Dose‐dependent acute clearance of hepatitis C genotype 1 virus with interferon alfa

To determine if the clearance of hepatitis C genotype 1 virus (HCV) is dependent on the dose of interferon alfa‐2b (IFN‐α2b), the acute clearance of HCV after a single dose of either 3, 5, or 10 mIU of IFN‐α was compared in patients with chronic hepatitis C. HCV‐RNA levels following IFN‐α administration were measured. At 24 hours, mean percentage serum viral reduction was 41.4%, 63.7%, and 85.5% for 3, 5, and 10 mIU, respectively (P < .001). At 48 hours, the mean viral reduction was consistently less than the reduction at 24 hours, averaging 22.9%, 61.9%, and 74.3%, respectively (P < .001), indicating that the drug effect diminishes before 48 hours. Regression analysis showed a positive correlation between dose and percent reduction of HCV‐ RNA levels (r = .6; P < .001). A mathematical model showed that such dose dependence is expected if IFN‐α partially blocks viral production. Minimum clearance and production rates of HCV were estimated from measurements of HCV‐RNA levels after the 10‐mIU dose. HCV decay followed an exponential decline with a minimum estimate of the viral clearance rate constant of 2.8 per day, corresponding to a virion half‐life of 0.3 days or less. A minimal estimate of the daily HCV production and clearance is 3.7 × 1011 virions per day, indicating a high rate of replication and turnover. These results indicate that there is a dose‐dependent effect of IFN‐α in clearance of HCV genotype 1. Because the virion production rate is very rapid and because the current recommended dose of IFN‐α (3 mIU) is often ineffective, larger doses should be considered to treat genotype 1‐infected patients.