Early viral clearance and sustained response in chronic hepatitis C: a controlled trial of interferon and ribavirin after high‐dose interferon induction

Abstract

High-dose induction with alpha-interferon induces early viral clearance of hepatitis C and combined with ribavirin enhances sustained response. We assess whether adding ribavirin after viral clearance obtained by alpha-interferon induction increased the rate of viral eradication.Forty-one naïve patients with chronic hepatitis C were randomised to receive, after 4 weeks of 10 mU daily of alpha-interferon (induction), 3 mU daily for 22 weeks and 3 mU thrice weekly for 26 weeks of either interferon alone (monotherapy) or interferon plus 1000-1200 mg daily of ribavirin (combination therapy). At the end of the induction phase, 23 (56%) subjects had cleared HCV-RNA. During therapy, breakthrough was observed in four patients on monotherapy, but never in patients on combination therapy. The rate of clearance of HCV-RNA was different between monotherapy and combination therapy at the end of treatment (40% vs. 76.1%, P=0.02) and at the end of follow-up (5% vs. 57.1%, P=0.001). Twelve of the 23 patients who cleared HCV-RNA during induction, but only one of the 18 still HCV-RNA-positive after 4 weeks of therapy, had a sustained response (52.2% vs. 5.6%, P=0.001). Clearance of HCV-RNA at 1 week had a high positive predictive value for sustained response in combination therapy (PPV=0.75), but not in monotherapy (PPV=0.33). Induction with high daily doses of alpha-interferon obtains suppression of hepatitis C in more than half of patients, but ribavirin is needed to maintain a sustained response. The rate of sustained response is a function of the time to HCV-RNA clearance. In patients not responding to induction therapy addition of ribavirin does not obtain a sustained virological response.

Impact of high-dose peginterferon alfa-2A on virological response rates in patients with hepatitis C genotype 1: A randomized controlled trial

“…[4][5][6][7][8][9][10][11] Most of these studies investigated standard interferon and included both HCV genotype 1 and non-1 patients, with variable periods of induction (4-14 weeks). Induction with standard interferon has improved initial HCV RNA decay 11 and initial virological responses, 8 but has in general failed to improve SVR.…”

“…Induction with standard interferon has improved initial HCV RNA decay 11 and initial virological responses, 8 but has in general failed to improve SVR. [6][7][8][9][10][11] The exception is the study by Ferenci et al that demonstrated significantly higher SVR rates with high-dose daily interferon among the subgroup of patients with HCV genotype 1, although not in the overall study population. 4 Limited data exists on the efficacy of induction therapy with peginterferon alfa in patients infected with HCV genotype 1.…”

“…[4][5][6][7][8][9][10][11] The rationale for this so-called induction strategy is that high-dose interferon may improve SVR by inducing a more rapid initial decline in HCV RNA. The relationships between interferon dose and early phase HCV kinetics, including phase I and II slope and time to undetectable HCV RNA, 12,13 and early virological responses and SVR support such a rationale.…”

“…1,[14][15][16] Studies utilizing induction therapy with (peg)interferon in patients with genotype 1 CHC have yielded mixed results, with some patients demonstrating an enhanced SVR 4,5 and others not. [6][7][8][9][10][11] However, there has been no published randomized trial of high-dose induction therapy with peginterferon alfa-2a/b (PEG-IFN␣-2a/b) in a large population of treatment-naïve patients with genotype 1 CHC.…”

Prolonged Negative HCV-RNA Status Led to a Good Outcome in Chronic Hepatitis C Patients with Genotype 1b and Super-High Viral Load

“…In patients with genotype 1b and a high viral load, various studies including induction-dosing trials showed greater rates of early viral clearance. However, there were a few reports suggesting that early viral clearance was associated with a high prevalence of SVR [37,39,40] . Vrolijk et al [41] demonstrated that daily induction therapy might be benefi cial for IFN-resistant patients, but only when combined with adequate maintenance therapy of long duration.…”