Association of hepatitis B viral precore mutations with fulminant hepatitis B in Japan.
We studied the precore DNA sequences of hepatitis B viral genomes in five patients with fulminant hepatitis B and in five with acute self-limited hepatitis B from Japan. Using the polymerase chain reaction, three to four independent HBV DNA clones from each patient were obtained and analyzed. We demonstrated that patients with fulminant hepatitis B carried HBV genomes with a G to A mutation at nucleotide positions 1898 (five of five patients; 18 of 18 clones, 100%) and 1901 (five of five patients; 12 of 18 clones, 66%) in the precore region. The first mutation results in an in-phase stop codon (TAG) in the precore open reading frame and the absence of HBeAg production. In contrast, a G to A mutation was found in 6 of 16 clones (37%) in position 1898 and in 0 of 16 clones (0%) in position 1901 from patients with acute self-limited hepatitis. We concluded that both of the precore mutations are commonly associated with fulminant hepatitis B and may contribute to the pathogenesis of fulminant hepatitis. A hypothetical model for the biological significance of these two mutations is proposed.
Department of Medicine, Harvard Medical School, Massachusetts General Hospital Cancer Center, Charlestown 02129.
K
K
Hasegawa
J K
JK
Huang
J R
JR
Wands
H
H
Obata
T J
TJ
Liang
D000328:Adult; D001483:Base Sequence; D003001:Cloning, Molecular; D005260:Female; D016679:Genome, Viral; D006509:Hepatitis B / Q000382:microbiology* / Q000503:physiopathology; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D015183:Restriction Mapping
D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D007075:Immunoglobulin M; D009838:Oligodeoxyribonucleotides