Hospices Civils de Lyon, Hepatology Department, Lyon, France.
Antiviral Res. 2011 Oct;92(1):90-5. doi: 10.1016/j.antiviral.2011.07.003. Epub 2011 Jul 13.
The combination of tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) is used extensively to treat HIV infection and also has potent activity against hepatitis B virus (HBV) infection. The aim of this study was to assess the efficacy and tolerance of TDF + FTC in patients with chronic hepatitis B (CHB).
Seventy eight consecutive CHB patients from five European centers were included. All started a TDF + FTC combination between October 2005 and March 2010. Virological, biochemical, and clinical data were recorded during follow-up. Tolerance was also monitored. Patients were classified into either treatment simplification (TS), where efficacy of the previous treatment was obtained at TDF + FTC initiation, and treatment intensification (TI), where the previous line of therapy had failed.
TDF + FTC was given as a TI to 54 patients (69%) and as a TS to 24 (31%). Among patients with TI, 83% were males. The median baseline HBV-DNA was 4.4 log10 IU/mL, and median alanine-transaminase (ALT) was 1.10 × ULN. Sixty percent were HBeAg positive, 47% had significant fibrosis (≥ F3 Metavir equivalent), and 29% had confirmed cirrhosis. Median treatment duration was 76 weeks (interquartile range 60-116). Kaplan-Meier analysis showed that, 48 weeks after TI, the probability of being HBV-DNA becoming undetectable was 76%, and reached 94% at week 96. No viral breakthrough occurred. Patients with TS (87% males, median baseline HBV-DNA 1.1 log10 IU/mL, median ALT 0.79 × ULN, 33% HBeAg positive, 61% with significant fibrosis) were treated for a median duration of 76 weeks. In this subgroup, all patients but one remained HBV-DNA undetectable and no ALT flare-up occurred during follow-up. Creatinine levels did not show kidney-function deterioration in either group of patients.
After a median follow-up of > 76 weeks, the TDF + FTC combination showed encouraging antiviral efficacy and a good safety profile in all patients with CHB. TDF + FTC may represent an interesting clinical option to simplify therapy and increase the barrier to resistance, which should be assessed in the long term.
富马酸替诺福韦二吡呋酯（TDF）联合恩曲他滨（FTC）的组合被广泛用于治疗 HIV 感染，并且对乙型肝炎病毒（HBV）感染也具有很强的活性。本研究的目的是评估 TDF + FTC 在慢性乙型肝炎（CHB）患者中的疗效和耐受性。
来自欧洲五个中心的 78 例连续 CHB 患者被纳入本研究。所有患者均于 2005 年 10 月至 2010 年 3 月期间开始使用 TDF + FTC 联合治疗。在随访期间记录病毒学、生化和临床数据。同时监测药物耐受性。根据治疗效果将患者分为治疗简化（TS）组和治疗强化（TI）组。TS 组患者先前的治疗方案已获得疗效，而 TI 组患者先前的治疗方案失败。
54 例（69%）患者因 TI 而接受 TDF + FTC 治疗，24 例（31%）患者因 TS 而接受 TDF + FTC 治疗。在 TI 组患者中，83%为男性。中位基线 HBV-DNA 为 4.4 log10 IU/mL，中位丙氨酸转氨酶（ALT）为 1.10 × ULN。60%的患者 HBeAg 阳性，47%的患者存在显著纤维化（≥ F3 Metavir 等效），29%的患者存在肝硬化。中位治疗时间为 76 周（四分位距 60-116）。Kaplan-Meier 分析显示，在 TI 后 48 周时，HBV-DNA 不可检测的概率为 76%，在第 96 周时达到 94%。未发生病毒突破。TS 组（87%为男性，中位基线 HBV-DNA 为 1.1 log10 IU/mL，中位 ALT 为 0.79 × ULN，33%的患者 HBeAg 阳性，61%的患者存在显著纤维化）的中位治疗时间为 76 周。在该亚组中，所有患者除 1 例外均保持 HBV-DNA 不可检测，在随访期间未发生 ALT 升高。两组患者的肌酐水平均未显示肾功能恶化。
在中位随访时间>76 周后，TDF + FTC 联合治疗在所有 CHB 患者中显示出令人鼓舞的抗病毒疗效和良好的安全性。TDF + FTC 可能是一种简化治疗并增加耐药性障碍的有前途的临床选择，这需要在长期内进行评估。
