Efficacy of Peginterferon Alpha Initially Combined with Lamivudine or Adefovir in Treatment of HBeAg-positive Chronic Hepatitis B: A Systematic Review and Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 CHENBang-tao ^1,2 ^# ,  LIJin ³ ^# , FENGXu-jiao ² , ZHANGYun ² , SONGShao-juan ² , LIUMing-she ² ,  ZHAOZhong-fu ²

1. Department of Infectious Disease, the First Affiliated Hospital of Shanxi Medical University, Taiyuan 030001, China;
2. Department of Infectious Disease, Heping Hospital of Changzhi Medical College, Changzhi 046000, China;
3. Department of Anesthesiology, Heping Hospital of Changzhi Medical College, Changzhi 046000, China;

Corresponding author：

ZHAOZhong-fu, Email: zhaozf_1226@163.com

Keywords：

Chronic hepatitis B; Adefovir; Lamivudine; Peginterferon alpha; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20160016

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Objective To systematically review the efficacy of peginterferon alpha (PEG-IFNα) initially combined with lamivudine (LAM) or adefovir (ADV) in treatment of HBeAg-positive chronic hepatitis B (CHB) patients. Methods We electronically searched databases including The Cochrane Library (Issue 11, 2014), PubMed, CBM, CNKI, VIP, and WanFang Data from inception to December 2014, to collect randomized controlled trials (RCTs) about PEG-IFNα initially combined with LAM or ADV for HBeAg-positive CHB. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.2 software. Results A total of 11 RCTs involving 2031 patients were included. The results of meta-analysis showed that: After 48 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus ADV group was significantly higher than that of the PEG-IFNα monotherapy group (8.6% vs. 0%, OR=7.73, 95%CI 1.53 to 39.05, P=0.01) or the ADV monotherapy group (8.5% vs. 0%, OR=7.75, 95%CI 1.07 to 56.23, P=0.04); and the HBsAg seroclearance rate in the combination therapy group was significantly higher than that of the ADV monotherapy group (10.5% vs. 1.2%, OR=5.56, 95%CI to 2.14 to 14.47, P=0.0004). After 52 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus LAM group was significantly higher than that of the PEG-IFNα monotherapy group (11.6% vs. 5.6%, OR=2.21, 95%CI 1.04 to 4.72, P=0.04). After 26 weeks of follow-up, no significant differences were found between the combination therapy group and the PEG-IFNα monotherapy group in HBsAg seroclearance rate and HBsAg seroconversion rate (all P values >0.05). Conclusion Current evidence shows that, compared with PEG-IFNα, LAM, or ADV monotherapy, PEG-IFNα plus LAM or ADV could improve the HBsAg seroclearance or seroconversion rate after 48-52 weeks of treatment for HBeAg-positive CHB, but this effect is still limited. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.

Citation： CHENBang-tao, LIJin, FENGXu-jiao, ZHANGYun, SONGShao-juan, LIUMing-she, ZHAOZhong-fu. Efficacy of Peginterferon Alpha Initially Combined with Lamivudine or Adefovir in Treatment of HBeAg-positive Chronic Hepatitis B: A Systematic Review and Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2016, 16(1): 79-86. doi: 10.7507/1672-2531.20160016 Copy

