DYNAMICS OF HEPATITIS-B VIRUS-INFECTION IN-VIVO

Background/Aims: Information on the kinetics of the pretreatment stead y-state of HBV can be obtained from serial measurements of serum hepat itis B virus (HBV) DNA concentrations following lamivudine ((-)enantio mer of 3'-thiacytidine)-induced perturbation of the balance between vi rus production and clearance, Methods: In a placebo-controlled, dose-r anging trial, lamivudine (5 to 600 mg per day) was administered for 4 weeks to 17 patients with chronic replicative hepatitis B, Serum HBV D NA levels were quantified by standard liquid hybridization techniques, The time-dependent concentrations of serum HBV DNA following lamivudi ne 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 res ponding 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 6.0 9x10(11) virions/day (range 0.26 to 21.06x10(11) virions/day). Compare d 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, respectiv ely, Four weeks after termination of lamivudine treatment, the relativ e amount of HBeAg was 1.04+/-0.19. Conclusions: The half-life of HBV i n chronically infected patients is longer and in vivo turnover rates a re higher compared to recently published data on the human immunodefic iency virus type 1 and the hepatitis C virus, The constant expression of HBeAg observed in the present study during a 28-day lamivudine trea tment period does not allow calculation of a definite decay rate for v irus-producing cells, Our data, however, imply that the minimum half-l ife of infected cells may exceed 100 days.