Type B fulminant hepatitis is closely associated with a highly mutated hepatitis B virus strain.
OBJECTIVE
Genome-wide sequences of hepatitis B virus strain associated with type B fulminant hepatitis have not been compared with those of acute self-limited hepatitis. We carried out full-length sequencing analysis of viral strains derived from patients with type B acute liver injury.


METHODS
Nine acute self-limited hepatitis and 6 fulminant hepatitis patients were the subjects of this study. Full-length sequencing analysis of viral DNA was done by PCR-direct sequencing.


RESULTS
Higher frequencies in fulminant hepatitis strains compared with acute hepatitis ones were observed in the T1762/A1764 (p < 0.05), A1896 (p = 0.09) and M1753 (M = C or A) (p = 0.09) mutations. Viruses related to fulminant hepatitis possessed the higher number of nucleotide substitutions than those related to acute hepatitis in the whole virus genome (p < 0.01) and various regions including preS/S gene (p < 0.05), precore/core gene (p < 0.01), polymerase gene (p < 0.05) and basic core promoter/core upstream regulatory sequence (p < 0.01). The high number of nucleotide substitutions in viruses related to fulminant hepatitis was predominantly non-synonymous in the preS/S and precore/core genes.


CONCLUSIONS
Development of type B fulminant hepatitis may be associated with a highly mutated hepatitis B virus strain.
Kanada
Aimi
A
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Takehara
Tetsuo
T
Ohkawa
Kazuyoshi
K
Tatsumi
Tomohide
T
Sakamori
Ryotaro
R
Yamaguchi
Shinjiro
S
Uemura
Akio
A
Kohga
Keisuke
K
Sasakawa
Akira
A
Hikita
Hayato
H
Hijioka
Taizo
T
Katayama
Kazuhiro
K
Deguchi
Matsuo
M
Kagita
Masanori
M
Kanto
Tatsuya
T
Hiramatsu
Naoki
N
Hayashi
Norio
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D003062:Codon / Q000235:genetics*; D004279:DNA, Viral / Q000032:analysis / Q000737:chemistry; D005260:Female; D016679:Genome, Viral; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D017114:Liver Failure, Acute / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA
D003062:Codon; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens