Clinical relevance of precore and basal core promoter variants of hepatitis B virus during natural hepatitis B e antigen seroconversion may be overstated.
BACKGROUND
Clinical relevance of nucleotide changes in precore and basal core promoters in the hepatitis B virus genome during hepatitis B e antigen seroconversion may be overstated. The authors investigated the existence and changes in the relative proportion of variants to wild virus that occur with seroconversion.


METHODS
Sera from 30 school-aged long-term hepatitis B virus carriers, including 11 tested before and after seroconversion during 1 to 8 years of follow-up, were evaluated for variations in nucleotide sequences of the basal core promoter (T1762 and A1764), precore region (A1869), and carboxyl-terminus of the X region of the hepatitis B virus genome using an amplification refractory mutation detection system with mutant-specific primers.


RESULTS
All variants were found to already exist before seroconversion at various wild-type/mutant ratios. The positive rates of these variants were not changed with loss of hepatitis B e antigen. Although there was a relative increase in the concentration of these mutants in wild-type/mutant mixed populations, most patients with only a wild-type population maintained the same pattern after loss of hepatitis B e antigen.


CONCLUSIONS
Our results indicate that hepatitis B virus exists as a quasi species, and correlations of nucleotide sequences with clinical and serologic findings must be done with caution.
Fukuda
R
R
Second Department of Internal Medicine, Shimane Medical University, Izumo-city, Shimane, Japan. rfukuda@shimane-u.ac.jp
Mohammad
R
R
Hamamoto
S
S
Ishimura
N
N
Ishihara
S
S
Akagi
S
S
Watanabe
M
M
Kinoshita
Y
Y
D000293:Adolescent; D002648:Child; D003430:Cross-Sectional Studies; D017931:DNA Primers; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D014644:Genetic Variation; D016679:Genome, Viral; D006509:Hepatitis B / Q000276:immunology / Q000821:virology*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011401:Promoter Regions, Genetic; D012680:Sensitivity and Specificity
D017931:DNA Primers; D006513:Hepatitis B e Antigens