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Mathematical Modeling of Triphasic Viral Dynamics in Patients with HBeAg-Positive Chronic Hepatitis B Showing Response to 24-Week Clevudine Therapy

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  • Hwi Young Kim
  • Hee-Dae Kwon
  • Tae Soo Jang
  • Jisun Lim
  • Hyo-Suk Lee

Abstract

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 Log10copies/mL, and on-treatment viral load decline was 5.683 Log10copies/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.

Suggested Citation

  • Hwi Young Kim & Hee-Dae Kwon & Tae Soo Jang & Jisun Lim & Hyo-Suk Lee, 2012. "Mathematical Modeling of Triphasic Viral Dynamics in Patients with HBeAg-Positive Chronic Hepatitis B Showing Response to 24-Week Clevudine Therapy," PLOS ONE, Public Library of Science, vol. 7(11), pages 1-8, November.
    • Handle: RePEc:plo:pone00:0050377
    DOI: 10.1371/journal.pone.0050377
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    1. Alan S. Perelson & Paulina Essunger & Yunzhen Cao & Mika Vesanen & Arlene Hurley & Kalle Saksela & Martin Markowitz & David D. Ho, 1997. "Decay characteristics of HIV-1-infected compartments during combination therapy," Nature, Nature, vol. 387(6629), pages 188-191, May.
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