恩替卡韦治疗慢性乙型肝炎肝硬化失代偿期患者的近期疗效及安全性

Efficacy and safety of entecavir therapy in decompensate cirrhosis patients with chronic hepatitis B

目的:观察恩替卡韦治疗慢性乙型肝炎(CHB)肝硬化失代偿期患者的近期疗效及安全性。方法:选取44例CHB肝硬化失代偿期患者,随机分为恩替卡韦组(22例)和拉米夫定组(22例)。两组患者均给予综合治疗,其中恩替卡韦组患者加用恩替卡韦0.5mg/次口服,1次/d;拉米夫定组患者加用拉米夫定100mg/次口服,1次/d。每周检测两组患者HBV DNA、ALT、Alb、TBil、PTA(凝血酶源活动度)及乳酸(Lactate)等指标变化,连续8周。结果:两组患者HBV DNA水平均从治疗第2周开始逐渐下降,但恩替卡韦组患者HBV DNA水平在治疗后第5周下降到低于检测下限(<5×102拷贝/ml),明显快于拉米夫定组。从治疗第5周开始,恩替卡韦组患者Alb、TBil及PTA指标较拉米夫定组患者有更明显的改善。在8周的观察期内,有9例患者死亡(MELD评分均>25),其中恩替卡韦组4例,拉米夫定组5例,两组之间病死率比较差异无显著性意义(P>0.05)。9例死亡患者均有不同程度的高乳酸血症(2.0～4.0 mmol/L),但无乳酸酸中毒发生。结论:恩替卡韦较拉米夫定有更显著的抗病毒活性,可在短期内较迅速改善CHB肝硬化失代偿期患者病情。恩替卡韦或拉米夫定均无明显的药物不良反应。血清乳酸水平的升高主要与患者病情严重有关。

Objective： To explore the short-term efficacy and safety of entecavir therapy as compared to lamivudine therapy in decompensate cirrhosis patients with chronic hepatitis B. Methods： The data were collected from 44 decompensate cirrhosis patients with chronic hepatitis B （ CHB）, who were randomly enrolled to one of the two treatments. All patients received compre- hensive treatments ; 22 patients were treated with entecavir, and the other 22 patients were treated with lamivudine. The serum levels of HBV DNA, alanine aminotransferase （ALT）, albumin （Alb）, total bilirubin （TBil）, prothrombin activity （PTA） and lactate were determined every 7 days for 8 weeks. Results： The serum HBV DNA levels in patients treated with either entecavir or with lamivudine declined gradually after the 2nd week of treatment. However, HBV DNA levels in the entecavir group fell to the lower limit of detection （ 〈 5 ×10^2 copies/ml） after the 5th week, which was more rapid than in the lamivudine group. In addition, the Alb, TBil and PTA of the patients with entecavir treatment showed a more significant improvement as compared to the patients treated with lamivudine from the start of the 5th week. In the 8-week treatment period, nine patients died （ all of MELD score 〉 25 ）, of which 4 cases with entecavir treatment, and 5 cases with lamivudine treatment. There were no differences in mortality between the two groups （ P 〉 0. 05 ） . Nine died cases developed varying degrees of hyperlactacidemia （2.0 - 4.0 mmol/L）, but without lactic acidosis occurrence. Conclusion ： Entecavir treatment is superior to lamivudine treatment in impro- ving the condition of patients with decompensate cirrhosis as a result of chronic HBV infection in the short-term by rapidly sup- pressing HBV replication. All patients tolerated entecavir or lamivudine treatment well. Elevated levels of serum lactate were mainly related with severe patient＇s condition.