Hepatitis C viral kinetics in difficult to treat patients receiving high dose interferon and ribavirin.
OBJECTIVE
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 (epsilon) 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 x 10(6) copies/ml). In this study an additional phase with a temporary rise in viral load was observed between the alpha and the beta phase.


CONCLUSIONS
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.
Bekkering
F C
FC
Department of Hepatogastroenterology, Erasmus University Hospital Rotterdam, The Netherlands.
Brouwer
J T
JT
Hansen
B E
BE
Schalm
S W
SW
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage* / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D012254:Ribavirin; D007372:Interferons