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.
Zeuzem
Stefan
S
Department of Medicine, University Hospital Homburg/Saar, Germany.
Herrmann
Eva
E
D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000378:metabolism / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008962:Models, Theoretical; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood* / Q000235:genetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy* / Q000378:metabolism
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a