Twenty-four hour kinetics of hepatitis C virus and antiviral effect of alpha-interferon

Numerous studies reported that patients infected by the genotype 1 of hepatitis C virus (HCV) and/or with a high baseline viral load responded poorly to antiviral therapy. Study of viral kinetics has provided clues to the understanding of non-response to alpha-interferon (IFN-alpha)-based therapy. The objective of this study was to clarify the influence of viral factors such as the genotype and baseline viral load on HCV resistance to treatment through the study of their impact on the first phase of viral decline. HCV RNA levels were determined frequently following the administration of 3 million units of IFN-alpha in 22 chronic HCV carriers. The evolution of HCV RNA level over 24 hr was different in genotype 1-infected patients, compared to that in patients infected by other genotypes. The viral load decline at 24 hr was lower in patients with genotype 1. Patients with a high baseline viral load exhibited a viral dynamics different from patients with a lower level of viremia; the extent of the first phase was also lower in these patients. Non-responder patients had a slower viral decay on day 1 of therapy than patients who cleared the virus under treatment. In conclusion, 24 hr HCV dynamics is regulated by genotype and baseline viral load. Genotype 1 strains and those that produce high viral loads are the most resistant to the antiviral action of IFN-alpha. Resistant HCV strains could be distinguished from sensitive viruses as early as a few hours after the beginning of the treatment.