恩替卡韦与拉米夫定治疗慢性乙型肝炎随机、双盲、双模拟对照研究

A double-blind,double-dummy,randomized,controlled study of entecavir versus lamivudine for treatment of chronic hepatitis B

目的以拉米夫定(LVD)为对照,评估恩替卡韦(ETV)治疗中国成人慢性乙型肝炎(CHB)的抗病毒疗效和安全性。方法多中心(26个中心)、随机、双盲、双模拟的对照研究。519例核苷类初治的CHB患者,随机分为ETV组(0.5mg/d)258例和LVD组(100mg/d)261例,用药时间至少52周。应用两种HBV定量法(bDNA和PCR)于12、24、36和48周检测血清病毒载量,每隔4周随访患者,记录不良事件和实验室异常的数据,以监测研究药物的安全性。结果ETV和LVD两组患者的基础人口学、临床和病毒学特征相似。经过48周的治疗,到达主要疗效终点者,ETV组为90%,LVD组仅69%(P<0.0001)。HBVDNA的载量(PCR定量),ETV组平均下降5.9lg拷贝/ml,LVD组平均下降4.3lg拷贝/ml,二者相差超过1.5lg拷贝/ml(P<0.0001)。用PCR法,ETV组中有76%的患者测不到病毒(<300拷贝/ml),而LVD组中仅为43%。ALT的复常,ETV组也优于LVD组,分别为90%和78%(P=0.0003)。两组患者HBeAg的血清学转换率分别为15%和18%,差异无统计学意义(P=0.39)。两组患者不良事件的发生率基本相似,分别为60%和56%,严重不良事件的发生率分别为3%和5%。在治疗期间,没有死亡病例。结论ETV治疗核苷类初治CHB患者,抑制病毒和改善肝脏生化功能方面均优于LVD,安全性与LVD相当。

Objective This study was to evaluate the antiviral efficacy and safety in nucleoside naive Chinese patients with chronic hepatitis B （CHB） treated with entecavir （ETV） or lamivadine （LVD）. Methods The trial was a randomized, double-blind, double-dummy and control design. 519 nucleoside naive CHB patients were treated with daily dose of ETV 0. 5 mg （258 patients ） or LVD 100 mg （261patients） for at least 52 weeks. The primary endpoint was a composite endpoint of HBV DNA 〈 0.7 MEq/ml by bDNA assay and ALT 〈 1.25 × ULN at week 48. HBV DNA levels were also measured by the Roche Cobas AmplicorTM PCR assay at weeks 12, 24, 36 and 48. Clinical and laboratory adverse events were recorded every 4 weeks. Results Baseline characteristics were well balanced between treatment groups. The primary end point were achieved in 90% of ETV treated patients versus 69% of LVD treated patients （P〈0.0001）. The mean HBV DNA level decreased 5.9 lg copies/ml （ by PCR assay ） from baseline in ETV group versus 4. 3 lg copies/ml in LVD group （ P 〈 0. 0001 ）. The serum HBV DNA become undetectable （ 〈300 copies/ml by PCR） in 76% of ETV group versus 43% of LVD group （P 〈0. 0001 ）. The normalization of ALT were 90% in ETV group versus 78% in LVD group （ P = 0. 0003）. The difference of HBeAg seroconversion rates between this 2 groups （15% vs 18% ） at week 48 was no statistically significant. The overall incidence of adverse events （AEs） was comparable： 60% of ETV patients and 56% of LVD patients reported AEs; and 3% of ETV patients and 5% of LVD patients reported serious AEs. Conclusions ETV achieves better virologic and biochemical improvements in nucleoside-naive patients with CHB while the safety profile is comparable to LVD.