Induction interferon therapy in naïve patients with chronic hepatitis C: increased end‐of‐treatment virological responses but absence of long‐term benefit

Abstract

INTRODUCTIONChronic hepatitis C is a severe health problem affecting a signi®cant proportion of the population world-wide, compromising quality of life and, if not treated in time, potentially leading to death.1±3 Since a vaccine has not yet been developed, most clinical efforts are being concentrated on therapy. The standard scheme with interferon-a (IFN-a) monotherapy, 3 million units (MU) three times a week for 1 year, has an overall sustained ef®cacy of less than 25%. 4±12 Even with the present optimal treatment with a combination of interferon and ribavirin, the response rates are not particularly high, while the side-effects become more severe.13, 14 Daily administration of IFN has been tried in the past in clinical trials, particularly from Japan, with promising results, but its ef®cacy compared to that of the conventional three-times-a-week schemes has hitherto remained unknown. Recent data from viral kinetic studies have renewed the clinical interest in daily IFN administration, suggesting that daily dosing of IFN-a during the initial period of treatment of chronic hepatitis C results in a faster and more frequent initial response rate compared to the same dose given three times a week. 15±17 However, because many different types of IFN, various doses and durations of daily administration of IFN have been tried, little can be deduced on the longterm ef®cacy of such treatment schemes. 9, 18±28

Treatment with daily consensus interferon (CIFN) plus ribavirin in non-responder patients with chronic hepatitis C: A randomized open-label pilot study

“…Preliminary data from a single center study presented in abstract form, suggested that daily dosing of CIFN in combination with ribavirin can achieve SVRs of 38-45% in non-responder patients to standard IFN and ribavirin depending on the CIFN dose [13]. High-doseinduction, although not effective in studies with standard IFN [14][15][16], seemed to have further improved the SVR in this study [13]. Cotler and colleagues [17] assessed the firstphase viral kinetics in 20 previous non-responders after a single dose of 15 or 30 mg CIFN and demonstrated a significantly sharper decline of the HCV-RNA with the higher dose after 24 h (0.8 and 1.5, respectively).…”

Randomized trial of high‐dose interferon‐α‐2b combined with ribavirin in patients with chronic hepatitis C: Correlation between amino acid substitutions in the core/NS5A region and virological response to interferon therapy

“…The limitation of use of the combination therapy for HCV infection with genotype 1b is due to the low response rate during therapy and high relapse rate after the therapy [McHutchison et al, 1998]. Several studies have evaluated the potential benefits of a larger dose of IFN with varying results [Lindsay et al, 1996;Fried et al, 2000;Ferenci et al, 2001;Hadziyannis et al, 2001;Di Marco et al, 2002;Brouwer et al, 2004]. Although treatment has been switched to the combination of PEG-IFN and RBV in recent years, it is important to know if a larger dose of IFN is beneficial to patients with chronic hepatitis C.…”

Review of consensus interferon in the treatment of chronic hepatitis C

“…Preliminary data from a single center study suggested that daily dosing of CIFN in combination with ribavirin can achieve SVRs of 38%–45% in non-responders to standard IFN and ribavirin depending on the CIFN dose (Kaiser et al 2005). High-dose-induction therapy seemed to further improve SVR in this study (Kaiser et al 2005), even though it was not effective in studies with standard IFN-α-2a or -2b (Carithers et al 2000; Fried et al 2000; Hadziyannis et al 2001). In a recent study it has been assessed that the first-phase viral kinetics in 20 previously non-responders after a single dose of 15 μg or 30 μg CIFN and demonstrated a significantly sharper decline (0.8 vs 1.5) of the HCV-RNA with the higher dose after 24 hours (Cotler et al 2003).…”