Moreover, the combination of pitavastatin, AR, and interferon alfa was overwhelmingly more effective, compared with the previous results for the combination treatment of interferon alfa with ribavirin 3 or the combination treatment of interferon alfa plus fluvastatin. 4 In particular, we could decrease the doses of interferon alfa and statin in order to get an IC 90 value by the combination of pitavastatin, AR, and interferon alfa, that is comparable with the results of the combination treatment of interferon alfa plus fluvastatin. 4 For example, in the former combination, pitavastatin and interferon alfa was 0.25 M and 1.0 IU/mL, respectively. On the other hand, in the latter combination, interferon alfa and fluvastatin was 4.0 IU/mL and 6.7 mol/L, respectively. 4 This would be meaningful in order to avoid the adverse effects of drugs.
Next, we also generated human hepatocyte-like cells from human induced pluripotent stem cells (iPSCs), 5 and we tried to investigate the hepatotoxicities for the combination of pitavastatin (0.25 M), AR (10 M), and interferon alfa (1.0 IU/mL) by using the normal human hepatocyte-like cells. 5 As a result, we found the activities of glutamic oxaloacetic transaminase and lactate dehydrogenase (LDH) in the culture medium of the normal human hepatocytelike cells were not significantly different between the combination of pitavastatin (0.25 M), AR (10 M), and interferon alfa (1.0 IU/mL) and the combination of interferon alfa (4.0 IU/mL) plus ribavirin (25 M). Therefore, considering the abovementioned observations, the antiviral effects and safeties for the combination therapy of pitavastatin (0.25 M), AR (10 M), and interferon alfa (1.0 IU/mL) could be confirmed.
However, by using the patient-specific hepatocyte-like cells differentiated from human iPSCs of patients with hepatitis C virus 1b (HCV-1b) infection, the efficacies and toxicities of the abovementioned combination therapy for the individual patients with HCV-1b infection should be more precisely evaluated in the near future.
In conclusion, we found a novel combination therapy for HCV-1b infection by using our replicon system 2 and human iPSCs.