Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy

Little is know about the viral dynamics (production and clearance) of hepatitis C virus (HCV) infection and its response to antiviral therapy with interferon alpha. In this paper by Neumann et al., complex mathematical modeling was used to investigate the dynamics of HCV infection and the response to treatment with interferon alpha. The data were obtained from based 23 patients who received different doses of interferon alpha. From the model, it appears that the major initial affect of interferon alpha is to block virus production and release.

The estimated half-life of a viral particle was 2.7 hours with production and clearance of about one trillion viral particles a day. This rate of HCV production is significantly greater than that estimated for human immunodeficiency virus (HIV) in infected individuals. The estimated infected cell death rate varied considerably from patient to patient ranging from 1.7 days to 70 days. Fast death rates were predictive of HCV being undetectable by reverse transcription-polymerase chain reaction in serum after three months of treatment.

The results of this study provide important information about the replication of HCV in infected individuals and its clearance from the body in response to treatment with interferon alpha. The high viral production rate explains why HCV mutates frequently in infected individuals and possibly why infection is often difficult to treat.

Neumann, A. U., Lam, N. P., Dahari, H., Gretch, D. R., Wiley, T. E., Layden, T. J., and Perelson, A. S. 1998. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy.
Science. 282:103-107.

By Howard J. Worman, M. D.

 

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