Dynamics of hepatitis B virus infection in vivo.
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.
Zeuzem
S
S
Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt a.M., Germany.
de Man
R A
RA
Honkoop
P
P
Roth
W K
WK
Schalm
S W
SW
Schmidt
J M
JM
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*
D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine