dlDNA标志着乙肝相关肝病进展

StephenW

dlDNA marks progression of HBV-related liver disease
Published on June 30, 2015 at 9:15 AM · No Comments

   

By Shreeya Nanda, Senior medwireNews Reporter

The level of serum duplex-linear DNA (dlDNA) increases markedly with liver disease progression and development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection, suggests research published in Gut.

Viral dlDNA has been shown to be the primary precursor of HBV DNA integration into host chromosomes, a process that can have oncogenic consequences, explain the researchers, adding that their main result “supports the notion that dlDNA may play a role in HCC oncogenesis and suggests that therapeutic reduction of dlDNA may reduce the risk of HCC development.”

Using a peptide nucleic acid-mediated quantitative real-time polymerase chain reaction clamping assay developed for the purpose of detecting dlDNA, the proportion of serum dlDNA relative to total HBV DNA was found to be a median of 7.24% in the 143 chronic HBV patients.


This rose significantly to a median of 14.14% in the 20 patients with liver cirrhosis (p=0.001) and to 20.30% in the 55 patients with liver cirrhosis-related HCC (p<0.001).

Among patients with chronic HBV, median serum dlDNA proportion was significantly higher in those with abnormal compared with normal alanine aminotransferase (ALT) levels, at 8.18% and 4.84% (p<0.001), respectively. The difference between groups remained significant when patients were matched by gender, age, and HBV DNA level and genotype (p<0.001).

When just those patients treated with pegylated interferon-α-2b were considered, serum dlDNA proportion was significantly higher in the 10 patients who responded to treatment than in the 20 who did not (11.54 vs 6.64%; p=0.028)

And experiments using HBV transfected HepG2 cells showed that treatment with inflammatory cytokines, such as interleukin (IL)-10, tumour necrosis factor-α and interferon-γ, had an effect on dlDNA levels, with IL-10 resulting in a dose-dependent increase in dlDNA proportion while the other cytokines had a “bell-shaped effect”.

“This might reveal the mechanism of association between abnormal alanine aminotransferase levels and elevated dlDNA proportion, and further provide evidence that chronic inflammation might contribute to the development of liver cancer by increasing the level of dlDNA”, speculate Xiao-Ben Pan (Peking University People’s Hospital, Beijing, China) and co-investigators.

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StephenW

dlDNA标志着乙肝相关肝病进展
发表于二○一五年六月三十日上午9:15·没有评论

   

通过Shreeya南大，高级medwireNews记者

血清双工线性DNA（dlDNA）的水平与肝脏疾病进展和肝癌的发展（HCC）患者慢性乙型肝炎病毒（HBV）感染增加显着，表明在发表研究肠道。

病毒dlDNA已被证明是HBV-DNA整合的初级前体引入宿主染色体，可以有致癌后果，解释研究者一过程中，加入他们的主要结果：“支持的概念，即dlDNA可能在HCC肿瘤发生中发挥作用，并提出治疗性降低dlDNA可降低肝癌发展的风险。“

使用的肽为检测dlDNA，相对血清dlDNA的比例与总HBV DNA的目的而开发的核酸介导的定量实时聚合酶链反应夹​​紧测定结果为7.24％，在143的慢性HBV患者的中值。


这显著上升至14.14％，中位数在20例肝硬化患者（P = 0.001）和20.30％，在55例肝硬化 - 肝癌相关（P <0.001）。

其中慢性HBV，中值血清dlDNA比例显著高于那些具有异常与正常丙氨酸转氨酶（ALT）的水平相比，在8.18％和4.84％（P <0.001），分别。组之间的差异仍然显著当患者相匹配的性别，年龄，和HBV DNA水平和基因型（P <0.001）。

如果只是与聚乙二醇化干扰素α-2b治疗的患者进行了审议，血清dlDNA比例显著高于10例谁回答治疗比20谁没有（11.54 VS 6.64％，P = 0.028）

和使用的HBV转染的HepG2细胞的实验表明，与炎性细胞因子，如白介素（IL）-10的治疗，肿瘤坏死因子α和干扰素γ，对dlDNA水平的效果，与IL-10产生的剂量依赖性增加dlDNA比例，而其他细胞因子进行了“钟形效应”。

“这可能显示不正常的谷丙转氨酶水平和高架dlDNA比例之间的关联机制，进一步提供证据表明，慢性炎症可能通过增加dlDNA水平有助于肝癌的发展”，推测晓奔潘（北京大学人民医院，北京，中国）和联合调查。

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小民百姓

dlDNA是什么东西？

小民百姓

北京大学人民医院？中国人的论文？

StephenW

小民百姓 发表于 2015-7-8 09:04
dlDNA是什么东西？

乙肝病毒有两种基因组的DNA形式，宽松环状(relaxed circular)DNA（rcDNA）和双工线性(duplex linear)DNA（dlDNA）的。相比rcDNA，dlDNA已证明更频繁地整合到宿主细胞的染色体中，可以具有致癌的后果.

中国人的论文？是(在中国和美国).

