恩替卡韦治疗中重度肝纤维化慢性乙型肝炎患者48周的疗效分析

目的III期临床研究结果显示恩替卡韦(ETV)治疗48周,在组织学改善、ALT复常和HBVDNA抑制方面均优于拉米夫定(LMV);肝纤维化的改善在核苷类似物初治患者中2个治疗组相似,在拉米夫定失效患者中,ETV明显优于LMV。对基线时表现为中重度肝纤维化/硬化患者(Ishak评分:4-6)进行亚组分析,评估ETV或LMV治疗48周的疗效。方法纤维化评分是由1位病理学家对基线和48周时标本进行评估,治疗组及标本先后顺序均对他设盲。结果对HBeAg( )核苷类似物初治的患者,48周时肝纤维化发生改善的患者比例ETV组为57%,LMV组为49%;肝纤维化没变化的患者比例ETV组35%,LMV组为28%;肝纤维化恶化的患者比例ETV组为0,LMV组为6%;对HBeAg(-)核苷类似物初治的患者,48周时肝纤维化发生改善的患者比例ETV组为59%,LMV组为53%;肝纤维化没变化的患者比例ETV组为31%,LMV组为18%;肝纤维化恶化的患者比例ETV组为2%,LMV组为5%;对HBeAg( )LMV失效的患者,48周时肝纤维化发生改善的患者比例ETV组为43%,LMV组为33%;肝纤维化没变化的患者比例ETV组为35%,LMV组为29%;肝纤维化恶化的患者比例ETV组为0,LMV组为19%。结论接受ETV治疗的中重度肝纤维化/硬化患者比接受LMV治疗更可能获得纤维化改善或不变,这些数据与其他治疗终点(全组人群的病毒学、生化学和Knodell评价的组织学改善情况)结果一致,均为ETV优于LMV。

Effect of entecavir or lamivudine treatment on HBV patients with advanced liver fibrosis/cirrhosis for 48 weeks

Objective Entecavir(ETV) was superior to lamivudine(LMV) in achieving histologic improvement,ALT normalization and HBV DNA suppression at week 48 in phase III trials. Improvement in fibrosis was similar between treatments in nucleoside-naive patients and superior in ETV treated LMV-refractory patients. A subset analysis was performed for those patients having advanced liver fibrosis/ cirrhosis at baseline( Ishak score :4-6), evaluating the impact of 48 weeks of ETV or LMV treatment. Method Fibrosis was evaluated at baseline and at week 48 by a central histopathologist blinded to treatment and to the sequence of samples. Results At week 48,among HBeAg( ) nucleoside-naive patients, liver fibrosis had been improved in 57% of ETV group and 49% of LMV group, showed no changes in 35% of ETV group and 28% of LMV group and became worse in 0% of ETV group and 6% of LMV group. Among HBeAg(-) nucleoside-naive patients, liver fibrosis had been improved in 59% of ETV group and in 53% of LMV group, showed no changes in 31% of ETV group and 18% of LMV group and became worse in 2% of ETV group and 5% of LMV group. Among HBeAg( ) LMV-refractory patients, liver fibrosis had been improved in 43% of ETV group and 33% of LMV group, showed no changes in 35% of ETV group and 29% of LMV group and became worse in 0% of ETV group and 19% of LMV group. Conclusions Patients with advanced liver fibrosis/cirrhosis who received ETV were more likely to experience either improvement or no change in the appearance of their biopsy than LMV-treated patients. These data are consistent with other treatment end points (virologic,biochemical and overall histologic improvement by Knodell from the overall study population) which demonstrated superiority of ETV over LMV.