Access & Contact

Project Chief.
Kunitada Shimotohno

Research Center for Hepatitis and Immunology National Center for Global Health and Medicine

Address:
1-7-1 Kohnodai Ichikawa 272-8516, Chiba, Japan

phone:
81-47-375-4742 (ext 1435)
81-47-375-4750 (direct)

fax:
81-47-375-4766

mail address:
kunitada.shimotohno@it-chiba.ac.jp


Researches

It is estimated that about 1.7 and 3 million people are infected with HCV and HBV, respectively, in the world. HCV frequently persists after infection and, subsequently, leads to cirrhosis and HCC. Persistent inflammation concomitant with HCV infection is thought to contribute to liver disease progression.It has not yet been demonstrated conclusively that HCV infection results in immortalization or transformation of in vitro cultured hepatocytes. In addition, HCV is rarely found in tumor cells derived from HCV-related cancer. Thus, it is thought that HCV is not solitary responsible for tumorigenesis. Rather, it seems to function/contribute and/or establish tumor prone-microenvironment in the pre-early stage(s) of tumorigenesis. Discovering the mechanisms by which persistent infection of HCV produces the appropriate microenvironment for tumor development would contribute significantly to our understanding of the tumorigenic activity of HCV.Patients with steato-hepatitis by excess dietary intake often develop liver disease. Meanwhile, hepatic steatosis is often seen in many HCV patients. It is noteworthy that they have similarities that excess lipid accumulates in liver and that HCC emerges from those with abnormal lipid metabolism and with high inflammation. Activating lipid metabolism seems to be required, at least in part, in establishing the microenvironment required for tumor initiation. It is unknown how HCV infection leads to altered regulation of lipid metabolism upon infection, while recent demonstration of the requirement of lipid droplet as well as of transfer mechanism of lipoprotein(s) on virus propagation has shed light on HCV infection/tumor initiation. This observation suggests that control of lipid metabolism is critical in regulating HCV propagation that, in turn, could prevent the development of liver disease.We have been focusing on elucidating methods capable of inhibiting persistent viral infection. Specifically we are investigating the mechanisms of activating host lipid metabolism, to reveal factors related to inflammation, and to determine the role of excess lipid metabolism on cell fate caused by HCV. Our ultimate aim is to establish methods of eliminating virus and of preventing virus-related liver diseases.