title: 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.
authors.affiliation: Cattedra di Gastroenterologia, Clinica Medica, University of Palermo, Palermo, Italy. vito.dimarco@tin.it
authors.forename: V
authors.initials: V
authors.lastname: Di Marco
authors.forename: D
authors.initials: D
authors.lastname: Ferraro
authors.forename: P
authors.initials: P
authors.lastname: Almasio
authors.forename: A
authors.initials: A
authors.lastname: Vaccaro
authors.forename: P
authors.initials: P
authors.lastname: Parisi
authors.forename: M
authors.initials: M
authors.lastname: Cappello
authors.forename: N
authors.initials: N
authors.lastname: Cino
authors.forename: R
authors.initials: R
authors.lastname: Di Stefano
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxì
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014766:Viremia / Q000188:drug therapy
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D012254:Ribavirin