title: The pattern of response to interferon alpha (alpha-IFN) predicts sustained response to a 6-month alpha-IFN and ribavirin retreatment for chronic hepatitis C. TVVH Study Group.
abstract: OBJECTIVE
  In chronic hepatitis C, interferon-alpha (alpha-IFN) and ribavirin combination therapy improves sustained response compared to alpha-IFN monotherapy, both in naive patients and in previous alpha-IFN relapsers, but the efficacy of such therapy remains limited in non-responder cases. The aim of this study was to assess whether the pattern of response to alpha-IFN alone may predict sustained response to combination therapy during retreatment.
  
  
  METHODS
  Fifty previous alpha-IFN relapsers and 50 previous alpha-IFN non-responders were retreated with a high alpha-IFN dose (6 MU/thrice weekly for 2 months; induction phase) and then randomised to continue with alpha-IFN alone (3 MU/thrice weekly) or to receive combination therapy (3 MU/thrice weekly of alpha-IFN and 1000-1200 mg/daily of ribavirin) for an additional 6 months according to the biochemical response to alpha-IFN shown after the induction phase. All patients were also evaluated for virological and histological response.
  
  
  RESULTS
  Eleven of 25 (44%) relapsers treated with combination therapy and 4/25 (16%) treated with alpha-IFN alone achieved a sustained response. The corresponding figures among non-responders were 1/25 (4%) and 0/25, respectively. Among 26 patients with a complete ALT and HCV-RNA response after 2 months of alpha-IFN, sustained response was seen in 11/14 (79%) treated with combination therapy and in 4/12 (33%) treated with alpha-IFN alone (p=0.05). On the other hand, of 74 cases still HCV-RNA positive after 2 months of alpha-IFN alone, biochemical and virological end of therapy response was better with combination therapy (11/36; 30.5%) compared to alpha-IFN alone (4/38; 10.5%), but only one patient developed a sustained response (1/36; 3%).
  
  
  CONCLUSIONS
  The retreatment with a 6-month combination therapy was associated with a high rate of sustained response only in patients showing a complete biochemical and virological response to alpha-IFN alone. Longer retreatment with combination therapy may be needed to achieve a sustained response in patients without a prompt virological response to alpha-IFN.
authors.affiliation: Department of Clinical and Experimental Medicine, Clinica Medica 5, Padova University, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cavalletto
authors.forename: L
authors.initials: L
authors.lastname: Chemello
authors.forename: C
authors.initials: C
authors.lastname: Donada
authors.forename: P
authors.initials: P
authors.lastname: Casarin
authors.forename: F
authors.initials: F
authors.lastname: Belussi
authors.forename: E
authors.initials: E
authors.lastname: Bernardinello
authors.forename: F
authors.initials: F
authors.lastname: Marino
authors.forename: P
authors.initials: P
authors.lastname: Pontisso
authors.forename: A
authors.initials: A
authors.lastname: Gatta
authors.forename: A
authors.initials: A
authors.lastname: Alberti
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D019233:Retreatment; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin