Background: Hepatitis C virus infection is a major burden after liver transplantation. The effective treatment for patients who underwent liver transplantation has not been well established. Management of these patients is the most challenging task. Cyclophilins are essential host factors for HCV replication. We report here the efficacy of divided administration of IFN plus cyclosporine A in the treatment of chronic hepatitis C patients who failed Peg-IFN or IFN combined ribavirin. Patients and method: We prospectively included 59 patients (median age, 63) with genotype 1b and, failures to combination IFN plus ribavirin or combination pegylated IFN plus ribavirin. The present treatments consisted of an induction therapy, an intensified therapy and a maintenance therapy. The induction therapy comprised intravenous 1 MU IFN every 4 hours for the first 3 days, 1.5 MU IFN every 6 hours for the next 4 days and 2 MU IFN every 8 hours for the following 3 weeks, totaling 168 MU of IFN . The intensified therapy was induction therapy shortened to 2 weeks. The maintenance therapy comprised of pegylated IFN 2b and ribavirin. CsA was given 4 times daily during the induction and the intensified therapies. Ribavirin was given twice daily during the maintenance therapy. Results: The end treatment response and sustained virological response rate of the present study were 73 % (43/59) and 59% (35/59), respectively. The relapse rate was 19 %(8/43). Non-responders was 16 % (3/19). All adverse effects were completely reversible. The treatment protocol was well tolerable. Conclusion: We concluded that our protocol should be effective in failures to the previous combination therapies. Host factor targeting treatment will become a promising treatment option.