Background & Aims
In hepatitis C virus genotype 1 (HCV-1) patients with a rapid viral decline within
the first month of therapy, a 24-week course of pegylated interferon (PEG-IFN) alpha
and ribavirin treatment has been claimed to be as efficient as the standard 48-week
duration.
Methods
We performed a meta-analysis of 7 randomized controlled trials comparing less than
48 weeks to 48 weeks PEG-IFN alpha/ribavirin treatment in 807 HCV-1 patients with rapid viral decline.
Results
SVR was significantly less frequent with short treatment duration than with 48 weeks of therapy, with a mean difference of −13.6% (95% CI: −22.8% to −4.4%, p=0.004). This difference was related to a higher relapse rate (mean difference: 9.9%,
95% CI: 4.1–15.7%, p< 0.001). In a sensitivity analysis restricted to studies using only a weight-based
ribavirin regimen, shorter therapy was also less efficient. In the subgroup of patients
with undetectable HCV-RNA at week 4 and a low baseline HCV-RNA level (⩽400,000 IU/ml), there was no significant difference in SVR rates between 24 and 48 weeks of treatment (mean difference: −3.10%, 95% CI: −8.6% to 2.4%, NS).
Conclusions
In HCV-1 patients with a rapid virological response, 24 weeks of combination therapy with PEG-IFN alpha and ribavirin should be considered
only in subjects with low baseline viral load. However, the optimal cut-off defining
low baseline viral load and the impact of the presence of other factors capable of
altering treatment response, remain subject to debate.
Abbreviations:
ALT (alanine aminotransferase), EMEA (European Medical Association), HCV (hepatitis C virus), NTT (number needed to treat), PEG-IFN (pegylated interferon), RCT (randomized controlled trial), RVR (rapid virological response), SVR (sustained virological response)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of HepatologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Diagnosis, management, and treatment of hepatitis C.Hepatology. 2004; 39: 1147-1171
- Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.N Engl J Med. 2002; 347: 975-982
- Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.Lancet. 2001; 358: 958-965
- Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C.Hepatology. 2003; 38: 645-652
- Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 KD)/ribavirin.J Hepatol. 2005; 43: 425-433
- Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon alpha-2a (40 kd)/ribavirin therapy.Hepatology. 2006; 43: 954-960
- Pegylated interferon-alpha-2a plus ribavirin for treatment-naive Asian patients with hepatitis C virus genotype 1 infection: a multicenter, randomized controlled trial.Clin Infect Dis. 2008; 47: 1260-1269
- Individualized treatment duration for hepatitis C genotype 1 patients: a randomized controlled trial.Hepatology. 2008; 47: 43-50
- Rapid virological response and treatment duration for chronic hepatitis C genotype 1 patients: a randomized trial.Hepatology. 2008; 47: 1884-1893
- 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.J Hepatol. 2006; 44: 97-103
Pegasys product label, Roche 2005. Available at: http://www.rocheusa.com/products/pegasys/pi.pdf.
PEG-Intron product label, Schering-Plough 2005. Available at: http://www.spfiles.com/pipeg-intron.pdf.
- Meta-analysis of randomized controlled trials.N Engl J Med. 1987; 19: 450-455
- The retrieval of randomized clinical trials in liver disease from the medical literature. A comparison of MEDLARS and manual methods.Control Clin Trials. 1985; 6: 271-279
- Methods for combining randomized clinical trials: strengths and limitations.Stat Med. 1987; 6: 341-350
- Meta-analysis in clinical trials.Control Clin Trials. 1986; 7: 177-188
- The combination of estimates from different experiments.Biometrics. 1954; 10: 101-129
- Suitable treatment period in patients with virological response during combination therapy of peginterferon and ribavirin for chronic hepatitis C.Intern Med. 2008; 47: 1301-1307
- Individualized treatment duration with peginterferon-alfa-2b and ribavirin for 24, 30 or 36 weeks in HCV genotype 1-infected patients with undetectable HCV-RNA early during therapy (indiv-2 study).J Hepatol. 2009; 50: S236
- Peginterferon alfa-2a and ribavirin for 24 weeks in hepatitis C type 1 and 4 patients with rapid virological response.Gastroenterology. 2008; 135: 451-458
- Clinical trial: individualized treatment duration for hepatitis C virus genotype 1 with peginterferon-alpha 2a plus ribavirin.Aliment Pharmacol Ther. 2008; 27: 810-819
- Should patients with early loss of serum HCV-RNA during alpha interferon therapy for chronic hepatitis C be treated for 6 or 12 months?.J Hepatol. 1999; 30: 8-13
- Individualized treatment strategy with peginterferon alpha-2b (peg-IFN alfa) plus ribavirin according to early viral kinetics in hepatitis C virus (HCV) type 1 infected patients.J Hepatol. 2006; 44: A559
- A randomized trial of 24- versus 48-week peginterferon alfa-2a plus ribavirin for treatment-naïve Taiwanese patients with hepatitis C virus genotype 1 infection.Hepatology. 2008; 48: A26
- Predictors of rapid virologic response (RVR) in HCV genotype 1 chronic infected pts: results of a randomized controlled trial on individualized treatment. 2006; 44: A1124
- High prevalence of cure in HCV genotype 1 patients with a low viral load achieving an RVR treated for 24 weeks with Peginterferon alfa-2a (Pegasys®) plus Ribavirin (Copegus®): prospective, randomized, controlled study comparing 24 and 48 weeks of treatment.Hepatology. 2007; : A1316
- Evaluation of the efficacy of an 18 week short treatment duration in HCV type 1 infected patients based upon early viral kinetics: an approach to recognise «super-responders».Hepatology. 2006; 44: A346
- The results of a randomized trial looking at 24 weeks vs 48 weeks of treatment with peginterferon alpha-2a (40 kDa) and ribavirin combination therapy in patients with chronic hepatitis C genotype 1.J Viral Hepat. 2006; 13: 552-559
- International, multicenter, randomized, controlled study comparing dynamically individualized versus standard treatment in patients with chronic hepatitis C.J Hepatol. 2005; 43: 250-257
- Quantifying heterogeneity in a meta-analysis.Stat Med. 2002; 21: 1539-1558
- Bias in meta-analysis detected by a simple, graphical test.BMJ. 1997; 315: 629-634
- What is the impact of higher sensitivity assay on response-guided therapy in hepatitis C virus (HCV)? Comparative analysis between Taqman and Amplicor tests from two large randomized international trials of Pegasys plus Copegus.Hepatology. 2007; 46: 813A
- Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose.Ann Intern Med. 2004; 140: 346-355
- Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients.Gastroenterology. 2005; 128: 636-641
- Impact of obesity on treatment of chronic hepatitis C.Hepatology. 2006; 43: 1177-1186
- Pegylated interferon-alpha2b plus ribavirin: an efficacious and well-tolerated treatment regimen for patients with hepatitis C virus related histologically proven cirrhosis.Antivir Ther. 2008; 13: 663-673
Article info
Publication history
Published online: October 23, 2009
Accepted:
August 3,
2009
Received in revised form:
July 13,
2009
Received:
May 7,
2009
Identification
Copyright
© 2009 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
