The mechanism of development of chronicity after acute hepatitis B infectio
n has not been elucidated fully. Following a single source outbreak of hepa
titis B among 79 adult women, three patients (4%) became chronic carriers o
f hepatitis B virus (HBV). We compared features of the virus and antibody r
esponse of the latter three patients with those of 12 HBeAg-positive cases
with resolving infection. The virus genotype was D, antigenic subtype ayw(2
). Base sequence analysis of S- and C-gene regions revealed no differences
between the two groups. During the acute illness the three patients who dev
eloped chronicity had a remarkable transient reduction of HBsAg, HBeAg, and
HBV DNA levels at 14-20 weeks after infection, the time of HBeAg seroconve
rsion in the patients who cleared the infection. One HBeAg-specific monoclo
nal antibody (HBOT.95A) used as solid-phase antibody in a sandwich enzyme i
mmunoassay detected an increased HBeAg signal in 2 of the 3 patients that d
eveloped chronicity and in 1 of the 12 patients who recovered. The latter p
atient had an exceptional long period of HBsAg antigenemia. Standard HBeAg
assays detected HBeAg in all cases. HBeAg and anti-HBe-positive serum sampl
es from the patients who recovered could inhibit the HBOT.95A response. The
results suggest that chronic hepatitis B develops after an interruption of
immune clearance. Differentiation of the antibody response to HBeAg may he
lp to find patients with an increased risk for this interrupted immune clea
rance who might be candidates for an early intervention therapy. (C) 1999 W
iley-Liss, Inc.