Combination of Entecavir and IFN-<i>α</i> for Chronic Hepatitis B: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

 GONGZeng-feng ¹ , JIANGNi ² , SHUAITian-kui ¹

1. Comprehensive Internal Medicine, Donggang Department, First Hospital of Lanzhou University, Lanzhou 730000, China;
2. Institute of Infectious Diseases, First Hospital of Lanzhou University, Lanzhou 730000, China;

Corresponding author：

Keywords：

Hepatitis B; Entecavir; IFN-α; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20140200

Video：

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Objective To systematically review the combination of entecavir and interferon-α (IFN-α) in treating hepatitis B compared to entecavir alone. Methods PubMed, EMbase, The Cochrane Library (Issue 12, 2013), Web of Science, CBM, CNKI, WanFang Data and VIP were searched for the randomized controlled trials (RCTs) on entecavir and interferon-α (IFN-α) in treating hepatitis B from inception to December 2013. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of included studies. Then meta-analysis was performed using RevMan 5.2.5. Results A total of 7 RCTs were finally included involving 543 cases. The results of meta-analysis revealed that, compared to entecavir alone, 24-week combined therapy was more effective in improving negative conversion rates of serum HBV-DNA (OR=2.93, 95%CI 1.79 to 4.79, P < 0.000 1), conversion rates of HBeAg (OR=2.36, 95%CI 1.35 to 4.14, P=0.003), and recovery rates of ALT (OR=2.73, 95%CI 1.73 to 4.32, P < 0.000 1). No statistical significance was found in terms of side effects. Conclusion Current evidence shows that combination of entecavir and IFN-α is more effective than entecavir alone in treating hepatitis B. Due to limited quality and quantity of the included studies, the abovementioned conclusion still needs to be verified by conducting more high quality studies.

Citation： GONGZeng-feng, JIANGNi, SHUAITian-kui. Combination of Entecavir and IFN-α for Chronic Hepatitis B: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2014, 14(10): 1241-1246. doi: 10.7507/1672-2531.20140200 Copy

