恩替卡韦与阿德福韦酯治疗乙肝肝硬化患者的疗效及预后比较

Comparison of efficacy and prognosis of entecavir and adefovir in treating patients with hepatitis B cirrhosis

目的探讨恩替卡韦、阿德福韦酯治疗乙肝肝硬化患者的近期疗效及远期预后的差异。方法选取2011年9月至2015年1月皖北煤电集团总医院确诊并接受治疗的代偿期乙肝肝硬化患者86例,参照随机数表法将其分为恩替卡韦组和阿德福韦酯组,每组43例。恩替卡韦组患者在常规治疗基础上加入恩替卡韦治疗,阿德福韦酯组患者在常规治疗基础上加入阿德福韦酯。治疗均持续48周,治疗开始后随访3年。采集治疗前后晨起空腹外周血,比较两组患者病毒学指标(HBV-DNA载量、HBVDNA转阴率)、肝纤维化指标[Ⅲ型胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)、层粘连蛋白(LN)、透明质酸酶(HA)]的变化,记录治疗期间药物不良反应发生率和随访期内不良结局(肝硬化失代偿、原发性肝癌、全因死亡)发生率。结果治疗48周后,恩替卡韦组外周血中HBV-DNA的水平低于阿德福韦酯组,HBV-DNA转阴率高于阿德福韦酯组,血清中PCⅢ、Ⅳ-C、LN、HA的水平低于阿德福韦酯组,差异均有统计学意义(P <0. 05)。治疗期间,两组药物不良反应发生率差异无统计学意义(P> 0. 05)。随访期内,恩替卡韦组患者的肝硬化失代偿、原发性肝癌、全因死亡发生率均低于阿德福韦酯组患者,差异有统计学意义(P <0. 05)。结论与阿德福韦酯相比,恩替卡韦治疗代偿期乙肝肝硬化用于在病毒学应答及纤维化进程抑制方面更具优势,且可积极降低远期不良结局发生率。

Objective To investigate the short term efficacy and long-term prognosis of entecavir and adefovir dipivoxil in treatment of patients with hepatitis B cirrhosis. Methods Eighty-six cases of compensatoryhepatitis B cirrhosis patients in our hospital during Sept 2011 to Jan 2015 were randomly divided into entecavir group （ n =43） and adefovir group （ n =43）. Patients in entecavir group were treated with entecavir on the basis of routine treatment and those in adefovir group with adefovir dipivoxil on the basis of routine treatment, both lasting for 48 weeks and followed up for 3 years after treatment. Vierendeel peripheral blood before and after treatment was collected and virology indexes （HBV-DNA load, HBV-DNA negative rate）, liver fibrosis index [type Ⅲ collagen （PC Ⅲ）, type Ⅳ collagen （IV -C）, laminin （LN） and hyaluronidase （HA）] were compared between the two groups. The incidence of adverse drug reactions during the treatment, incidence of adverse outcomes （decompensated cirrhosis, primary liver cancer and all-cause death） during follow-up period were recorded. Results Forty-eight weeks after treatment, the level of HBV-DNA in peripheral blood in entecavir group was lower than that in adefovir group, HBV-DNA negative conversion rate was higher than that in adefovir group, serum levels of PC Ⅲ, Ⅳ-C, LN and HA were lower than those in adefovir group, and the differences of these indexes were statistically significant（ P 〈0.05）. During treatment, there was no significant difference in the incidence of adverse drug reactions between the two groups（ P 〉0.05）. During the follow-up period, the rate of decompensation, primary liver cancer, all cause death in entecavir group were lower than those in adefovir group, and the difference was statistically significant （ P 〈0.05）. Conclusion Compared with adefovir, entecavir is more advantageous in virological response and inhibition of fibrosis process in compensatory liver cirrhosis, which can actively reduce the incidence of bad outcome.