兰州地区HCV疑似2i/2a基因重组变异病例与干扰素α应答关系的探讨

Cases of hepatitis C virus infection with 2i/2a recombination genotype in the Lanzhou area and effects of related genetic variations on interferon alpha response

目的 探讨兰州地区9例丙型肝炎患者5＇-非编码区（5＇-NCR）和C区基因型变异及与干扰素α（IFN α）疗效的关系.方法 应用限制性内切酶分析和NCBI基因分型方法检测9例经IFN α-2b治疗的HCV感染患者的5＇-NCR和C区基因型,筛选HCV前后基因型不一致的病例. 结果 9例IFNα治疗的丙型肝炎患者中,5例获得持续病毒学应答,其中2例HCV基因型为2a型,3例为无MboⅠ切点的1b型.4例IFNα抵抗的病例,其中1例HCV基因型为2a型,但存在着1b与2a混合状态;另1例HCV 5 ＇-NCR为2i基因型,C区和NS5区为2a基因型;其余2例HCV 5＇-NCR和C区均为1b型.9例IFNα抗病毒治疗的丙型肝炎患者中,除HCV基因型为2型的患者之外,在HCV 1型患者中,-221bp位点均为无MboⅠ切点株,在这7例普通IFα无效病例中,改用聚乙二醇IFN α-2a联合利巴韦林抗病毒治疗后,其中5例HCV RNA阴转,阴转率为71.4‰ 结论 兰州地区经普通IFNα治疗无效的HCV患者中存在基因型前后不一致现象,基因重组患者经聚乙二醇IFN α-2a联合利巴韦林治疗持续病毒学应答率明显优于普通IFNα联合利巴韦林.

Objective To investigate Lanzhou area cases of hepatitis C virus （H-CV） infection with a 5＇-non coding region （NCR） 2i genotype and core （C）,envelope protein （E） and non-structural protein （NS5） 2a genotype and the relationship with therapeutic response to interferon-alpha （IFNα）.Methods Nine patients who received IFNα-based treatment for HCV between 2007 and 2009 at the Second People＇s Hospital of Gansu Province were selected for analysis.Restriction enzyme analysis was carried out for the 5＇-NCR and sequencing was carried out for the other gene areas.The relationship between genetic variants and IFNαresponse was examined.Results Of the total nine HCV cases treated with IFNα-based therapies,five of the patients achieved sustained virological response （SVR）,which included two cases with type 2 genotype and three cases with no MboI restriction enzyme point of tangency （i.e.type 1b）.The remaining four patients that did not achieve SVR included one case of type 2a,with a 1b and 2a mixed state,and one case with 5＇-NCR 2i genotype and C area,NS5 area 2a genotype; the other two cases had 5＇-NCR and C area type 1b.Of the five cases with 5＇-NCR 2i genotype,all had C 2a genotype and two had C/E 2a and NS5 2a genotypes.The seven patients that showed no response to ordinary IFNα were converted to long-term IFNα plus ribavirin combination antiviral treatment; five （71.4%） of the cases showed response in HCV RNA level and the patients treated with the pegylated form showed greater response.Conclusion HCV genotyping can only provide information on the particular region of gene sequence examined,and it is important to sequence all gene regions where mutations related to antiviral drug response are located.Peg-IFNα-2a combined with ribavirin may achieve better therapeutic effect in patients infected with 2i/2a recombinant forms of HCV.