M. Oketani et al., Low level wild-type and pre-core mutant hepatitis B viruses and HBeAg negative reactivation of chronic hepatitis B, J MED VIROL, 58(4), 1999, pp. 332-337
A qualitative and a quantitative mutation-site specific polymerase chain re
action assay (MSSA) was used to detect low level wild-type and pre-core mut
ant hepatitis B virus (HBV)-DNA. Serum samples from 11 anti-hepatitis B e (
anti-HBe)-positive asymptomatic HBV carriers (Group A) and 10 anti-HBe-posi
tive chronic hepatitis B patients who achieved alanine transaminase (ALT) n
ormalization after antiviral therapy (Group B) were tested. Eleven patients
had both wild-type and pre-core mutant HBV-DNA (52%, 4 from Group A and 7
from Group B), whereas 3 patients had only pre-core mutant HBV-DNA (14%, 2
from Group A and 1 from Group B) by qualitative MSSA assay. During a 3-year
follow-up period, relapses were observed in 3 patients from Group B and in
termittent ALT elevation was observed in 4 patients from Group A and 3 pati
ents from Group B. The wild-type HBV-DNA concentration in the patients with
reactivation was 10(2.06+/-2.62) copies/ml, whereas that in all patients w
ithout reactivation was below 10(2) copies/ml (P < .05). The pre-core mutan
t HBV-DNA concentration in the patients with reactivation was also signific
antly higher than that in the patients without reactivation (10(3.94+/-2.25
) vs. 10(0.65+/-1.45) copies/ml, P < .001). All patients with both HBV-DNA
concentrations below 102 copies/ml did not exhibit reactivation. Our result
suggest that a high prevalence of coexistence of low level wild-type and p
re-core mutant HBV-DNA has the potential for reactivation in anti-HBe-posit
ive patients. Furthermore, quantification of wild-type and pre-core mutant
HBV-DNA was useful to predict the prognosis of anti-HBe-positive infection
and evaluate the efficacy of antiviral therapy. J. Med. Virol. 58:332-337,
1999. (C) 1999 Wiley-Liss, Inc.