兰州地区HCV基因变异与干扰素免疫应答关系的探讨.doc

兰州地区HCV 基因变异与干扰素-α应答关系的探讨 张文杰1 杜绍财2 饶慧瑛2 李朝霞 1甘肃省第二人民医院感染科，2 北京大学人民医院，北京大学肝病研究所 [摘要] 目的 探讨兰州地区丙型肝炎病毒（HCV）1b基因型5’非编码区（5’NCR）基因变异株的感染状态，及其与干扰素-α疗效的关系。方法 应用限制性内切酶酶切分析检测40例HCV 1b型中5’-NCR基因变异，以及9例干扰素-α治疗患者中的5’-NCR基因变异。结果 在40例HCV 1b型中存在5种感染状态（1）有Mbo I切点24/40（60.0%）（2）无Mbo I切点变异株5/40（12.5%）（3）有Mbo I和无Mbo I切点混合感染株7/40（17.5%）（4）有BamH I切点变异株2/40（5%）（5）有Mbo I双切点变异株2/40（5%）。9例干扰素-α治疗的丙型肝炎患者中，5例获得持续病毒学应答（SVR），4例无应答，对其进行5’-NCR变异株检测。其检测结果表明，5例干扰素-α应答病例中，2例为2a型，3例为无MboI切点的1b型。4例抗干扰素-α病例中，1例为2a型，但在某节段存在着1b与2a混合状态，另3例为无MboI。结论 本文研究结果提示，在丙型肝炎患者血清中存在单一的Mbo I切点的样品，24/40（60.0%）可能是HCV野生株感染的状态本文报道的9例干扰素-α抗病毒的丙肝病人中，除2型之外，在1型中，-221位均为无Mbo I切点株，在这7例普通干扰素-α无效病例中，改用长效干扰素-α联合抗病毒治疗后，其中5例HCV RNA阴转，相当于71.4%。[关键词]；基因；干扰素-α Lanzhou and the Interferon-α Induced Immune Response ZHANG Wen-jie1, DU Shao-cai2, RAO Hui-ying2 ,LI Zhao-xia1 （1 Second Peoples Hospital of Gansu Province，Lanzhou 7300002 Hepatology Institute, Peking University People’s Hospital, Beijing 100044）【Abstract】Objective To study the relationship between gene mutation of 5’ noncoding region (5’NCR) of hepatitis C virus (HCV) genotype 1b with infection state interferon-alpha (IFN-α) therapy effect of chronic hepatitis C. Methods Sera of 9 patients were collected before, during and after IFNα therapy and sera of 40 HCV 1b patients were collected. HCV 5’NCR fragments were amplified from these samples by use of RT-PCR assay and sequenced after using restriction endonuclease Mbo I and BamH I. Results There were 5 infection states of 40 HCV 1b patients: (1) 24 patients (24/40, 60.0%) with Mbo I restriction site, (2) 5 patients’ (5/40, 12.5%) variant without Mbo I restriction site, (3) 7 patients’ (7/40, 17.5%) coinfection variant with and without of Mbo I restriction site, (4) 2 patients’ (2/40, 0.5%) variant with BamH I restriction site, (5) 2 patients’ (2/40, 0.5%) variant with two Mbo I restriction sites. In the 5 patietns with sustained virological response (SVR), 2 for HCV genotype 2a, 3 for HCV genotype 1b without Mb