Effectiveness and Safety of Different Doses of Interferon Alfa in the Treatment of Chronic Hepatitis C: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

SU Na , WU Fengbo ,  XU Ting

Department of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

XU Ting, Email: sunahxyy@163.com

Keywords：

Interferon alfa; Chronic hepatitis C; Dose; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20130036

Video：

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Objective 　To evaluate the effectiveness and safety of different doses of interferon alfa (INF-α) in the treatment of chronic hepatitis C (CHC).
Methods 　Such databases as MEDLINE, EMbase, CENTRAL, CBM, CNKI, VIP and WanFang Data were searched to collect the randomized controlled trials (RCTs) on different doses of INF-α in the treatment of CHC published before August, 2012. According to the inclusion and exclusion criteria, two reviewers independently screened literature, extracted data and evaluated the quality of the included studies, and then meta-analysis was performed using RevMan 5.0 software.
Results 　A total of 13 RCTs involving 1 442 patients were included. The results of meta-analysis on different doses of INF-α showed that, a) There was no significant difference in the complete response rate between the 3 MU dose group and the 1 MU dose group (RR=0.83, 95%CI 0.52 to 1.32, P=0.43), but there was significant difference in the sustained response rate between those 2 groups (RR=1.89, 95%CI 1.00 to 3.59, P=0.05); and b) No significant differences were found in the complete response rate among the 3 MU dose group, the 6 MU dose group, and the 1 MU dose group.
Conclusion 　INF-α in dose of 3 MU, 3 times daily, is effective in treating CHC, but it would not rule out that higher dose takes more effective action. When INF-α is used to treat CHC, an individualized medication should be applied according to patients’ tolerance and economic status.

Citation： SU Na,WU Fengbo,XU Ting. Effectiveness and Safety of Different Doses of Interferon Alfa in the Treatment of Chronic Hepatitis C: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2013, 13(2): 210-217. doi: 10.7507/1672-2531.20130036 Copy

1.	Koretz RL, Stone O, Gitnick GL. The long-term course of non A,non B post-transfusion hepatitis. Gastroenterology, 1980, 79(5 Pt 1): 893-898.
2.	Hartwell D, Shepherd J. Pegylated and non-pegylated interferon-alfa and ribavirin for the treatment of mild chronic hepatitis C: a systematic review and meta-analysis. Int J Technol Assess Health Care, 2009, 25(1): 56-62.
3.	Kjaergard LL, Krogsgaard K, Gluud C. Interferon alfa with or without ribavirin for chronic hepatitis C: systematic review of randomised trials. BMJ, 2001, 323(7322): 1151-1155.
4.	Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from: www.cochrane-handbook.org.
5.	Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 [updated February 2008]. The Cochrane Collaboration, 2008.
6.	Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med, 2002, 21(11): 1539-1558.
7.	Hakozaki Y, Shirahama T, Katou M. A controlled study to determine the optimal dose regimen of interferon-alpha 2b in chronic hepatitis C. The American journal of gastroenterology, 1995, 90(8): 1246-1249.
8.	Bjoro K, Krarup H, Bell H. Two dose regimens of recombinant interferon-alpha-2b in chronic hepatitis C virus infection. Biochemistry, hepatitis C virus RNA, and liver histology as response indices. Scandinavian journal of gastroenterology, 1995, 30(11): 1119-1124.
9.	Tassopoulos NC, Karvountzis G, Touloumi G. Comparative efficacy of a high or low dose of interferon alpha 2b in chronic hepatitis C: a randomized controlled trial. The American Journal of Gastroenterology, 1996, 91(9): 1734-1738.
10.	Imai Y, Kawata S, Tamura S. Recombinant interferon-alpha-2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study. Liver, 1997, 17(2): 88-92.
11.	Ohmiya M, Hayashi J, Furusyo N. Large dose natural interferon alpha therapy for patients with chronic hepatitis C. Fukuoka Igaku Zasshi, 1997, 88(12): 380-388.
12.	Piccinino F, Felaco FM, Sagnelli E. Long-term lymphoblastoid interferon-alpha therapy for non-cirrhotic chronic hepatitis C: an Italian multicentre study on dose and duration of IFN alpha treatment. Research in Virology, 1998, 149(5): 283-291.
13.	姚光弼, 计焱焱. 两种剂量重组干扰素α2a治疗慢性丙型肝炎随机对照研究. 中华内科杂志, 1998, 37(2): 59-62.
14.	Matsumoto A, Tanaka E, Suzuki T. Viral and host factors that contribute to efficacy of interferon-a2a therapy in patients with chronic hepatitis C. Dig Dis Sci, 1994, 39(6): 1273-1280.
15.	Lin R, Roach E, Zimmerman M, et al. Interferon alfa-2b for chronic hepatitis C: effects of dose increment and duration of treatment on response rates. J Hepatol, 1995, 23(5): 487-496.
16.	Hagiwara H, Hayashi N, Mita E. Quantitative analysis of hepatitis C virus RNA in serum during interferon alfa therapy. Gastroenterology, 1993, 104(3): 877-883.
17.	Chemello L, Bonetti P, Cavalletto L. Randomized trial comparing three different regimens of alpha-2a-interferon in chronic hepatitis C. Hepatology, 1995, 22(3): 700-706.
18.	Marcellin P, Pouteau M, Martinot-Peignoux M. Lack of benefit of escalating dosage of interferon alfa in patients with chronic hepatitis C. Gastroenterology, 1995, 109(1): 156-165.
19.	Saracco G, Rosina F, Abate ML. Long term follow-up of patients with chronic hepatitis C Treated with different doses of interferon-a2b. Hepatology, 1993, 18(6): 1300-1305.
20.	谢尧, 徐道振. HCV基因型对慢性丙型肝炎干扰素疗效的影响. 中华肝脏病杂志, 2004,12(2): 72-75.
21.	金生, 周卫平. 丙型肝炎抗病毒治疗的影响因素及疗效预测. 中华肝脏病杂志, 2004, 12(2): 124-125.
22.	Fried MW, Hoofnagle JH. Therapy of hepatitis C. Semin Liver Dis, 1995, 15(1): 82-91.

