A 24-week, Parallel-group, Open-label, Randomized Clinical Trial Comparing the Early Antiviral Efficacy of Telbivudine and Entecavir in the Treatment of HBeAg-positive Chronic Hepatitis B in Adult Chi

此研究由我院陈永平教授研究团队组织实施，全文已发表在国际杂志clinical therapeutics（2010年4月），链接：http://www.clinicaltherapeutics.com/1209/issues/v32n4/649_zhe.pdf。全文中文版本将尽快发布。a 24-week, parallel-group, open-label, randomized clinical trial comparing the early antiviral efficacy of telbivudine and entecavir in the treatment of hepatitis b e antigen-positive chronic hepatitis b virus infection in adult chinese patients. clin ther. 2010;32(4):649-58.温州医学院附属第一医院感染内科郑明华

该文同时被2010年欧肝肝病大会（easl）录用， 并在维也纳本届大会上进行壁报交流，发表在其官方杂志 j hepatol。信息： a 24-week, parallel-group, open-label, randomized clinical trial comparing the early antiviral efficacy of telbivudine and entecavir in the treatment of hbeag-positive chronic hepatitis b. j hepatol. 2010;52:s401.

摘要：

objective: to compare, in a parallel-group, open-label, randomized trial, the early antiviral efficacy of telbivudine and entecavir in the treatment of hbeag-positive chronic hepatitis b (chb).

methods: adult patients positive for hbeag, with hepatitis b virus (hbv) dna ≥10⁶ copies/ml, alanine transaminase (alt) ≥ 2×upper limit of normal were randomized to receive telbivudine 600 mg (n=65) or entecavir 0.5 mg (n=66) daily for 24 weeks. blood samples were collected at the baseline, 12, and 24 weeks after the treatment. the primary endpoint was the mean reduction in the serum hbv-dna level at week 24. secondary endpoints included the mean reduction in the serum hbv-dna level at week 12, the absence of serum hbv-dna, hbeag loss, and hbeag seroconversion at weeks 12 and 24, and the normalization of serum alt at week 24 and occurrence of adverse events within week 24.

results: a total of 131 patients were enrolled in the study. they were 91 men and 40 women, with a mean age of 32.5 ± 8.9 years. all patients were ethnic han and the baseline demographic characteristics and serum hbv-dna levels in the two treatment groups were well matched. the mean reduction in the serum hbv-dna levels was 6.00 log10 and 5.80 log10 copies/ml at week 24, respectively. in telbivudine and entecavir groups, with the reduction being 4.99 log10 and 4.69 log10 copies/ml at week 12, respectively (both p>0.05). at weeks 24 and 12, hbv-dna was undetectable in 67.7% (44/65) and 43.1% (28/65) of telbivudine group, and in 57.6% (38/66) and 34.8% (23/66) of entecavir group, respectively (both p>0.05). at week 24, hbeag loss and hbeag seroconversion rates were 36.9% (24/65) and 24.6% (16/65) in telbivudine group, and 28.8% (19/66) and 13.6% (9/66) in entecavir group, respectively (both p>0.05). at week 12, hbeag loss and hbeag seroconversion rates were significantly greater in telbivudine group than in entecavir group (20.0% (13/65) vs. 3.0% (2/66), p=0.002; and 13.8% (9/65) vs. 3.0% (2/66), p=0.025, respectively). in addition, the normalization of alt levels was observed in 78.5% (51/65) and 74.2% (49/66) of patients treated with telbivudine and entecavir, respectively, at week 24 (p=0.570). both drugs were well tolerated. most frequent adverse events included upper respiratory tract infection, fatigue, diarrhea and coughing, most of which were of mild-to-moderate severity. there was no significant difference in the frequency and severity of adverse events between the two groups.

conclusion: both telbivudine and entecavir have the ability to suppress hbv replication rapidly in patients with hbeag-positive chb. however, the study failed to demonstrate differences in efficacy or tolerability after 24 weeks in this population of adult, chinese, previously untreated chb patients.

目的：旨在比较替比夫定与恩替卡韦治疗e抗原阳性慢性乙肝早期抗病毒疗效的开放标签平行组随机对照。

方法：e抗原阳性成人患者，病毒载量≥10⁶ copies/ml，alt ≥ 2倍正常值上限，随机接受替比夫定600mg（n=65）或恩替卡韦0.5mg（n=66）共计24周，每天服用一次。在治疗前、治疗12周与24周留取血标本。主要终点指标是24周时的hbvdna下降量。次要终点指标是12周时的hbvdna下降量，12周与24周时的hbvdna转阴率、e抗原消失与e抗原血清转换率，24周时的alt复常率，24周时的不良事件发生率。

结果：24周时替比夫定与恩替卡韦组平均hbvdna下降为6.00 log10与5.80 log10 copies/ml，而12周时相应的hbvdna下降为4.99 log10 and 4.69 log10 copies/ml（p>0.05）。12周与24周hbvdna的转阴率在替比夫定组分别是67.7%和43.1%，恩替卡韦组是57.6%  和34.8%（p>0.05）。12周时，e抗原消失率与e抗原血清转换率替比夫定组比恩替卡韦组高，分别是20.0% vs. 3.0%, p=0.002和13.8%vs. 3.0%, p=0.025。24周时两组e抗原血清转换率与e抗原消失率没有明显差异。此外，alt复常率在24时，替比夫定组与恩替卡韦组分别为78.5% and 74.2%(p=0.570)。两组间不良事件发生率没有统计学差异。

结论：替比夫定与恩替卡韦在e抗原阳性慢性乙肝患者中均可快速抑制hbv的复制。