Interferon alpha (IFN) has been the standard treatment for hepatitis C virus (HCV) infection. Using the kinetic curves of viral clearance, this study compared three treatment regimes based on IFN alone or in combination with Amantadine or Ribavirin to determine the mechanisms of action and the most suitable way to use these drugs. The early clearance kinetics of HCV were studied in 22 patients with chronic hepatitis C under different antiviral treatments: IFN 3 MU daily (7 pts); IFN 3 MU daily plus Amantadine 200 mg (7 pts); and IFN 3 MU daily plus Ribavirin 1-1.2 gr (8 pts), for 6 months. HCV-RNA was assessed qualitatively and quantitatively on serial samples. The HCV-RNA decay curves suggested a different behaviour of viral clearance induced by the three treatments. While no significant differences were present in the first 6 hours, between 6 to 12 hours Ribavirin induced a rapid decline in the viral load. Amantadine seemed to accelerate it in the third phase (12 to 30 hours) and to provoke a more pronounced viral decline when compared to IFN alone (P < 0.05) or to IFN plus Ribavirin (P < 0.025) (baseline to 30 hours). Thus, while IFN remains the principal antiviral drug, Amantadine upholds the viral decline. Ribavirin, although synergistic with IFN, does not seem to improve the IFN effect during the earliest phase of treatment but probably supports the effects of IFN later on. A new dynamic approach to HCV treatment can therefore be developed.
Background: Hepatitis C virus (HCV) infection is a worldwide problem of public health. Epidemiological studies have shown a significant higher prevalence of infection in the elderly. Amantadine is an antiviral agent active against the influenza A virus that has been used in cases of chronic hepatitis C. Objectives: To evaluate the antiviral activity and the safety of amantadine (200 mg daily for 6 months) in elderly patients with chronic hepatitis C. Methods: The study group consisted of 23 consecutive patients over 65 years suffering from chronic hepatitis C. Aminotransferase (ALT) levels were tested at baseline, at 15 days and then monthly until the end of therapy. HCV genotype was determined at baseline. A quantitative HCV-RNA measurement was performed at baseline, at 15 days and at the 1st, 3rd and 6th month of treatment. Results: 13 males and 10 females were enrolled (mean age 70.1 ± 3.4 years; range: 65–75). The mean ALT levels did not change significantly during therapy except in 1 patient subsequently returned normal. The HCV-RNA remained detectable in all patients, but a significant difference in response was observed in patients infected by genotype 1b. Conclusions: Our results confirm the antiviral activity of amantadine against HCV, mainly for genotype 1b with initial high viral load. No consistent effects on aminotransferases were observed.
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