Mathematical modeling of triphasic viral dynamics in patients with HBeAg-positive chronic hepatitis B showing response to 24-week clevudine therapy.

Journal Article (Clinical Trial, Phase III;Journal Article)

BACKGROUND: Modeling of short-term viral dynamics of hepatitis B with traditional biphasic model might be insufficient to explain long-term viral dynamics. The aim was to develop a novel method of mathematical modeling to shed light on the dissociation between early and long-term dynamics in previous studies. METHODS: We investigated the viral decay pattern in 50 patients from the phase III clinical trial of 24-week clevudine therapy, who showed virological response and HBsAg decline. Immune effectors were added as a new compartment in the model equations. We determined some parameter values in the model using the non-linear least square minimization method. RESULTS: Median baseline viral load was 8.526 Log(10)copies/mL, and on-treatment viral load decline was 5.683 Log(10)copies/mL. The median half-life of free virus was 24.89 hours. The median half-life of infected hepatocytes was 7.39 days. The viral decay patterns were visualized as triphasic curves with decreasing slopes over time: fastest decay in the first phase; slowest in the third phase; the second phase in between. CONCLUSIONS: In the present study, mathematical modeling of hepatitis B in patients with virological response and HBsAg decline during 24-week antiviral therapy showed triphasic viral dynamics with direct introduction of immune effectors as a new compartment, which was thought to reflect the reduction of clearance rate of infected cells over time. This modeling method seems more appropriate to describe long-term viral dynamics compared to the biphasic model, and needs further validation.

Full Text

Duke Authors

Cited Authors

  • Kim, HY; Kwon, H-D; Jang, TS; Lim, J; Lee, H-S

Published Date

  • 2012

Published In

Volume / Issue

  • 7 / 11

Start / End Page

  • e50377 -

PubMed ID

  • 23209728

Pubmed Central ID

  • PMC3508925

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0050377

Language

  • eng

Conference Location

  • United States