe Ag,and the positive rate of anti-HBe were observed for 12 months between two groups.Results HBV DNA viral load and resistance mutation site during lamivudine administration and upon drug resistance did not significantly differ between two groups（all P〈0.05）.In the study group,the negative rate of HBV DNA was 74%,100% and 100% at 6,9 and 12 months after treatment,significantly higher compared with that in the control group at corresponding time point（all P〈0.05）.In the study group,the negative rate of HBe Ag at 9 and 12 months was 43% and 49%,significantly higher than that in the control group（both P〈0.05）.The positive rate of anti-HBe at each time point did not significantly differ between two groups（all P〉0.05）.Conclusion Entecavir combined with adefovir is an efficacious treatment for chronic HBV patients who are resistant to combined administration of lamivudine and adefovir.