[Hepatitis C-virus --virus kinetics and resistance mechanisms].
Typically, a biphasic decay of viremia can be observed during the first few weeks of interferon-based treatment in patients with chronic hepatitis C. The mathematical and statistical analysis of viral kinetics enables the estimation of individual kinetic parameters. Especially, the infected cell loss, the degradation rate of free virus, and an efficiency factor on blocking viral production can be estimated. Furthermore, mathematical models of viral kinetics have the potential to reveal mechanisms of antiviral therapy. The lower sustained virologic response rates in several patient populations are reflected by impaired kinetic parameters. Besides host-specific and treatment-related differences, especially hepatitis C virus genotype strongly correlates with initial and long-term virologic responses. Reasons for virologic response or non-response to interferon-based therapy for individual patients are unknown. Beside host- and treatment-related causes it is assumed that HCV is able to specifically evade the antiviral actions of interferon. So far, three HCV proteins [envelope (E)2, non-structural (NS) protein 3/4A, and NS5A protein] have been associated with interferon resistance mechanisms. However, within the E2 (HVR2, CD81 binding domains, PePHD) and NS3/4A proteins no specific mutations in correlation with virologic response to interferon-based antiviral therapy were observed. For the NS5A protein, mutations within the interferon sensitivity determining region (ISDR) and the complete NS5A protein may be of importance for virologic treatment response in patients infected with genotype HCV-1a/b isolates.
Herrmann
E
E
Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II, Homburg/Saar.
Sarrazin
C
C
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004351:Drug Resistance / Q000502:physiology; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D007700:Kinetics; D008954:Models, Biological; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
D000998:Antiviral Agents; D014759:Viral Envelope Proteins; D007372:Interferons