Detection of precore-mutant hepatitis B virus genome in patients with acute and fulminant hepatitis using mutation site-specific assay (MSSA).
OBJECTIVE
Precore mutation of hepatitis B virus was recently been suggested to be involved in the pathogenesis of fulminant hepatitis. In this study, we analyzed the occurrence of precore mutants in patients with acute and fulminant hepatitis B using new simple rapid and sensitive MSSA (mutation site-specific assay) and evaluated this method for predicting prognosis.


METHODS
We analyzed HBV-DNA of 10 patients with fulminant hepatitis B, 15 patients with acute self-limited hepatitis, and 4 patients with acute severe hepatitis using MSSA. Precore point mutation (G to A; 83rd base of precore region) was examined using a mutation-trapped oligonucleotide primer, which would yield a polymerase chain reaction amplification product only with precore mutants.


RESULTS
We distinguished precore mutants from wild type according to the presence or absence of the band at 203 bp, which was amplified in only precore mutants by polymerase chain reaction. Mutation of the precore region was observed in all 10 patients with fulminant hepatitis, in 3 of the 4 patients with severe hepatitis, and 11 of 15 patients with self-limited hepatitis. Negative pre-C mutants in patients with HBeAg indicates good prognosis of hepatitis.


CONCLUSIONS
Precore mutant strains of HBV-DNA play an important role but are not specific for fulminant hepatitis, and the mere presence of precore mutants may not directly lead to fulminant hepatitis or severe hepatitis. However, this method is useful for predicting outcome of patients with acute HBV hepatitis, especially in HBeAg-positive state.
Shiraki
Katsuya
K
First Department of Internal Medicine, Mie University School of Medicine, Tsu 514-8507, Japan. katsuyas@clin.medic.mie-u.ac.jp
Hamada
Minoru
M
Sugimoto
Kazushi
K
Ito
Takeshi
T
Yamanaka
Takenari
T
Wagayama
Hidetaka
H
Shimizu
Atsuya
A
Makino
Yukirou
Y
Takase
Koujirou
K
Nakano
Takeshi
T
Tameda
Yukihiko
Y
D000293:Adolescent; D000328:Adult; D005260:Female; D016679:Genome, Viral; D006509:Hepatitis B / Q000235:genetics* / Q000401:mortality; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008297:Male; D016297:Mutagenesis, Site-Directed; D011379:Prognosis