阿德福韦酯联合方案治疗失败的慢性乙型肝炎患者换用替诺福韦酯优化治疗效果分析

Efficacy of tenofovir disoproxil fumarate switch therapy in chronic hepatitis B for suboptimal response to adefovir-based combination therapy

目的：分析对阿德福韦酯（Adefovir dipivoxil，ADV）为基础的联合方案治疗失败的慢性乙型肝炎患者换用替诺福韦酯（Tenofovir disoproxil fumarate，TDF）优化治疗的长期疗效及安全性。方法：回顾性评价替诺福韦酯优化治疗50例对阿德福韦酯联合方案治疗失败患者的疗效及安全性。结果：50例患者年龄23．0～51．0（35．0±17．3）岁。基线平均血清HBV DNA水平为（4．8±1．6）log IU／mL。48例HBeAg阳性（96．0％）。50例患者中，ADV）联合拉米夫定（Lamivudine，LAM）、联合替比夫定替比夫定（Telbivudine， LdT）、联合恩替卡韦恩替卡韦（Entecavir，ETV）治疗失败的患者分别有17（34．0％）例、14（28．0％）例、19（38．0％）例。治疗失败后换用TDF优化治疗，经过24．0～192．0（102．0±47．3）周治疗，不同时间点的病毒学应答率为12周38．0％，24周70．0％，36周77．1％，48周87．2％，60周83．7％，72周85．7％，84周92．1％，96周90．3％，108周95．8％，ALT复常率为12周34．0％，24周44．0％，36周54．2％，48周57．9％，60周62．9％，72周66．7％，84周71．3％，96周77．0％，108周82．8％。48例基线 HBeAg阳性患者中，有5例（10．4％）发生HBeAg血清学转换。随访期间，6例患者出现病毒学突破，其中3例（2例TDF单药，1例TDF ＋ ETV治疗）患者未能达到病毒学应答。没有严重不良事件发生。结论：对ADV为基础的联合治疗方案治疗失败的慢性乙型肝炎患者，换用TDF是一种安全、有效的优化治疗方案。

Objective：To analyze the efficacy and safety of tenofovir disoproxil fumarate （TDF ） switch therapy in chronic hepatitis B patients for suboptimal response to adefovir（ADV）-based combination therapy in real life. Methods：To evaluate the efficacy and safety of TDF switch therapy in 50 chronic hepatitis B patients after suboptimal response to ADV-based combination therapy. Results：The median follow-up duration was 102 weeks （24~192 weeks）and median age was 35 years （range,23 to 51）. The mean serum HBV DNA level was 4.8±1.6 log IU/mL at baseline. 48 patients were HBeAg-positive （96%）. 17（34%）,14（28%）,19（38%） patients was treated by prior lamivudine （LAM ） plus ADV,telbivudine （LdT ） plus ADV,ETV plus ADV, respectively. The cumulative probability of achieving virological response at 12,24,36,48,60,72,84,96, and 108 weeks were 38.0%,70.0%,77.1%,87.2%,83.7%,85.7%,92.1%,90.3%,95.8%,respectively. The cumulative probability of normal ALT at 12,24,48,60,72,84,96 and 108 weeks were 34.0%,44.0%,nbsp;54.2%,57.9%,62.9%,66.7%,71.3%,77.0%,82.8%. HBeAg seroconversion occured in 5 of 48 patients （10. 4%）. During the follow-up,6 patients suffered from virological breakthrough,of whom 3 （2 cases was treated with TDF,and 1 case with TDf＋ETV）failed to achieve virological response.No serious adverse event was reported. Conclusion：TDF switch therapy is an effective and safe for chronic hepatitis B patients with suboptimal response to ADV-based combination therapy in real-life.