阿德福韦酯治疗失败的慢性乙型肝炎两种挽救治疗方案比较

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目的比较替诺福韦酯单药序贯治疗与恩替卡韦单药序贯治疗在挽救阿德福韦酯(adefovir dipivoxil,ADV)抗病毒治疗后应答不佳,或发生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120例对ADV初治失败的慢性乙型肝炎患者随机分为替诺福韦酯(tenofovir disoproxil fumarate,TDF)组和恩替卡韦(entecavir,ETV)组,每组60例。TDF组给予TDF 300 mg/d,序贯治疗;ETV组给予ETV 0.5 mg/d治疗,所有患者均治疗48周。给药的治疗基线、12周、24周和48周分别进行病毒学、生化学、血清学检测。分析比较两组患者上述治疗时间点的完全病毒学应答率、ALT复常率、病毒学突破率和HBe Ag血清学转换率及观察肾功能损害情况。结果 TDF组治疗48周后完全病毒学应答率为63.3%(38/60),ETV组为78.3%(47/60),两组比较差异具有统计学意义(P<0.05)。TDF组的ALT复常率、HBe Ag血清学转换率、病毒学突破率分别为57.8%(26/45)、13.6%(6/44)、0,ETV组分别为60.4%(29/48)、14.9%(7/47)、0,两组比较差异无统计学意义。两组患者对药物耐受性均良好,治疗过程中未发生因血肌酐升高停药的明显不良反应。结论对于ADV治疗后疗效欠佳或发生病毒学突破的慢性乙型肝炎患者,恩替卡韦单药序贯治疗是一种疗效理想、安全的挽救治疗方案,抗病毒疗效优于替诺福韦酯单药序贯治疗。 Objective To compare the efficacy of tenofovir dipivoxil monotherapy with sequential entecavir monotherapy in response to rescue adefovir dipivoxil (ADV) antiviral therapy, or virological breakthrough in chronic hepatitis B Clinical efficacy and safety of patients. Methods A total of 120 chronic hepatitis B patients with initial failure of ADV were randomly divided into tenofovir disoproxil fumarate (TDF) group and entecavir (ETV) group, 60 cases in each group. TDF group was given TDF 300 mg / d, sequential treatment; ETV group was given ETV 0.5 mg / d treatment, all patients were treated for 48 weeks. Baseline treatment, 12 weeks, 24 weeks and 48 weeks were virological, biochemical, serological tests. The complete virological response rate, ALT normalization rate, virological breakthrough rate and HBeAg seroconversion rate and renal damage were observed and compared between the two groups. Results The complete virological response rate was 63.3% (38/60) in the TDF group and 78.3% (47/60) in the ETV group after 48 weeks of treatment. The difference between the two groups was statistically significant (P <0.05). The rates of ALT recovery, HBeAg seroconversion and virological breakthrough rates in TDF group were 57.8% (26/45), 13.6% (6/44), 0 and 60.4% (29/48) in ETV group respectively , 14.9% (7/47), 0, no significant difference between the two groups. The two groups of patients were well tolerated by the drug and no obvious adverse reactions were observed during the course of treatment due to withdrawal of elevated serum creatinine. Conclusions The sequential therapy of entecavir monotherapy is an ideal and safe salvage therapy for patients with chronic hepatitis B who are ineffective or have virological breakthrough after ADV. The antiviral efficacy is superior to tenofovir disoproxil monotherapy Sequential treatment.
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