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BACKGROUND: Retreatment for 6 months with the association ribavirin-interferon of HCV-related chronic active hepatitis relapser patients has high probability of failure, mostly in those with genotype 1b. We evaluated the efficacy of extending the therapy from 6 to 12 months without or with the addition of amantadine. METHODS: Forty-nine genotype 1b relapser patients were treated with 3 MU of IFN-alpha2b three times per week and ribavirin 1000-1200 mg daily (double therapy). Twenty-four patients, who did not respond after 6 months of treatment, were randomized to continue for further 6 months either with the same schedule or with also the addition of amantadine 200 mg daily (triple therapy). RESULTS: A sustained virological response was observed in 15/37 subjects (41%) treated for 12 months of double therapy. In the arm of the study evaluating amantadine, end of treatment virologic response was observed in 0/12 patients of double therapy group and in 4/12 of triple therapy (P=0.09). After 6 months of follow-up, a sustained virologic response (SVR) was observed in two patients treated with the triple therapy. CONCLUSIONS: This study confirms poor results of retreatment (even if 12 months double or triple therapy) in relapser patients with HCV hepatitis, genotype 1b. No gain was obtained in prolonging from 6 to 12 months the standard double therapy, while triple therapy with amantadine as an additional regimen for this difficult subgroup of patients showed some cases of SVRs: amantadine addition deserves to be evaluated in larger trials.