Moriishi Kohji, Matsuura Yoshiharu
Department of Molecular Virology Research Institute for Microbial Diseases, Osaka University 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Uirusu. 2007 Dec;57(2):141-9. doi: 10.2222/jsv.57.141.
Hepatitis C virus (HCV) infects approximately 170 million people worldwide including 2 million in Japan and induces serious chronic hepatitis that results in the development of steatosis, cirrhosis and ultimately hepatocellular carcinoma. The current combination therapy using pegylated interferon alpha and a nucleotide analogue ribavirin achieved a sustained virological response in about half population of individuals infected with HCV genotypes la and lb. More than two-thirds of the HCV-positive population has been chronically infected with genotype 1 in Western countries and Japan. Therefore, more effective therapeutics and preventative measures are needed for the treatment of hepatitis C patients who are not responsive to the current chemotherapy. HCV core protein is well known to be the viral capsid protein as well as the pathogenic factor that induces steatosis and hepatocellular carcinoma in the transgenic mice. In this review, we summarize the current status of our knowledge regarding the molecular mechanism by which HCV core protein induces liver steatosis and hepatocellular carcinoma and discuss on a future perspective for the development of novel therapeutics for chronic hepatitis C.
丙型肝炎病毒（HCV）在全球约感染1.7亿人，其中日本有200万人感染，它会引发严重的慢性肝炎，进而导致脂肪变性、肝硬化，最终发展为肝细胞癌。目前使用聚乙二醇化干扰素α和核苷酸类似物利巴韦林的联合疗法，在约一半感染HCV 1a型和1b型的个体中实现了持续病毒学应答。在西方国家和日本，超过三分之二的HCV阳性人群长期感染1型。因此，对于对当前化疗无反应的丙型肝炎患者，需要更有效的治疗方法和预防措施。HCV核心蛋白是众所周知的病毒衣壳蛋白，也是在转基因小鼠中诱导脂肪变性和肝细胞癌的致病因子。在本综述中，我们总结了目前关于HCV核心蛋白诱导肝脂肪变性和肝细胞癌分子机制的知识现状，并讨论了慢性丙型肝炎新型治疗方法开发的未来前景。
