Us. Akarca et al., DETECTION OF PRECORE HEPATITIS-B VIRUS MUTANTS IN ASYMPTOMATIC HBSAG-POSITIVE FAMILY MEMBERS, Hepatology, 19(6), 1994, pp. 1366-1370
Precore hepatitis B virus mutants have been detected mainly in HBeAg-n
egative patients with active liver disease. We previously reported two
novel mutations: M(1) (C-to-T change at nucleotide 1856 [proser at co
don 15]) and M(3) (G-to-A change at nucleotide 1898 [gly-ser at codon
29]) in addition to two well-described mutations: M(2) (G-to A change
at nucleotide 1896 [trp-stop at codon 28]); and M(4) (G-to-A change at
nucleotide 1899 [gly-asp at codon 29]) in Chinese patients. The aims
of this study were to determine (a) the prevalence of precore HBV muta
tions in asymptomatic carriers and (b) whether family members share th
e same mutated sequence as the index patients. Fifty-three index patie
nts and 89 HBsAg-positive family members were studied by means of dire
ct sequencing of polymerase chain reaction-amplified hepatitis B virus
DNA. M(o), a conserved mutation (T-to-C at nucleotide 1858, codon 15)
, was detected in 81% and 12% family members of index patients with an
d without M(o), respectively (p < 0.0001). The clustering of M(o) indi
cates that most subjects were infected through intrafamilial transmiss
ion. M(1) was detected in ah the family members of patients with M(1)
but in none of the family members of patients with wild-type or M(2) s
equences (p < 0.0001). M(2) was detected in 25%, 0% and 15% of family
members of patients with M(2), M(1), and WT sequences, respectively (p
= 0.19). M(3) was detected in five and M(4) in four family members. M
(1) was equally distributed among HBeAg-positive and HBeAg-negative fa
mily members, 19.5% vs. 9% (p = 0.34), whereas M(2) was detected more
frequently in HBeAg-negative family members: 45.5% vs. 4.5% in HBeAg-p
ositive family members (p < 0.0001). Ten (77%) of 13 family members wi
th M(2) and all 15 family members with M(1) had normal serum aminotran
sferase levels. The family members with M(2) were significantly older
than those with wild-type or M(1) sequences (mean ages, respectively,
37.9 +/- 5, 23 +/- 1.4 and 24.1 +/- 3 yr; p = 0.0005). In addition, M(
2) was more frequently detected in family members who were older than
the index patients. Longitudinal studies documented progression from w
ild-type sequence to M(2) in some family members, but progression from
wild-type to M(1) or M(1) to M(2) was not observed. Our data showed t
hat precore HBV mutants can be detected in 33% asymptomatic carriers.
M(1) appears to be present at the onset of infection, whereas M(2) eme
rges (from wild-type but not M(1)) during the course of infection. Ini
tiation of infection with M(2) only seems to be rare.