1. Koretz RL, Stone O, Gitnick GL. The long-term course of non A,non B post-transfusion hepatitis. Gastroenterology, 1980, 79(5 Pt 1): 893-898.
2. Hartwell D, Shepherd J. Pegylated and non-pegylated interferon-alfa and ribavirin for the treatment of mild chronic hepatitis C: a systematic review and meta-analysis. Int J Technol Assess Health Care, 2009, 25(1): 56-62.
3. Kjaergard LL, Krogsgaard K, Gluud C. Interferon alfa with or without ribavirin for chronic hepatitis C: systematic review of randomised trials. BMJ, 2001, 323(7322): 1151-1155.
4. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from: www.cochrane-handbook.org.
5. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 [updated February 2008]. The Cochrane Collaboration, 2008.
6. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med, 2002, 21(11): 1539-1558.
7. Hakozaki Y, Shirahama T, Katou M. A controlled study to determine the optimal dose regimen of interferon-alpha 2b in chronic hepatitis C. The American journal of gastroenterology, 1995, 90(8): 1246-1249.
8. Bjoro K, Krarup H, Bell H. Two dose regimens of recombinant interferon-alpha-2b in chronic hepatitis C virus infection. Biochemistry, hepatitis C virus RNA, and liver histology as response indices. Scandinavian journal of gastroenterology, 1995, 30(11): 1119-1124.
9. Tassopoulos NC, Karvountzis G, Touloumi G. Comparative efficacy of a high or low dose of interferon alpha 2b in chronic hepatitis C: a randomized controlled trial. The American Journal of Gastroenterology, 1996, 91(9): 1734-1738.
10. Imai Y, Kawata S, Tamura S. Recombinant interferon-alpha-2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study. Liver, 1997, 17(2): 88-92.
11. Ohmiya M, Hayashi J, Furusyo N. Large dose natural interferon alpha therapy for patients with chronic hepatitis C. Fukuoka Igaku Zasshi, 1997, 88(12): 380-388.
12. Piccinino F, Felaco FM, Sagnelli E. Long-term lymphoblastoid interferon-alpha therapy for non-cirrhotic chronic hepatitis C: an Italian multicentre study on dose and duration of IFN alpha treatment. Research in Virology, 1998, 149(5): 283-291.
13. 姚光弼, 计焱焱. 两种剂量重组干扰素α2a治疗慢性丙型肝炎随机对照研究. 中华内科杂志, 1998, 37(2): 59-62.
14. Matsumoto A, Tanaka E, Suzuki T. Viral and host factors that contribute to efficacy of interferon-a2a therapy in patients with chronic hepatitis C. Dig Dis Sci, 1994, 39(6): 1273-1280.
15. Lin R, Roach E, Zimmerman M, et al. Interferon alfa-2b for chronic hepatitis C: effects of dose increment and duration of treatment on response rates. J Hepatol, 1995, 23(5): 487-496.
16. Hagiwara H, Hayashi N, Mita E. Quantitative analysis of hepatitis C virus RNA in serum during interferon alfa therapy. Gastroenterology, 1993, 104(3): 877-883.
17. Chemello L, Bonetti P, Cavalletto L. Randomized trial comparing three different regimens of alpha-2a-interferon in chronic hepatitis C. Hepatology, 1995, 22(3): 700-706.
18. Marcellin P, Pouteau M, Martinot-Peignoux M. Lack of benefit of escalating dosage of interferon alfa in patients with chronic hepatitis C. Gastroenterology, 1995, 109(1): 156-165.
19. Saracco G, Rosina F, Abate ML. Long term follow-up of patients with chronic hepatitis C Treated with different doses of interferon-a2b. Hepatology, 1993, 18(6): 1300-1305.
20. 谢尧, 徐道振. HCV基因型对慢性丙型肝炎干扰素疗效的影响. 中华肝脏病杂志, 2004,12(2): 72-75.
21. 金生, 周卫平. 丙型肝炎抗病毒治疗的影响因素及疗效预测. 中华肝脏病杂志, 2004, 12(2): 124-125.
22. Fried MW, Hoofnagle JH. Therapy of hepatitis C. Semin Liver Dis, 1995, 15(1): 82-91.

Chinese Journal of Evidence-Based Medicine

Effectiveness and Safety of Different Doses of Interferon Alfa in the Treatment of Chronic Hepatitis C: A Systematic Review

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