High predictive value of early viral kinetics in retreatment with peginterferon and ribavirin of chronic hepatitis C patients non-responders to standard combination therapy☆
Introduction
The current optimal therapy for patients with chronic hepatitis C (CHC) is the combination of peginterferon (PEG-IFN) and ribavirin (RBV) [1]. Data from four large, randomized controlled trials have shown that PEG-IFN alfa-2a or PEG-IFN alfa-2b, with or without ribavirin, achieved significantly higher sustained virological response (SVR) rates in comparison with standard IFN, with or without RBV in naïve patients [2], [3], [4], [5]. As the treatment of CHC has improved, the question has arisen as to whether patients who failed previous treatment regimens should be retreated. A large randomized controlled trial has shown that retreatment with IFN and RBV of relapsers to IFN monotherapy allowed to achieve a 49% SVR rate [6]. Several studies have established that a small but significant increase in SVR resulted when non-responders to IFN monotherapy were retreated with IFN and RBV [7], [8], [9]. Given the superior results observed with PEG-IFN and RBV in naïve population, it is now appropriate to consider whether retreating previous relapsers and non-responders to standard IFN and RBV will be more effective with this strategy. Recent trials have shown that PEG-IFN and RBV combination was effective in a substantial number of these patients [10], [11], [12], [13]. Of note, these studies included selected patients and different populations of non-responders (IFN monotherapy, IFN plus RBV) and did not systematically assess the predictive value of early viral kinetics. This study describes the effects of retreatment, outside of trials, with PEG-IFN alfa-2b and RBV, and the factors associated with SVR, in a population of unselected consecutive patients who have failed to achieve SVR with standard combination therapy. Influence of early viral kinetics on SVR has been particularly assessed.
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Patient population
Patients, consecutively included in the study, were relapsers or non-responders to standard IFN+RBV. Non-response was defined as having detectable HCV RNA in serum at the end of treatment, with a minimal duration of 12 weeks. Relapse was defined as recurrence of viremia after undetectable HCV RNA in serum at the end of treatment.
Study design
Patients were treated with PEG-IFN alfa-2b (Pegintron®, Schering-Plough Corp.) at a dose of 1.5 μg/kg/week and RBV (Rebetol®, Schering-Plough Corp.) either 1000 mg/day
Patient population
The study population consisted of 154 consecutive patients, followed up in the hepatology departments of Beaujon hospital (Clichy) and Saint Joseph hospital (Marseille) in France between January 2001 and December 2003. Clinical characteristics of these patients are summarized in Table 1. There were 101 non-responders and 53 relapsers to standard IFN+RBV. Mean age of patients was 49.6 years; 64.9% were male. Mean BMI was 26.1 kg/m2. Intravenous drug use and blood transfusion were the principal
Discussion
Limited data are available about retreatment of CHC patients, non-responders or relapsers to standard IFN and RBV combination. Our study evaluated the efficacy of peginterferon alfa-2b plus ribavirin in the retreatment, outside of trials, of unselected patients with CHC who previously failed to respond or relapsed following standard combination therapy. The need for retreatment of these patients may be urgent, especially in case of advanced fibrosis. However, these patients, and especially
References (40)
- et al.
Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial
Lancet
(2001) - et al.
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.
Interferon and ribavirin for patients with chronic hepatitis C who did not response to previous interferon therapy: a meta-analysis of controlled and uncontrolled trials
Hepatology
(2001) - et al.
Combination of interferon and ribavirin in chronic hepatitis C: Re-treatment of nonresponders to interferon
Hepatology
(2001) - et al.
Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment
Gastroenterology
(2004) - et al.
Peginterferon alfa-2b and ribavirin for treatment-refractory chronic hepatitis C
J Hepatol
(2005) - et al.
An algorithm for the grading of activity in chronic hepatitis C
Hepatology
(1996) - et al.
Natural history of liver fibrosis progression with chronic hepatitis C
Lancet
(1997) - et al.
Predictors of sustained response to alpha interferon therapy in chronic hepatitis C patients
J Hepatol
(1998) - et al.
The impact of interferon plus ribavirin on response to therapy in black patients with chronic hepatitis C. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial
Gastroenterology
(2000)
High body mass index is an independent risk factor for non response to antiviral treatment in chronic hepatitis C
Hepatology
Effect of significant histologic steatosis or steatohepatitis on response to antiviral therapy in patients with chronic hepatitis C
Clin Gastroenterol Hepatol
The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients
J Hepatol
Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients
Gastroenterology
Randomized controlled trial with IFN combined with ribavirin with or without amantadine sulphate in non-responders with chronic hepatitis C
J Hepatol
Amantadine triple therapy for non-responder hepatitis C patients. Clues for controversies
J Hepatol
Early virologic response to treatment with peginterferon Alfa-2a plus ribavirin in patients with chronic hepatitis C
Hepatology
Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a ribavirin
J Hepatol
Treatment with daily consensus interferon plus ribavirin in non-responder patients with chronic hepatitis C: a randomized open-label pilot study
J Hepatol
Prognostic factors and early predictability of sustained viral response with peginterferon alfa-2a
J Hepatol
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Hepatitis C viral kinetics in Latino patients: A comparison to African American and Caucasian patients
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Mechanisms of non-response to antiviral treatment in chronic hepatitis C
2011, Clinics and Research in Hepatology and GastroenterologyCitation Excerpt :The presence of a rapid virological response (RVR, defined by an undetectable HCV RNA at week 4 of therapy), an early virological response (EVR, defined by an HCV RNA level which is detectable at week 4 but undetectable at week 12), a delayed virological response (defined by a more than 2 Log10 HCV RNA drop with detectable HCV RNA at week 12), or no significant decrease of the viral load (less than a 2 Log10 drop at week 12) helps predict the likelihood of achieving an SVR. Indeed, patients with an RVR have the greatest chance to achieve an SVR (>85%) [32], whereas patients who do not display a substantial viral load decrease are unlikely to respond to therapy [27,33–35]. Responsiveness to HCV therapy strongly depends on host factors.
Practice guidelines for the treatment of hepatitis C: Recommendations from an AISF/SIMIT/SIMAST expert opinion meeting
2010, Digestive and Liver DiseaseRetreatment with pegylated interferon plus ribavirin of chronic hepatitis C non-responders to interferon plus ribavirin: A meta-analysis
2009, Journal of HepatologyCitation Excerpt :Therefore, an effective regimen of retreatment is a major goal in the long-term management of these patients. Several studies of retreatment with pegylated IFN (PEG-IFN) plus ribavirin in patients who failed to respond to the combination of pegylated and non-pegylated IFN plus ribavirin have been published [3–22]. The results of these studies are inconclusive or conflicting because of the relatively small samples and the differences in patient characteristics, study design combining relapsers and non-responders, doses of IFN and ribavirin administered in the first course, and retreatment regimens.
High Response Rate to Pegylated Interferon Alpha and Ribavirin Combination Therapy in Hemophilic Children with Chronic Hepatitis C; A Case-Control Study
2015, Pediatric Hematology and Oncology
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The authors who have taken part in this study declared that they have no relationship with the manufacturers of the drugs involved either in the past or present and did not receive funding from the manufacturers to carry out their research. The authors did not receive funding from any source to carry out this study.