恩替卡韦联合阿德福韦酯对既往核苷类似物治疗失败的慢性乙肝患者疗效分析

摘要

目的 评价恩替卡韦(ETV)联合阿德福韦酯(ADV)对既往核苷类似物(Nas)治疗失败的慢性乙肝(CHB)患者的疗效和安全性,并分析可能影响应答的因素.方法 回顾性分析既往Nas治疗失败,经ETV和ADV治疗24周以上(随访中位数18周)的45例CHB和代偿期肝硬化患者,比较治疗24和48周病毒学应答率(VR)、生化学应答率(BR)及联合应答率(CR).运用单因素分析可能影响疗效的因素.结果 24周时VR率、BR率和cR率分别是66.7%、77.8%和57.8%;48周时VR率、BR率和CR率分别是76.2%、78.6%和61.9%.与基线相比,24周VR率(Z=-4.796,P=0.000)、BR率(Z=-5.196,P=0.000)及CR率(Z=-3.606,P=0.000)均显著提高.48VR率(Z=-3.742,P=0.000)、BR率(Z=-4.472,P=0.000)及CR率(Z=-4.690,P=0.000)均显著提高.单因素分析显示肝硬化患者比非肝硬化BR率低(24周:BR率17.1%vs82.9%,x2=4.546,P=0.048;48周BR率23.8%vs76.2%,x2=6.364,P=0.023)有统计学意义;联合基线HBVDNA水平3～6 Log10 copies/ml与>6 Log10 copies/ml相比,前者48周VR率高于后者(85.2%vs40%,Z=-4.796,P=0.037)有统计学意义.结论 ETV联合ADV对既往Nas治疗失败的CHB患者是一种安全有效的补救治疗方案.治疗前HBVDNA水平低的非肝硬化患者疗效更优.%Objective To evaluate the safety and efficacy of the combined therapy with entecavir (ETV) and adefovir (ADV) in patients with chronic hepatitis B (CHB) who experienced failure of treatment with single or multiple nudeoside analogs, and analyze the factors that affect the patients' response to the treatment. Methods Forty-five CHB patients who experienced treatment failure with sequential or/and combined nucleoside analogs received the combined therapy with entecavir and adefovir lasting for at least 6 months. The viroloigcal response (VR), biochemical response (BR) and combined response (CR) at 24 and 48 weeks of the treatment were evaluated. Univairante analysis was used to identify the factors that affect the response to the anti-viral therapy. Results The VR, BR and CR were 67.7%, 77.8% and 57.8% at 24 weeks, as compared to 76.2%, 78.6% and 61.9% at 48 weeks, respectively. The VR differed significantly between patients with a baseline HBV DNA level [lg(copies/ml)] of 3-6 and those with a level over 6 (85.2% vs 40%, Z=-4.796, P=0.037) at 48 weeks. The presence and absence of cirrhosis at the initial treatment significantly affected the BR at 24 weeks (17.1% vs 82.9%, P=0.048) and at 48 weeks (23.8% vs 76.2%, P= 0.023). Conclusion Entecavir combined with adefovir is an effective rescue therapy in CHB patients after failure of treatment with nucleoside analogs. Patients with a lower baseline HBV DNA level without cirrhosis may have better response to the combined treatment.