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

在西方国家和日本，丙型肝炎病毒是导致肝细胞癌的重要病原体。另一方面，长江沿岸地区是中国地区肝癌发病率最高的地区之一。因此，为了获得关于该地区存在的丙型肝炎病毒分离株的基因组特征与肝细胞癌之间的关系的信息，我们调查了该地区慢性肝病患者和肝细胞癌患者中丙型肝炎病毒的患病率和基因组异质性。这些患者大多感染了乙肝病毒，但抗-丙型肝炎病毒和丙型肝炎病毒核糖核酸的感染率很低，在供者血液中占0.7%，在慢性肝病患者中占11.6%。此外，我们的结果逆转了高流行的II型和II型，中国和日本的丙型肝炎病毒分离株具有相似性，并且肝细胞癌患者的丙型肝炎病毒核心基因有比慢性肝炎患者更多的核苷酸(NT)替换的趋势。此外，在核心区5‘端的第二亲水结构域中，NT替换不均匀地分布在基因组中，存在一系列错义突变和颠换。聚集性可变区(CVR)错义突变和颠换的发生率高于其他核心区。这些发现表明，CVR中发生的突变可能与来自宿主免疫系统的选择性压力有关，并与肝病向肝细胞癌的进展密切相关。

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.