Abstract
BackgroundHigh dose interferon induction treatment of hepatitis C viral infection blocks viral production over 95%. Since dose reduction is often performed due to clinical considerations, the effect of dose reduction on hepatitis C virus kinetics was studied.MethodsA new model that allowed longitudinal changes in the parameters of viral dynamics was used in a group of genotype-1 patients (N = 15) with dose reduction from 10 to 3 million units of interferon daily in combination with ribavirin, in comparison to a control group (N = 9) with no dose reduction.ResultsDose reduction gave rise to a complex viral kinetic pattern, which could be only explained by a decrease in interferon effectiveness in blocking virion production. The benefit of the rapid initial viral decline following the high induction dose is lost after dose reduction. In addition, in some patients also the second phase viral decline slope, which is highly predictive of success of treatment, was impaired by the dose reduction resulting in smaller percentage of viral clearance in the dose reduction group.ConclusionsThese findings, while explaining the failure of many induction schedules, suggest that for genotype-1 patients induction therapy should be continued till HCVRNA negativity in serum in order to increase the sustained response rate for chronic hepatitis C.
Highlights
High dose interferon induction treatment of hepatitis C viral infection blocks viral production over 95%
Here we investigated the longitudinal changes in viral dynamics in patients going through a dose reduction in order to asses the effect of dose on the second slope
We report that early dose reduction is followed by a rise in viral load, that can only be explained by a decrease in interferon effectiveness; so the potential benefit of a rapid viral decline following high dose induction is often lost
Summary
High dose interferon induction treatment of hepatitis C viral infection blocks viral production over 95%. [5–7] The pattern of viral decline seems to be biphasic, with a rapid viral decline within the first 24– 48 hours followed by a much slower second phase of viral decline This biphasic decline is hypothetically caused by a direct anti-viral effect of interferon in blocking virion production from infected cells [5]. It has been shown that it is the second slope which is the best predictor for response to treatment [5,9] This slower second phase slope of viral decline has large variability between patients, and cross sectional analysis of its dose dependence is hindered. We report that early dose reduction is followed by a rise in viral load, that can only be explained by a decrease in interferon effectiveness; so the potential benefit of a rapid viral decline following high dose induction is often lost
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