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目的 了解HCV慢性感染过程中高变区序列变化及其临床意义。方法 对 8例急性丙肝及 2 0例慢性丙肝随访 2年 ,相隔半年抽血 ,用逆转录多聚酶联反应及直接序列法分析不同时期HCV HVR的序列变化。结果 2 8例丙肝的HVR序列均有不同程度的变化 ,92 %变化的核苷酸导致相应氨基酸的变化 ,仅 8%为同义替换 ,2 7个氨基酸的每年变化范围为 1～ 2 0 ,平均 8个 (30 % ) ,HVR密码子中 ,以第一及第二变化最为常见 ,分别为 6 2 %及 31%。急性肝炎年基因位点为 0 .89× 10 -1,慢性丙肝年基因位点为 2 .31× 10 -1,两者有统计意义。年基因位点与HCV亚型无关。ALT反复波动者的HVR变异率明显高于ALT相对稳定者。结论 在HCV感染过程中 ,HVR序列变化可能是HCV为逃避人体免疫系统作用的一种适应性反应 ,在HCV持续感染及肝炎发作中 ,可能也起着主要的作用
Objective To understand the sequence change of hypervariable region in chronic HCV infection and its clinical significance. Methods 8 cases of acute hepatitis C and 20 chronic hepatitis C were followed up for 2 years and blood was collected for half a year. The sequence changes of HCV HVR in different periods were analyzed by reverse transcriptase polymerase chain reaction and direct sequencing. Results HVR sequences of 28 hepatitis C patients all had different degrees of change. 92% of the nucleotide changes resulted in the corresponding amino acid changes, with only 8% being synonymous substitutions. The 27 amino acids varied from 1 to 20 years per year, With an average of 8 (30%), the first and second changes were the most common HVR codons, 62% and 31% respectively. The annual gene locus of acute hepatitis was 0.89 × 10 -1 and the locus of chronic hepatitis C was 2.31 × 10 -1, both of which had statistical significance. The annual gene locus is not related to the HCV subtype. The mutation rate of HVR in those with repeated volatility was significantly higher than that of ALT. Conclusions During the course of HCV infection, HVR sequences may be an adaptive response to HCV’s escape from human immune system and may play a major role in HCV persistent infection and hepatitis attack