Dynamics of hepatitis B virus infection in vivo

Abstract

Background/Aims: 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 6.09×10 11 virions/day (range 0.26 to 21.06×10 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.