Study on the effects of hepatites B virus X-gene expression on hepato-carcinogenesis.

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In patients with type B chronic hepatitis, X protein was expressed in cytoplasm of hepatocyte. The distribution of X protein-positive hepatocytes was correlated with that of HBcAg-positive ones. Furthermore, serum HBV DNA levels of X protein-positive patients were significantly higher than those of X protein-negative ones, suggesting that X protein which was expressed in liver tissue might enhance the replication of HBV in vivo. When we examined three cases of patients with type B hepatocellular carcinoma (HCC), X protein was not expressed in cancerous region of all three patients, but was expressed in non-cancerous region of two of three patients. These findings suggested that X protein had some relations to a early stage of hapato-carcinogenesis. However, it was unlikely that X protein might function to maintain HCC. Furthermore, in patients with type B chronic hepatitis and liver cirrhosis, the frequency of the expression of c-myc was significantly higher in patients with X protein … More than that without X protein. However, the distribution of X protein was different from that of c-myc. Therfore, at present, it is unclear whether, in patients with type B chronic liver disease, the expression of oncogenes such as c-myc and c-Ha-ras were directly induced by X protein or indirectly induced as a result of inflammation. From this point of view, further study is necessary.Moreover, we examined a relationship between HBV replication and the ability of HBV-infected hepatocytes to express HLA antigen, using HB611 cell line which was developed from HUH6 cell line by integrating HBV-DNA. In this cell line, X protein was observed in peri-nuclear cytoplasm. Pretreatment of this HB611 with acyclocir to inhibit HBV replication increased the expression of HLA class I antigen on HB611, suggesting that HBV replication might suppress the expression of HLA antigen. Decreased expression of HLA antigen might impair the ability of immunosurveillance system to recognize antigens and is considered to have some relations to malignancy. Further study is necessary to be concluded. Less