Genetic heterogeneity in the precore region of hepatitis B virus in hepatitis B e antigen-negative chronic hepatitis B patients: spontaneous seroconversion and interferon-induced seroconversion.
To elucidate the relationship between the clinical severity of chronic liver disease and the precore mutations in hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) carriers, mutations were investigated in the precore region of HBV DNA in 20 chronic hepatitis B patients who seroconverted either spontaneously or after the administration of alpha-interferon (IFN), and 5 asymptomatic carriers. The precore mutation with a stop codon at nucleotide 1896 was found in all patients, irrespective of the histology and in all asymptomatic carriers. The second mutation at nucleotide 1899 was found in 40% of cases studied but always followed by the first mutation at nucleotide 1896. The mixed viral infection of precore mutant and wild-type HBV virus was found in 40% of seroconverted cases after IFN treatment and in sera of HBV carriers obtained within a year after the spontaneous seroconversion. These data suggest that the precore mutants prevail over wild-type HBV in all HBeAg-negative HBV carriers within several years after the seroconversion, but their prevalence could not confine the clinical severity of chronic liver disease.
Karasawa
T
T
First Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Aizawa
Y
Y
Zeniya
M
M
Kuramoto
A
A
Shirasawa
T
T
Toda
G
G
D000328:Adult; D000368:Aged; D001483:Base Sequence; D002353:Carrier State / Q000821:virology; D016022:Case-Control Studies; D002908:Chronic Disease; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D006509:Hepatitis B / Q000453:epidemiology / Q000628:therapy / Q000821:virology*; D006510:Hepatitis B Antibodies / Q000097:blood* / Q000235:genetics; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D015995:Prevalence; D011994:Recombinant Proteins; D013728:Terminator Regions, Genetic
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D007370:Interferon Type I; D011994:Recombinant Proteins