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☆
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,
References (19)
- et al.
For the International Hepatitis Interventional Therapy Group (IHIT): randomised trial of interferon α2b plus ribavirin for 48 weeks or for 24 weeks versus interferon α2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus
Lancet
(1998) - et al.
Hepatitis Interventional Therapy Group. A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C
Hepatology
(2001) - et al.
Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial
Lancet
(2001) - et al.
Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3
J Hepatol
(2004) - et al.
International Hepatitis Interventional Therapy Group. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C
Gastroenterology
(2002) - et al.
Neumann AU for the DITTO-HCV Study Group. International, multicenter, randomized, controlled study comparing dynamically individualized versus standard treatment in patients with chronic hepatitis C
J Hepatol
(2005) - et al.
Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C
Hepatology
(2003) - et al.
Hepatitis C virus infection
N Engl J Med
(2001) Natural history of chronic hepatitis C
Hepatology
(2002)
Cited by (451)
Clinical Evaluation of Terap C Vaccine in Combined Treatment with Interferon and Ribavirin in Patients with Hepatitis C
2017, Current Therapeutic Research - Clinical and ExperimentalCitation Excerpt :For this reason, we believe that the observed changes in the viral load were too small to be sure that they were related to that vaccine candidate.66,75 Approximately 90% of patients who experience a rapid virological response develop SVR.76,77 Unfortunately, in this study, no virological response at Week 4 of treatment with IFN α-2b and RBV was evaluated, but it could be a parameter to consider for future studies.
Comparison of Three Different Methods for Detection of IL28 rs12979860 Polymorphisms as a Predictor of Treatment Outcome in Patients with Hepatitis C Virus
2016, Osong Public Health and Research PerspectivesDiagnostics in hepatitis C: The end of response-guided therapy?
2016, Journal of HepatologyMexican consensus on the diagnosis and management of hepatitis C infection
2015, Annals of HepatologyGenotype 3 is the predominant hepatitis C genotype in a multi-ethnic Asian population in Malaysia
2015, Hepatobiliary and Pancreatic Diseases International
- ☆
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.