拉米夫定和阿德福韦酯初始联合与恩替卡韦单药治疗高病毒载量慢性乙型肝炎疗效观察

De novo combination therapy with lamivudine and adefovir dipivoxii versus entecavir monotherapy for naive chronic hepatitis B patients with high viral loads

目的观察拉米夫定和阿德福韦酯初始联合治疗与恩替卡韦单药治疗高病毒载量（HBVDNA≥10^7拷贝／mL）慢性乙型肝炎（CHB）患者的疗效、耐药率及安全性。方法选择2007年5月-2009年1月江苏省江阴市人民医院70例高病毒载量CHB患者，采用随机数字表法分为联合治疗组和单药治疗组，联合治疗组服用拉米夫定（100mg／d）和阿德福韦酯（10mg／d），疗程为96周：对照组服用恩替卡韦（0．5mg／d），疗程为96周。采用爿。检验对两组的ALT复常率、病毒学应答情况和HBeAg血清学转换率进行比较。结果治疗96周后，联合治疗组的ALT复常率、HBVDNA转阴率和HBeAg血清学转换率分别为97．1％（34／35）、94．3％（33／35）和48．6％（17／35），单药治疗组分别为77．1％（27／35）、77．1％（27／35）和17．1％（6／35），两组比较差异有统计学意义（X^2=6．248、4．200和7．835，P〈0．05或P〈0．01）。治疗96周，联合组没有出现病毒学突破，而单药组累计有2例患者出现病毒学突破，且这2例患者都检测到恩替卡韦相关耐药基因位点。两组均未发现与药物相关的严重不良反应。结论对于高病毒载量的CHB患者，拉米夫定和阿德福韦酯初始联合治疗的疗效优于恩替卡韦单药治疗，能够强效抑制病毒复制，降低耐药发生率，提高HBeAg血清学转换率。

Objective To evaluate the efficacy, drug resistance and safety of combination therapy with lamivudine （ LAM ） and adefovir dipivoxil （ ADV ） or enteeavir （ ETV ） monotherapy for chronic hepatitis B （CHB） patients with high viral loads （HBV DNA ≥ 10^7 eopies/mL）. Methods Seventy CHB patients with high viral loads were collected from Jiangyin People＇ s Hospital in Jiangsu Province during May 2007 and January 2009. All patients were randomized into combination therapy group and monotherapy group. Combination therapy group was treated with lamivudine （ 100 mg/d） and adefovir dipivoxil （ 10 my,/ d） for 96 weeks, and monotherapy group was treated with enteeavir （0, 5 mg/d） for 96 weeks. X^2 test was used to compare the ALT normalization rates, HBV DNA negative rates and HBeAg seroconversion rates between two groups. Results After 96 weeks＇ treatment, the ALT normalization rate, HBV DNA negative rate and HBeAg seroconversion rate of combination therapy group were 97.1% （34/35）, 94.3 % （33/35） and 48.6% （ 17/35 ）, respectively; those of monotherapy group were 77.1% （27/35）, 77.1% （27/35） and 17.1% （ 27/35 ）, respectively ; the differences were of statistical significance （X^2 = 6. 248, 4. 200 and 7. 835, P 〈0.05 or P 〈 0.01 ）. There was no virological breakthrough in combination therapy group during 96 weeks＇ treatment, but it was found that 2 patients had virological breakthrough in monotherapy group and they were ETV-resistant. No severe adverse reaction was found in both groups. Conclusion LAM ＋ ADV combination therapy is better in viral suppression, and has lower resistance and higher HBeAg seroconversion rate than ETV monotherapy for CHB patients with high viral load.