Liver Disease Prevention Center, Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, 19107-5587, USA,
Hepatol Int. 2008 Jun;2(2):244-9. doi: 10.1007/s12072-008-9045-6. Epub 2008 Feb 28.
We retrospectively compared the antiviral effect of tenofovir disoproxil fumarate (TDF) with that of adefovir dipivoxil (ADV) for patients with chronic hepatitis B (CHB) who developed resistance to lamivudine (LAM).
One hundred nine patients (86 males), all Asian-American except 1 Caucasian male, with LAM resistance received TDF or ADV. HBV DNA levels were measured every 3 months. The HBeAg loss and ALT normalization were assessed at 12 months on therapy.
Forty-four patients (37 males) received TDF (12 with LAM) and 65 (49 males) received ADV (18 with LAM). Median ages (years) for TDF and ADV were 49 (32-68) and 45 (22-68), respectively. Median duration of therapy was 13 months (6-38) and 17 months (6-34) for the TDF and ADV groups. Baseline HBV DNA levels (log(10) copies/ml) were 6.2 +/- 1.7 for the TDF and 6.5 +/- 1.6 for ADV groups. Baseline ALT (IU/l) levels were 77.0 +/- 86.0 and 100 +/- 195 for the TDF and ADV (P = 0.46) groups, respectively. At 12 months, mean levels of log(10) HBV DNA were 1.5 +/- 1.0 and 4.3 +/- 2.2 for TDF and ADV (P = 0.01). HBeAg loss and ALT normalization at 12 months showed no differences. Using a single factor, ANOVA (2-tailed P value), 4 groups, TDF (n = 32), TDF + LAM (12), ADV (47), and ADV + LAM (18), were compared. HBV DNA reduction at 12 months was the greatest for TDF + LAM (P < 0.001).
Our results suggest that for LAM-resistant HBV, TDF, alone or combined with LAM exerts greater viral reduction than ADV. However, no difference in HBeAg loss was observed. It appears that stronger HBV DNA reduction may not necessarily accelerate HBeAg loss.
我们回顾性比较了替诺福韦酯(TDF)与阿德福韦酯(ADV)治疗对拉米夫定(LAM)耐药的慢性乙型肝炎(CHB)患者的抗病毒疗效。
109 例患者(86 例男性),除 1 例白人男性外均为亚裔美国人,接受 LAM 耐药治疗,接受 TDF 或 ADV 治疗。每 3 个月检测 HBV DNA 水平。治疗 12 个月时评估 HBeAg 丢失和 ALT 正常化。
44 例(37 例男性)患者接受 TDF(12 例联合 LAM)治疗,65 例(49 例男性)接受 ADV(18 例联合 LAM)治疗。TDF 和 ADV 组的中位年龄(岁)分别为 49(32-68)和 45(22-68)。TDF 和 ADV 组的中位治疗时间分别为 13 个月(6-38)和 17 个月(6-34)。TDF 组和 ADV 组的基线 HBV DNA 水平(log10 拷贝/ml)分别为 6.2±1.7 和 6.5±1.6。TDF 和 ADV 组的基线 ALT(IU/l)水平分别为 77.0±86.0 和 100±195(P=0.46)。治疗 12 个月时,TDF 和 ADV 组的平均 log10HBV DNA 水平分别为 1.5±1.0 和 4.3±2.2(P=0.01)。治疗 12 个月时,HBeAg 丢失和 ALT 正常化无差异。采用单因素方差分析(双侧 P 值),比较了 4 组 TDF(n=32)、TDF+LAM(12)、ADV(47)和 ADV+LAM(18)。12 个月时 HBV DNA 降低最明显的是 TDF+LAM(P<0.001)。
我们的结果表明,对于 LAM 耐药的 HBV,TDF 单独或联合 LAM 比 ADV 具有更强的病毒抑制作用。然而,未观察到 HBeAg 丢失的差异。似乎更强的 HBV DNA 降低不一定会加速 HBeAg 丢失。