International Journal of Technology Assessment in Health Care

General Essays

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

Debbie Hartwella1 and Jonathan Shepherda1

a1 University of Southampton


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.


The authors acknowledge Jeremy Jones, Peter Davidson, Alison Price, and Norman Waugh, who were all involved in the original health technology assessment report. Thanks are also due to the HTA UK mild HCV trial team for access to their publications, and in particular Professor Howard Thomas for professional advice in the original health technology assessment report. D.H. and J.S. contributed to the development of the protocol, inclusion screening, data extraction/critical appraisal, writing of the original health technology assessment report, drafting of the article, critical revision of the article for intellectual content, and final approval of the article. This project was completed as part of an update review funded by the NIHR Health Technology Assessment Programme (project no. 04/49/01) and commissioned on behalf of the National Institute for Health and Clinical Excellence (NICE). It has been published in full in Health Technology Assessment 2007, Vol. 11, No. 11. See the HTA Programme Web site ( for further project information. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Department of Health. No ethics approval are required.