TY - JOUR

T1 - Dose-dependent acute clearance of hepatitis C genotype 1 virus with interferon alfa

AU - Lam, Nancy P.

AU - Neumann, Avidan U.

AU - Gretch, David R.

AU - Wiley, Thelma E.

AU - Perelson, Alan S.

AU - Layden, Thomas J.

PY - 1997/7

Y1 - 1997/7

N2 - 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 x 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.

AB - 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 x 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.

UR - http://www.scopus.com/inward/record.url?scp=0031009603&partnerID=8YFLogxK

U2 - 10.1002/hep.510260130

DO - 10.1002/hep.510260130

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C2 - 9214474

AN - SCOPUS:0031009603

SN - 0270-9139

VL - 26

SP - 226

EP - 231

JO - Hepatology

JF - Hepatology

IS - 1

ER -