HIGH-DEGREE OF CONSERVATION IN THE HEPATITIS-B VIRUS CORE GENE DURINGTHE IMMUNE TOLERANT PHASE IN PERINATALLY ACQUIRED CHRONIC HEPATITIS-BVIRUS-INFECTION
H. Bozkaya et al., HIGH-DEGREE OF CONSERVATION IN THE HEPATITIS-B VIRUS CORE GENE DURINGTHE IMMUNE TOLERANT PHASE IN PERINATALLY ACQUIRED CHRONIC HEPATITIS-BVIRUS-INFECTION, Journal of hepatology, 26(3), 1997, pp. 508-516
Background: Mutations in the hepatitis B virus genome have been implic
ated in the persistence of hepatitis B virus infection and the pathoge
nesis of hepatitis B virus related liver disease, In view of the heter
ogeneity in published sequences, data from cross-sectional studies of
unrelated subjects cannot differentiate true mutations from infections
with variant sequences. Aims/Methods: We compared the hepatitis B vir
us core gene sequences of 42 HBsAg positive subjects from 11 Chinese f
amilies with those of the index patients (maternal carriers) to determ
ine the frequency and rate of true hepatitis B virus core gene mutatio
ns in patients with chronic hepatitis B virus infection. Results: Comp
letely identical nucleotide sequences were present in all the family m
embers and index patients in two families, suggesting that the hepatit
is B virus core gene can be conserved for more than 20 years, The high
degree of sequence conservation in these families is related to the y
oung age of the subjects (mean 19.2 +/- 8.9 years), the fact that they
were all HBeAg positive and that 75% of them had persistently normal
aminotransferase levels. Longitudinal studies confirmed that mutations
were rare in those who remained HBeAg positive with normal aminotrans
ferase levels (immune tolerant phase), but significantly more common i
n HBeAg positive subjects who had elevated aminotransferase levels and
in those who cleared HBeAg (immune clearance phase), the rates of nuc
leotide and amino acid changes were respectively: 0.28 +/- 0.12 vs 1.3
0 +/- 0.26/103 nt position/yr and 0.04 +/- 0.01 vs 0.18 +/- 0.5/10(2)
codon/yr. Conclusions: Identical nucleotide differences could be found
in the sequences of all the subjects in some families, These differen
ces were more likely to be due to intra-familial transmission of stabl
e variants, Sequence analysis based on comparisons with published sequ
ences would have led to over-reporting of mutations, The hepatitis B v
irus core gene can remain highly conserved for more than two decades d
uring the immune tolerant phase of perinatally acquired chronic hepati
tis B virus infection, However, significant changes can occur within 2
-3 years during the immune clearance phase.