Lai Ching-Lung, Gane Edward, Liaw Yun-Fan, Hsu Chao-Wei, Thongsawat Satawat, Wang Yuming, Chen Yagang, Heathcote E Jenny, Rasenack Jens, Bzowej Natalie, Naoumov Nikolai V, Di Bisceglie Adrian M, Zeuzem Stefan, Moon Young Myoung, Goodman Zachary, Chao George, Constance Barbara Fielman, Brown Nathaniel A
University Department of Medicine, Queen Mary Hospital, Hong Kong, China.
N Engl J Med. 2007 Dec 20;357(25):2576-88. doi: 10.1056/NEJMoa066422.
Reducing hepatitis B virus (HBV) replication to minimal levels is emerging as a key therapeutic goal for chronic hepatitis B.
In this double-blind, phase 3 trial, 1370 patients with chronic hepatitis B were randomly assigned to receive 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy end point was noninferiority of telbivudine to lamivudine for therapeutic response (i.e., a reduction in serum HBV DNA levels to fewer than 5 log10 copies per milliliter, along with loss of hepatitis B e antigen [HBeAg] or normalization of alanine aminotransferase levels). Secondary efficacy measures included histologic response, changes in serum HBV DNA levels, and HBeAg responses.
At week 52, a significantly higher proportion of HBeAg-positive patients receiving telbivudine than of those receiving lamivudine had a therapeutic response (75.3% vs. 67.0%, P=0.005) or a histologic response (64.7% vs. 56.3%, P=0.01); telbivudine also was not inferior to lamivudine for these end points in HBeAg-negative patients. In HBeAg-positive and HBeAg-negative patients, telbivudine was superior to lamivudine with respect to the mean reduction in the number of copies of HBV DNA from baseline, the proportion of patients with a reduction in HBV DNA to levels undetectable by polymerase-chain-reaction assay, and development of resistance to the drug. Elevated creatine kinase levels were more common in patients who received telbivudine, whereas elevated alanine aminotransferase and aspartate aminotransferase levels were more common in those who received lamivudine.
Among patients with HBeAg-positive chronic hepatitis B, the rates of therapeutic and histologic response at 1 year were significantly higher in patients treated with telbivudine than in patients treated with lamivudine. In both the HBeAg-negative and the HBeAg-positive groups, telbivudine demonstrated greater HBV DNA suppression with less resistance than did lamivudine. (ClinicalTrials.gov number, NCT00057265 [ClinicalTrials.gov].).
将乙型肝炎病毒（HBV）复制降低至最低水平正成为慢性乙型肝炎的关键治疗目标。
在这项双盲3期试验中，1370例慢性乙型肝炎患者被随机分配，分别接受每日一次600mg替比夫定或100mg拉米夫定治疗。主要疗效终点是替比夫定在治疗反应方面不劣于拉米夫定（即血清HBV DNA水平降至每毫升少于5 log10拷贝，同时乙肝e抗原[HBeAg]消失或丙氨酸氨基转移酶水平恢复正常）。次要疗效指标包括组织学反应、血清HBV DNA水平变化和HBeAg反应。
在第52周时，接受替比夫定治疗的HBeAg阳性患者中，治疗反应（75.3%对67.0%，P = 0.005）或组织学反应（64.7%对56.3%，P = 0.01）的比例显著高于接受拉米夫定治疗的患者；在HBeAg阴性患者中，替比夫定在这些终点方面也不劣于拉米夫定。在HBeAg阳性和HBeAg阴性患者中，替比夫定在从基线开始HBV DNA拷贝数平均降低、HBV DNA降至聚合酶链反应检测不到水平的患者比例以及对药物耐药性的发生方面均优于拉米夫定。接受替比夫定治疗的患者肌酸激酶水平升高更为常见，而接受拉米夫定治疗的患者丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平升高更为常见。
在HBeAg阳性慢性乙型肝炎患者中，接受替比夫定治疗1年时的治疗反应率和组织学反应率显著高于接受拉米夫定治疗的患者。在HBeAg阴性和HBeAg阳性组中，替比夫定均显示出比拉米夫定更强的HBV DNA抑制作用且耐药性更低。（ClinicalTrials.gov编号，NCT00057265 [ClinicalTrials.gov]。）
