title: Triple combination of interferon alpha-2b, ribavirin, and amantadine for treatment of chronic hepatitis C.
abstract: Retreatment of interferon-resistant chronic hepatitis C represents a significant clinical challenge. In an open-label, pilot study, the safety and efficacy of interferon alpha-2b, ribavirin, and amantadine were assessed. Twenty patients with chronic hepatitis C who had previously failed to respond to a course of interferon monotherapy followed by a course of combination therapy (10 patients received interferon alpha-2b [3 million units three times a week] plus ribavirin [800 mg/d] and 10 patients received interferon alpha-2b [3 million units three times a week] plus amantadine [200 mg/d]) were enrolled in this retreatment protocol. One month after discontinuation of their last regimen, patients started treatment with interferon alpha-2b (3 million units three times a week), ribavirin (1,000-1,200 mg/d), and amantadine (200 mg/d). Biochemical and virologic end points were monitored. Patients with hepatitis C virus (HCV) RNA levels of <100 copies/mL at the end of 24 weeks of therapy completed a 48-week course of interferon alpha-2b, ribavirin, and amantadine treatment. Of the enrolled subjects, 60% were male, 85% were white, 85% had HCV genotype 1, and 20% had histologic cirrhosis. The mean age +/- SD of the patients was 44.1 +/- 4.9 years, the mean baseline HCV RNA level +/- SD was 1,845,150 +/- 1,279,069 copies/mL, and the mean baseline alanine aminotransferase level +/- SD was 130 +/- 100 U/L. Five patients (25%) became HCV RNA negative (<100 copies/mL) after 24 weeks of treatment, with only three patients (15%) remaining HCV RNA negative at the end of 48 weeks of treatment. This end of treatment response was sustained 6 months after the discontinuation of treatment in only two patients (10%). In this interferon-resistant group, a treatment regimen of interferon alpha-2b, ribavirin, and amantadine was associated with only a 10% sustained viral eradication rate.
authors.affiliation: The Cleveland Clinic Foundation, Ohio, USA.
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Mullen
authors.forename: Sandra
authors.initials: S
authors.lastname: Hodnick
authors.forename: David S
authors.initials: DS
authors.lastname: Barnes
authors.forename: William D
authors.initials: WD
authors.lastname: Carey
authors.forename: Arthur C
authors.initials: AC
authors.lastname: McCullough
authors.forename: Kirk
authors.initials: K
authors.lastname: Easley
authors.forename: Terry
authors.initials: T
authors.lastname: Gramlich
authors.forename: Belinda Yen
authors.initials: BY
authors.lastname: Liebermann
mesh_terms: D000328:Adult; D000547:Amantadine / Q000627:therapeutic use*; D000740:Anemia / Q000139:chemically induced; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D000547:Amantadine