HBV前S基因突变与HBV感染者慢加急性肝衰竭的相关研究  

The Correlation Between HBV S Mutation and Chronic Acute Liver Failure in HBV Infected Patients

作　　者：马建和 徐飞[1,2] 王雅杰 MA Jian-he;XU Fei;WANG Ya-jie(Beijing Ditan Hospital Capital Medical University,Beijing 100015,China;Beijing Institute of Infectious Diseses of Combication of Chinese Trditional and Western Medicine,Beijing 100015,China)

机构地区：[1]首都医科大学附属北京地坛医院检验科,北京100015 [2]北京市中西医结合感染性疾病研究所,北京100015

出　　处：《标记免疫分析与临床》2018年第10期1460-1463,共4页Labeled Immunoassays and Clinical Medicine

摘　　要：目的探讨HBV前S区位点变异与慢加急性肝衰竭(acute-on-chronic liver failure,ACLF)之间的关系。方法共收集80例患者样本,其中40例HBV相关ACLF患者为研究组,40例慢性乙型肝炎(chronic hepatitis B,CHB)患者为对照组。采用聚合酶链反应及基因测序的方法对患者血清标本的HBV前S区基因位点突变进行检测,分析ACLF发生与HBV前S区位点突变的关系。结果 CHB患者病毒载量平均值为1. 18×105copies/m L,ACLF患者病毒载量平均值为1. 03×107copies/m L;对照组中的CHB患者基因型均为C型。ACLF患者基因型分别为B型14例(14/40),C型26例(26/40)。共有27个核苷酸位点在ACLF患者发生显著变异,其中I108F、I108M、C120M、A158V和A172V为ACLF常见突变位点。在40例ACLF患者中的突变发生率分别为62. 5%(25/40)、55%(22/40)、65%(26/40)、77. 5%(31/40)、67. 5%(27/40),显著高于CHB患者(P <0. 05 F=31. 6,P=0. 0432);对HBV患者B、C基因型的突变分析发现,I108M、A158V这2个位点在B基因型ACLF组中突变显著高于CHB组;I108F、V154A和A172V这3个突变在C基因型ACLF组中显著高于CHB组。I108(M/F)、A158V这2个位点突变在B基因型显著高于C基因型CHB患者。ACLF组中的C2875、G3191、C105位点变异高于CHB组。HBV相关的ACLF患者与CHB患者在ALT水平升高方面无明显差异。总胆红素水平及凝血酶原活动度比值两者差异具有统计学意义(P <0. 05 F=24. 31,P=0. 046;P <0. 01 F=85. 68,P=0. 006)。结论HBV基因中I108(M/F)与A158V核苷酸突变与ACLF密切相关;HBV S区的突变对于ACLF发生起着重要作用,可为ACLF的发病提供重要的参考依据。Objective To investigate the association between Pre- S mutations and the development of acute- on- chronic liver failure （ACLF）in patients with chronic HBV infection. Methods A total of 80 patients were enrolled in the study,and 40 patients with acute- on- chronic liver failure （ACLF）as the research object,while 40 patients with chronic hepatitis B （CHB）as the control group.The mutations at HBV Pre- S were determined by the nested polymerase chain reaction and direct sequencing methods. Results In chronic hepatitis B patients,the viral load average was 1.18×10 5 copies/ml,while acute- on- chronic liver failure patient had mean value of 1.03×10 7 copies/mL.All the control group patients with chronic hepatitis B had the genotypes of C,while acute- on- chronic liver failure patients had the genotype B in cases （14/40）,C type in 26 cases （26/40）.A total of 27 amino acid sites had significant mutations for patients with acute- on- chronic liver failure,in which I108F I108M,C120M,A158V,and A172V were ACLF common mutations.The mutation rate with ACLF was 62.5% （25/40）,55% （22/40）,65% （26/40）,77.5%（31/40）,and 67.5% （27/40）,respectively in 40 patients.ACLF mutation rate was significantly higher than in patients with chronic mild hepatitis（ P 〈0.05 F =31.6, P =0.0432.ACLF nucleotide mutation rate was higher than that of CHB;In patients with HBV B,C genotypes,the mutation analysis found that I108F,I108M,and A158V loci of type B gene mutations in ACLF group were significantly higher than that of CHB group;while I108F,V154A and A172V loci of ACLF mutant in C group was significantly higher than that of CHB group.The two loci of A158V and I108 （M/F）in type B genotype was significantly higher than C HBV infection group.For patients with HBV- ACLF,the ALT aminotransferase levels had no differences compared with patients with HBV.Both the total bilirubin level and thrombin activity ratio had significant differences between groups （ P 〈0.05, F =24.31, P =0.046; P 〈0.01, F =85

关 键 词：乙型肝炎病毒 慢加急性肝衰竭 点突变 

分 类 号：R512.62[医药卫生—内科学] R575.3[医药卫生—临床医学]