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

我们建立了HCV基因型（HCVI、II、III和IV）的分类方法。大多数患者被发现感染HCVII和HCVIII。干扰素治疗对HCVIII患者（完全缓解率：约60%）比HCVII患者（20%）明显更有效。为了研究不同基因型患者对治疗反应差异的机制，我们采用竞争性PCR法测定了血清中HCV的含量。HCV在HCVIII患者中的含量明显低于HCVII患者。研究HCV基因型在肝病不同阶段的发病率。重度疾病的HCVII患病率略高于轻度疾病，而HCVIII患病率则相反，但差异不大。不同阶段肝病患者的HCV含量无明显差异。HCV的E2/NS1区被认为是突变率最高的区域。我们测定了5例患者E2/NS1区的核苷酸序列，发现在同一血清中存在许多不同的突变体（准异体性质）。一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则完全没有变化。这种HCV变异率的不同可能归因于宿主免疫反应的不同，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.