替诺福韦酯对抗病毒治疗病毒学应答不佳的慢性乙型肝炎患者疗效

Tenofovir rescue therapy for chronic hepatitis B patients after suboptimal response to treatment with lamivudine plus adefovir dipivoxil

目的 观察替诺福韦酯（TDF）对拉米夫定（LAM）初治失败后,LAM联合阿德福韦酯（ADV）方案病毒学应答不佳的慢性乙型肝炎患者的疗效,同时与治疗队列中恩替卡韦（ETV）单药挽救治疗的疗效进行比较.方法 对LAM初治失败后应用LAM联合ADV方案病毒学应答不佳的57例患者给予单药TDF 300 mg/d,在12周、24周和48周检测HBV DNA、肝肾功能、HBV标志物等指标.与慢性乙型肝炎患者治疗队列中ETV 1 mg/d（40例）挽救治疗组疗效进行比较.结果 两组患者采用挽救治疗之前的基线情况差异无统计学意义.挽救治疗24周时,ETV组仅有1例（2.5％）达到HBV DNA转阴,TDF组则有49例（86.0％）达到HBV DNA转阴,x2=22.26,P＜0.001.治疗48周时,ETV组5例（12.5％）HBV DNA转阴,31例（77.5％） ALT复常,而TDF组50例（87.7％）患者HBV DNA转阴,48例（84.2％）达到ALT复常.HBV DNA转阴率TDF组明显高于ETV组（x2=24.17,P＜0.001）.ALT复常率比较两组差异无统计学意义（x2=0.702,P=0.431）.ETV组和TDF组在48周时各有1例患者发生血清HBeAg阴转（2.5％比1.8％,P=0.964）.结论 对于LAM治疗失败后LAM联合ADV方案病毒学应答不佳的慢性乙型肝炎患者,采用TDF 300 mg/d的挽救方案较ETV 1 mg/d方案更为有效,可以实现更好的病毒学应答.

Objective To evaluate the efficacy of tenofovir （TDF） 300 mg/d,comparing with entecavir （ETV）,in adults with chronic HBV infection who had previously virologic failure with lamivudine （LAM） and failed with rescue treatment of LAM combined adefovir （ADV）.Methods Fifty-seven patients of chronic hepatitis B on rescue treatment with TDF were analyzed retrospectively.The serum HBV DNA levels,HBeAg,ALT and serum creatinine （Cr） were detected after treatment for 12,24 and 48 weeks respectively.In addition,data of 40 cases treated with ETV 1 mg per day as a control group were also collected.Results The baseline characteristics including HBV viral loads,median age,serum levels of ALT and Cr were compatible between TDF group and ETV group.At the time point of 24 weeks,there was only one patient （2.5%） in ETV group with HBV DNA 〈 100 IU/ml,which means negative viral replication,while 49 patients in TDF group reached HBV negativity （86.0% vs 2.5%,x2 =22.26,P 〈0.001）.At the time point of 48 weeks,the proportion of patients with HBV DNA 〈 100 IU/ml in TDF group was significantly higher than that in ETV group （87.7% vs 12.5%,x2 =24.17,P 〈0.001）.The ratios of ALT normalization （84.2% vs 77.5%,P =0.431） and HBeAg seroconversion were similar in both groups.Elevated Cr was not found in both cohorts at the end of treatment.Conclusions Tenofovir （300 mg/d） is an effective and safe rescue therapy in chronic hepatitis B patients who failed initial treatment with LAM and secondary treatment of LAM plus ADV.