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Digestive Diseases and Sciences

, Volume 50, Issue 5, pp 970–975 | Cite as

Pegylated Interferon α-2b, Ribavirin and Amantadine for Chronic Hepatitis C

  • Zobair M. Younossi
  • Arthur C. McCullough
  • David S. Barnes
  • Anthony Post
  • Janus P. Ong
  • Robert O’shea
  • Lisa M. Martin
  • Diane Bringman
  • Denise Farmer
  • Gavin Levinthal
  • Kevin D. Mullen
  • William D. Carey
  • Anthony S. Tavill
  • Roy Ferguson
  • Terry Gramlich
Article

Abstract

In an attempt to improve the efficacy of antiviral therapy for chronic hepatitis C, a three-drug combination of pegylated interferon α-2b, ribavirin, and amantadine has been suggested. Despite the initial enthusiasm, the role of amantadine in the treatment of chronic hepatitis C remains controversial. In a multi-center, open-label clinical trial, the potential efficacy and safety of this triple combination regimen were assessed. In this open-label pilot study, two separate patient populations with chronic hepatitis C and viremia were enrolled: treatment-naive and those who had failed a previous course of treatment. Patients were started on pegylated interferon α-2b at a dose of 1.5 μg/kg weekly with ribavirin, 1000–1200 mg/day, and amantadine, 200 mg/day, for 4 weeks, followed by pegylated interferon α-2b, 0.5 μg/kg weekly, ribavirin, 1000–1200 mg/day, and amantadine, 200 mg/day, for another 20 weeks. Patients with undetectable HCV RNA at week 24 continued this regimen for a total of 48 weeks and were followed for another 24 weeks. Patients with undetectable virus (< 50 IU/mL) after 24 weeks of follow-up were considered to have SVR. Health-related quality of life and safety data were also collected. Sixty-nine treatment-naive and 99 nonresponder patients with chronic hepatitis C were enrolled in the study. Of all patients enrolled, 74% were male, aged 47.27 ± 5.76 years; their body mass index (BMI) was 28.87 ± 5.05 kg/m2, 79.4% were white, 85% had HCV genotypes 1 and 4, and 36% had cirrhosis. Their baseline HCV RNA was 689,242 ± 698,030 IU/mL, with a baseline ALT of 107.25 ± 79.08. Of the entire cohort, 35 (21%) discontinued early due to side effects or loss to follow-up. Significant anemia (hemoglobin, < 10 g/dL) occurred in 11% (19/168), while severe anemia (hemoglobin, < 8.5 g/dL) occurred in 0.6% (1/168). In the treatment-naive group, sustained virologic response (SVR) was 34.3%, versus 19.4% for the group who had previously failed to respond to a course of treatment (P = 0.01). For both groups combined, virologic response after 24 weeks of therapy was 40.5%, with an end-of-treatment virologic response of 35.7% and a SVR of 26.2%. Patients with genotypes 1 and 4 had lower response rates than those with genotypes 2 and 3 (SVR, 21 vs. 46%; P = 0.001). Patients with advanced fibrosis (Metavir stages 3 and 4) tended to have lower response rates than those with minimal or mild fibrosis (Metavir stages 0–2) (SVR, 10 vs. 30%; P = 0.08). African-American patients with HCV had lower response rates than Caucasians or other ethnic groups (SVR, 4 vs. 29 vs. 20%; P = 0.04). Age, gender, and BMI did not affect SVR. The addition of amantadine to pegylated interferon α-2b and ribavirin does not seem to increase the efficacy of this antiviral regimen.

Key Words

chronic hepatitis C amantidine pegylated interferon α-2b ribavirin antiviral therapy HCV therapy Triple combination Amantadine 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Zobair M. Younossi
    • 1
    • 5
  • Arthur C. McCullough
    • 2
  • David S. Barnes
    • 3
  • Anthony Post
    • 4
  • Janus P. Ong
    • 1
  • Robert O’shea
    • 4
  • Lisa M. Martin
    • 1
  • Diane Bringman
    • 2
  • Denise Farmer
    • 1
  • Gavin Levinthal
    • 3
  • Kevin D. Mullen
    • 3
  • William D. Carey
    • 3
  • Anthony S. Tavill
    • 2
    • 3
  • Roy Ferguson
    • 3
  • Terry Gramlich
    • 3
  1. 1.Center for Liver DiseasesInova Fairfax HospitalClevelandUSA
  2. 2.Departments of GastroenterologyMetrohealth Medical CenterClevelandUSA
  3. 3.The Cleveland Clinic FoundationClevelandUSA
  4. 4.Case Western Reserve UniversityClevelandUSA
  5. 5.Center for Liver Diseases, Department of MedicineInova Fairfax HospitalUSA

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