阿德福韦酯联合拉米夫定治疗拉米夫定耐药慢性乙型肝炎

目的：观察阿德福韦酯（ADV）联合拉米夫定（LAM）挽救治疗LAM耐药慢性乙型肝炎的疗效和安全性。方法：91例LAM耐药的慢性乙型肝炎患者随机分为观察组46例与对照组45例。观察组以ADV 10 mg·d^-1＋LAM 100 mg·d^-1联合治疗48周；对照组采用ADV 10 mg·d^-1＋LAM 100 mg·d^-1联合治疗4周，后单用ADV 10 mg·d^-1治疗44周。观察两组患者治疗前后血清HBV DNA载量、乙型肝炎病毒标志物、肝功能及基因型耐药情况。结果：两组治疗24周、48周HBV DNA水平和ALT水平与治疗前比较，差异有统计学意义（P〈0.01），观察组治疗12周和24周 HBV DNA 水平低于对照组（P 〈0.05），观察组治疗12周、24周、36周和48周HBV DNA转阴率和丙氨酸氨基转移酶（ALT）复常率均明显优于对照组（P〈0.05）；治疗24周和48周时，观察组血清HBeAg阴转率为26.1%、33.3%，血清HBeAg/抗-HBeAb转换率为8.7%、17.4%，略高于对照组，但差异无统计学意义（P〉0.05）；观察组基线水平≥105拷贝/ml的患者治疗12周、24周、36周、48周HBV DNA转阴率和ALT复常率明显高于对照组（P〈0.05）。两组患者的基因型耐药率分别为0和2.2%（1/45），对照组1例耐药，患者为rtN236T变异。结论：LAM耐药慢性乙型肝炎患者采用ADV和LAM联合治疗有效。

Efficacy of Adefovir Dipivoxil Combined with Lamivudine in the Treatment of Lamivudine resistant Chronic Hepatitis B Patients

Objective： To observe the efficacy and safety of adefovir dipivoxil （ADV） combined with lamivudine （LAM） in the treatment of LAM-resistant chronic hepatitis B patients. Methods： Ninety-one LAM-resistant chronic hepatitis B patients were random- ly divided into the observation group（ n = 46 ） and the control group（ n = 45 ）. The patients in the observation group received 10mg ADV and 100mg LAM once a day for 48 weeks. In the control group, the patients received ADV Combined with LAM in the first 4 weeks and then replaced by ADV alone for the following 44 weeks. Before and after the treatment, HBV DNA level and HBV markers were measured; liver function and drug-resistant genotypes were compared between the two groups. Results： Compared with those be- fore the treatment, the level of HBV DNA and ALT were decreased remarkably after the 24- and 48-week treatment in the two groups （P 〈 0.01 ）. The level of HBV DNA was lower in the observation group than that in the control group after the 12- and 24-week treat- ment（P 〈 0.05 ）, and at the end of the 12th, 24th, 36th and 48th week, the HBV DNA negative rate and ALT recovery rate were sig- nificantly higher in the observation group than those in the control group（P 〈0.05）. After the 24- and 48-week treatment, the HBeAg negative rate（26.1% and 33.3% ） and conversion rate （ 8.7% and 17.4% ） in the observation group were slightly higher than those in the control group without significant difference （P 〉 0.05）. At the end of the 12th, 24th, 36th and 48th week, the HBV DNA neg- ative rate and ALT recovery rate were significantly higher in the observation group （baseline HBV DNA ≥ 105 copies/ml） than those in the control group（ P 〈 0.05 ）. The rate of drug-resistant genotype was 0 in the observation group and 2.2% （ 1/45 ） in the control group with rtN236T mutation. Conclusion： Adefovir dipivoxil combined with lamivudine is effective in the treatment of LAM-resistant chronic hepatitis B patients.