title: High-dose prolonged combination therapy in non-responders to interferon monotherapy for chronic hepatitis C.
abstract: BACKGROUND
  Therapy of chronic hepatitis C non- responders to interferon monotherapy with standard doses of interferon plus ribavirin is usually ineffective.
  
  
  OBJECTIVE
  To evaluate the efficacy and tolerability of high-dose prolonged combination retreatment in non- responder patients.
  
  
  METHODS
  Patients were retreated for 6 months with 6 MU alphaIFN on alternate days and 1000 or 1200 mg/day ribavirin. HCV-RNA negative patients continued therapy for an additional 6 months.
  
  
  RESULTS
  Forty patients (29 males, mean age 49.7 years, 34 genotype 1b, 11 with F3 fibrosis) were treated. At 6 months, 20 (50%) patients were HCV-RNA negative but six of them discontinued therapy because of adverse events. A sustained response was achieved in 28% of patients (11/40). A sustained response was more frequent among patients with genotype non-1b than in those with genotype 1b (67 vs. 21%, P=0.005) and clearance of HCV-RNA in the first 3 months had a high predictive value for sustained response (100% of sustained responders vs. 24% of non-responders, P=0.0001).
  
  
  CONCLUSIONS
  High-dose prolonged combination therapy in non-responders to IFN monotherapy leads to a higher rate of sustained response than the standard combination regimen. Tolerability may be a rate-limiting factor. Maximal effectiveness can be predicted in patients with non-1b genotype and in those who clear HCV-RNA soon after starting retreatment.
authors: Cattedra e Divisione di Gastroenterologia, University of Palermo, Italy. vito.dimarco@tin.it
authors: V
authors: V
authors: Di Marco
authors: A
authors: A
authors: Vaccaro
authors: D
authors: D
authors: Ferraro
authors: G
authors: G
authors: Alaimo
authors: V
authors: V
authors: Rodolico
authors: P
authors: P
authors: Parisi
authors: S
authors: S
authors: Peralta
authors: R
authors: R
authors: Di Stefano
authors: P L
authors: PL
authors: Almasio
authors: A
authors: A
authors: Craxì
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005355:Fibrosis; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D012254:Ribavirin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D012254:Ribavirin