Hou Jinlin, Yin You-Kuan, Xu Daozhen, Tan Deming, Niu Junqi, Zhou Xiaqiu, Wang Yuming, Zhu Limin, He Yongwen, Ren Hong, Wan Mobin, Chen Chengwei, Wu Shanming, Chen Yagang, Xu Jiazhang, Wang Qinhuan, Wei Lai, Chao George, Constance Barbara Fielman, Harb George, Brown Nathaniel A, Jia Jidong
Nanfang Hospital, Guangzhou, China.
Hepatology. 2008 Feb;47(2):447-54. doi: 10.1002/hep.22075.
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 lamivudine 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.
In Chinese patients with chronic hepatitis B, telbivudine treatment for 52 weeks provided greater antiviral and clinical efficacy than lamivudine, with less resistance.
慢性乙型肝炎及其危及生命的后遗症在中国极为普遍。需要有效的新疗法来抑制乙型肝炎病毒（HBV）复制并改善肝病。在本研究中，我们比较了核苷类似物替比夫定与拉米夫定对中国患者的疗效。在中国进行的这项III期双盲多中心试验中，332例代偿性乙型肝炎e抗原（HBeAg）阳性或HBeAg阴性慢性乙型肝炎患者被随机分配接受每日600mg替比夫定或100mg拉米夫定治疗104周。主要疗效终点是治疗第52周时血清HBV DNA水平的降低。次要终点包括将HBV DNA清除至检测不到的水平、HBeAg消失和血清学转换、治疗反应以及丙氨酸氨基转移酶（ALT）正常化。评估了病毒耐药性和安全性。在第52周时，在290例HBeAg阳性患者中，替比夫定治疗组血清HBV DNA的平均降低幅度显著大于拉米夫定治疗组（6.3 log₁₀对5.5 log₁₀，P < 0.001），替比夫定治疗组中HBV DNA聚合酶链反应阴性的患者显著多于拉米夫定治疗组（67%对38%，P < 0.001）。替比夫定组的ALT正常化（87%对75%，P = 0.007）、治疗反应（85%对62%，P = 0.001）和HBeAg消失（31%对20%，P = 0.047）也显著更常见。在较小的HBeAg阴性组（n = 42）中，治疗效果呈现相似模式。替比夫定治疗组的病毒耐药性约为拉米夫定治疗组的一半；然而，这种差异无统计学意义。两个治疗组的临床不良事件相似。
在中国慢性乙型肝炎患者中，替比夫定治疗52周比拉米夫定具有更强的抗病毒和临床疗效，且耐药性更低。
