Leung Nancy, Peng Cheng-Yuan, Hann Hie-Won, Sollano Jose, Lao-Tan Judy, Hsu Chao-Wei, Lesmana Laurentius, Yuen Man-Fung, Jeffers Lennox, Sherman Morris, Min Albert, Mencarini Kimberly, Diva Ulysses, Cross Anne, Wilber Richard, Lopez-Talavera Juan
Alice Ho Miu Ling Nethersole Hospital, Taipo, Hong Kong SAR, China.
Hepatology. 2009 Jan;49(1):72-9. doi: 10.1002/hep.22658.
This study was undertaken to compare the early antiviral activity and viral kinetic profiles of entecavir (ETV) versus adefovir (ADV) in hepatitis B e antigen positive nucleoside-naïve adults with chronic hepatitis B (CHB). Sixty-nine nucleoside-naïve CHB patients with baseline HBV DNA of 10(8) copies/mL or more were randomized 1:1 to open-label treatment with entecavir 0.5 mg/day or adefovir 10 mg/day for a minimum of 52 weeks. The primary efficacy analysis compared mean reduction in HBV DNA at week 12 adjusted for baseline levels using linear regression. Entecavir was superior to adefovir for mean change from baseline in HBV DNA at week 12 (-6.23 log(10) copies/mL versus -4.42 log(10) copies/mL, respectively; mean difference -1.58 log(10) copies/mL; P < 0.0001). Both drugs demonstrated biphasic viral kinetics, with a first phase of rapid decline lasting 10 days. A significant difference favoring ETV was reached at day 10 (day 10 ETV-ADV difference estimate: -0.66 log(10) copies/mL; 95% CI [-0.30, -0.01]). Early virological response was found to be predictive of subsequent virological response, with those having lower HBV DNA levels at day 10 being more likely to achieve HBV DNA of less than 300 copies/mL at week 48. In addition, there was considerably less variability in the extent of HBV DNA reductions in patients treated with entecavir versus adefovir. Both the mean decrease in serum HBV DNA and the proportion of patients achieving HBV DNA less than 300 copies/mL were greater in entecavir-treated than adefovir-treated patients at weeks 2, 4, 8, 12, 24, and 48. At week 48, one (3%) ETV-treated versus 15 (47%) ADV-treated patients had HBV DNA of 10(5) copies/mL or more. Both antivirals were well tolerated.
Entecavir therapy resulted in earlier and superior reduction in HBV DNA compared with adefovir in nucleoside-naïve HBeAg-positive patients with CHB.
本研究旨在比较恩替卡韦（ETV）与阿德福韦（ADV）在初治的乙肝e抗原阳性慢性乙型肝炎（CHB）成年患者中的早期抗病毒活性和病毒动力学特征。69例基线乙肝病毒脱氧核糖核酸（HBV DNA）水平为10⁸拷贝/毫升或更高的初治CHB患者按1:1随机分组，接受开放标签治疗，分别为每日0.5毫克恩替卡韦或每日10毫克阿德福韦，治疗至少52周。主要疗效分析采用线性回归比较第12周时经基线水平校正后的HBV DNA平均下降幅度。恩替卡韦在第12周时HBV DNA相对于基线的平均变化方面优于阿德福韦（分别为-6.23 log₁₀拷贝/毫升和-4.42 log₁₀拷贝/毫升；平均差异为-1.58 log₁₀拷贝/毫升；P < 0.0001）。两种药物均表现出双相病毒动力学，第一阶段快速下降持续10天。在第10天时达到了有利于恩替卡韦的显著差异（第10天恩替卡韦 - 阿德福韦差异估计值：-0.66 log₁₀拷贝/毫升；95%置信区间[-0.30, -0.01]）。发现早期病毒学应答可预测后续病毒学应答，第10天时HBV DNA水平较低的患者在第48周时更有可能实现HBV DNA低于300拷贝/毫升。此外，与阿德福韦治疗的患者相比，恩替卡韦治疗的患者HBV DNA下降程度的变异性要小得多。在第2、4、8、12、24和48周时，恩替卡韦治疗的患者血清HBV DNA的平均下降幅度和实现HBV DNA低于300拷贝/毫升的患者比例均高于阿德福韦治疗的患者。在第48周时，1例（3%）接受恩替卡韦治疗的患者与15例（47%）接受阿德福韦治疗的患者HBV DNA水平达到10⁵拷贝/毫升或更高。两种抗病毒药物耐受性均良好。
在初治的HBeAg阳性CHB患者中，与阿德福韦相比，恩替卡韦治疗可使HBV DNA更早且更显著地下降。