1.	Fact sheets:hepatitis B. Geneva:World Health Organization, July. 2013.
2.	He XS, Nanda S, Ji X, et al. Differential Transcriptional Responses to Interferon-alpha and Interferon-gamma in Primary Human Hepatocytes. J Interferon Cytokine Res, 2010, 30(5):311-320.
3.	Janssen HL, Zonneveld MV, Senturk, et al. Pegylated inteferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B:a randomised trial. Lancet, 2005, 365:123-129.
4.	干扰素治疗慢性乙型肝炎专家讨论组.干扰素治疗慢性乙型肝炎专家建议.中华传染病杂志, 2007, 25(10):577-583.
5.	万谟彬, 翁心华.干扰素治疗慢性乙型肝炎专家建议的若干补充.中华传染病杂志, 2012, 30(12):705-710.
6.	Moher D, Liberati A, Tetzlaf J, et al. Preferred reporting items for systematic reviews and meta analyses:the PRISMA statement. PLoS Med, 2009, 6(7):e1000097.
7.	中华医学会肝病学分会、感染病学分会.慢性乙型肝炎防治指南.肝脏, 2005, 10(4):348-357.
8.	Higgins J, Green S. Cochrane handbook for systematic reviews of interventions Version 5.1.0[updated March 2011]. The Cochrane Collaboration, 2011. Available at:http://www.cochrane.org/.
9.	Liu CJ, Wang CC, Yang SS, et al. Entecavir plus Peg-Interferon alfa-2a vs. Entecavir alone in the treatment of Hepatitis B e antigen-positive chronic Hepatitis B. J Hepatol, 2013 (58):S308-309.
10.	曾文, 袁静, 刘映霞, 等.聚乙二醇干扰素alpha-2a联合恩替卡韦治疗高病毒载量HBeAg阳性慢性乙型肝炎的临床研究.中华实验和临床病毒学杂志, 2013, 27(2):115-118.
11.	周一鸣, 曹建彪, 郭汉斌, 等.恩替卡韦联合干扰素治疗e抗原阳性慢性乙型肝炎疗效观察.临床内科杂志, 2013, 30(7):470-472.
12.	李晶. α-干扰素联合恩替卡韦治疗慢性乙型肝炎早期疗效.肝脏, 2012, 17(10):714-716.
13.	毛惠国.恩替卡韦和干扰素序贯联合治疗HBeAg阳性慢性乙型肝炎的疗效分析.现代实用医学, 2012, 24(5):550-551.
14.	范红顺, 何国伟, 彭玲.恩替卡韦与干扰素序贯治疗高病毒载量慢性乙型肝炎的临床疗效.药物与临床, 2012, 2(10):75-76.
15.	李勇.干扰素a-2b与恩替卡韦联合治疗慢性乙型肝炎患者疗效观察.中国实用医药, 2011, 6(35):136-138.
16.	杨琴.恩替卡韦治疗慢性乙型肝炎YMDD变异株的临床分析.现代中西医结合杂志, 2011, 20(36):4668-4669.
17.	罗玮敏, 张迎春, 刘中景.恩替卡韦治疗慢性乙型肝炎的早期临床观察.临床肝胆病杂志, 2008, 24:26-28.
18.	Gao AH, Wang XL, Jiang QH, et al. Clinical observation on influence of livweiwuling tablets combined with entecavir on chronic hepatitis B patients with HBeAg positive. Chin J Liver Dis (Electren Vers), 2011, 3(1):35-37.
19.	苏立稳, 赵凯丰, 王国华.恩替卡韦联合复方肝欣合剂治疗失代偿期乙型肝炎肝硬化临床研究.中西医结合肝病杂志, 2013, 23(2):86-87.
20.	Marcllin P, Bonino F, Lau GK, et al. Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peg-interferon alpha-2a. Gastroenterol, 2009, 136(7):2169-2179.
21.	Piratvisuth T, Lau G, Chao YC, et al. Sustained response to peg-interferon alfa-2a (40KD) with or without lamivudine in Asian patients with HBeAg-positive and HBeAg-negative chronic hepatitis B. Hepatol Int, 2008, 2(1):102-110.
22.	陈新月, 柳雅立.干扰素联合核苷(酸)类似物治疗慢性乙型肝炎的评价与探索.中华传染病杂志, 2014, 32(1):55-58.
23.	European Association for the Study of the Liver. EASL Clinical Practice Guidelines:Management of chronic hepatitis B. J Hepatol, 2009, 50 (23):227-242.
24.	Sprinzl MF, Kittner JM, Russo C, et al. Add-on interferon a therapy for increases HBV specific T cell responses in patients with chronic hepatitis B under efficient antiviral nucleoside therapy. Hepatol, 2012, 56(4 Suppl):1058A.
25.	邹川, 苏国彬, 卢富华, 等.一例乙肝相关性肾炎伴肾功能衰竭患者的循证治疗.中国循证医学杂志, 2012, 12(3):360-364.
26.	Sun J, Hou J L, Xie Q, et al. Randomised clinical trial:efficacy of peg-interferon alfa-2a in HBeAg positive chronic hepatitis B patients with lamivudine resistance. J Hepatol, 2011, 34(4):424-431.

