Dynamics of hepatitis B virus infection in vivo

doi:10.1016/S0168-8278(97)80345-5

Journal of Hepatology

Volume 27, Issue 3, September 1997, Pages 431-436

https://doi.org/10.1016/S0168-8278(97)80345-5 Get rights and content

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 6.09×10¹¹ virions/day (range 0.26 to 21.06×10¹¹ 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.

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Dynamics of hepatitis B virus infection in vivo

Abstract

Hepatology

J Biol Chem

Biophys J

Gastroenterology

J Hepatol

J Biol Chem

EMBO J

The molecular biology of the hepatitis B viruses

Annu Rev Biochem

Molecular virology and pathogenesis of hepatitis B

Lancet

Hepatitis B virus DNA in the sera of HBsAg carriers: a marker of active hepatitis B virus replication in the liver

Hepatology

HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy

Science

Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection

Nature

HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time

Science

Viral dynamics in human immunodeficiency virus type 1 infection

Nature

Inhibition of the replication of hepatitiss B virus in vitro by 2′,3′-dideoxy-3′-thiacytidine and related analogues

Proc Natl Acad Sci USA

Mechanism of inhibition of duck hepatitis B virus polymerase by (−)-beta-L-2′,3′-dideoxy-3′-thiacytidine

Antimicrob Agents Chemother