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

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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.	敖飛健, 馬為民, 周伯平, 等. 聚乙二醇干擾素-2a、阿德福韋酯單用及聯合應用治療HBeAg陽性慢性乙型肝炎患者的療效及安全性比較. 中華傳染病雜志, 2010, 28(4): 214-217.
7.	丁蔚茅. 長效干擾素聯合阿德福韋酯治療慢性乙型肝炎22例療效觀察. 中國現代藥物應用, 2010, 4(22): 164-165.
8.	袁健志. 聚乙二醇干擾素α-2b聯合阿德福韋酯與單用聚乙二醇干擾素α-2b治療HBeAg陽性慢性乙型肝炎48周療效比較. 汕頭: 汕頭大學, 2012.
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10.	李文兵, 丁繼光, 孫慶豐, 等. 聚乙二醇干擾素-2a與阿德福韋酯聯合治療HBeAg陽性慢性乙型肝炎患者的研究. 中華醫院感染學雜志, 2013, 23(6): 1250-1252.
11.	梁江萍, 張祥明, 夏俊, 等. 干擾素聯合阿德福韋酯治療慢性乙型肝炎療效觀察. 中華醫院感染學雜志, 2013, 23(14): 3498-3500.
12.	韓思源, 榮光, 王燕. 聚乙二醇干擾素α-2a聯合阿德福韋酯治療HBeAg陽性慢性乙型肝炎療效觀察. 中國實用醫藥, 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.	陶興飛, 駱小燕, 樓蓮青, 等. 聚乙二醇干擾素a-2a聯合拉米夫定治療HBeAg陽性慢性乙型肝炎療效觀察. 中國微生態學雜志, 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.	陳思路, 趙彩彥. 乙型肝炎病毒表面抗原清除的相關因素研究進展. 中華臨床感染病雜志, 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. 敖飛健, 馬為民, 周伯平, 等. 聚乙二醇干擾素-2a、阿德福韋酯單用及聯合應用治療HBeAg陽性慢性乙型肝炎患者的療效及安全性比較. 中華傳染病雜志, 2010, 28(4): 214-217.
7. 丁蔚茅. 長效干擾素聯合阿德福韋酯治療慢性乙型肝炎22例療效觀察. 中國現代藥物應用, 2010, 4(22): 164-165.
8. 袁健志. 聚乙二醇干擾素α-2b聯合阿德福韋酯與單用聚乙二醇干擾素α-2b治療HBeAg陽性慢性乙型肝炎48周療效比較. 汕頭: 汕頭大學, 2012.
9. 陳海鷗, 劉洪娟, 胡小宣. 阿德福韋酯聯合聚乙二醇干擾素-2a治療的療效觀察. 胃腸病學和肝病學雜志, 2013, 22(5): 456-458.
10. 李文兵, 丁繼光, 孫慶豐, 等. 聚乙二醇干擾素-2a與阿德福韋酯聯合治療HBeAg陽性慢性乙型肝炎患者的研究. 中華醫院感染學雜志, 2013, 23(6): 1250-1252.
11. 梁江萍, 張祥明, 夏俊, 等. 干擾素聯合阿德福韋酯治療慢性乙型肝炎療效觀察. 中華醫院感染學雜志, 2013, 23(14): 3498-3500.
12. 韓思源, 榮光, 王燕. 聚乙二醇干擾素α-2a聯合阿德福韋酯治療HBeAg陽性慢性乙型肝炎療效觀察. 中國實用醫藥, 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. 陶興飛, 駱小燕, 樓蓮青, 等. 聚乙二醇干擾素a-2a聯合拉米夫定治療HBeAg陽性慢性乙型肝炎療效觀察. 中國微生態學雜志, 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. 陳思路, 趙彩彥. 乙型肝炎病毒表面抗原清除的相關因素研究進展. 中華臨床感染病雜志, 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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