Background

Chronic hepatitis B (CHB) patients who had exposed to lamivudine (LAM) and telbivudine (LdT) had high risk of developing entecavir (ETV)-resistance after long-term treatment. We aimed to conduct a systematic review and a network meta-analysis on the efficacy and cost-effectiveness on antiviral regimens in CHB patients with ETV-resistance.

Data sources

We searched PubMed, EMBASE and Web of Science for studies on nucleos(t)ide analogues (NAs) treatment [including tenofovir disoproxil fumarate (TDF)-based rescue therapies, adefovir (ADV)-based rescue therapies and double-dose ETV therapy] in CHB patients with ETV-resistance. The network meta-analysis was conducted for 1-year complete virological response (CVR) and biological response (BR) rates using GeMTC and ADDIS. A cost-effective analysis was conducted to select an economic and effective treatment regimen based on the 1-year CVR rate.

Results

A total of 6 studies were finally included in this analysis. The antiviral efficacy was estimated. On network meta-analysis, the 1-year CVR rate in ETV-TDF [odds ratio (OR) = 22.30; 95 % confidence interval (CI): 2.78-241.93], LAM-TDF (OR = 70.67; 95 % CI: 5.16-1307.45) and TDF (OR = 16.90; 95 % CI: 2.28-186.30) groups were significantly higher than that in the ETV double-dose group; the 1-year CVR rate in the LAM-TDF group (OR = 14.82; 95 % CI: 1.03-220.31) was significantly higher than that in the LAM/LdT-ADV group. The 1-year BR rate of ETV-TDF (OR = 28.68; 95 % CI: 1.70-1505.08) and TDF (OR = 21.79; 95 % CI: 1.43-1070.09) therapies were significantly higher than that of ETV double-dose therapy. TDF-based therapies had the highest possibility to achieve the CVR and BR at 1 year, in which LAM-TDF combined therapy was the most effective regimen. The ratio of cost/effectiveness for 1-year treatment was 8 526, 17 649, 20 651 Yuan in the TDF group, TDF-ETV group, and ETV-ADV group, respectively.

Conclusions

TDF-based combined therapies such as ETV-TDF and LAM-TDF therapies were the first-line treatment if financial condition is allowed.

中文翻译：

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恩替卡韦耐药乙型肝炎抗病毒方案的疗效和成本效益：系统评价和网络荟萃分析

背景

暴露于拉米夫定 (LAM) 和替比夫定 (LdT) 的慢性乙型肝炎 (CHB) 患者在长期治疗后发生恩替卡韦 (ETV) 耐药性的风险很高。我们旨在对 ETV 耐药的 CHB 患者进行抗病毒治疗的有效性和成本效益进行系统评价和网络荟萃分析。

数据源

我们在 PubMed、EMBASE 和 Web of Science 中搜索关于核苷（酸）类似物 (NAs) 治疗的研究[包括基于富马酸替诺福韦二吡呋酯 (TDF) 的挽救疗法、基于阿德福韦 (ADV) 的挽救疗法和双剂量 ETV 疗法]在 ETV 耐药的 CHB 患者中。使用 GeMTC 和 ADDIS 对 1 年完全病毒学应答 (CVR) 和生物应答 (BR) 率进行了网络荟萃分析。进行了成本效益分析，以根据 1 年 CVR 率选择经济有效的治疗方案。

结果

最终共纳入 6 项研究。估计了抗病毒功效。在网络荟萃分析中，ETV-TDF 的 1 年 CVR 率 [优势比 (OR) = 22.30；95% 置信区间 (CI)：2.78-241.93]、LAM-TDF（OR = 70.67；95% CI：5.16-1307.45）和 TDF（OR = 16.90；95% CI：2.28-186.30）显着高于该组在 ETV 双剂量组中；LAM-TDF 组的 1 年 CVR 率（OR = 14.82；95% CI：1.03-220.31）显着高于 LAM/LdT-ADV 组。ETV-TDF（OR=28.68；95%CI：1.70-1505.08）和TDF（OR=21.79；95%CI：1.43-1070.09）治疗的1年BR率显着高于ETV双剂量治疗. 基于 TDF 的疗法在 1 年时达到 CVR 和 BR 的可能性最高，其中 LAM-TDF 联合疗法是最有效的方案。

结论

如果经济条件允许，基于 TDF 的联合疗法如 ETV-TDF 和 LAM-TDF 疗法是一线治疗。