title: Efficacy and tolerability of combination therapy with interferon-alfa plus ribavirin in patients with chronic hepatitis C virus infection: a single-center study in relapsers and nonresponders to previous treatment with high-dose interferon-alfa monotherapy.
abstract: BACKGROUND
  In chronic hepatitis C virus (HCV) infection, interferon (IFN) monotherapy usually is carried out at doses of 3 to 6 million units (MU) 3 times per week, but treatment efficacy is low.
  
  
  OBJECTIVE
  The aim of our study was to assess the efficacy and tolerability of IFN-alfa2b in combination with ribavirin in relapsers and nonresponders to high-dose IFN treatment (5 to 6 MU 3 times per week). We measured the biochemical and virologic responses to treatment and the risk for relapse during the 24 weeks following the end of treatment.
  
  
  METHODS
  Patients with chronic HCV infection (relapsers and nonresponders to a previous treatment with high-dose IFN) received IFN-alfa2b, 3 MU 3 times per week, and ribavirin, 1000 or 1200 mg/d for 24 or 48 weeks. The patients were then followed up for an additional 24 weeks. Sustained response was defined as normal serum alanine aminotransferase (ALT) level and undetectable HCV RNA 24 weeks after treatment was stopped.
  
  
  RESULTS
  Forty-three patients (32 men, 11 women; mean [SD] age, 45 [2] years; 10 relapsers, 33 nonresponders) were included in the study. Four patients were withdrawn from the study at week 4 of treatment because of treatment-related adverse events, and 1 dropped out. At the end of the treatment period, normalization of serum ALT levels and undetectable HCV RNA levels were seen in 58.1% and 30.2% of patients, respectively. No significant difference in virologic response at the end of treatment was found between nonresponders (10/33 [30.3%]) to previous IFN therapy and relapsers (3/10 [30.0%]). At the end of follow-up, 3 (7.0%) treated patients had sustained response (2 nonresponders to the first IFN course and 1 relapser). All of the patients with sustained response were treated for 24 weeks.
  
  
  CONCLUSIONS
  Based on the results of our study, combination therapy with IFN-alfa and ribavirin may be of value in a limited number of patients with chronic HCV infection who do not respond to, or relapse after, a first course of treatment with high-dose IFN monotherapy.
authors.affiliation: Department of Internal Medicine, Spedali Civili and Medical School, Brescia, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Benini
authors.affiliation: Department of Internal Medicine, Spedali Civili and Medical School, Brescia, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Distefano
authors.affiliation: Department of Internal Medicine, Spedali Civili and Medical School, Brescia, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Baisini
authors.affiliation: Department of Internal Medicine, Spedali Civili and Medical School, Brescia, Italy.
authors.forename: Marie Graciella
authors.initials: MG
authors.lastname: Pigozzi
authors.affiliation: Department of Internal Medicine, Spedali Civili and Medical School, Brescia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lanzini
keywords: chronic hepatitis C virus; combination therapy; high-dose interferon; ribavirin