[Study on efficacy and safety of lamivudine and interferon-alpha in treatment of hepatitis B virus transgenic mice with pregnancy].
OBJECTIVE
To observe the efficacy and safety of lamivudine and interferon-alpha (IFN-alpha) therapy on decrease of serum hepatitis B virus (HBV) loading of HBV transgenic mice during pregnancy.


METHODS
Thirty-five transgenic mice replicating high levels of hepatitis B virus were randomly allocated into 5 groups, each of seven. Pregnant HBV transgenic mice in experimental groups 1 and 2 were given orally lamivudine [100 mg/(kg x d)] from pregnancy day 5 or 10 to delivery, mice in experimental groups 3 and 4 were given intramuscular (im) injection of IFN-alpha [5MU/(m(2) x 2d)], and mice in experimental group 5 were given normal saline at the same times. The changes of serum HBsAg, HBV DNA before and after the treatment were detected. At the same time, eighteen C57BL/6J female mice (clean level) were randomly allocated into control groups 1, 2 and 3 (each group of six), which were given lamivudine, IFN-alpha and saline respectively (the dosage was the same as that of experimental groups). The safety indexes of pregnant mice, fetus and newborns in experimental groups and control groups were observed.


RESULTS
(1) The changes of serum HBsAg titers: The average serum HBsAg titers from mice in experimental group 1 were lowered significantly from (166 +/- 98) ng/ml to (82 +/- 59) ng/ml after drug treatment (P < 0.05). Those from mice in experimental group 2 were also reduced from (159 +/- 49) ng/ml to (82 +/- 60) ng/ml after drug treatment, but there was no significant difference between before and after the treatment (P > 0.05). There was no significant difference in serum HBsAg between before and after the treatment in other groups (P > 0.05). (2) The changes of HBV DNA titers: The serum HBV DNA titers from mice in experimental groups 1 and 2 were significantly decreased, from (5.50 +/- 0.86) copies/ml to (2.58 +/- 2.01) copies/ml, with significant difference between before and after the treatment (P < 0.01). Those from mice in experimental groups 3 and 4 were reduced from (5.55 +/- 0.24) copies/ml to (5.46 +/- 0.45) copies/ml, without significant difference between before and after the treatment (P > 0.05). The serum HBV DNA titer from mice in experimental group 5 was not different between before and after the treatment (P > 0.05). (3) Observation of safety indexes: no evidence in toxicity were observed in mice from experimental groups and control groups. No significant abnormalities of live fetus were observed. The postnatal survival and weight of live pups were not different between the groups (P > 0.05). (4) Comparison of the rate of dead fetus and the rate of maternal dead fetus: The rate of dead fetus and the rate of maternal dead fetus from mice in experimental groups 1 and 2 were 8.3% and 50.0% respectively, those from mice in experimental groups 3 and 4 were 8.2% and 66.7% respectively, and those from mice in experimental group 5 were 9.7% and 66.7%. There was no significant difference in the rate of dead fetus and the rate of maternal dead fetus from mice between the groups (P > 0.05).


CONCLUSIONS
Effective lamivudine treatment during gestation can reduce hepatitis B viremia in pregnant HBV transgenic mice, thus lowering the risk of intrauterine infection. It has no significant adverse effect on safety of pregnant mice and their offspring.
Li
Duan
D
Department of Epidemiology, Fourth Military Medical University, Xi'an 710032, China.
Yan
Yong-ping
YP
Xu
De-zhong
DZ
Men
Ke
K
Zhang
Jing-xia
JX
Lei
Xiao-ying
XY
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy* / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D011897:Random Allocation; D019562:Viral Load / Q000187:drug effects
D000998:Antiviral Agents; D016898:Interferon-alpha; D019259:Lamivudine