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

我们建立了丙型肝炎病毒基因分型方法(HCVI、II、III和IV)。大多数患者被发现感染了丙型肝炎病毒和丙型肝炎病毒。干扰素治疗对丙型肝炎病毒感染者(完全应答率：大约60%)比丙型肝炎病毒感染者(20%)有效得多。为探讨不同基因型别治疗反应差异的机制，我们采用竞争性聚合酶链式反应方法检测了血清中的丙型肝炎病毒含量。丙型肝炎患者的丙型肝炎病毒载量明显低于丙型肝炎患者。重症患者的HCVII感染率略高于轻度患者，而在HCVIII患者中则相反，但这些差异很小。不同肝病分期患者的丙型肝炎病毒含量无明显差异，丙型肝炎病毒E2/NS1区被认为是变异率最高的区域。我们测定了5例患者的E2/NS1区核苷酸序列，发现同一血清中存在多个不同的突变(准特异性)。有些患者的核苷酸序列发生了快速变化，而另一些患者的核苷酸序列没有发生变化。这种不同的变异率可能是由于宿主免疫反应的差异所致，研究正在进行中。

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.