Chronic hepatitis C. New therapeutic strategies.

Background: Aim of this work was to evaluate the early viral decay induced by a daily therapy with alfa-interferon (IFN) and the presence of any synergistic effects of amantadine and ribavirin.

Methods: Twenty patients with a diagnosis of chronic hepatitis C were randomly assigned to receive a course of treatment with: IFN 3MU daily (6 pts); or IFN 3MU daily plus amantadine 200 mg (7 pts): or IFN 3MU daily plus ribavirin 1-1.2 g (7 pts) for 6 months. Blood samples were drown at baseline, at 6, 12, 24, 30 and 48 hrs after the first dose of IFN; at 3, 7, 15 days and at every month. Serum was separated within two hours from the collection and stored at -80 degrees C until use. Viraemia was evaluated qualitatively by the Cobas Amplicor (cut-off 1.00E+02 copies/ml) (Roche Diagnostics, Monza, Milan, Italy) and quantitatively by the Cobas Amplicor Monitor (cut-off 1.00E+03 copies/ml). The HCV genotype was determined for each patient by Inno-LiPA HCV II (Innogenetics, Ghent, Belgium). Liver function tests were evaluated at baseline, at 7 and 15 days and at every month.

Results: The analysis of the decay curves showed the presence of a three phase decline in the viraemia. At the end of therapy 7 out of the 20 patients (35%) had normal ALT and undetectable HCV-RNA (2 out of 6 in the IFN group: 33.3%, 3 out of 7: 42.8%; 2 out of 7: 28.6%, in the IFN plus amantadine and IFN plus ribavirin groups respectively).

Conclusions: IFN is the major antiviral effector in the early stage of therapy. The observation of the kinetic curves shows a tendency for the ribavirin to induce a slightly steeper slope of decay in the first 48 hrs, while amantadine seems to induce a slightly deeper abatement of circulating viraemia after 48 hrs.