Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.
J Viral Hepat. 2013 Apr;20(4):e37-46. doi: 10.1111/jvh.12025. Epub 2012 Dec 27.
In the phase-III GLOBE/015 studies, telbivudine demonstrated superior efficacy vs lamivudine during 2-year treatment in HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB). After completion, 847 patients had an option to continue telbivudine treatment for further 2 years. A total of 596 (70%) of telbivudine-treated patients, who were serum HBV DNA positive or negative and without genotypic resistance to telbivudine at the end of the GLOBE/015 trials, were enrolled into a further 2-year extension study. A group of 502 patients completed 4 years of continuous telbivudine treatment and were included in the telbivudine per-protocol population. Amongst 293 HBeAg-positive patients, 76.2% had undetectable serum HBV DNA and 86.0% had normal serum ALT at the end of 4 years. Notably, the cumulative rate of HBeAg seroconversion was 53.2%. Amongst 209 HBeAg-negative patients, 86.4% had undetectable HBV DNA and 89.6% had normal serum ALT. In patients who had discontinued telbivudine treatment due to HBeAg seroconversion, the HBeAg response was durable in 82% of patients (median 111 weeks of off-treatment follow-up). The cumulative 4-year resistance rate was 10.6% for HBeAg-positive and 10.0% for HBeAg-negative patients. Most adverse events were mild or moderate in severity and transient. Renal function measured by estimated glomerular filtration rate (eGFR) increased by 14.9 mL/min/1.73 m(2) (16.6%) from baseline to 4 years (P < 0.0001). In conclusion, in HBeAg-positive and HBeAg-negative CHB patients without resistance after 2 years, two additional years of telbivudine treatment continued to provide effective viral suppression with a favourable safety profile. Moreover, telbivudine achieved 53% of HBeAg seroconversion in HBeAg-positive patients.
在 GLOBE/015 三期研究中，替比夫定在 HBeAg 阳性和 HBeAg 阴性慢性乙型肝炎（CHB）患者的两年治疗中显示出优于拉米夫定的疗效。完成治疗后，847 名患者有选择继续替比夫定治疗两年。GLOBE/015 试验结束时，共有 596 名（70%）血清 HBV DNA 阳性或阴性且无替比夫定基因型耐药的替比夫定治疗患者入组进一步的两年扩展研究。一组 502 名患者完成了四年连续替比夫定治疗，纳入替比夫定方案人群。在 293 名 HBeAg 阳性患者中，76.2%的患者在第 4 年时血清 HBV DNA 不可检测，86.0%的患者血清 ALT 正常。值得注意的是，HBeAg 血清学转换的累积率为 53.2%。在 209 名 HBeAg 阴性患者中，86.4%的患者 HBV DNA 不可检测，89.6%的患者血清 ALT 正常。在因 HBeAg 血清学转换而停用替比夫定的患者中，82%的患者 HBeAg 应答具有持久性（中位停药随访 111 周）。HBeAg 阳性和 HBeAg 阴性患者的 4 年累积耐药率分别为 10.6%和 10.0%。大多数不良事件的严重程度为轻度或中度，且为一过性。肾小球滤过率（eGFR）估计值从基线到 4 年时增加了 14.9 mL/min/1.73 m2（16.6%）（P < 0.0001）。总之，在两年后无耐药的 HBeAg 阳性和 HBeAg 阴性 CHB 患者中，再接受两年的替比夫定治疗可继续提供有效的病毒抑制，且安全性良好。此外，替比夫定使 HBeAg 阳性患者中的 HBeAg 血清学转换率达到 53%。
