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（HCV）是导致肝细胞癌（HCC）的重要病原体。另一方面，长江沿岸地区是中国HCC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的关联信息，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。这些患者大多为乙型肝炎病毒（HBV）感染，但抗- hcv和HCV-RNA的发生率很低，在供者血液中仅为0.7%，在慢性肝病患者中为11.6%。此外，我们的研究结果揭示了基因型II和基因型II的高流行率，中国和日本的HCV分离株具有相似性，HCC患者的HCV核心基因核苷酸（nt）替换的趋势比HCV核心基因替换的趋势在HCC患者中比慢性肝炎患者多。此外，nt取代不均匀地分散在基因组上，在核心区域5'端第2亲水结构域出现了一组错义突变和翻转。聚类可变区（CVR）的错义突变和翻转发生率高于其他核心区。这些发现提示CVR中发生的突变可能与宿主免疫系统的选择性压力有关，并且与肝脏疾病向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.