Yao Guang-bi, Zhu Mei, Wang Yu-ming, Xu Dao-zhen, Tan De-ming, Chen Cheng-wei, Hou Jin-lin
Clinical Immunology Research Center, Shanghai Jing An Qu Central Hospital, Shanghai 200040, China.
Zhonghua Nei Ke Za Zhi. 2006 Nov;45(11):891-5.
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).
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 (261 patients) 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 x ULN at week 48. HBV DNA levels were also measured by the Roche Cobas Amplicor(TM) PCR assay at weeks 12, 24, 36 and 48. Clinical and laboratory adverse events were recorded every 4 weeks.
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.
ETV achieves better virologic and biochemical improvements in nucleoside-naive patients with CHB while the safety profile is comparable to LVD.
本研究旨在评估恩替卡韦（ETV）或拉米夫定（LVD）治疗初治的慢性乙型肝炎（CHB）中国患者的抗病毒疗效和安全性。
该试验采用随机、双盲、双模拟和对照设计。519例初治的CHB患者接受每日剂量的ETV 0.5mg（258例患者）或LVD 100mg（261例患者）治疗至少52周。主要终点是在第48周时通过分支DNA分析法检测HBV DNA<0.7MEq/ml且ALT<1.25×ULN的复合终点。在第12、24、36和48周时也通过罗氏Cobas Amplicor™PCR分析法测量HBV DNA水平。每4周记录临床和实验室不良事件。
治疗组之间的基线特征平衡良好。ETV治疗的患者中有90%达到主要终点，而LVD治疗的患者中这一比例为69%（P<0.0001）。ETV组的平均HBV DNA水平较基线下降了5.9lg拷贝/ml（通过PCR分析法），而LVD组下降了4.3lg拷贝/ml（P<0.0001）。ETV组中76%的患者血清HBV DNA变得不可检测（通过PCR<300拷贝/ml），而LVD组为43%（P<0.0001）。ETV组ALT正常化的比例为90%，LVD组为78%（P = 0.0003）。两组在第48周时HBeAg血清学转换率的差异（15%对18%）无统计学意义。不良事件（AE）的总体发生率相当：60%的ETV患者和56%的LVD患者报告了AE；3%的ETV患者和5%的LVD患者报告了严重AE。
ETV在初治的CHB患者中实现了更好的病毒学和生化改善，同时安全性与LVD相当。
