title: Dynamics of hepatitis B virus infection in vivo.
abstract: OBJECTIVE
  Information on the kinetics of the pretreatment steady-state of HBV can be obtained from serial measurements of serum hepatitis B virus (HBV) DNA concentrations following lamivudine ((-)enantiomer of 3'-thiacytidine)-induced perturbation of the balance between virus production and clearance.
  
  
  METHODS
  In a placebo-controlled, dose-ranging trial, lamivudine (5 to 600 mg per day) was administered for 4 weeks to 17 patients with chronic replicative hepatitis B. Serum HBV DNA levels were quantified by standard liquid hybridization techniques. The time-dependent concentrations of serum HBV DNA following lamivudine administration were subjected to iterative least-squares regression in order to obtain kinetic data on HBV life-time and viremia.
  
  
  RESULTS
  In patients with stable HBe-antigen positive chronic hepatitis B responding to lamivudine, HBV DNA declined exponentially with a half-life of approximately 2-3 days. The minimum virus production and clearance per day in patients with chronic hepatitis B was calculated to be 6.09 x 10(11) virions/day (range 0.26 to 21.06 x 10(11) virions/day). Compared to the HBeAg levels before treatment, relative amounts of HBeAg were 1.00 +/- 0.16 and 0.96 +/- 0.20 at days 22 and 28 of treatment, respectively. Four weeks after termination of lamivudine treatment, the relative amount of HBeAg was 1.04 +/- 0.19.
  
  
  CONCLUSIONS
  The half-life of HBV in chronically infected patients is longer and in vivo turnover rates are higher compared to recently published data on the human immunodeficiency virus type 1 and the hepatitis C virus. The constant expression of HBeAg observed in the present study during a 28-day lamivudine treatment period does not allow calculation of a definite decay rate for virus-producing cells. Our data, however, imply that the minimum half-life of infected cells may exceed 100 days.
authors.affiliation: Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt a.M., Germany.
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
authors.forename: R A
authors.initials: RA
authors.lastname: de Man
authors.forename: P
authors.initials: P
authors.lastname: Honkoop
authors.forename: W K
authors.initials: WK
authors.lastname: Roth
authors.forename: S W
authors.initials: SW
authors.lastname: Schalm
authors.forename: J M
authors.initials: JM
authors.lastname: Schmidt
mesh_terms: D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007700:Kinetics; D019259:Lamivudine / Q000627:therapeutic use*; D016018:Least-Squares Analysis; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine