Dynamics of hepatitis C virus infection.

Viremia shows only minor fluctuations in untreated patients chronically infected with hepatitis C virus. The steady state situation of balanced viral production and clearance in untreated patients can be disturbed by active antiviral treatment. After initiating interferon- alpha therapy, a typical biphasic decline of viremia can be observed and analyzed. Evaluation of mathematical models of viral dynamics during the initial phase of antiviral treatment shows high turnover rates of pre-treatment viral production and clearance of about 10(11) -10(13) virions each day and in-vivo half-lives of a few hours for free hepatitis C virions. During the first 24 to 48 hours of therapy, a dose-dependent first phase of interferon-alpha induced viral kinetics is characterized by a rapid exponential decline of serum viral load. Then viral decline enters a second phase of a relatively slow exponential decay during the following weeks of therapy which mainly reflects the death rate of infected hepatocytes. This second phase decay is predictive for the virologic end-of-treatment and even more the sustained response. Non-responding patients typically show constant viremia or even a rebound during this second phase.