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源自单剪接RNA的缺陷型乙型肝炎病毒颗粒的表达与肝脏疾病有关。

Expression of defective hepatitis B virus particles derived from singly spliced RNA is related to liver disease.

作者信息

Soussan Patrick, Pol Jonathan, Garreau Florianne, Schneider Veronique, Le Pendeven Catherine, Nalpas Bertrand, Lacombe Karine, Bonnard Philippe, Pol Stanislas, Kremsdorf Dina

机构信息

Pathogenèse des Hépatites Virales B et Immunothérapie, Institut National de la Santé et de la Recherche Médicale U845, Paris, France.

出版信息

J Infect Dis. 2008 Jul 15;198(2):218-25. doi: 10.1086/589623.

DOI:10.1086/589623
PMID:18532883
Abstract

BACKGROUND

Defective hepatitis B virus (HBV) particles, generated from singly spliced HBV RNA, have been detected in chronic carriers of HBV. The present study was designed to quantify the expression of defective HBV (dHBV) and wild-type HBV (wtHBV) genomes in the serum of patients with HBV infection and its relation to the severity of liver disease.

METHODS

HBV and dHBV loads were determined by quantitative polymerase chain reaction in the serum of 89 untreated HBV-infected patients (31 coinfected with human immunodeficiency virus [HIV] type 1) with liver disease of different stages. The ratio of dHBV DNA to total (wtHBV plus dHBV) HBV DNA (dHBV/HBV ratio) was used to express data independently of the level of viral replication.

RESULTS

Despite a global correlation between dHBV and wtHBV load, the dHBV/HBV ratio ranged from 0.001% to 69%. The variation in dHBV/HBV ratio was independent of HIV coinfection, HBV genotype, and precore mutations. The mean dHBV/HBV ratio was higher in patients with severe liver necrosis and fibrosis.

CONCLUSIONS

Our data indicate that an elevated dHBV/HBV ratio is associated with liver necroinflammation and fibrosis disease, suggesting a regulation of dHBV expression according to the severity of the liver disease. The dHBV/HBV ratio may help to better define liver disease stage during HBV infection.

摘要

背景

在慢性乙肝病毒(HBV)携带者中已检测到由单剪接HBV RNA产生的缺陷型乙肝病毒颗粒。本研究旨在量化HBV感染患者血清中缺陷型HBV(dHBV)和野生型HBV(wtHBV)基因组的表达及其与肝病严重程度的关系。

方法

采用定量聚合酶链反应测定89例未经治疗的不同肝病阶段的HBV感染患者(31例合并人类免疫缺陷病毒1型[HIV]感染)血清中的HBV和dHBV载量。用dHBV DNA与总(wtHBV加dHBV)HBV DNA的比值(dHBV/HBV比值)来独立于病毒复制水平表达数据。

结果

尽管dHBV和wtHBV载量总体呈相关性,但dHBV/HBV比值范围为0.001%至69%。dHBV/HBV比值的变化与HIV合并感染、HBV基因型和前核心突变无关。严重肝坏死和纤维化患者的平均dHBV/HBV比值更高。

结论

我们的数据表明,dHBV/HBV比值升高与肝坏死性炎症和纤维化疾病相关,提示dHBV表达根据肝病严重程度受到调控。dHBV/HBV比值可能有助于更好地界定HBV感染期间的肝病阶段。

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