不同感染状态下乙型肝炎病毒反转录酶区准种异质性特点及其临床意义  

Characteristics of quasispecies heterogeneity in reverse transcriptase region of hepatitis B virus at different phases and its clinical significance

作　　者：刘斐 刘春涛 傅晓晴[1] 武瑞 武静 刘寿荣 LIU Fei;LIU Chun-tao;FU Xiao-qing;WU Rui;WU Jing;LIU Shou-rong(Department of Severe Liver Disease,Hangzhou Xixi Hospital ffiliated to Zhejiang University School of Medicine,Hangzhou,Zhejiang 310023,China;不详)

机构地区：[1]浙江大学医学院附属杭州市西溪医院重症肝病科,浙江杭州310023 [2]浙江大学医学院附属杭州市西溪医院肝病实验室,浙江杭州310023

出　　处：《中国卫生检验杂志》2022年第13期1594-1598,1610,共6页Chinese Journal of Health Laboratory Technology

基　　金：浙江省医药卫生科技计划项目(2022KY276);杭州市医药卫生科技计划项目(0020190542)。

摘　　要：目的研究乙型肝炎病毒(HBV)感染不同状态下血清病毒反转录酶(RT)区准种异质性特点及临床意义。方法纳入2019年1月-2021年6月本院就诊治疗的24例患者为研究对象,其中慢性乙型病毒性肝炎(CHB)患者12例和慢加急性肝衰竭(ACLF)患者12例,留取2组患者抗病毒治疗前血清标本,比较2组患者抗病毒治疗前准种异质性差异点,采用Pearson相关性分析准种异质性与HBV DNA病毒载量、基因型的相关性。结果ACLF患者的准种复杂度(包括核苷酸水平、氨基酸水平)和准种多样性(平均遗传距离平均同义替换数、平均非同义替换位数)均高于CHB患者,差异有统计学意义(P<0.001)。ACLF组B基因型患者准种平均遗传距离核苷酸水平平均同义替换数、平均非同义替换数高于C基因型患者,差异有统计学意义(P<0.05)。B基因型患者准种复杂度核苷酸水平高于C基因型患者异有统计学意义(P<0.05),准种复杂度氨基酸水平与C基因型患者比较,差异无统计学意义(P>0.05)。CHB.组患者平均遗传距离的氨基酸水平、复杂度的氨基酸水平与HBV DNA有相关性(r值分别为0.6335、0.5811,P<0.05)。结论ACLF患者的准种构成情况较CHB患者复杂,复杂的HBV准种分布特征可能导致肝衰竭发生。B基因型ACLF患者较C基因型患者具有更高的准种异质性,ACLF患者准种多样性、复杂度与HBV DNA载量之间无明显相关性。Objective To investigate the characteristics of quasispecies( QS) heterogeneity in reverse transcriptase( RT)region of hepatitis B virus( HBV) infection at different phases and its clinical significance. Methods A total of 24 patients with chronic HBV infections were enrolled in the present study,including 12 patients with chronic hepatitis B( CHB) and 12patients with acute-on-chronic liver failure( ACLF). Serum samples were collected from both groups before antiviral treatment. Differences of quasispecies heterogeneity before antiviral treatment were compared between the two groups. Pearson correlation analysis was applied to test the correlation between quasispecies heterogeneity with HBV DNA viral load and genotype.Results The quasispecies complexity( including nucleotide level and amino acid level) and the quasispecies diversity( mean genetic distance,mean synonymous substitution number and mean non-synonymous substitution number) in ACLF patients were higher than those in CHB patients,with the difference statistically significant( P < 0. 001). In ACLF group,the mean genetic distance in nucleotide level,mean synonymous substitution number and mean non-synonymous substitution number of patients with genotype B were higher than those with genotype C,with the differences statistically significant( P < 0. 05). The QS complexity in nucleotides level with genotype B in ACLF patients were higher than genotype C,with the differences statistically significant( P < 0. 05),and the level of QS complexity amino acids in patients with genotype B was higher than that with genotype C,but the difference is not statistically significant( P > 0. 05). In CHB group,the amino acid level of the mean genetic distance and complexity were correlated with HBV DNA( r = 0. 633 5, r = 0. 581 1, P < 0. 05).Conclusion The quasispecies composition of ACLF patients is more complex than that of CHB patients,and the complicated distribution characteristics of HBV quasispecies may lead to liver failure. The quasispecies heterogeneity of patients

关 键 词：慢性乙型肝炎 肝衰竭 准种 异质性 

分 类 号：R37[医药卫生—病原生物学]