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

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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.	干擾素治療慢性乙型肝炎專家討論組.干擾素治療慢性乙型肝炎專家建議.中華傳染病雜志, 2007, 25(10):577-583.
5.	萬謨彬, 翁心華.干擾素治療慢性乙型肝炎專家建議的若干補充.中華傳染病雜志, 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.	中華醫學會肝病學分會、感染病學分會.慢性乙型肝炎防治指南.肝臟, 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, 袁靜, 劉映霞, 等.聚乙二醇干擾素alpha-2a聯合恩替卡韋治療高病毒載量HBeAg陽性慢性乙型肝炎的臨床研究.中華實驗和臨床病毒學雜志, 2013, 27(2):115-118.
11.	周一鳴, 曹建彪, 郭漢斌, 等.恩替卡韋聯合干擾素治療e抗原陽性慢性乙型肝炎療效觀察.臨床內科雜志, 2013, 30(7):470-472.
12.	李晶. α-干擾素聯合恩替卡韋治療慢性乙型肝炎早期療效.肝臟, 2012, 17(10):714-716.
13.	毛惠國.恩替卡韋和干擾素序貫聯合治療HBeAg陽性慢性乙型肝炎的療效分析.現代實用醫學, 2012, 24(5):550-551.
14.	范紅順, 何國偉, 彭玲.恩替卡韋與干擾素序貫治療高病毒載量慢性乙型肝炎的臨床療效.藥物與臨床, 2012, 2(10):75-76.
15.	李勇.干擾素a-2b與恩替卡韋聯合治療慢性乙型肝炎患者療效觀察.中國實用醫藥, 2011, 6(35):136-138.
16.	楊琴.恩替卡韋治療慢性乙型肝炎YMDD變異株的臨床分析.現代中西醫結合雜志, 2011, 20(36):4668-4669.
17.	羅瑋敏, 張迎春, 劉中景.恩替卡韋治療慢性乙型肝炎的早期臨床觀察.臨床肝膽病雜志, 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.	蘇立穩, 趙凱豐, 王國華.恩替卡韋聯合復方肝欣合劑治療失代償期乙型肝炎肝硬化臨床研究.中西醫結合肝病雜志, 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.	陳新月, 柳雅立.干擾素聯合核苷(酸)類似物治療慢性乙型肝炎的評價與探索.中華傳染病雜志, 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.	鄒川, 蘇國彬, 盧富華, 等.一例乙肝相關性腎炎伴腎功能衰竭患者的循證治療.中國循證醫學雜志, 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. 干擾素治療慢性乙型肝炎專家討論組.干擾素治療慢性乙型肝炎專家建議.中華傳染病雜志, 2007, 25(10):577-583.
5. 萬謨彬, 翁心華.干擾素治療慢性乙型肝炎專家建議的若干補充.中華傳染病雜志, 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. 中華醫學會肝病學分會、感染病學分會.慢性乙型肝炎防治指南.肝臟, 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, 袁靜, 劉映霞, 等.聚乙二醇干擾素alpha-2a聯合恩替卡韋治療高病毒載量HBeAg陽性慢性乙型肝炎的臨床研究.中華實驗和臨床病毒學雜志, 2013, 27(2):115-118.
11. 周一鳴, 曹建彪, 郭漢斌, 等.恩替卡韋聯合干擾素治療e抗原陽性慢性乙型肝炎療效觀察.臨床內科雜志, 2013, 30(7):470-472.
12. 李晶. α-干擾素聯合恩替卡韋治療慢性乙型肝炎早期療效.肝臟, 2012, 17(10):714-716.
13. 毛惠國.恩替卡韋和干擾素序貫聯合治療HBeAg陽性慢性乙型肝炎的療效分析.現代實用醫學, 2012, 24(5):550-551.
14. 范紅順, 何國偉, 彭玲.恩替卡韋與干擾素序貫治療高病毒載量慢性乙型肝炎的臨床療效.藥物與臨床, 2012, 2(10):75-76.
15. 李勇.干擾素a-2b與恩替卡韋聯合治療慢性乙型肝炎患者療效觀察.中國實用醫藥, 2011, 6(35):136-138.
16. 楊琴.恩替卡韋治療慢性乙型肝炎YMDD變異株的臨床分析.現代中西醫結合雜志, 2011, 20(36):4668-4669.
17. 羅瑋敏, 張迎春, 劉中景.恩替卡韋治療慢性乙型肝炎的早期臨床觀察.臨床肝膽病雜志, 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. 蘇立穩, 趙凱豐, 王國華.恩替卡韋聯合復方肝欣合劑治療失代償期乙型肝炎肝硬化臨床研究.中西醫結合肝病雜志, 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. 陳新月, 柳雅立.干擾素聯合核苷(酸)類似物治療慢性乙型肝炎的評價與探索.中華傳染病雜志, 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. 鄒川, 蘇國彬, 盧富華, 等.一例乙肝相關性腎炎伴腎功能衰竭患者的循證治療.中國循證醫學雜志, 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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