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

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，为了获得关于HCC和该地区HCV分离株基因组特征之间相关性的信息，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。这些患者大多数是B肝炎病毒（HBV）感染者，但抗-HCV和HCV-RNA的检出率很低，献血员仅为0.7%，慢性肝病患者为11.6%。此外，我们的研究结果逆转了高流行率的基因型II，基因型II，中国和日本的HCV分离株的相似性，和更多的核苷酸（nt）替换在HCC患者的HCV核心基因比那些替换在HCC患者的HCV核心基因比那些慢性肝炎。此外，nt取代不均匀地沿基因组分布沿着，在核心区5 '端的第二个亲水结构域中存在一簇错义突变和颠换。错义突变和颠换的发生率在聚集可变区（CVR）比在其他核心区域更大。这些结果表明，该CVR中发生的突变可能是宿主免疫系统选择性压力的原因，并与肝脏疾病向HCC的进展密切相关。

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.