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印度东部急性乙型肝炎的病毒学特征:与慢性感染的关键差异

Virological Characteristics of Acute Hepatitis B in Eastern India: Critical Differences with Chronic Infection.

作者信息

Sarkar Neelakshi, Pal Ananya, Das Dipanwita, Saha Debraj, Biswas Avik, Bandopadhayay Bhaswati, Chakraborti Mandira, Ghosh Mrinmoy, Chakravarty Runu

机构信息

ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, West Bengal, India.

Department of Virology, Calcutta School of Tropical Medicine, Kolkata, West Bengal, India.

出版信息

PLoS One. 2015 Nov 16;10(11):e0141741. doi: 10.1371/journal.pone.0141741. eCollection 2015.

Abstract

Hepatitis B Virus (HBV) manifests high genetic variability and is classifiable into ten genotypes (A-J). HBV infection can lead to variable clinical outcomes, ranging from self-limiting acute hepatitis to active chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study characterizes HBV strains circulating among patients with acute (AHB) and chronic HBV infection (CHB). Among a total of 653 HBsAg positive cases, 40 manifested acute infection. After sequencing the surface(S), basal core promoter/pre-core(BCP/PC) and the X gene regions, phylogenetic tree was constructed using MEGA4 by neighbor-joining method. Statistical robustness was established with bootstrap analysis. Nucleotide diversity was determined by Shannon entropy per site using the Entropy program of the Los Alamos National Laboratories. Analyses of acute patients revealed that HBV/D2 is the major circulating sub-genotype and commonly associated with sexual promiscuity and the age group between15-30 years. Comparison of AHB and CHB patients revealed that HBeAg positivity, ALT levels and genotype D were significantly high in AHB, whereas CHB patients were predominantly male, had a high viral load, and were commonly associated with genotype C. The frequencies of mutations in the S, BCP/PC, and X gene were low in AHB as compared to CHB. Drug resistant mutations were not detectable in the polymerase gene of AHB. Average nucleotide diversity in AHB was considerably low as compared to CHB. Further, the highest average ΔH (average difference in entropy between chronic and acute infection) was observed in the BCP/PC region implying that this region was most vulnerable to mutations upon HBV persistence, especially in case of genotype C. Additionally, among all substitutions, the A1762T and G1764A BCP mutations were the strongest indicators of chronicity. In conclusion, the study exhibits a general portrait of HBV strains circulating among acute hepatitis B patients in Eastern India and their intricate differences with chronic patients which should be useful from the clinical point of view.

摘要

乙型肝炎病毒(HBV)具有高度的遗传变异性,可分为十种基因型(A - J)。HBV感染可导致多种不同的临床结局,从自限性急性肝炎到活动性慢性肝炎、肝硬化和肝细胞癌。本研究对急性(AHB)和慢性HBV感染(CHB)患者中流行的HBV毒株进行了特征分析。在总共653例HBsAg阳性病例中,40例表现为急性感染。对表面(S)、核心启动子/前核心(BCP/PC)和X基因区域进行测序后,使用MEGA4软件通过邻接法构建系统发育树。通过自展分析确定统计稳健性。使用洛斯阿拉莫斯国家实验室的Entropy程序,通过每个位点的香农熵来确定核苷酸多样性。对急性患者的分析表明,HBV/D2是主要流行的亚基因型,通常与性乱交以及15 - 30岁年龄组相关。AHB和CHB患者的比较显示,AHB患者中HBeAg阳性率、ALT水平和D基因型显著更高,而CHB患者以男性为主,病毒载量高,且通常与C基因型相关。与CHB相比,AHB患者中S、BCP/PC和X基因的突变频率较低。在AHB患者的聚合酶基因中未检测到耐药突变。与CHB相比,AHB患者的平均核苷酸多样性相当低。此外,在BCP/PC区域观察到最高的平均ΔH(慢性感染和急性感染之间熵的平均差异),这意味着该区域在HBV持续存在时最易发生突变,尤其是在C基因型的情况下。此外,在所有替换中,A1762T和G1764A BCP突变是慢性感染的最强指标。总之,该研究展示了印度东部急性乙型肝炎患者中流行的HBV毒株的总体情况以及它们与慢性患者的复杂差异,这从临床角度来看应该是有用的。

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