Shin Jung Woo, Jung Seok Won, Park Bo Ryung, Kim Chang Jae, Eum Jun Bum, Kim Byung Gyu, Du Jeong In, Bang Sung-Jo, Park Neung Hwa
Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea.
Antivir Ther. 2012;17(2):387-94. doi: 10.3851/IMP1945. Epub 2011 Nov 2.
The aim of this study was to investigate the relationship between HBV DNA levels at baseline and on-treatment and the virological response at 96 weeks after adefovir add-on therapy in chronic hepatitis B (CHB) patients with lamivudine resistance.
Lamivudine and adefovir combination therapy was administered to 122 CHB patients for >24 months.
Virological response (HBV DNA negativity) was achieved in 53 (43.3%) and 62 patients (50.8%) at 48 and 96 weeks, respectively. The receiver operating characteristic curve analysis showed that the HBV DNA level at week 24 had a greater power (area under the receiver operating characteristic curve 0.978; 95% CI 0.949, 1.000; P<0.001) to predict the virological response at week 96 of treatment than did the pre-treatment HBV DNA level (area under the receiver operating characteristic curve 0.771; 95% CI 0.640, 0.902; P<0.001). The best cutoff value for the HBV DNA level, at week 24, for the prediction of the virological response at week 96 was 200 IU/ml (3 log(10) copies/ml), with a sensitivity and specificity of 90.3% and 95.0%, respectively. Using this time frame and cutoff value, 56 (90.3%) out of 62 patients that had a virological response at 96 weeks had <200 IU/ml HBV DNA at 24 weeks.
Although the HBV DNA level at baseline is often used to predict the antiviral potency of lamivudine and adefovir combination treatment in CHB patients with lamivudine resistance, the results of this study suggest that the HBV DNA level at 24 weeks is a better marker for the virological response.
本研究旨在探讨慢性乙型肝炎(CHB)拉米夫定耐药患者在阿德福韦加用治疗时基线及治疗期间的HBV DNA水平与96周时病毒学应答之间的关系。
对122例CHB患者给予拉米夫定和阿德福韦联合治疗超过24个月。
分别在48周和96周时,53例(43.3%)和62例(50.8%)患者获得病毒学应答(HBV DNA转阴)。受试者工作特征曲线分析显示,与治疗前HBV DNA水平相比,第24周时的HBV DNA水平对预测治疗第96周时的病毒学应答具有更强的预测能力(受试者工作特征曲线下面积为0.978;95%可信区间为0.949, 1.000;P<0.001),而治疗前HBV DNA水平的受试者工作特征曲线下面积为0.771;95%可信区间为0.640, 0.902;P<0.001)。第24周时用于预测第96周病毒学应答的HBV DNA水平的最佳截断值为200 IU/ml(3 log(10)拷贝/ml),敏感性和特异性分别为90.3%和95.0%。采用此时间点和截断值,96周时获得病毒学应答的62例患者中有56例(90.3%)在第24周时HBV DNA<200 IU/ml。
虽然基线时的HBV DNA水平常被用于预测拉米夫定耐药的CHB患者拉米夫定和阿德福韦联合治疗的抗病毒效力,但本研究结果提示第24周时的HBV DNA水平是病毒学应答的更好标志物。