经拉米夫定联合阿德福韦酯治疗失败的慢性乙型肝炎患者的挽救治疗

Retreatment of chronic hepatitis B patients with failure of lamivudine and adefovir combination therapy

目的探讨拉米夫定(LAM)联合阿德福韦酯(ADV)治疗失败的慢性乙型肝炎(CHB)患者的挽救治疗方法。方法选取解放军第302医院2013年3月至2014年3月LAM联合ADV挽救治疗失败的CHB患者100例为研究对象,依据患者的经济情况和意愿分为对照组和挽救组,每组50例。对照组继续给予LAM(100 mg/d)联合ADV(10 mg/d)治疗;挽救组患者每日给予300 mg替诺福韦酯(TDF)联合0.5 mg恩替卡韦(ETV),所有患者均连续治疗48周。治疗基线、12周、24周和48周时分别进行病毒学、生物化学和血清学检测。回顾性分析比较两组患者上述治疗时间点的HBV DNA低于检测下限率、肝功能复常率、病毒学突破率、HBe Ag血清学转换率及药物的不良反应。结果挽救组患者治疗48周后HBV DNA低于检测下限率、肝功能复常率和病毒学突破率分别为94.0%(47/50)、89.2%(33/37)和0.0%(0/50),对照组分别为34.0%(17/50)、25.7%(9/35)和14.0%(7/50),差异有统计学意义(P均<0.05)。治疗48周后,挽救组和对照组患者HBe Ag血清学转换率分别为15.4%(4/26)和16.7%(4/24),差异无统计学意义(χ~2=0.023,P=0.769)。两组患者的耐受性均良好,未出现因严重不良反应而导致停药的病例。结论对于LAM联合ADV治疗后疗效欠佳或发生病毒学突破的CHB患者,TDF联合ETV是一种效果理想且安全的挽救治疗方案。

Objective To explore the retreatment of chronic hepatitis B patients with failure of lamivudine and adefovir combination therapy. Methods Total of 100 chronic hepatitis B （CHB） patients with treatment failure by LAM and ADV combined therapy were selected and divided into control group and remedy group according to fnancial condition and the will of the patients, 50 cases in each group. Patients in control group were continually given LAM （100 mg/d） and ADV （10 mg/d） treatment. Patients in remedy group were treated with TDF （300 mg/d） joint ETV （0.5 mg/d）. All patients were treated for 48 weeks. Virology, biochemistry, serology tests were implemented at treatment baseline, 12 weeks, 24 weeks and 48 weeks after treatment. The serum HBV DNA negative conversion rate, liver function recovery rate, virological breakthrough rate,HBeAg seroconversion rate and adverse effects were retrospectively evaluated. Results After 48 weeks, the HBV DNA negative conversion rate, liver function recovery rate, virological breakthrough rate were 94.0% （47/50）, 89.2% （33/37） and 0.0% （0/50） in remedy group; in control group, the above indicators were 34.0% （17/50）, 25.7% （9/35） and 14.0% （7/50）, the differences were statistically signifcant （P 〈 0.05）. After 48 weeks, the seroconversion rate （from HBeAg to HBeAb） was 15.4% （4/26） in remedy group and 16.7% （4/24） in control group, the differences had no statistical signifcance （χ2 = 0.023, P = 0.769）. Patients in both groups were well tolerated, without any case of drug withdrawal caused by severe adverse effects. Conclusions The therapy of TDF combined with ETV is an effective and safe therapeutic strategy for CHB patients with treatment failure by LAM combined with ADV therapy.