1. Fact sheets:hepatitis B. Geneva:World Health Organization, July. 2013.
2. He XS, Nanda S, Ji X, et al. Differential Transcriptional Responses to Interferon-alpha and Interferon-gamma in Primary Human Hepatocytes. J Interferon Cytokine Res, 2010, 30(5):311-320.
3. Janssen HL, Zonneveld MV, Senturk, et al. Pegylated inteferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B:a randomised trial. Lancet, 2005, 365:123-129.
4. 干扰素治疗慢性乙型肝炎专家讨论组.干扰素治疗慢性乙型肝炎专家建议.中华传染病杂志, 2007, 25(10):577-583.
5. 万谟彬, 翁心华.干扰素治疗慢性乙型肝炎专家建议的若干补充.中华传染病杂志, 2012, 30(12):705-710.
6. Moher D, Liberati A, Tetzlaf J, et al. Preferred reporting items for systematic reviews and meta analyses:the PRISMA statement. PLoS Med, 2009, 6(7):e1000097.
7. 中华医学会肝病学分会、感染病学分会.慢性乙型肝炎防治指南.肝脏, 2005, 10(4):348-357.
8. Higgins J, Green S. Cochrane handbook for systematic reviews of interventions Version 5.1.0[updated March 2011]. The Cochrane Collaboration, 2011. Available at:http://www.cochrane.org/.
9. Liu CJ, Wang CC, Yang SS, et al. Entecavir plus Peg-Interferon alfa-2a vs. Entecavir alone in the treatment of Hepatitis B e antigen-positive chronic Hepatitis B. J Hepatol, 2013 (58):S308-309.
10. 曾文, 袁静, 刘映霞, 等.聚乙二醇干扰素alpha-2a联合恩替卡韦治疗高病毒载量HBeAg阳性慢性乙型肝炎的临床研究.中华实验和临床病毒学杂志, 2013, 27(2):115-118.
11. 周一鸣, 曹建彪, 郭汉斌, 等.恩替卡韦联合干扰素治疗e抗原阳性慢性乙型肝炎疗效观察.临床内科杂志, 2013, 30(7):470-472.
12. 李晶. α-干扰素联合恩替卡韦治疗慢性乙型肝炎早期疗效.肝脏, 2012, 17(10):714-716.
13. 毛惠国.恩替卡韦和干扰素序贯联合治疗HBeAg阳性慢性乙型肝炎的疗效分析.现代实用医学, 2012, 24(5):550-551.
14. 范红顺, 何国伟, 彭玲.恩替卡韦与干扰素序贯治疗高病毒载量慢性乙型肝炎的临床疗效.药物与临床, 2012, 2(10):75-76.
15. 李勇.干扰素a-2b与恩替卡韦联合治疗慢性乙型肝炎患者疗效观察.中国实用医药, 2011, 6(35):136-138.
16. 杨琴.恩替卡韦治疗慢性乙型肝炎YMDD变异株的临床分析.现代中西医结合杂志, 2011, 20(36):4668-4669.
17. 罗玮敏, 张迎春, 刘中景.恩替卡韦治疗慢性乙型肝炎的早期临床观察.临床肝胆病杂志, 2008, 24:26-28.
18. Gao AH, Wang XL, Jiang QH, et al. Clinical observation on influence of livweiwuling tablets combined with entecavir on chronic hepatitis B patients with HBeAg positive. Chin J Liver Dis (Electren Vers), 2011, 3(1):35-37.
19. 苏立稳, 赵凯丰, 王国华.恩替卡韦联合复方肝欣合剂治疗失代偿期乙型肝炎肝硬化临床研究.中西医结合肝病杂志, 2013, 23(2):86-87.
20. Marcllin P, Bonino F, Lau GK, et al. Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peg-interferon alpha-2a. Gastroenterol, 2009, 136(7):2169-2179.
21. Piratvisuth T, Lau G, Chao YC, et al. Sustained response to peg-interferon alfa-2a (40KD) with or without lamivudine in Asian patients with HBeAg-positive and HBeAg-negative chronic hepatitis B. Hepatol Int, 2008, 2(1):102-110.
22. 陈新月, 柳雅立.干扰素联合核苷(酸)类似物治疗慢性乙型肝炎的评价与探索.中华传染病杂志, 2014, 32(1):55-58.
23. European Association for the Study of the Liver. EASL Clinical Practice Guidelines:Management of chronic hepatitis B. J Hepatol, 2009, 50 (23):227-242.
24. Sprinzl MF, Kittner JM, Russo C, et al. Add-on interferon a therapy for increases HBV specific T cell responses in patients with chronic hepatitis B under efficient antiviral nucleoside therapy. Hepatol, 2012, 56(4 Suppl):1058A.
25. 邹川, 苏国彬, 卢富华, 等.一例乙肝相关性肾炎伴肾功能衰竭患者的循证治疗.中国循证医学杂志, 2012, 12(3):360-364.
26. Sun J, Hou J L, Xie Q, et al. Randomised clinical trial:efficacy of peg-interferon alfa-2a in HBeAg positive chronic hepatitis B patients with lamivudine resistance. J Hepatol, 2011, 34(4):424-431.

Chinese Journal of Evidence-Based Medicine

Combination of Entecavir and IFN-α for Chronic Hepatitis B: A Systematic Review

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