1.	European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol, 2012, 57(1): 167-185.
2.	Liaw YF, Kao JH, Piratvisuth T ,et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int, 2012, 6(3): 531-561.
3.	Li WC, Wang MR, Kong LB, et al. Peginterferon alpha-based therapy for chronic hepatitis B focusing on HBsAg clearance or seroconversion: a meta-analysis of controlled clinical trials. BMC Infect Dis, 2011, 11: 165.
4.	Huang R, Hao Y, Zhang J, et al. Interferon-alpha plus adefovir combination therapy versus interferon-alpha monotherapy for chronic hepatitis B treatment: A meta-analysis. Hepatol Res, 2013, 43(10): 1040-1051.
5.	Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0[updated March 2011]. Available at: http://handbook.cochrane.org/.
6.	敖飞健, 马为民, 周伯平, 等. 聚乙二醇干扰素-2a、阿德福韦酯单用及联合应用治疗HBeAg阳性慢性乙型肝炎患者的疗效及安全性比较. 中华传染病杂志, 2010, 28(4): 214-217.
7.	丁蔚茅. 长效干扰素联合阿德福韦酯治疗慢性乙型肝炎22例疗效观察. 中国现代药物应用, 2010, 4(22): 164-165.
8.	袁健志. 聚乙二醇干扰素α-2b联合阿德福韦酯与单用聚乙二醇干扰素α-2b治疗HBeAg阳性慢性乙型肝炎48周疗效比较. 汕头: 汕头大学, 2012.
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10.	李文兵, 丁继光, 孙庆丰, 等. 聚乙二醇干扰素-2a与阿德福韦酯联合治疗HBeAg阳性慢性乙型肝炎患者的研究. 中华医院感染学杂志, 2013, 23(6): 1250-1252.
11.	梁江萍, 张祥明, 夏俊, 等. 干扰素联合阿德福韦酯治疗慢性乙型肝炎疗效观察. 中华医院感染学杂志, 2013, 23(14): 3498-3500.
12.	韩思源, 荣光, 王燕. 聚乙二醇干扰素α-2a联合阿德福韦酯治疗HBeAg阳性慢性乙型肝炎疗效观察. 中国实用医药, 2014, 9(20): 1-2.
13.	Janssen HL, van Zonneveld M, Senturk H, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet, 2005, 365(9454): 123-129.
14.	Lau GK, Piratvisuth T, Luo KX, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med, 2005, 352(26): 2682-2695.
15.	Buster EH, Flink HJ, Cakaloglu Y, et al. Sustained HBeAg and HBsAg loss after long term follow-up of HBeAg-positive patients treated with peginterferon α-2b. Gastroenterology, 2008, 135(2): 459-467.
16.	陶兴飞, 骆小燕, 楼莲青, 等. 聚乙二醇干扰素a-2a联合拉米夫定治疗HBeAg阳性慢性乙型肝炎疗效观察. 中国微生态学杂志, 2013, 25(11): 1330-1332.
17.	Chan HL, Hui AY, Wong VW ,et al. Long-term follow-up of peginterferon and lamivudine combination treatment in HBeAg-positive chronic hepatitis B. Hepatology, 2005, 41(6): 1357-1364.
18.	陈思路, 赵彩彦. 乙型肝炎病毒表面抗原清除的相关因素研究进展. 中华临床感染病杂志, 2014, 7(4): 377-381.
19.	Gish RG, Chang TT, Lai CL ,et al. Loss of HBsAg antigen during treatment with entecavir or lamivudine in nucleoside-naive HBeAg-positive patients with chronic hepatitis B. J Viral Hep, 2010, 17(1): 16-22.
20.	Chang TT, Lai CL, Kew KS, et al. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology, 2010, 51(2): 422-430.
21.	Heathcote EJ, Marcellin P, Buti M, et al. Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B. Gastroenterology, 2011, 140(1): 132-143.
22.	Heathcote EJ, Gane EJ, deMan RA, et al. Long term (4 year) efficacy and safety of tenofovir disoproxil fumarate (TDF) treatment in HBeAg-positive patients (HBeAg+) with chronic hepatitis B (Study 103): preliminary results. Hepatology, 2010, 52(S1): 477A.

