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RIBAVIRIN-INTERFERON VS INTERFERON ([alpha]2b-IFN) ALONE IN NON RESPONDERS TO [alpha]-IFN IN CHRONIC HEPATITIS C

Author: French Multicenter Study Group under the coordination of S. Pol, P. Berthelot and C. Brechot, Hopital Necker, Paris, France.

Aim. To compare the combination of [alpha]2b-IFN-Ribavirin to [alpha]2b-IFN alone in non responders to a previous standard 6-month course of 3 MU [alpha]2b-IFN.

Therapeutic schedule. 127 patients (83 men, 44 women, including 34 cirrhosis) were randomized to receive a long and reinforced [alpha]2b-IFN treatment (6 MU 6 months then 3 MU 6 months thrice weekly subcutaneously) in combination (n=62) or not (n=65) with Ribavirin (at a daily dosage of 1.0 or 1.2 gm according to the body weight < or > 70 kg for 4 months: 2 months alone and 2 months in combination with [alpha]2b-IFN). Efficacy was defined by the percentage of normal aminotransferase activities and by the disappearance of HCV RNA by PCR and bDNA test during and at the end of therapy and 6 months after the end of the 12-month course of [alpha]2b-IFN therapy.

Results. A significant decrease in aminotransferase was observed after 2 months in patients receiving Ribavirin (92 vs. 149 IU/I initially) as in those treated by [alpha]2b-IFN alone (86 vs. 141 IU/I). After 3 months of therapy, normal aminotransferase was observed in 35% in both groups. Tolerance of the combination was fair: hemolysis (-0.45 of Hb between M4 and M0), toxiderma (n=3), gingivitis (n=3) and cough (n=3) were related to Ribavirin and usually self-limited. Treatment withdrawal was necessary in 8 patients treated by the combination and in 6 patients with [alpha]2b-IFN alone.

A negative PCR at month 4 was observed in 33.3% of patients who were given the combination and in 37.7% of those who received [alpha]2b-IFN alone. At the end of [alpha]2b-IFN, HCV RNA was not detected in 14.0% of patients who received Ribavirin and in 7.6% (NS) of those who did not. The 36 evaluable patients who had a six-month follow-up after the end of treatment all had detectable HCV RNA.

Conclusion. This large controlled study: 1. shows an overall good tolerance to the sequential combination Ribavirin-[alpha]2b-IFN and 2. provides however no indication for an improved rate of primary or long term response with the combination in non responders to [alpha]2b-IFN since most of patients had no long term response

Source: American Association for the Study of Liver Diseases - 1996 Annual Meeting


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