Elsevier

Journal of Hepatology

Volume 44, Issue 1, January 2006, Pages 97-103
Journal of Hepatology

Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia

https://doi.org/10.1016/j.jhep.2005.10.003Get rights and content

Background/Aims

Previous studies using standard interferon and ribavirin combination therapy suggested that patients infected with HCV-1 and a low pretreatment HCV-RNA level can be treated for 24 weeks without compromising sustained virologic response rates. The aim of the present study was to investigate this schedule in the era of pegylated interferon-α plus ribavirin.

Methods

Patients chronically infected with HCV-1 (n=235) and a screening viremia ≤600,000 IU/mL (real-time PCR) were treated with peginterferon alfa-2b 1.5 μg/kg subcutaneously once weekly plus ribavirin 800–1400 mg/day based on body weight for 24 weeks.

Results

End-of-treatment and sustained virologic response rates were 80 and 50%, respectively. The 48-week historical control (Manns et al., Lancet 2001;358:958–65) had similar end-of-treatment (74%) but higher sustained virologic response rates (71%). This difference was due to a high virologic relapse rate after 24 weeks of therapy (37%) compared with the historical control (4%). A subset of patients who had undetectable serum HCV-RNA at treatment week 4, however, achieved similar sustained virologic response rate (89%) as in the control group (85%).

Conclusions

HCV-1 infected patients with a low baseline HCV-RNA concentration who become HCV-RNA negative at week 4 may be treated for 24 weeks without compromising sustained virologic response rates.

Introduction

Hepatitis C virus (HCV) infection may progress to chronic hepatitis, cirrhosis, and its sequelae [1], [2], [3]. Treatment of HCV-infected patients with interferon-α can achieve viral clearance and improve histology and prognosis [4], [5]. In the era of standard interferon alfa plus ribavirin, the duration of treatment in patients with chronic hepatitis C was tailored according to HCV genotype and baseline viremia; patients infected with HCV genotype 1 (HCV-1) and high baseline viremia were treated for 48 weeks, while patients infected with HCV-1 and low baseline viremia as well as all patients infected with HCV-2 or HCV-3 were treated for 24 weeks [6], [7], [8].

More recently, standard interferons have been chemically modified using polyethylenglycol (PEG) to improve antiviral efficacy. Higher sustained virologic response rates in patients with chronic hepatitis C have been reported for the pegylated forms of interferons compared with standard interferons both in monotherapy as well as in combination therapy with ribavirin [9], [10], [11], [12]. In these trials patients were treated for 48 weeks. Additional prospective trials in patients chronically infected with genotypes HCV-2 or HCV-3 showed that the treatment duration can be reduced from 48 to 24 weeks without compromising antiviral efficacy [13], [14]. Data regarding optimal duration of treatment for patients infected with HCV-1, however, are sparse.

The aim of the present study was to investigate efficacy and safety of peginterferon alfa-2b plus ribavirin administered for 24 weeks in patients chronically infected with HCV-1 and a low baseline serum HCV RNA concentration.

Section snippets

Patients

Male and female patients aged 18–70 years with compensated chronic HCV-1 infection not previously treated with interferon, ribavirin and/or amantadine were eligible for enrollment. Eligible patients tested positive for HCV-RNA by reverse transcription-polymerase chain reaction with a concentration ≤600,000 IU/mL, had a liver biopsy taken within 12 months prior to the screening visit showing chronic hepatitis, and had at least one elevated serum alanine aminotransferase (ALT) level at screening

Results

For this study, which was performed between October 2001 and October 2004 in 43 European centers, 724 patients were screened and 237 patients were enrolled. Two patients did not have adequate information for analysis (Fig. 1), and, therefore, will be presented in demographics and adverse events, but not in the efficacy analyses. Of the remaining 235 patients, two did not receive treatment and are included in the efficacy analysis as nonresponders. The baseline characteristics of the patients

Discussion

This study demonstrates that 24 weeks of therapy with peginterferon alfa-2b 1.5 μg/kg/week plus weight-based ribavirin dosing is insufficient for the treatment of patients infected with HCV-1 and a baseline HCV-RNA level equal or below 600,000 IU/mL. Using the data of the study by Manns et al. [11], a sustained virologic response rate of 69% was predicted if the patients in the present study would have been treated for 48 weeks. This estimated sustained virologic response rate fell outside the

Acknowledgements

This study was supported by research grants from Schering-Plough Research Institute, Kenilworth, NJ. In addition to the authors the following investigators were involved in the present study: Austria: W. Vogel, Innsbruck; Belgium: N. Bourgeois, Bruxelles; France: D. Dhumeaux, C. Hezode, Creteil; N. Boyer-Darrigrand, P. Marcellin, Clichy; P. Couzigou, V. de Ledinghen, Bordeaux; V. Leroy, J.-P. Zarski, Grenoble; C. Trepo, M. Maynard-Muet, Lyon; J.-P. Bronowicki, M.-A. Bigard, Nancy; T. Poynard,

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The authors who have taken part in this study have declared a relationship with the manufacturers of the drugs involved and they received funding from the drug companies involved to carry out their research. Data of the present study were presented in part at the 40th Annual Meeting of the European Association for the Study of the Liver (EASL), April 13–17, 2005, Paris, France and at the Digestive Disease Week, May 14–19, 2005, Chicago, IL, USA.

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