[Mechanisms of the effect of interferon (IFN) therapy in patients with type B and C chronic hepatitis]

Abstract

The relationship between 2', 5'-oligoadenylate synthetase (2-5AS) and HLA class I antigen in the hepatocyte of patients with type B or type C chronic hepatitis with and without interferon (IFN) therapy was investigated. The expression of HLA class I antigen of hepatocytes of biopsied specimen and PBL HLA class I antigen expression showed relevancy. Then, the HLA antigen expression of peripheral blood lymphocyte (PBL) and the 2-5AS activity of peripheral blood mononuclear cell (PBMC) were analyzed. In patients with type B or type C hepatitis, the mean activity of PBMC 2-5AS was significantly higher than that of healthy controls. Also the HLA class I antigen expression of PBL was significantly intense in patients with type B or type C hepatitis compared with healthy controls. In the acute exacerbated phase of type B chronic hepatitis, the HLA class I antigen expression of PBL and 2-5AS activity of PBMC increased along with elevation of serum GPT and then decreased with the remission of serum GPT. These results suggest that endogenously produced IFN leads the lysis of hepatocyte infected with hepatitis B virus (HBV) by cytotoxic T cells, and the restriction of HBV replication by activation of the 2-5A system simultaneously, and then leads the elimination of HBV. The activity of PBMC 2-5AS and the expression of PBL HLA class I antigen increased significantly during IFN therapy. In type B chronic hepatitis, the effective cases showed relatively high activity of serum 2-5AS compared with the non-effective cases. On the other hand, there were no significant differences in PBL HLA class I antigen expression between effective cases and non-effective cases. In type C chronic hepatitis, most patients with type III and type IV HCV genotype showed disappearance of HCV-RNA regardless of serum 2-5AS activity. In patients with type II HCV genotype, the serum 2-5AS activity was related to the anti-viral effect of IFN therapy.