Integrated studies for inhibition of progression of chronic hepatitis Cleading to hepatocellular

本研究从临床和分子水平阐明其抑制慢性丙型肝炎进展和抑制肝细胞癌的作用机制。对丙型肝炎病毒的分子分析表明，NS5A区具有反式激活功能，Rac-1、核糖体蛋白、Rab4和MIF等肝细胞蛋白已结合在NS5A区。干扰素的疗效与该NS5A区的突变数有关，尤其是在2209~2248之间。此外，E2/NS1和NS5B区的氨基酸序列突变与干扰素治疗后慢性肝炎的加重有关。此外，尽管最近发展了对GBV-C的分析，但在肝细胞中几乎没有检测到GBV-C的负链。多中心研究表明，丙型肝炎病毒载量和亚型是预测干扰素治疗疗效的重要因素，不仅干扰素清除丙型肝炎病毒核糖核酸，生化反应也能降低肝细胞癌的发病率，尤其是F3期的肝硬变前期患者。在这些患者中，几年后组织学也有改善。AFP组分、DCP、MAGE-4的动态检测除定期超声检查外，还可提供早期发现肝癌的线索。

Present study was conducted to clarify the mechanisms for inhibition of progression of chronic hepatitis C and for suppression of hepatocellular carcinoma from the clinical and molecular points of views. The molecular analysis on the HCV revealed that NS5A region have transactivating function, where hepatocyte proteins of Rac-1, ribosomal protein, Rab4 and MIF have been found to bind. Efficacy of interferon (IFN) was related to the number of mutation of this NS5A region, especially ranging from nt 2209 to nt 2248. In addition, mutation of amino acid sequence was accumulated in the region of E2/NS1 and NS5B in association with the aggravation of chronic hepatitis after IFN therapy. In addition, although an analysis on GBV-C has been developed recently, a minus strand of GBV-C was scarcely detected in hepatocytes. These data suggested that this GBV-C have little effect on the progression of liver disease leading to HCC from the clinical point of view.Multicentered studies on analysis of role of IFN on suppression of HCC were performed, indicating that HCV viral load and subtypes are important factors for predicting the efficacy of IFN therapy, and that not only the eradication of HCV RNA by IFN but biochemical response were found to reduce the incidence of HCC,especially precirrhotic patients of stage F3. Among these patients, histological improvement was also demonstrated several years later. For earlier detection of HCC,serial measurement of AFP fraction, DCP and MAGE-4 may provide clue in addition to periodical check up using ultrasonography.