Hepatitis B virus strains with mutations in the core promoter in patients with fulminant hepatitis.
OBJECTIVE
Fulminant hepatitis B can be induced by hepatitis B virus (HBV) strains with mutations in the precore region that cannot encode hepatitis B e antigen (HBeAg). Such mutations are rarely seen in HBV DNA clones from patients with fulminant hepatitis B in the United States and France. Thus, the other mutations in HBV strains causing fulminant hepatitis B need to be identified.


METHODS
Retrospective clinical, serologic, and molecular biological studies of patients with fulminant hepatitis B.


METHODS
University and city hospitals in Japan.


METHODS
43 patients with fulminant hepatitis B.


METHODS
The precore region coding for a part of the HBeAg precursor and the core promoter regulating the transcription of precore messenger RNA were sequenced in HBV DNA clones.


RESULTS
A point mutation from G to A at nucleotide 1896 in the precore region was detected in 519 (98%) of 529 HBV DNA clones from 38 patients. Two point mutations in the core promoter, from A to T at nucleotide 1762 and from G to A at nucleotide 1764, were detected in all 130 clones from the remaining 5 patients, who did not have mutations in the precore region, and in 20 (63%) of 32 clones from a patient with chronic hepatitis B who had transmitted HBV to 1 of these other 5 patients. Mutations in the core promoter were also detected in clones from 26 (68%) of the 38 patients with the precore mutation at nucleotide 1896. Neither HBeAg nor antibody to HBeAg was detected in 37 (90%) of the 41 patients tested.


CONCLUSIONS
In Japan, fulminant hepatitis B is closely associated with HBV strains that do not produce HBeAg because of mutations in the precore region, which affect translation of HBeAg, or because of mutations in the core promoter, which affect transcription of the HBeAg coding region.
Sato
S
S
Iwate Medical University, Iwate-Ken, Japan.
Suzuki
K
K
Akahane
Y
Y
Akamatsu
K
K
Akiyama
K
K
Yunomura
K
K
Tsuda
F
F
Tanaka
T
T
Okamoto
H
H
Miyakawa
Y
Y
Mayumi
M
M
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006509:Hepatitis B / Q000821:virology*; D006513:Hepatitis B e Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies
D004279:DNA, Viral; D006513:Hepatitis B e Antigens