恩替卡韦和阿德福韦酯治疗代偿期乙肝肝硬化临床疗效及远期预后

Clinical efficacy and long-term prognosis of entecavir and adefovir dipivoxil in the treatment of compensatory hepatitis B cirrhosis

目的:评价应用恩替卡韦和阿德福韦酯治疗代偿期乙肝肝硬化临床疗效及远期预后的差异。方法:选择2012年1月至2014年8月间于我院就诊的代偿期乙肝肝硬化患者160例,随机数表法分为ADV组和ETV组,分别给予阿德福韦酯和恩替卡韦进行抗病毒治疗,比较两组患者治疗48周和3年后的肝脏纤维化弹性指数、肝纤维化治疗疗效,病毒学指标[如乙型肝炎病毒(HBV)-DNA载量、HBV-DNA转阴率和乙型肝炎E抗原(HBe Ag)转换率]以及远期预后(3年死亡率、原发性肝癌和肝硬化失代偿发生率)。结果:治疗48周后,ETV组患者的肝脏纤维化弹性指数[(1.89±0.23)m/s和(1.49±0.28)m/s,P=0.000 16];ADV组和ETV组肝纤维化治疗总有效率分别为66.25%和81.25%,ETV组明显高于ADV组(P=0.033)。治疗3年后,ETV组患者的HBV-DNA载量[(2.91±0.90)log10 IU/mL和(2.26±0.68)log10 IU/mL,P=0.000 007 5]和无应答率明显低于ADV组(2.50%和11.25%,P=0.029),HBV-DNA转阴率(86.25%和68.75%,P=0.008)和HBe Ag转换率显著高于ADV组(27.50%和11.25%,P=0.009)。ETV组患者的肝功能失代偿发生率和全因死亡率分别为26.25%和6.25%均明显低于ADV组(43.75%和17.50%,P=0.020,P=0.028);两组患者的原发性肝癌发生率分别为13.75%和5.00%(P=0.058),ADV组患者的肝癌发生风险明显高于ETV组[HR=2.996,95%CI(1.009,7.656),P=0.048]。ADV组和ETV组患者相关不良反应的总发生率间不存在明显的统计学差异(13.75%和11.25%,P>0.05)。结论:与阿德福韦酯相比,应用恩替卡韦治疗代偿期乙肝肝硬化具有较高的临床疗效和病毒学应答,并可有效改善患者的远期预后。

AIM： To evaluate the clinical efficacy and long-term prognosis of patients with compensatory hepatitis B cirrhosis treated with entecavir and adefovir dipivoxil. METHODS： One hundred and sixty patients with compensatory hepatitis B cirrhosis from January 2012 to August 2014 were randomly divided into ADV group and ETV group（ 80 cases in each group）. Patients in ADV and ETV group were treated by entecavir and adefovir dipivoxil for antiviral therapy. The liver fibrosis index,liver fibrosis treatment efficacy, virologic indicators（ HBV-DNA load, HBV-DNA negative rate and HBe Ag conversion rate） before and 48 weeks after the treatment were comparatively analyzed,the longterm prognosis（ 3-year mortality,hepatocellular carcinoma and cirrhosis decompensation rate） in two groups were evaluated by the Kaplan-Meier survivorship curve. RESULTS： Forty-eight weeks after treatment,the fibrosis index of the treatment group were significantly lower than those before treatment,among which,those in ETV group were more obvious than ADV group [（ 2. 91 ± 0. 90） log10 IU/mL and（ 2. 26 ± 0. 68） log10 IU/mL, P =0. 000 007 5]. The total effective rate of liver fibrosis in ADV group and ETV group were 66. 25% and81. 25%,respectively（ P = 0. 033）. The HBVDNA load reduce[（ 2. 91 ± 0. 90） log10 IU/mL and（ 2. 26 ± 0. 68） log10 IU/mL,P = 0. 000 007 5]and non-response rate of ETV group were significantly better than those of ADV group（ 2. 50% and11. 25%,P = 0. 029）,the HBV-DNA negative conversion rate（ 86. 25% and 68. 75%,P = 0. 008） and HBe Ag conversion rate were much higher than ADV group（ 27. 50% and 11. 25%,P = 0. 009）. The incidence of liver decompensation and all-cause mortality were significantly lower in the ETV group than those in the ADV group（ 43. 75% and 17. 50%,P= 0. 020,P = 0. 028）,respectively. The incidence of liver cancer in the ADV and ETV group was13. 75% and 5. 00%（ P 0. 05）,and the risk of HCC was significantly higher in ADV group than that in ETV group [HR = 2. 996,95% CI（ 1. 009,7. 656）,P = 0. 048]. There was no significant difference between the ADV group and the ETV group in the total incidence of adverse reactions（ 13. 75% and 11. 25%,P = 0. 058）. CONCLUSION： Compared with adefovir dipivoxil,the application of entecavir in the treatment of compensatory hepatitis B cirrhosis has better clinical efficacy and virological response, and can significantly reduce the liver cirrhosis,and improve the patient ＇s longterm prognosis effectively.