1. European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol, 2012, 57(1): 167-185.
2. Liaw YF, Kao JH, Piratvisuth T ,et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int, 2012, 6(3): 531-561.
3. Li WC, Wang MR, Kong LB, et al. Peginterferon alpha-based therapy for chronic hepatitis B focusing on HBsAg clearance or seroconversion: a meta-analysis of controlled clinical trials. BMC Infect Dis, 2011, 11: 165.
4. Huang R, Hao Y, Zhang J, et al. Interferon-alpha plus adefovir combination therapy versus interferon-alpha monotherapy for chronic hepatitis B treatment: A meta-analysis. Hepatol Res, 2013, 43(10): 1040-1051.
5. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0[updated March 2011]. Available at: http://handbook.cochrane.org/.
6. 敖飞健, 马为民, 周伯平, 等. 聚乙二醇干扰素-2a、阿德福韦酯单用及联合应用治疗HBeAg阳性慢性乙型肝炎患者的疗效及安全性比较. 中华传染病杂志, 2010, 28(4): 214-217.
7. 丁蔚茅. 长效干扰素联合阿德福韦酯治疗慢性乙型肝炎22例疗效观察. 中国现代药物应用, 2010, 4(22): 164-165.
8. 袁健志. 聚乙二醇干扰素α-2b联合阿德福韦酯与单用聚乙二醇干扰素α-2b治疗HBeAg阳性慢性乙型肝炎48周疗效比较. 汕头: 汕头大学, 2012.
9. 陈海鸥, 刘洪娟, 胡小宣. 阿德福韦酯联合聚乙二醇干扰素-2a治疗的疗效观察. 胃肠病学和肝病学杂志, 2013, 22(5): 456-458.
10. 李文兵, 丁继光, 孙庆丰, 等. 聚乙二醇干扰素-2a与阿德福韦酯联合治疗HBeAg阳性慢性乙型肝炎患者的研究. 中华医院感染学杂志, 2013, 23(6): 1250-1252.
11. 梁江萍, 张祥明, 夏俊, 等. 干扰素联合阿德福韦酯治疗慢性乙型肝炎疗效观察. 中华医院感染学杂志, 2013, 23(14): 3498-3500.
12. 韩思源, 荣光, 王燕. 聚乙二醇干扰素α-2a联合阿德福韦酯治疗HBeAg阳性慢性乙型肝炎疗效观察. 中国实用医药, 2014, 9(20): 1-2.
13. Janssen HL, van Zonneveld M, Senturk H, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet, 2005, 365(9454): 123-129.
14. Lau GK, Piratvisuth T, Luo KX, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med, 2005, 352(26): 2682-2695.
15. Buster EH, Flink HJ, Cakaloglu Y, et al. Sustained HBeAg and HBsAg loss after long term follow-up of HBeAg-positive patients treated with peginterferon α-2b. Gastroenterology, 2008, 135(2): 459-467.
16. 陶兴飞, 骆小燕, 楼莲青, 等. 聚乙二醇干扰素a-2a联合拉米夫定治疗HBeAg阳性慢性乙型肝炎疗效观察. 中国微生态学杂志, 2013, 25(11): 1330-1332.
17. Chan HL, Hui AY, Wong VW ,et al. Long-term follow-up of peginterferon and lamivudine combination treatment in HBeAg-positive chronic hepatitis B. Hepatology, 2005, 41(6): 1357-1364.
18. 陈思路, 赵彩彦. 乙型肝炎病毒表面抗原清除的相关因素研究进展. 中华临床感染病杂志, 2014, 7(4): 377-381.
19. Gish RG, Chang TT, Lai CL ,et al. Loss of HBsAg antigen during treatment with entecavir or lamivudine in nucleoside-naive HBeAg-positive patients with chronic hepatitis B. J Viral Hep, 2010, 17(1): 16-22.
20. Chang TT, Lai CL, Kew KS, et al. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology, 2010, 51(2): 422-430.
21. Heathcote EJ, Marcellin P, Buti M, et al. Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B. Gastroenterology, 2011, 140(1): 132-143.
22. Heathcote EJ, Gane EJ, deMan RA, et al. Long term (4 year) efficacy and safety of tenofovir disoproxil fumarate (TDF) treatment in HBeAg-positive patients (HBeAg+) with chronic hepatitis B (Study 103): preliminary results. Hepatology, 2010, 52(S1): 477A.

Chinese Journal of Evidence-Based Medicine

Efficacy of Peginterferon Alpha Initially Combined with Lamivudine or Adefovir in Treatment of HBeAg-positive Chronic Hepatitis B: A Systematic Review and Meta-analysis

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