Relationship of HCV genotypes and mutations to progression of liver disease and response to therapy

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We established the method to classify HCV genotypes (HCVI, II, III, and IV). Most of the patients were found to be infected with HCVII and HCVIII.Interferon therapy was significantly more effective in the patients with HCVIII (complete response rate : approximately 60%) than in those with HCVII (20%). To investigate the mechanism of difference in response to therapy among genotypes, we determined the amount of HCV in sera using competitive PCR method. The amount of HCV was significantly smaller in the patients with HCVIII than in those with HCVII.The rates of HCV genotypes in different stages of liver diseases were investigated. The rate of HCVII was slightly higher in the severe diseases than in the mild, and the reverse is true in HCVIII, while those differences were thin. The amount of HCV was not different among the patients with different stages of liver diseases.E2/NS1 region of HCV is regarded to be the region with the highest mutation rates. We determined the nucleotide sequences of E2/NS1 region in five patients, and found that many different mutants were present in the same serum (quasispesies nature). The nucleotide sequences were rapidly changed in some patients, while they did not changed at all in the others this different in the mutation rates of rates of HCV may be attributed to the difference in the host immune response, and the investigation is progress.