Background/Aims: Hepatitis C viral (HCV) kinetic studies have demonstrated the increased antiviral effect of higher than standard dosages of interferon and of daily treatment schedules. Since interferon has a short half-life, twice-daily administration of interferon may be even more effective. Methods: We evaluated the HCV kinetics in daily vs. twice-daily high dose interferon (IFN) therapy in combination with ribavirin in 24 difficult to treat patients. Patients were randomised to 10 MU IFN daily or 5 MU twice-daily for 4 weeks. Results: Interferon efficacy (ε) was similar and very high for both groups (range 99.83-99.97%). Clearance of infected cells (beta phase) tended to be slightly faster for patients on 5 MU bd (T1/2 70 vs. 90 h, ns). Clearance of infected cells was strongly related to initial viral load (T1/2 103 vs. 53 h, P = 0.002, for above versus below 2 × 106 copies/ml). In this study an additional phase with a temporary rise in viral load was observed between the alpha and the beta phase. Conclusion: Daily high induction dose is associated with nearly complete inhibition of viral replication even in difficult to treat patients. A twice-daily schedule did not lead to further improvement. Clearance rate of infected cells was significantly correlated with initial viral load.

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Journal of Hepatology
Department of Gastroenterology & Hepatology

Bekkering, F.C, Brouwer, J.T, Hansen, B.E, & Schalm, S.W. (2001). Hepatitis C viral kinetics in difficult to treat patients receiving high dose interferon and ribavirin. Journal of Hepatology, 34(3), 435–440. doi:10.1016/S0168-8278(00)00033-7