Chen Yan, Michitaka Kojiro, Matsubara Hiroshi, Yamamoto Kazuhisa, Horiike Norio, Onji Morikazu
Third Department of Internal Medicine, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan.
J Hepatol. 2003 Jan;38(1):84-90. doi: 10.1016/s0168-8278(02)00325-2.
BACKGROUND/AIMS: There is a paucity of information regarding hepatitis B virus (HBV) from patients with fulminant hepatitis (FH) without precore (pre-C, nt 1896) and core promoter (CP, nt 1762, 1764) mutations.
Pre-C and CP mutations were studied in eight patients with FH and 26 patients with acute hepatitis (AH) due to HBV. One patient with FH (FH1) was infected with HBV without these mutations. Interestingly, the sera of the infectious source (IS1) and of a patient with AH (AH1) infected from IS1 were available. Complete HBV genomes from these three patients were analyzed.
These mutations were found in seven of eight FH and five of 26 AH (P<0.01). HBV from FH1, IS1 and AH1 belonged to genotype D. Nucleotide difference between FH1 and AH1 was six of 3182 bases (nt 493, 998, 1173, 2928, 3067, and 3078). Two and five substitutions of deduced amino acid sequences were found in the pre-S1 and polymerase regions, respectively. The same nucleotide substitutions at nt 493, 1173, 2928 and 3067 were found in several patients with FH in our laboratory or GenBank.
These six nucleotide substitutions of HBV DNA could be candidates of mutations relating to FH.
背景/目的:关于暴发性肝炎(FH)患者中无前核心(前C区,第1896位核苷酸)和核心启动子(CP区,第1762、1764位核苷酸)突变的乙型肝炎病毒(HBV)的信息匮乏。
对8例FH患者和26例因HBV导致的急性肝炎(AH)患者进行前C区和CP区突变研究。1例FH患者(FH1)感染的HBV无这些突变。有趣的是,有感染源(IS1)的血清以及1例由IS1感染的AH患者(AH1)的血清可供研究。对这3例患者的完整HBV基因组进行了分析。
在8例FH患者中有7例、26例AH患者中有5例发现了这些突变(P<0.01)。FH1、IS1和AH1的HBV属于D基因型。FH1和AH1之间的核苷酸差异为3182个碱基中的6个(第493、998、1173、2928、3067和3078位核苷酸)。在前S1区和聚合酶区分别发现了2个和5个推导氨基酸序列的替换。在我们实验室或GenBank的几例FH患者中也发现了第493、1173、2928和3067位核苷酸相同的替换。
HBV DNA的这6个核苷酸替换可能是与FH相关的突变候选位点。