乙型肝炎病毒（HBV）的前S缺失配置文件与慢性HBV感染的临床

StephenW

J Clin Virol. 2016 Jun 29;82:27-32. doi: 10.1016/j.jcv.2016.06.018. [Epub ahead of print]
PreS deletion profiles of hepatitis B virus (HBV) are associated with clinical presentations of chronic HBV infection.Li X1, Qin Y1, Liu Y1, Li F2, Liao H1, Lu S1, Qiao Y1, Xu D3, Li J4.
Author information

• 1Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China.
• 2The Second Liver Cirrhosis Medical Center, Beijing 302 Hospital, Beijing 100039, China.
• 3Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China. Electronic address: [email protected].
• 4Medical Department, Beijing 302 Hospital, Beijing 100039, China. Electronic address: [email protected].
  

AbstractBACKGROUND: The association of hepatitis B virus (HBV) preS1 and preS2 deletions with progressive liver diseases are not fully understood.
OBJECTIVE: The study aimed to investigate characteristics of HBV preS deletion in HBV-infected patients with different illness categories.
STUDY DESIGN: Total of 539 HBV-infected patients were enrolled in the study, including 146 with chronic hepatitis B (CHB), 111 with HBV-related liver cirrhosis (LC), 146 with HBV-related acute-on-chronic liver failure (ACLF), and 136 with HBV-related hepatocellular carcinoma (HCC). PreS deletion was determined by sequencing. Replicons containing representative preS1 and preS2 deletion mutants and wild-type were respectively constructed and transfected into HepG2 cells for phenotypic analysis.
RESULTS: The detection rates of overall preS deletion were 15.8%, 26.1%, 24.0%, and 34.6% in CHB, LC, ACLF, and HCC patients, respectively. PreS1 deletion was most frequently detected in LC patients while preS2 deletion was most frequently detected in HCC patients, both frequencies were significantly higher than that in CHB patients (17.1% vs. 4.8%, P<0.01; 19.1% vs. 4.8%, P<0.01). The deletion patterns across preS gene were different among the 4 illness categories. Compared with wild-type strain, the preS1 deletion mutant had defected preS1 expression, significantly decreased viral mRNA level and SP II promoter activity; while preS2 deletion mutant had defected preS2 expression, and significantly decreased viral mRNA level.
CONCLUSIONS: HBV preS deletion was associated with advancement of liver diseases not only presented in preS deletion incidence, but also in the deletion pattern. Patients with preS2 deletion might have a higher risk to develop HCC.
Copyright © 2016 Elsevier B.V. All rights reserved.


KEYWORDS: Acute-on-chronic liver failure; Hepatitis B virus; Hepatocellular carcinoma; Liver cirrhosis; PreS deletion

PMID:27415434DOI:10.1016/j.jcv.2016.06.018

StephenW

Ĵ临床病毒学杂志。 2016年6月29日82：27-32。 DOI：10.1016 / j.jcv.2016.06.018。 [打印EPUB提前]
乙型肝炎病毒（HBV）的前S缺失配置文件与慢性HBV感染的临床表现有关。
李X1，Y1勤，刘Y1，李F2，廖H1，鲁S1，乔Y1，徐D3，李J4。
作者信息

    1Research中心临床和转化医学，北京302医院，北京100039，中国。
    2The第二肝硬化医学中心，北京302医院，北京100039，中国。
    3Research中心临床和转化医学，北京302医院，北京100039，中国。电子地址：[email protected]。
    4Medical部，北京302医院，北京100039，中国。电子地址：[email protected]。

抽象
背景：

乙型肝炎病毒（HBV）前S1和前S2缺失与进行性肝脏疾病的关联是不充分的理解。
目的：

旨在研究探讨在HBV感染患者的病情不同类别的前S乙肝病毒删除的特性。
学习规划：

539 HBV感染者总在被纳入研究，其中包括146慢性乙型肝炎（CHB），111 HBV相关肝硬化（LC），146与乙肝相关的急性发作，慢性肝功能衰竭（ACLF）和136与HBV相关肝细胞癌（HCC）。前S缺失通过测序来确定。分别构建和转染HepG2细胞用于表型分析含有代表前S1和前S2缺失突变体和野生型复制子。
结果：

整体前S缺失的检出率分别为15.8％，26.1％，24.0％和34.6％，在CHB，LC，ACLF和肝癌患者。而前S2缺失HCC患者最常检测到的LC患者前S1抗原缺失最常检测到的，两个频率均高于CHB患者（17.1％对4.8％，P <0.01显著提高; 19.1％对4.8％，P <0.01）。整个前S基因缺失图案分别为4类疾病中是不同。与野生型菌株相比，前S1缺失突变叛逃前S1表达，显著降低病毒mRNA水平和SP II启动子活性;而前S2缺失突变体叛逃前S2表达，显著减少病毒mRNA水平。
结论：

乙型肝炎病毒前S缺失用肝疾病不仅在前S缺失发生率呈现的前进有关，而且在删除模式。患者前S2缺失可能有较高的风险制定肝癌。

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关键词：

急性发作，慢性肝功能衰竭;乙型肝炎病毒;肝细胞癌;肝硬化;前S缺失

结论：
    27415434
DOI：
    10.1016 / j.jcv.2016.06.018