StephenW

Gut. 2015 Jun 4. pii: gutjnl-2014-308989. doi: 10.1136/gutjnl-2014-308989. [Epub ahead of print]
Serum viral duplex-linear DNA proportion increases with the progression of liver disease in patients infected with HBV.
Zhao XL1, Yang JR2, Lin SZ3, Ma H1, Guo F4, Yang RF1, Zhang HH1, Han JC1, Wei L1, Pan XB1.
    1Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, P.R. China.
    2Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
    3Department of Hepato-Biliary-Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China.
    4Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, P.R. China Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Doylestown, Pennsylvania, USA.
Abstract
OBJECTIVE:

HBV has two forms of genomic DNA, relaxed-circular DNA (rcDNA) and duplex-linear DNA (dlDNA). Compared to rcDNA, dlDNA has been demonstrated to integrate more frequently into host cellular chromosomes, which may have oncogenic consequences. However, the dlDNA proportion relative to total HBV DNA and its clinical significance in patients remain to be investigated.
DESIGN:

Based on the structural difference between rcDNA and dlDNA, we developed a peptide nucleic acid (PNA)-mediated quantitative real-time PCR (qPCR) clamping assay to measure the proportions of dlDNA in total HBV DNA in sera obtained from patients with chronic hepatitis B (CHB), liver cirrhosis (LC) or LC-developed hepatocellular carcinoma (HCC). The factors that influence the proportion of dlDNA were also investigated.
RESULTS:

The average dlDNA proportion was approximately 7% in the sera of chronic HBV-infected patients and was elevated in CHB patients with abnormal levels of alanine aminotransferase. The sera dlDNA proportions increased to approximately 14% and 20% in the patients with LC and HCC, respectively. Interferon-α treatment slightly increased the dlDNA proportion in the responders; and nucleotide analogue therapy spuriously elevated the proportion. Moreover, treatment of human hepatoma cells supporting HBV replication with inflammatory cytokines significantly altered the dlDNA proportion in vitro.
CONCLUSIONS:

Using a novel PNA-mediated qPCR clamping assay, we first showed that serum dlDNA proportions progressively increased during the development of HBV-related liver diseases. The dlDNA proportion can be regulated by inflammatory cytokines, suggesting an association among inflammation, increased production of HBV dlDNA and development of HCC.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
KEYWORDS:

CYTOKINES; HEPATITIS B; HEPATOCELLULAR CARCINOMA; INFLAMMATION; POLYMERASE CHAIN REACTION

StephenW

肠道。 2015年4月PII：gutjnl-2014-308989。 DOI：10.1136 / gutjnl-2014-308989。 [打印EPUB的提前]
血清病毒双链线性DNA的比例增加了与肝病的患者感染HBV的进展。
赵XL1，杨JR2，林SZ3，马H1，​​郭F4，杨RF1，张HH1，韩JC1，魏L1，潘XB1。
    1Peking大学人民医院，北京大学肝病研究所，丙型肝炎和免疫治疗的北京市重点实验室肝病，中国北京。
    临床教研室实验室，附属第一医院温州医学院，温州，浙江，中国公关。
    3Department的肝胆胰腺外科，附属第一医院，浙江大学医学院，杭州，浙江，中国公关的。
    4Peking大学人民医院，北京大学肝病研究所，丙型肝炎和免疫治疗的北京市重点实验室肝病，北京，微生物学和免疫学公关中国部，德雷塞尔生物技术研究所和病毒学研究，医学，宾夕法尼亚州Doylestown的德雷克塞尔大学学院，美国。
抽象
目的：

乙肝病毒有两种形式的基因组DNA，宽松环状DNA（rcDNA）和双工线性DNA（dlDNA）的。相比rcDNA，dlDNA已证明更频繁地整合到宿主细胞的染色体中，可以具有致癌的后果。然而，dlDNA比例相对要总HBV DNA及其临床意义的患者仍有待调查。
设计：

基于rcDNA和dlDNA之间的结构差异，我们开发肽核酸（PNA）介导的实时定量PCR（定量PCR）检测夹紧衡量dlDNA的患者慢性乙型肝炎获得总HBV DNA血清中的比例（CHB），肝硬化（LC）或LC-开发肝细胞癌（HCC）。影响dlDNA的比例的因素进行了研究。
结果：

平均dlDNA比例大约7％的慢性HBV感染患者的血清中和升高慢性乙型肝炎患者的丙氨酸氨基转移酶水平异常。血清dlDNA比例增加至约14％和20％，在LC患者和HCC分别。 α干扰素治疗略有增加，在反应的dlDNA比例;和核苷酸类似物治疗假性升高的比例。此外，治疗肝癌细胞支持HBV的复制与炎性细胞因子的改变显著体外dlDNA比例。
结论：

采用新颖的PNA介导的定量PCR检测夹紧，我们首先发现，血清dlDNA比例HBV相关性肝病的发展过程中逐步增加。该dlDNA比例可由炎症因子调控，提示肝癌的炎症之间的关联，HBV dlDNA增加生产和开发。

出版的英国医学杂志出版集团有限公司。允许使用（其中尚未根据许可授予）请到http://group.bmj.com/group/rights-licensing/permissions。
关键词：

细胞因子;乙型肝炎;肝癌;炎症;聚合酶链反应

小民百姓

谢谢热心的楼主！