title: High-dose interferon alfa-2b and ribavirin in patients previously treated with interferon: results of a prospective, randomized, controlled trial.
abstract: BACKGROUND
  Kinetic studies have demonstrated a more rapid reduction in hepatitis C virus (HCV) RNA levels among patients taking high daily doses of interferon compared with those taking standard-dose interferon.
  
  
  OBJECTIVE
  To compare the efficacy and safety of high-dose interferon alfa-2b and ribavirin with standard-dose interferon alfa-2b and ribavirin in chronic hepatitis C patients previously treated with interferon.
  
  
  METHODS
  One hundred seven patients (30 interferon relapsers and 77 interferon nonresponders) were randomized to take either high-dose interferon alfa-2b in combination with ribavirin (group A) (consisting of 5 MU/d for 4 weeks, 5 MU three times weekly for 8 weeks, and then 3 MU three times weekly for 36 weeks) or standard-dose interferon alfa-2b and ribavirin (group B) for 48 weeks. Serum alanine transaminase (ALT), HCV RNA levels, and safety data were prospectively collected and compared during treatment and at week 24 of follow-up.
  
  
  RESULTS
  The mean serum ALT and HCV RNA levels, as well as the proportion of patients with genotype 1 and cirrhosis and who were African American, were similar in the two treatment groups at study entry. The rates of suppression of HCV RNA to undetectable levels at weeks 4, 12, and 48 were similar. In addition, the sustained virologic response rates at week 24 of follow-up were similar in groups A and B (29% vs. 39%, respectively, p = 0.277). Clinical variables that correlated with a sustained virologic response included a history of relapse to previous interferon therapy and non-1 HCV genotype ( p < 0.01).
  
  
  CONCLUSIONS
  Short-term, high-dose interferon alfa-2b and ribavirin failed to demonstrate a tangible benefit compared with standard-dose interferon alfa-2b and ribavirin. However, our study results and others suggest that standard-dose interferon and ribavirin for 48 weeks should be considered for selected patients who did not respond to previous interferon therapy.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA. Rfontana@umich.edu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.forename: John
authors.initials: J
authors.lastname: Walsh
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Moyer
authors.forename: Anna S F
authors.initials: AS
authors.lastname: Lok
authors.forename: Steven
authors.initials: S
authors.lastname: Webster
authors.forename: Steven
authors.initials: S
authors.lastname: Klein
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin