Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection.
The outcome of acute hepatitis B virus (HBV) infection is variable, influenced by host and viral factors. From 1982 through 2004, 301 patients with acute HBV infection entered a multi-center cross-sectional study in Japan. Patients with fulminant hepatitis (n = 40) were older (44.7 +/- 16.3 vs. 36.0 +/- 14.3 years, P < .0017), less predominantly male (43% vs. 71%, P = .0005), less positive for hepatitis B e antigen (HBeAg) (23% vs. 60%, P < .0001), less infected with subgenotype Ae (0% vs. 13%, P < .05), and more frequently with Bj (30% vs. 4%, P < .0001) than those with acute self-limited hepatitis (n = 261). Precore (G1896A) and core-promoter (A1762T/G1764A) mutations were more frequent in patients with fulminant than acute self-limited hepatitis (53% vs. 9% and 50% vs. 17%, P < .0001 for both). HBV infection persisted in only three (1%) patients, and they represented 2 of the 23 infected with Ae and 1 of the 187 with the other subgenotypes (9% vs. 0.5%, P = .032); none of them received antiviral therapy. In multivariate analysis, age 34 years or older, Bj, HBeAg-negative, total bilirubin 10.0 mg/dL or greater, and G1896A mutation were independently associated with the fulminant outcome. In in vitro transfection experiments, the replication of Bj clone was markedly enhanced by introducing either G1896A or A1762T/G1764A mutation. In conclusion, persistence of HBV was rare (1%) and associated with Ae, whereas fulminant hepatitis was frequent (13%) and associated with Bj and lack of HBeAg as well as high replication due to precore mutation in patients with acute HBV infection.
Ozasa
Atsushi
A
Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Tanaka
Yasuhito
Y
Orito
Etsuro
E
Sugiyama
Masaya
M
Kang
Jong-Hon
JH
Hige
Shuhei
S
Kuramitsu
Tomoyuki
T
Suzuki
Kazuyuki
K
Tanaka
Eiji
E
Okada
Shunichi
S
Tokita
Hajime
H
Asahina
Yasuhiro
Y
Inoue
Kazuaki
K
Kakumu
Shinichi
S
Okanoue
Takeshi
T
Murawaki
Yoshikazu
Y
Hino
Keisuke
K
Onji
Morikazu
M
Yatsuhashi
Hiroshi
H
Sakugawa
Hiroshi
H
Miyakawa
Yuzo
Y
Ueda
Ryuzo
R
Mizokami
Masashi
M
D000208:Acute Disease; D000328:Adult; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006509:Hepatitis B / Q000453:epidemiology / Q000821:virology*; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011863:Radioimmunoassay; D012189:Retrospective Studies; D014758:Viral Core Proteins / Q000235:genetics*; D014779:Virus Replication
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D014758:Viral Core Proteins