Truong Bui Xuan, Yano Yoshihiko, Seo Yasushi, Phuong Tran Minh, Tanaka Yasuhito, Kato Hirotaka, Miki Akira, Utsumi Takako, Azuma Takeshi, Trach Nguyen Khanh, Mizokami Masashi, Hayashi Yoshitake, Kasuga Masato
Kobe University Graduate School of Medicine, Clinical Molecular Medicine, Kobe, Japan.
J Med Virol. 2007 Sep;79(9):1293-304. doi: 10.1002/jmv.20934.
Hepatitis B virus (HBV) subgenotypes Cs (C1) and Ce (C2) are common in East Asia. To investigate the genomic difference of HBV genotype C between two separated regions, 50 subgenotype Cs-infected Vietnamese and 70 subgenotype Ce-infected Japanese patients were enrolled for analysis. The patients were categorized to either a hepatocellular carcinoma group (HCC) or a non-HCC group including liver cirrhosis, chronic hepatitis, and asymptomatic carriers. HBV serology, HBV-DNA level, and variations in core promoter/pre-core region were examined. Phylogenetic analysis based on the full genome sequences and nucleotide sequences partly in the S gene and in the P gene revealed that all Japanese strains (70/70) were subgenotype Ce, and nearly all of the Vietnamese strains (50/51) were subgenotype Cs, excluding one subgenotype C5. C1858 and G1775 were common in the Vietnamese (64% and 40%) but not in the Japanese (0%). The prevalence of C/A1753 in Vietnamese was higher than that in the Japanese (32% vs. 17.1%), however the frequency of A1896 in the Japanese was significantly higher (32.9% vs. 12%, P < 0.05). Most of the Vietnamese patients with HCC had a high level of HBV-DNA, the Japanese HCC had a relatively low level. In the Vietnamese, C/A1753 and C1858 were associated closely with T1762A1764, higher HBV-DNA levels and higher HCC incidence. The multivariate analysis revealed that male, T1653 and C/A1753 were independent risk factors for HCC. The subgenotypes and unique mutations of HBV genotype C in the Vietnamese and Japanese differed, and C/A1753 and C1858 variants might play a role in the pathogenesis of liver disease in Vietnamese patients.
乙型肝炎病毒(HBV)C 亚型(C1)和 Ce 亚型(C2)在东亚地区较为常见。为了研究两个不同地区 HBV C 基因型的基因组差异,招募了 50 例感染 C 亚型的越南患者和 70 例感染 Ce 亚型的日本患者进行分析。这些患者被分为肝细胞癌组(HCC)或非 HCC 组,后者包括肝硬化、慢性肝炎和无症状携带者。检测了 HBV 血清学、HBV-DNA 水平以及核心启动子/前核心区的变异情况。基于全基因组序列以及 S 基因和 P 基因部分核苷酸序列的系统发育分析显示,所有日本毒株(70/70)均为 Ce 亚型,几乎所有越南毒株(50/51)为 C 亚型,仅排除 1 株 C5 亚型。C1858 和 G1775 在越南人中较为常见(分别为 64%和 40%),而在日本人中未出现(0%)。越南人中 C/A1753 的流行率高于日本人(32%对 17.1%),然而日本人中 A1896 的频率显著更高(32.9%对 12%,P < 0.05)。大多数越南 HCC 患者的 HBV-DNA 水平较高,而日本 HCC 患者的 HBV-DNA 水平相对较低。在越南人中,C/A1753 和 C1858 与 T1762A1764、更高的 HBV-DNA 水平以及更高的 HCC 发病率密切相关。多因素分析显示,男性、T1653 和 C/A1753 是 HCC 的独立危险因素。越南人和日本人中 HBV C 基因型的亚型和独特突变存在差异,C/A1753 和 C1858 变异可能在越南患者肝病发病机制中发挥作用。