初治慢性乙型肝炎患者应用拉米夫定和阿德福韦酯联合与恩替卡韦单药治疗的疗效和耐药：一项荟萃分析。

Efficacy and resistance in de novo combination lamivudine and adefovir dipivoxil therapy versus entecavir monotherapy for the treatment-naive patients with chronic hepatitis B: a meta-analysis.

机构信息

Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Virol J. 2014 Mar 28;11:59. doi: 10.1186/1743-422X-11-59.

BACKGROUND

Currently, there is no consensus on the efficacy and resistance of de novo combination therapy versus monotherapy for treatment naive patients of chronic hepatitis B (CHB).

OBJECTIVES

The aim of this study was to evaluate the effectiveness and resistance of de novo combination of lamivudine (LAM) and adefovir dipivoxil (ADV) compared with entecavir (ETV) monotherapy for nucleos(t)ide-naive patients with CHB.

STUDY DESIGN

Publications on the effectiveness and resistance of LAM plus ADV versus ETV monotherapy for nucleos(t)ide-naive patients with CHB were identified by a search of PubMed, Embase, the Cochrane Library, Web of science, OVID, and CBM (Chinese Biological Medical Literature) until May 1, 2013. Biochemical response, hepatitis B e antigen seroconversion, and viroligic response were extracted and combined to obtain an integrated result. Viral resistance and safety were reviewed.

RESULTS

Five eligible studies (328 patients in total) were included in the analysis. LAM plus ADV combination therapy produced more rapid HBV DNA reduction rate at 12 weeks than that of ETV monotherapy. At 48 weeks, the combination group had superior viroligic response rates compared with ETV group (90.0% vs. 78.9%, P=0.01). The difference in the ALT normalization and HBeAg seroconversion rates was not found. At week 96, LAM + ADV was more effective than ETV in ALT normalization [RR = 1. 11, 95% CI (1.02, 1.21), P =0.01] and HBeAg seroconversion [RR = 2.00, 95% CI (1.26, 3.18, P=0.003)], and no significant difference was found in the virologic response (P =0.23). No viral resistance occurred in combination therapy and six patients in ETV group were experienced with viral breakthrough. Both groups were well tolerated.

CONCLUSION

The de novo LAM plus ADV combination therapy for treatment-naïve patients with CHB was greater than ETV monotherapy in both biochemical response and HBeAg seroconversion rate up to 96 weeks. The rate of emergence of viral resistance in the combination group was less than that in the ETV monotherapy.

背景

目前，对于初治的慢性乙型肝炎（CHB）患者，核苷（酸）初治联合治疗与单药治疗的疗效和耐药性尚无共识。

目的

本研究旨在评估拉米夫定（LAM）和阿德福韦酯（ADV）联合恩替卡韦（ETV）单药治疗初治 CHB 患者的疗效和耐药性。

研究设计

通过检索 PubMed、Embase、Cochrane 图书馆、Web of science、OVID 和 CBM（中国生物医学文献数据库），截至 2013 年 5 月 1 日，确定了 LAM 联合 ADV 与 ETV 单药治疗初治 CHB 患者的疗效和耐药性的相关文献。提取并综合生化应答、乙型肝炎 e 抗原血清学转换和病毒学应答等结果。同时，还对病毒耐药性和安全性进行了评价。

结果

共纳入 5 项符合条件的研究（共 328 例患者）。在 12 周时，LAM 联合 ADV 治疗组的 HBV DNA 下降速度快于 ETV 单药治疗组。在 48 周时，联合组的病毒学应答率优于 ETV 组（90.0%比 78.9%，P=0.01）。两组的 ALT 复常率和 HBeAg 血清学转换率无差异。在 96 周时，LAM+ADV 在 ALT 复常[RR=1.11，95%CI（1.02，1.21），P=0.01]和 HBeAg 血清学转换[RR=2.00，95%CI（1.26，3.18，P=0.003）]方面均优于 ETV，而在病毒学应答方面无差异（P=0.23）。联合组未发生病毒耐药，而 ETV 组有 6 例发生病毒突破。两组均具有良好的耐受性。