Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-23T03:50:27.475Z Has data issue: false hasContentIssue false

Pegylated and non-pegylated interferon-alfa and ribavirin for the treatment of mild chronic hepatitis C: A systematic review and meta-analysis

Published online by Cambridge University Press:  06 January 2009

Debbie Hartwell
Affiliation:
University of Southampton
Jonathan Shepherd
Affiliation:
University of Southampton

Abstract

Objectives: Traditionally, patients with chronic hepatitis C virus (HCV) infection have not received treatment until their infection reaches the moderate to severe stage. The aim of this systematic review was to assess the clinical effectiveness of pegylated (PEG) and non-pegylated interferon (IFN) alfa and ribavirin (RBV) for the treatment of adults with histologically mild HCV.

Methods: We performed a sensitive search of fourteen electronic bibliographic databases for literature that met criteria defined in a research protocol. Two reviewers independently selected studies, extracted data and assessed methodological quality.

Results: Ten randomized, controlled trials (RCTs) were included. Treatment with PEG + RBV combination therapy resulted in significantly higher sustained virological response (SVR) rates than treatment with IFN + RBV combination therapy. Treatment for 48 weeks with PEG + RBV was significantly more effective than the same treatment for 24 weeks. Significantly higher SVR rates were seen with IFN + RBV compared with either IFN monotherapy or no treatment. In the meta-analysis (four IFN trials), the relative risk of not experiencing an SVR was 0.59 (95 percent CI, 0.51 – 0.69) and was statistically significant (p < .00001). SVRs were higher for patients with genotype non-1 compared with genotype 1 for both PEG + RBV and IFN + RBV treatments.

Conclusions: Patients with histologically mild HCV can be successfully treated with both PEG and IFN combination therapy, and response rates are broadly comparable with those achieved in patients with advanced disease. Treating patients in the early milder stages of HCV is, therefore, a clinically effective option.

