慢性重型乙型肝炎患者血清病毒全长基因特点及其临床意义  

The characterization of serum hepatitis B virus full-length genome in chronic severe hepatitis B patients and its clinical significance

作　　者：黄素园[1] 于德敏[1] 刘峰[1] 陈立[1] 韩悦[1] 李新华[1] 张欣欣[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院感染科,200025

出　　处：《中华传染病杂志》2011年第7期401-405,共5页Chinese Journal of Infectious Diseases

摘　　要：目的 探讨血清HBV全长基因组的准种特性及其与慢性乙型肝炎（CHB）重症化的关系.方法 未接受过抗病毒治疗的CHB、慢性重型乙型肝炎（CSHB）各4例患者,扩增外周血清中HBV全长基因组并克隆、测序,每个标本选取14～16个克隆进行DNA测序及生物信息学分析.计量资料采用独立样本t检验,计数资料采用x2检验.结果 CHB组和CSHB组8例患者共获得120个HBV全长基因组序列.每例患者均为单一基因B型或C型感染.两组全长克隆序列中均发现G1896A突变、A1762T/G1764A、T1753C/G突变,以及前S2区、前S1区起始密码子缺失,CSHB组1例患者还发现A1762T/G1764A/C1766T突变,CSHB组发生一个或多个突变的克隆数占100.0%（60/60）,明显多于CHB组的76.7%（46/60）（x2=15.85,P〈0.01）.在核苷酸和氨基酸水平上,CSHB组的全长基因组、S基因、X基因、P基因和反转录酶编码序列区的准种复杂度和平均遗传距离均比CHB组大,C基因的则比CHB组小,但差异均无统计学意义.结论 慢性重型乙型肝炎患者血清中HBV的各种突变率及准种异质性差异均大于慢性乙型肝炎患者,可能与CHB重症化有关,值得扩大样本进一步研究其临床意义.Objective To characterize serum hepatitis B virus（HBV）full-length genome quasispecies and to investigate its ralationship with severe exacerbation of chronic hepatitis B（CHB）.Methods HBV full-length genome was amplified and cloned from four treatment naive CHB patients and four treatment naive CSHB patients.Fourteen to sixteen clones per sample were selected,sequenced and analyzed by bioinformatics software.The measurement data was compared by independent-samples t test and count data was analyzed by x2 test. Results Totally 120 HBV fulllength genome sequences were obtained.All the patients had either genotype B or C virus monoinfection.One hundred percent clones（60/60）from CSHB patients showed mutations including G1896A,A1762T/G1764A（one patient even carried A1762T/G1764A/C1766T mutations）,T1753C/G and start codon mutations in preS2,preS1,which were more common than those from CHB patients（46/60,76.7%;x2=15.85,P〈0.01）.The quasispecies complexity and diversity were higher in CSHB patients than CHB patients within full-length genome,S,X,P genes and reverse transcriptase region,but lower within C gene at both nucleotide and amino acid levels.But the difference were not statistically significant in all regions.Conclusion The mutation frequency and quasispeeies heterogeneity in HBV genome are higher in CSHB patients than in CHB patients,which may play a role in the severe exacerbation of CHB and needs further investigation in large scale studies.

关 键 词：肝炎病毒 乙型 肝炎 乙型 慢性 突变 遗传异质性 重型肝炎 准种 

分 类 号：R512.62[医药卫生—内科学]