Combined pre-S deletion and core promoter mutations related to hepatocellular ca

StephenW

<http://onlinelibrary.wiley.com/doi/10.1111/j.1872-034X.2010.00732.x/abstract>

Combined pre-S deletion and core promoter mutations related to hepatocellular
carcinoma: A nested case-control study in China

Li-Shuai Qu1,†, Tao-Tao Liu1,†, Fei Jin1, Yan-Mei Guo1, Tao-Yang Chen2,
Zheng-Pin Ni2, Xi-Zhong Shen1,*Article first published online: 25 OCT 2010

DOI: 10.1111/j.1872-034X.2010.00732.x
© 2010 The Japan Society of Hepatology
Issue

Abstract

Aim:  To investigate the roles of biomedical factors, hepatitis B virus (HBV)
DNA levels, genotypes, and specific viral mutation patterns on the progression
of hepatocellular carcinoma (HCC) in Qidong, China.

Methods:  A total of 2387 males (aged 20–65 years) who were seropositive for
the hepatitis B surface antigen (HBsAg), but had not been diagnosed with HCC,
were recruited to a community-based HCC screening study from August, 1996.
Evaluation of virological parameters at recruitment was determined for 196 HCC
patients during 10 years of follow-up and 323 controls.

Results:  After adjustment for age at recruitment, history of cigarette
smoking and alcohol consumption, alanine aminotransferase (ALT) elevation,
alpha-fetoprotein (AFP) levels >20 ng/mL, hepatitis B e antigen positive, HBV
DNA levels ≥4.00 log10 copies/mL, pre-S deletion, T1653 mutation, T1762/A1764
double mutations, and T1766 and/or A1768 mutations were associated with
subsequent risk of HCC. A significant biological gradient of HCC risk by HBV DNA
levels from less than 2.69 log10 copies/mL to 6.00 log10 copies/mL or greater
was observed. HBV with a complex mutation combination pattern (pre-S deletion,
T1762/A1764 double mutations, and T1766 and/or A1768 mutations) rather than a
single mutation was associated with the development of HCC. The longitudinal
observation demonstrated a gradual combination of pre-S deletion, T1762/A1764
double mutations, and T1766 and/or A1768 mutations during the development of
HCC.

Conclusions:  AFP levels >20 ng/mL, high HBV DNA levels, pre-S deletion, and
T1762/A1764 double mutations at recruitment were independent risk factors of
HCC. Combination of pre-S deletion and core promoter mutations increased the
risk of HCC.
                           
联合预- S的缺失和核心启动子突变与肝癌
癌：巢式病例对照研究在中国


Li-Shuai Qu1,†, Tao-Tao Liu1,†, Fei Jin1, Yan-Mei Guo1, Tao-Yang Chen2,
Zheng-Pin Ni2, Xi-Zhong Shen1
，*条第一发表时间：2010年10月25日

分类号：10.1111/j.1872-034X.2010.00732.x
© 2010日本文化协会的杂志发行

摘要

目的：探讨生物医学因素，乙型肝炎病毒（HBV）的角色
DNA水平，基因型，和具体的进展病毒突变模式
启东肝癌，中国（肝癌）。

方法：2387总男性（年龄20-65岁）谁是为阳性
乙型肝炎表面抗原（HBsAg），但没有被诊断为肝癌，
被招募到以社区为基础的肝癌从1996年8月筛选研究。
在招聘病毒学指标综合评价，确定196肝癌
患者在10年的后续行动和控制323年。

结果：在调整了年龄在招聘，香烟的历史
吸烟和饮酒，谷丙转氨酶（ALT）升高，
α-甲胎蛋白（AFP）水平“20毫微克/毫升，B型肝炎e抗原阳性，乙肝病毒
DNA水平≥4.00 log10拷贝/毫升，前- S的缺失，T1653突变，T1762/A1764
双突变，T1766和/或A1768突变与
随后肝癌的风险。一个重要的生物梯度肝癌风险乙型肝炎病毒DNA
从不到2.69 log10拷贝数/毫升至6.00 log10拷贝/ ml或以上
进行了观察。乙肝病毒变异与复杂组合模式（预S缺失，
T1762/A1764双突变，T1766和/或A1768突变），而不是一
单基因突变与肝癌的发展。纵向
观察表现出了前- S的缺失，T1762/A1764渐进融合
在发展双突变，T1766和/或A1768突变
肝癌。

