Telbivudine versus lamivudine in Chinese patients with chronic hepatitis B: Results at 1 year of a randomized, double-blind trial
Telbivudine versus lamivudine in Chinese patients with chronic hepatitis B: Results at 1 year of a randomized, double-blind trial
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DOI：
10.1002/hep.22075
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发表时间：
2008-02-01
期刊：
影响因子：
13.5
通讯作者：
Jia, Jidong
中科院分区：
文献类型：
--
作者：
Hou, Jinlin;Yin, You-Kuan;Jia, Jidong
慢性B型肝炎及其危及生命的后遗症在中国高度流行。需要有效的新疗法来抑制B型肝炎病毒（HBV）复制并改善肝病。在这项研究中，我们比较了替比夫定，一种核苷类似物，与拉尼夫定在中国患者的疗效。在中国进行的一项III期、双盲、多中心试验中，332例代偿期B e抗原（HBeAg）阳性或HBeAg阴性的慢性B型肝炎患者被随机分配至替比夫定组和拉米夫定组，分别接受每日600 mg和100 mg的替比夫定治疗，持续104周。主要疗效终点是治疗52周时血清HBV DNA水平降低。次要终点包括HBV DNA清除至检测不到的水平、HBeAg消失和血清转换、治疗反应和丙氨酸转氨酶（ALT）正常化。评估病毒耐药性和安全性。第52周时，在290例HBeAg阳性患者中，替比夫定组血清HBV DNA的平均降幅显著大于拉米夫定组（6-3 log（10）vs 5.5 log（10），P < 0.001），且替比夫定组HBV DNA聚合酶链反应阴性患者显著多于拉米夫定组（67% vs 38%，P < 0.001）。ALT正常化（87%对75%，P = 0.007）、治疗反应（85%对62%，P = 0.001）和HBeAg下降（31%对20%，P = 0.047）在替比夫定组中也更常见。在较小的HBeAg阴性组（n = 42）中，治疗效果显示出相似的模式。替比夫定接受者的病毒耐药性大约是拉米夫定的一半，但是这种差异没有统计学意义。两个治疗组的临床不良事件相似。结论：在中国慢性B型肝炎患者中，替比夫定治疗52周提供了比拉米夫定更大的抗病毒和临床疗效，耐药性更低。
Chronic hepatitis B and its life-threatening sequelae are highly prevalent in China. There is a need for effective new therapies to suppress hepatitis B virus (HBV) replication and ameliorate liver disease. In this study, we compared the efficacy of telbivudine, a nucleoside analogue, with larnivudine in Chinese patients. In this phase III, double-blind, multicenter trial conducted in China, 332 patients with compensated hepatitis B e antigen (HBeAg)positive or HBeAg-negative chronic hepatitis B were randomly assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine daily for 104 weeks. The primary efficacy endpoint was reduction in serum HBV DNA levels at week 52 of treatment. Secondary endpoints included clearance of HBV DNA to undetectable levels, HBeAg loss and seroconversion, therapeutic response, and alanine aminotransferase (ALT) normalization. Viral resistance and safety were assessed. At week 52, among 290 HBeAg-positive patients, mean reductions of serum HBV DNA were significantly greater in telbivudine recipients than lamivudine recipients (6-3 log(10) versus 5.5 log(10), P < 0.001), and HBV DNA was polymerase chain reaction-negative in significantly more telbivudine recipients than lamivudine recipients (67% versus 38%, P < 0.001). ALT normalization (87% versus 75%, P = 0.007), therapeutic response (85% versus 62%, P = 0.001), and HBeAg loss (31% versus 20%, P = 0.047) were also significantly more common in the telbivudine group. Treatment effects showed similar patterns in the smaller HBeAg-negative group (n = 42). Viral resistance in telbivudine recipients was approximately half that observed with lamivudine; however, this difference was not statistically significant. Clinical adverse events were similar in the two treatment groups. Conclusion: In Chinese patients with chronic hepatitis B, telbivudine treatment for 52 weeks provided greater antiviral and clinical efficacy than lamivudine, with less resistance.