e抗原阴性乙型肝炎失代偿期肝硬化患者初始拉米夫定联合阿德福韦酯治疗的疗效观察

发布时间：2018-06-18 04:55

本文选题：e抗原阴性 + 肝硬化失代偿　；参考：《新乡医学院》2014年硕士论文

【摘要】：背景：失代偿期肝硬化属晚期肝病,具有并发症多、治疗困难等特点。据相关报道,肝硬化失代偿期5年的生存率只有14%,因此失代偿期肝硬化患者的治疗尤为重要,其根本为抗病毒治疗。目的：观察初始拉米夫定(LAM)联合阿德福韦酯(ADV)对e抗原阴性乙型肝炎失代偿期肝硬化患者的治疗效果及安全性；对比单用阿德福韦酯和单用拉米夫定对这类患者的治疗效果；初步探讨初始联合治疗(LAM+ADV)降低乙肝病毒耐药性的原理及效果。方法：研究南阳市中心医院感染科收治的e抗原阴性乙型肝炎失代偿期肝硬化患者共200例,随机分为联合治疗组(LAM+ADV组)80例、单药治疗组共120例：其中拉米夫定单药组(LAM组)60例、阿德福韦酯单药组(ADV组)60例。LAM+ADV组给予LAM100mg/d+ADV10mg/d,LAM组给予LAM100mg/d,ADV组给予ADV10mg/d。各组的保肝治疗方案相同。观察比较各组患者在治疗前及治疗后12周、24周和48周血清HBV DNA水平；治疗前及治疗后2周、4周、6周和8周肝功能转归以及Child-Pugh评估,同时观察临床症状改善情况及药物的不良反应。结果：统计分析治疗12周、24周和48周联合治疗组和各单药组病毒学应答情况：在治疗12周时LAM+ADV组HBV DNA阴转率尤为突出,即LAM+ADV组的HBV DNA阴转率达到95%,而LAM组和ADV组的HBV DNA阴转率分别为83.3%和66.7%,具有显著差异(P0.05)；在治疗12周和24周时,LAM组HBV DNA阴转率(83.3%、90%)都高于ADV组(66.7%、80%),具有显著差异(P0.05)；在治疗48周时LAM+ADV组、LAM组及ADV组HBV DNA阴转率分别为97.5%、83.3%和80%,联合治疗组与各单药组均具有显著性差异(P0.05); LAM组HBV DNA阴转率(83.3%)与ADV组HBV DNA阴转率(80%)无差异(P0.05)。各治疗组患者HBV DNA阴转率随着时间的延长也有所提高,治疗24周后HBV DNA阴转率不再增加。研究还发现LAM+ADV组与LAM组、ADV组在治疗48周后HBV DNA阴转率均未达100%。统计分析在治疗2、4、6和8周时肝功能主要指标以及Child-Pugh评分情况：各个治疗组在治疗8周以后的ALT、AST、TBiL和ALB均有明显改善,与治疗前相比差异具有统计学意义(P0.05); LAM+ADV组在第6周时肝功能已基本复常,而LAM组、ADV组均在第8周时才有明显改善,LAM+ADV组优于LAM组及ADV组；8周时LAM+ADV组、LAM组和ADV组Child-Pugh评估分别为6.8±1.0、7.1±1.3和7.3±1.2,与各组治疗前相比差异均有统计学意义(P0.05)。三组均未见明显的不良反应,无肾功能异常。结论：对e抗原阴性乙型肝炎失代偿期肝硬化患者,初始拉米夫定联合阿德福韦酯的治疗效果优于单用拉米夫定或阿德福韦酯治疗效果。
[Abstract]:Background: decompensated cirrhosis is a late liver disease with many complications and difficulties in treatment. According to relevant reports, the 5-year survival rate of decompensated cirrhosis is only 14%, so the treatment of decompensated cirrhosis is particularly important, which is basically antiviral therapy. Objective: to observe the efficacy and safety of lamivudine combined with adefovir dipivoxil (ADV) in the treatment of hepatitis B patients with decompensated liver cirrhosis with negative e antigen, and to compare the efficacy of adefovir alone and lamivudine alone in the treatment of these patients. To explore the principle and effect of initial combined therapy with laminar ADV (Lam ADV) in reducing drug resistance of hepatitis B virus (HBV). Methods: a total of 200 patients with liver cirrhosis in decompensated phase of hepatitis B with negative e antigen were randomly divided into two groups: the combined treatment group (n = 80) and Lam ADV group (n = 80). There were 120 cases in single drug treatment group: 60 cases in lamivudine group with lamivudine group and 60 cases in single drug group with adefovir dipivoxil group. 60 cases in lamivudine group were given 100 mg / d ADV10 mg / d of LAM100 mg / d ADV10 mg / d in lamivudine group. The liver protection regimen was the same in each group. The serum HBV DNA levels were observed and compared before treatment and 12 weeks and 48 weeks after treatment, liver function and Child-Pugh were evaluated before treatment and 2 weeks after treatment, 6 weeks and 8 weeks after treatment, and before treatment and 2 weeks after treatment, the changes of liver function and Child-Pugh were evaluated. At the same time, the improvement of clinical symptoms and adverse drug reactions were observed. Results: the virological responses of the combined treatment group and each single drug group at 12 weeks and 48 weeks after treatment were statistically analyzed. The HBV DNA negative conversion rate in LamADV group was particularly significant at 12 weeks after treatment. That is to say, the HBV DNA negative conversion rate of LamADV group was 95, while the HBV DNA negative conversion rate of Lam group and ADV group was 83.3% and 66.7%, respectively, with significant difference (P0.05), and the HBV DNA negative conversion rate of LAM group was 83.390 at 12 weeks and 24 weeks after treatment, which was significantly higher than that of ADV group (66.70.80%). At 48 weeks after treatment, the negative conversion rates of HBV DNA in Lam ADV group and ADV group were 97.53.3% and 80%, respectively. There was significant difference between the combined treatment group and the single drug group (P 0.05), but there was no significant difference between the Lam group and the ADV group (83.3%) and the ADV group (80%). The negative conversion rate of HBV DNA in all treatment groups was also increased with the prolongation of time, and the negative conversion rate of HBV DNA did not increase after 24 weeks of treatment. It was also found that the negative rate of HBV DNA in both LAMADV and Lamb ADV groups did not reach 100% 48 weeks after treatment. The main indexes of liver function and Child-Pugh score at 2 weeks and 8 weeks after treatment were statistically analyzed. Compared with before treatment, the difference was statistically significant (P 0.05), the liver function in LamADV group had basically returned to normal at the 6th week, but the improvement of Lamm ADV group was better than that of Lam ADV group and ADV group at the 8th week. At 8 weeks, the Child-Pugh assessment of laminar group and ADV group were 6.8 卤1.0 卤7.1 卤1.3 and 7.3 卤1.2, respectively, which were significantly different from those before treatment (P 0.05). There were no obvious adverse reactions and no abnormal renal function in the three groups. Conclusion: the efficacy of lamivudine combined with adefovir in the treatment of hepatitis B patients with decompensated cirrhosis is better than that of lamivudine or adefovir alone.
【学位授予单位】：新乡医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.62;R575.2

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