Chronic active hepatitis with hepatitis B virus DNA and antibody against e antigen in the serum. Disturbed synthesis and secretion of e antigen from hepatocytes due to a point mutation in the precore region.
Some patients with type B chronic active hepatitis have a high titer of hepatitis B virus DNA despite antibody against e antigen in the serum. Clones of hepatitis B virus were propagated from the sera of seven patients with this disease, and the precore region was sequenced. Essentially all clones (128/131 or 98%) showed a point mutation from guanine to adenine at nucleotide 83, converting codon 28 for tryptophan (TGG) to a stop codon (TAG); the second guanine-to-adenine point mutation at nucleotide 86 was identified in only 29 clones from two patients. In patients followed up since they had hepatitis B e antigen, a shift from guanine to adenine was observed at nucleotide 83 along with the seroconversion to the antibody to e antigen. The precore-region product is required for the synthesis and secretion of e antigen from hepatocytes. A point mutation from guanine to adenine at nucleotide 83 observed in the seven patients, therefore, would be responsible for disturbed secretion of e antigen.
Akahane
Y
Y
First Department of Internal Medicine, Yamanashi Medical College, Japan.
Yamanaka
T
T
Suzuki
H
H
Sugai
Y
Y
Tsuda
F
F
Yotsumoto
S
S
Omi
S
S
Okamoto
H
H
Miyakawa
Y
Y
Mayumi
M
M
D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000097:blood*; D006509:Hepatitis B / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006521:Hepatitis, Chronic / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens