Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
J Med Virol. 2010 Nov;82(11):1835-42. doi: 10.1002/jmv.21898.
No study has reported on the comparative effect of adefovir (ADV) add-on lamivudine (LAM) versus switching to entecavir (ETV) in LAM-resistant patients with chronic hepatitis B. From October 2007 to September 2008, 92 consecutive LAM-resistant patients were enrolled (47 LAM+ADV and 45 ETV 1 mg). All patients were followed for at least 12 months. The parameters assessed included normalization of ALT, HBeAg seroconversion, undetectable HBV DNA, reduction of HBV DNA, and predictors of virologic response. In the LAM+ADV and ETV groups, the baseline DNA levels were 7.61 (5.19-9.49) and 7.10 (5.43-9.74)log(10)copies/ml, respectively. At month 12, a virologic response occurred in 18/47 (38.3%) and 11/45 (24.4%; P=0.182) patients; ALT normalization, in 39/41 (95.1%) and 36/40 (90.0%; P=0.432); HBeAg seroconversion, in 5.1% and 2.4% (P=0.606); and virologic breakthrough, in 2.1% and 11.1% (P=0.107), respectively. The mean reduction from the baseline HBV DNA level was greater in the LAM+ADV group at month 12 (3.80 ± 1.12 vs. 2.7 ± 1.32 log(10)copies/ml; P<0.001). In the multivariate analysis, the independent parameters related to a virologic response at month 12 were baseline ALT (OR=1.003, 95% CI=1.000-1.006, P=0.026) and baseline HBV DNA (OR=0.495, 95% CI=0.298-0.823, P=0.007). Compared with switching to ETV monotherapy, ADV add-on LAM therapy was more effective at reducing the viral load in patients with LAM resistance, and the baseline HBV DNA and ALT levels were independent predictors of the virologic response. However, ADV add-on therapy had limitations in patients with a higher baseline HBV DNA in LAM rescue therapy.
尚无研究报道阿德福韦酯（ADV）加用拉米夫定（LAM）与转换用恩替卡韦（ETV）治疗拉米夫定耐药慢性乙型肝炎患者的疗效比较。2007 年 10 月至 2008 年 9 月，连续纳入 92 例拉米夫定耐药患者（LAM+ADV 组 47 例，ETV 1mg 组 45 例）。所有患者均至少随访 12 个月。评估的参数包括 ALT 复常、HBeAg 血清学转换、HBV DNA 不可检测、HBV DNA 下降以及病毒学应答的预测因素。在 LAM+ADV 组和 ETV 组中，基线 DNA 水平分别为 7.61（5.19-9.49）和 7.10（5.43-9.74）log10 拷贝/ml。在第 12 个月时，18/47（38.3%）和 11/45（24.4%；P=0.182）例患者发生病毒学应答；ALT 复常率分别为 39/41（95.1%）和 36/40（90.0%；P=0.432）；HBeAg 血清学转换率分别为 5.1%和 2.4%（P=0.606）；病毒学突破率分别为 2.1%和 11.1%（P=0.107）。LAM+ADV 组在第 12 个月时 HBV DNA 从基线的平均下降幅度大于 ETV 组（3.80±1.12 对 2.7±1.32 log10 拷贝/ml；P<0.001）。多因素分析显示，第 12 个月病毒学应答的独立参数为基线 ALT（OR=1.003，95%CI=1.000-1.006，P=0.026）和基线 HBV DNA（OR=0.495，95%CI=0.298-0.823，P=0.007）。与转换用 ETV 单药治疗相比，ADV 加用 LAM 治疗在拉米夫定耐药患者中更有效地降低病毒载量，基线 HBV DNA 和 ALT 水平是病毒学应答的独立预测因素。然而，在 LAM 挽救治疗中，基线 HBV DNA 较高的患者，ADV 加用治疗存在局限性。
