Pilot dose-finding trial on interferon alpha in combination with ribavirinfor the treatment of chronic hepatitis C in patients not responding to interferon alone

Background, Effectiveness of combination therapy with standard interferon a lpha doses and ribavirin is far from being demonstrated in patients with he patitis C non responders to interferon alpha monotherapy. Recent kinetic st udies revealed that these doses may be suboptimal. Aims. To find the criteria for optimisation of the interferon dose, to be u sed in combination with ribavirin in patients with hepatitis C non responde rs to interferon alpha monotherapy. Patients. Sixty-three patients enrolled in a pilot controlled trial were tr eated for 6 months with ribavirin (1000-1200 mg daily) and were randomised to concurrently receive interferon alpha;Ib for 6 months at: 3 Million Unit s thrice weekly [group A (21 patients)], 5 MU thrice weekly [group B (21 pa tients)] and 5 million units daily [group C (21 patients)]. Results. A sust ained virological response was observed in: 1 patient from group A (5%), 2 patients from group B (9%) and 8 patients from group C (38%; p=0.02 vs grou p A, p=0.03 vs group B). Side-effects were not significantly different betw een the 3 groups. Multivariate analysis showed that infection by hepatitis C virus genotypes 2 or 3 and interferon alpha dosage of 5 million units dai ly were independent predictors of sustained response. Conclusions, These results suggest that higher interferon doses administere d daily in combination with ribavirin could be more effective in those pati ents with hepatitis C who had not responded to interferon alone.