阿德福韦酯联合恩替卡韦优化治疗拉米夫定和阿德福韦酯联合治疗失败的慢性乙型肝炎临床疗效分析

The optimal combination therapy with entecavir and adefovir is effective and safe in chronic hepatitis B patients with failure to lamivudine and adefovir combination therapy ： a 48 weeks, retrospective, single center study

目的 探讨阿德福韦酯联合恩替卡韦对拉米夫定联合阿德福韦酯治疗失败（包括发生疗效欠佳及病毒学突破）的慢性乙型肝炎患者的临床疗效及安全性.方法 将70例对拉米夫定联合阿德福韦酯治疗失败的慢性乙型肝炎患者随机分为对照组和优化组.对照组继续予拉米夫定（100 mg/d）联合阿德福韦酯（10 mg/天）治疗;优化组在服用阿德福韦酯（10 mg/d）的同时,联合使用恩替卡韦（0.5 mg/d）优化治疗.所有患者均治疗48周.治疗前、治疗12周、24周和48周分别进行生物化学、病毒学、血清学检测.回顾性分析、比较两组患者上述治疗时间点的生物化学应答率（BR）、完全病毒学应答率（CVR）、病毒学突破率（VBR）和HBeAg/HBeAb血清学转换率.结果 优化组患者治疗48周后BR、CVR、VBR分别为75.0％（12/16）、81.8％ （27/33）、3.0％（1/33）,对照组分别为26.3％ （5/19）、32.4％ （12/37）和21.6％ （8/37）,两组比较差异具有统计学意义（P值均＜0.01）.但两组患者治疗48周后,HBeAg/HBeAb血清学转换率分别为5.9％（1/17）和13.3％ （2/15）,两组比较差异无统计学意义（P＞0.05）.两组患者耐受性良好,无1例患者出现严重不良反应而导致停药.结论 对于拉米夫定联合阿德福韦酯治疗失败的慢性乙型肝炎患者,阿德福韦酯联合恩替卡韦是一种行之有效的优化治疗方案.

Objective To evaluate the efficacy and safety of a therapeutic strategy of combining entecavir（ETV） and adeforvir（ADV） therapy in chronic hepatitis B patients with treatment failure to LAM and ADV combined therapy.Methods Patients who showed treatment failure with HBV DNA ≥ 10 IU/ml after 48 weeks of LAM and ADV combined therapy were included.37 patients continued with ADV combined LAM for another 48 weeks served as group A ; other 33 patients were switched to ADV and ETV for another 48 weeks served as group B.The serum ALT,TBIL,ALB,HBV DNA were monitored with an interval of 12 weeks.Results After another 48 weeks follow up,the biochemical response（BR） rate（normalization of almandine aminotransferase levels）,the virological response（VR） rate （HBV-DNA level 〈 102 IU/ml）,the virologic breakthrough （VB） rate were 75.0% （12/16）、81.8 % （27/33） and 3.0% （1/33） in the optimal therapy group,respectively.Meanwhile,the BR rate,the VR rate and VB rate were 26.3% （5/19）,32.4% （12/37） and 21.6% （8/37） in group A,respectively with P value all less than 0.01 when the two groups were compared.But the seroconversion rate （from HBeAg to HBeAb） were 5.9% （1/17） and 13.3% （2/15）,respectively,and p value（0.471） did not show significant difference between two groups.Both groups showed comparably tolerant and safe to therapy.Conclusion The therapy of ETV plus ADV is an effective and safe therapeutic strategy for chronic hepatitis B patients with a treatment failure to LAM and ADV combined therapy.