title: A randomized trial of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon.
abstract: BACKGROUND
  Conventional interferon monotherapy fails to achieve virological clearance in most hepatitis C-infected patients. The use of high-dose induction regimens may improve the initial clearance of virus, while the addition of ribavirin appears to improve the rates of sustained response once clearance is achieved.
  
  
  OBJECTIVE
  To compare the efficacy and safety of re-treatment with an induction regimen of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon monotherapy.
  
  
  METHODS
  Previous virological non-responders to standard dose interferon (3-5 MU three times weekly for > or = 12 weeks) were randomized to receive, unblind, either 10 MU interferon alpha-2b daily for 10 days, then 5 MU daily for 74 days, then 5 MU three times weekly for 24 weeks (total 36 weeks) (group A), or the above regimen with the addition of ribavirin, 1000-1200 mg/day, at day 11 (group B). All patients were followed up for 24 weeks after completion of therapy.
  
  
  RESULTS
  End of treatment virological response was noted in one of 10 (10%) patients in group A and in eight of 15 (54%) patients in group B (P=0.04). The sole end treatment responder in group A and three in group B relapsed on follow-up. The apparent improvement in response in group B compared to group A nearly reached statistical significance (group B 5/15 vs. group A 0/10; P=0.06).
  
  
  CONCLUSIONS
  In this small pilot study, a 36-week high-dose induction interferon monotherapy protocol did not yield sustained responses in previous non-responders to standard dose interferon. However, the same regimen with ribavirin yielded a 33% sustained response rate, nearly reaching statistical significance. The therapy was well tolerated, despite the higher doses of interferon used and the addition of ribavirin. High-dose interferon with ribavirin appears to be a therapeutic option for non-responders to conventional interferon monotherapy.
authors.affiliation: Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390-9151, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Malik
authors.forename: K S
authors.initials: KS
authors.lastname: Kumar
authors.forename: P F
authors.initials: PF
authors.lastname: Malet
authors.forename: G
authors.initials: G
authors.lastname: Ostapowicz
authors.forename: G
authors.initials: G
authors.lastname: Adams
authors.forename: M
authors.initials: M
authors.lastname: Wood
authors.forename: K
authors.initials: K
authors.lastname: Yarbrough
authors.forename: A
authors.initials: A
authors.lastname: Jones
authors.forename: W M
authors.initials: WM
authors.lastname: Lee
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin