title: Mathematical modeling of triphasic viral dynamics in patients with HBeAg-positive chronic hepatitis B showing response to 24-week clevudine therapy.
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 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.
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hwi Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Hee-Dae
authors.initials: HD
authors.lastname: Kwon
authors.forename: Tae Soo
authors.initials: TS
authors.lastname: Jang
authors.forename: Jisun
authors.initials: J
authors.lastname: Lim
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003198:Computer Simulation; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D006511:Hepatitis B Antigens / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000378:metabolism; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D007107:Immune System; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D012044:Regression Analysis; D013997:Time Factors; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006511:Hepatitis B Antigens; D001086:Arabinofuranosyluracil; C034935:clevudine