Type
General Essays
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Arora, S, O'Brien, C, Zeuzem, S, et al. Treatment of chronic hepatitis C patients with persistently normal alanine aminotransferase levels with the combination of peginterferon alpha-2a (40 kDa) plus ribavirin: Impact on health-related quality of life. J Gastroenterol Hepatol. 2006;21:406412.CrossRefGoogle ScholarPubMed
2. Behler, CM, Vittinghoff, E, Lin, F, et al. Hematologic toxicity associated with interferon-based hepatitis C therapy in HIV type 1-coinfected subjects. Clin Infect Dis. 2007;44:13751383.CrossRefGoogle ScholarPubMed
3. Cheng, PN, Chow, NH, Hu, SC, et al. Clinical comparison of high-dose interferon-alpha2b with or without ribavirin for treatment of interferon-relapsed chronic hepatitis C. Dig Liver Dis. 2002;34:851856.CrossRefGoogle ScholarPubMed
4. Chung, RT, Andersen, J, Volberding, P, et al. Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. 2004;351:451459.CrossRefGoogle ScholarPubMed
5. Department of Health. Hepatitis C action plan for England. London: Department of Health; 2004.Google Scholar
6. Foster, GR, Goldin, RD, Thomas, HC. Chronic hepatitis C virus infection causes a significant reduction in quality of life in the absence of cirrhosis. Hepatology. 1998;27:209212.CrossRefGoogle ScholarPubMed
7. Hadziyannis, SJ, Sette, H Jr, Morgan, TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: A randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346355.CrossRefGoogle ScholarPubMed
8. Harris, KA, Gilham, C, Mortimer, PP, et al. The most prevalent hepatitis C virus genotypes in England and Wales are 3a and 1a. J Med Virol. 1999;58:127131.3.0.CO;2-K>CrossRefGoogle ScholarPubMed
9. Kim, TH, Kim, KA, Lim, YS, et al. Prediction of treatment outcome in chronic hepatitis C patients based on early viral dynamics during high-dose induction interferon and ribavirin therapy. Intervirology 2005;48:230238.CrossRefGoogle ScholarPubMed
10. Mangia, A, Villani, MR, Minerva, N, et al. Efficacy of 5 MU of interferon in combination with ribavirin for naive patients with chronic hepatitis C virus: A randomized controlled trial. J Hepatol. 2001;34:441446.CrossRefGoogle Scholar
11. Moher, D, Cook, DJ, Eastwood, S, et al. Improving the quality of reports of meta-analyses of randomised controlled trials: The QUOROM statement. Lancet. 1999;354:18961900.CrossRefGoogle ScholarPubMed
12. Mohsen, AH, Trent, HCV Study Group. The epidemiology of hepatitis C in a UK health regional population of 5.12 million. Gut. 2001;48:707713.CrossRefGoogle Scholar
13. National Institute for Health and Clinical Excellence (NICE). Peginterferon alfa and ribavirin for the treatment of mild chronic hepatitis C. NICE Technology Appraisal Guidance 106. London: National Institute for Health and Clinical Excellence; 2006.Google Scholar
14. NHS Centre for Reviews and Dissemination. Undertaking systematic reviews of research on effectiveness: CRD's guidance for those carrying out or commissioning reviews. 2nd ed. York: York Publishing Services Ltd; 2001.Google Scholar
15. Poynard, T, Leroy, V, Cohard, M, et al. Meta-analysis of interferon randomized trials in the treatment of viral hepatitis C: Effects of dose and duration. Hepatology. 1996;161:778789.CrossRefGoogle Scholar
16. Poynard, T, McHutchison, J, Goodman, Z, et al. Is an “a la carte” combination interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C? The ALGOVIRC Project Group. Hepatology. 2000;31:211218.CrossRefGoogle Scholar
17. Reichard, O, Norkrans, G, Fryden, A, et al. Randomised, double-blind, placebo-controlled trial of interferon alpha-2b with and without ribavirin for chronic hepatitis C. The Swedish Study Group. Lancet. 1998;351:8387.CrossRefGoogle ScholarPubMed
18. Ryder, SD, Irving, WL, Jones, DA, et al. Progression of hepatic fibrosis in patients with hepatitis C: A prospective repeat liver biopsy study. Gut. 2004;53:451455.CrossRefGoogle ScholarPubMed
19. Shepherd, J, Brodin, H, Cave, C, et al. Pegylated interferon a-2a and -2b in combination with ribavirin in the treatment of chronic hepatitis C: A systematic review and economic evaluation. Health Technol Assess. 2004;8:1140.CrossRefGoogle Scholar
20. Shepherd, J, Jones, J, Hartwell, D, et al. Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of mild chronic hepatitis C: A systematic review and economic evaluation. Health Technol Assess. 2007;11:1205.CrossRefGoogle ScholarPubMed
21. Strader, DB, Wright, T, Thomas, DL et al. American Association for the Study of Liver Diseases (AASLD) practice guidelines. Diagnosis, management, and treatment of hepatitis C. Hepatology. 2004;39:11471171.CrossRefGoogle Scholar
22. Verbaan, HP, Widell, HE, Bondeson, TL, et al. High sustained response rate in patients with histologically mild (low grade and stage) chronic hepatitis C infection. A randomized, double blind, placebo controlled trial of interferon alpha-2b with and without ribavirin. Eur J Gastroenterol Hepatol. 2002;14:627633.CrossRefGoogle ScholarPubMed
23. von Wagner, M, Huber, M, Berg, T, et al. Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology. 2005;129:522527.CrossRefGoogle ScholarPubMed
24. Wright, M, Forton, D, Main, J, et al. Treatment of histologically mild hepatitis C virus infection with interferon and ribavirin: A multicentre randomized controlled trial. J Viral Hepat. 2005;12:5866.CrossRefGoogle ScholarPubMed
25. Zeuzem, S, Diago, M, Gane, E, et al. Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels. Gastroenterology. 2004;127:17241732.CrossRefGoogle ScholarPubMed
Supplementary material: File

Hartwell supplementary tables

Hartwell supplementary tables

Download Hartwell supplementary tables(File)
File 404 KB