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Virological features of hepatitis C virus infection in patients with liver diseases in a high risk region for hepatocellular carcinoma in China

我国肝细胞癌高发地区肝病患者丙型肝炎病毒感染的病毒学特征

基本信息

批准号：
05670480
负责人：
ITO Susumu
金额：
$ 1.34万
依托单位：
University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670480/
关键词：
hepatitis C virus hepatocellular carcinoma molecular biology anti-HCV HCV-RNA China

项目摘要

Hepatitis C virus (HCV) is an important causative agent for hepatocellular carcinoma (HCC) in Western countries and Japan. On the other hand, the inshore area of the Yangtze River is known to have one of the highest incidences of HCC in China. Therefore, to obtain information on the association between HCC and the genomic characteristics of HCV isolates present in this region, we investigated the prevalence and the genomic heterogeneity of HCV in patients with chronic liver disease and HCC in this region. Most of such patients were infected by hepatitis B virus (HBV), but the incidence of anti-HCV and HCV-RNA were very low, observed with 0.7% in donor bloods, and 11.6% in patients with chronic liver diseases. Moreover, our results reveraled a high prevalence of genotype II,a genotype II,a similarity of Chinese and Japanses HCV isolates, and a tendency for more nucleotide (nt) substitutions in the HCV core gene in HCC patients than in those substitutions in the HCV core gene in HCC patients than in those with chronic hepatitis. In addition, nt substitutions were unevenly scattered along the genome with a cluster of missense mutations and transversions in the second hydrophilic domain from the 5'end of the core region. The rates of the occurrence of missense mutations and transversions were greater in the clustering variable region (CVR) than in the other core region. These findings suggested that the mutations occurring in this CVR may be responsible for a selective pressure from the host immune system, and closely related with progress of liver disease to HCC.

丙型肝炎病毒（HCV）是西方国家和日本肝细胞癌（HCC）的重要病原体。另一方面，长江沿岸地区是中国肝癌发病率最高的地区之一。因此，为了获得 HCC 与该地区 HCV 分离株基因组特征之间关联的信息，我们调查了该地区慢性肝病和 HCC 患者中 HCV 的患病率和基因组异质性。此类患者大多感染乙型肝炎病毒（HBV），但抗HCV和HCV-RNA的发生率很低，在供血中为0.7%，在慢性肝病患者中为11.6%。此外，我们的结果显示，HCC 患者的基因型 II、基因型 II、中国和日本 HCV 分离株的相似性以及 HCC 患者 HCV 核心基因中核苷酸 (nt) 取代的趋势高于慢性肝炎患者。此外，nt 取代沿着基因组分布不均匀，在核心区域 5' 端的第二个亲水结构域中存在一系列错义突变和颠换。聚类可变区（CVR）中错义突变和颠换的发生率高于其他核心区。这些发现表明，该CVR中发生的突变可能是来自宿主免疫系统的选择性压力的原因，并且与肝病进展为HCC密切相关。