title: A randomized trial of prolonged high dose of interferon plus ribavirin for hepatitis C patients nonresponders to interferon alone.
abstract: Retreatment of chronic hepatitis C patients nonresponders to interferon (IFN) alone with the standard dose of IFN [3 million units (MU) thrice weekly (TIW)] plus ribavirin for 24 weeks has yielded low sustained virological response (SVR), averaging 8%. The aim of the present, open-labelled, randomized study was to evaluate the efficacy of IFN induction therapy followed by prolonged high dose of IFN plus ribavirin in nonresponders. One hundred and fifty-one patients were randomized to receive 5 MU daily of IFN alfa-2b (group 1, n = 73) or 5 MU TIW of IFN alfa 2b (group 2, n = 78) for 4 weeks followed by IFN (5 MU TIW) plus ribavirin (1000/1200 mg/daily) for 48 weeks in both groups. In an intention-to-treat analysis, the sustained virological response (SVR) at 24-week follow-up was 33 and 23% for group 1 and 2, respectively (P = 0.17). The overall SVR was 52 and 18% in patients with genotype 2/3 and 1/4, respectively. Among genotype 1/4 patients the SVR was 29 and 11% for age younger or older than 40 years. Compared with genotype 2/3 patients, the risk (95% confidence interval) of nonresponse to retreatment was 3.0-fold (1.17-8.0) in younger genotype 1/4 patients and 8.4-fold (3.0-23.29) in older genotype 1/4 patients. In conclusion these results suggest that retreatment with a reinforced regimen should be focused in nonresponder genotype 2/3 patients and younger genotype 1/4 patients, who are most likely to benefit. Induction therapy does not improve SVR.
authors.affiliation: Servizio Autonomo Clinicizzato di Gastroenterologia, Università di Verona, Verona, Italy. giovanna_fattovich@tin.it
authors.forename: G
authors.initials: G
authors.lastname: Fattovich
authors.forename: I
authors.initials: I
authors.lastname: Zagni
authors.forename: M L
authors.initials: ML
authors.lastname: Ribero
authors.forename: E
authors.initials: E
authors.lastname: Castagnetti
authors.forename: E
authors.initials: E
authors.lastname: Minola
authors.forename: L
authors.initials: L
authors.lastname: Lomonaco
authors.forename: C
authors.initials: C
authors.lastname: Scattolini
authors.forename: P
authors.initials: P
authors.lastname: Fabris
authors.forename: S
authors.initials: S
authors.lastname: Boccia
authors.forename: M
authors.initials: M
authors.lastname: Giusti
authors.forename: G
authors.initials: G
authors.lastname: Abbati
authors.forename: M
authors.initials: M
authors.lastname: Felder
authors.forename: P
authors.initials: P
authors.lastname: Rovere
authors.forename: A
authors.initials: A
authors.lastname: Redaelli
authors.forename: A
authors.initials: A
authors.lastname: Tonon
authors.forename: A
authors.initials: A
authors.lastname: Tomba
authors.forename: R
authors.initials: R
authors.lastname: Montanari
authors.forename: C
authors.initials: C
authors.lastname: Paternoster
authors.forename: M
authors.initials: M
authors.lastname: Distasi
authors.forename: G
authors.initials: G
authors.lastname: Fornaciari
authors.forename: G
authors.initials: G
authors.lastname: Tositti
authors.forename: C
authors.initials: C
authors.lastname: Rizzo
authors.forename: S
authors.initials: S
authors.lastname: Suppressa
authors.forename: M
authors.initials: M
authors.lastname: Pantalena
authors.forename: F
authors.initials: F
authors.lastname: Noventa
authors.forename: A
authors.initials: A
authors.lastname: Tagger
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin