肝移植术后丙型肝炎病毒基因型及HVR1序列动态研究

目的通过对一例丙型肝炎肝硬化肝移植术后病人的HCV-HVR1区基因变异的持续一年动态研究,探讨肝移植对HCV基因变异的影响;方法用限制性酶切片段多态性方法测定其HCV基因型;用PCR产物直接测序法研究HCV-HVR1区基因序列随时间推移发生的动态变化。结果肝移植术后患者基因型无变化,仍为1b型;HVR1区核苷酸序列变异程度不大,可能与其应用免疫抑制剂有关;氦基酸序列在术后8个月至13个月时非同义突变率增幅很大,与患者免疫功能逐步恢复有关。结论HVR1区序列变异与患者免疫状态关系密切。

Objective To investigate the effects of post-liver-transplantation immune state to the hepatitis C virus （HCV） gene variaton, the hypervariable region 1（HVR1）gene variation of a recurrent case of HCV infection was studied dynamicty during a year after hepatic transplantation. Methods The patient＇s sample were genotyped by the PCR- RFLP analysis of 5＇ NCR region. The cDNAs of HCV-HVR1 derived from the samples were directly sequenced by dideoxynucleotide chain termination method to study their dynamic variation. Results The genotypes of the patient after hepatic transplantation have no variation and were all 1b; the variation degree of HVR1 sequence was low and maybe relate to the immunodeprssant application; but the amplification of the non-synonymous mutation of amino acid sequence is obvious during the 8 to 13 months after transplantation, this phenomenon maybe concerned with the gradual recovery of the immune function. Conclusion These observations suggest that the variation of HVR1 sequence is closely relate to the immune state of the patient.