High-dose prolonged combination therapy in non-responders to interferon monotherapy for chronic hepatitis C

Aliment Pharmacol Ther. 2001 Jul;15(7):953-8. doi: 10.1046/j.1365-2036.2001.01005.x.


Background: Therapy of chronic hepatitis C non- responders to interferon monotherapy with standard doses of interferon plus ribavirin is usually ineffective.

Aim: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Fibrosis
  • Genotype
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / pathology
  • Humans
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / pharmacology*
  • Interferon-alpha / therapeutic use
  • Male
  • Middle Aged
  • RNA, Viral / analysis
  • Ribavirin / administration & dosage
  • Ribavirin / pharmacology*
  • Ribavirin / therapeutic use
  • Treatment Outcome


  • Antiviral Agents
  • Interferon-alpha
  • RNA, Viral
  • Ribavirin