结论：AFP水平“20毫微克/毫升，HBV DNA水平高，前- S的删除，
T1762/A1764双突变在招聘的独立危险因素
肝癌。前- S的缺失和核心启动子突变组合增加
肝癌的风险。

deng245

治愈乙肝是关键、治愈乙肝也就一定程度预防了肝癌

富贵数字

看不懂 。。

StephenW

回复 富贵数字 的帖子

这文研究乙型肝炎表面抗原携带者将进展到肝癌症的危险因素.
一共有2387名男性（年龄20-65岁）被招募.
在启东,中国,从1996年8月筛选研究。跟随10年.
196肝癌患者在招募时的 病毒学参数被调查.
在招募时的 α-甲胎蛋白(AFP)水平>“20毫微克/毫升，HBV DNA水平高，病毒 前- S的删除，
T1762/A1764双突变为随后肝癌的独立危险因素. 前- S的缺失和核心启动子突变组合增加肝癌的风险
.

我希望这可以帮助您.

oceanseleven

stephen，你有这篇文章的pdf文件吗？我现在在家，没有办法看到全文。

pre-S deletion, and T1762/A1764 double mutations 是病毒整合引起的还是患者本身生来就有的？

谢谢。

StephenW

回复 oceanseleven 的帖子

这篇文章的pdf文件需要钱购买的.只有摘要是免费的.对不起，我没买.

病毒原来没有pre-S deletion, and T1762/A1764 double mutations .

The following extract explains some common mutations in HBV:

http://www.medscape.com/viewarticle/512346
The HBV genome contains 4 overlapping open reading frames: the S gene, which codes for the surface proteins (HBsAg); the X gene, which codes for the regulatory gene; the P gene, which codes for DNA polymerase; and the C (core) gene. The latter is divided into the precore region (29 amino acid codons) and the core region (181 codons) by 2 in-frame initiating ATG codons. This results in the transcription of the pregenomic RNA that is essential for HBV replication, and of the nucleocapsid protein or the precore RNA that translates into HBeAg protein that is released into the bloodstream of infected patients.[url=][2][/url] HBeAg is considered to be a marker for viral replication; thus, seroconversion from HBeAg to anti-HBe positivity usually indicates a low level of viral production and low serum HBV DNA levels. This generally correlates with improvement of liver disease.
There is a high error rate associated with the reverse transcription step in HBV replication. As a consequence, HBV has a mutation rate 10-fold higher than that of other DNA viruses. The most potent selective force during the natural course of HBV infection is the host immune response. As a consequence of the development of anti-HBe and the reduction in HBV viremia, "escape" mutants of anti-HBe are selected. Because HBeAg expression is not essential for virus replication, the virus can evade anti-HBe immunity by turning off or reducing HBeAg expression.

oceanseleven

我明天上班，找找看学校里有没有免费的access,如果有的话，我存下来。谢谢。

刚才在学校图书馆的网上查了一下ejournal list,好像没有hepatology research,只有hepatology.

StephenW

回复 oceanseleven 的帖子

Your school may have access to Wiley Online Library.

Login to Wiley Online Library
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oceanseleven

found the article, but cannot upload as pdf file. 555

StephenW

回复 oceanseleven 的帖子

Thanks, excellent work. May be you can just post the abstract and conclusion sections if you think they are useful.

I posted a summary of the following article:

<http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2010.02416.x/abstract>

Characteristics of adefovir resistance in patients with or without
lamivudine-resistant hepatitis B virus treated with adefovir: a 4-year
experience.

What is missing in the summary are the rates of adefovir resistance of patients without previous lamivudine. You may be able to find the article as it is also in the Wiley Online Library. The results should confirm the results posted by Bigben446. From my reading of some of the posts by Dr 王震宇, I understand he is an expert and proponent on the use of lamivudine for the treatment of HBV. He claims to be very confident that he can manage the issues of resistance to lamivudine. As he sees a lot of HBV patients, more than an average liver specialist in the West I presume, his claim must be respected. It is hoped that he can publish his experience with lamivudine. As I mentioned before, here in Australia and America, lamivudine is no longer the antiviral choice for treatment-navie patients. The doctors recommend using drugs with the least resistance profile. You ask me before about mutation. The natural type of the virus is called the "wild" type. Once inside a human body, the virus mutates into types selected by the patient's immune system and drugs used. As drugs for HBV have only been in use for the last 10 years, the long term consequences of anti-viral treatments and resistance are unknown. Hope I am not boring you with all these.