AASLD 2011:Quantitative HBeAg Is The Best Predictor Of HBeAg Seroconversion

StephenW

Quantitative HBeAg Is The Best Predictor Of HBeAg Seroconversion
S. Lim1, 2; A. Myat Oo1; Y. Cheng2; B. Seet2
1. Dept of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore.
2. Dept of Medicine, Yong Yoo Lin School of Medicine, National University of Singapore, Singapore, Singapore.


INTRODUCTION: We hypothesize that HBV quasispecies play an important role in pathogenesis of HBeAg seroconversion based on our finding that patients who undergo HBeAg seroconversion have significantly increased HBV viral quasispecies evolution and viral diversity before HBeAg seroconversion (Lim etal. Gastroenterology 2007;133: 951-8). In this study we sought to determine virological factors that could predict seroconversion. We therefore explored the potential of viral diversity and other viral markers (HBeAg levels, precore stop codon frequency, viral load and genotype) as baseline predictors of HBeAg seroconversion.
METHODS: A total of 42 HBeAg seroconverters and 25 non-HBeAg seroconverters whose pre-seroconversion serum was available were included. Genotyping was performed using restriction fragment length polymorphisms. The HBeAg levels were quantified using the HBeAg ELISA kit (Architect, Abbott Labs) and the Paul-Ehrlich (PE) reference standard,and expressed as Paul-Ehrlich International Units (PE IU/ml). PCR, cloning and sequencing of precore/core gene for HBV DNA from these patients were carried out (>20 clones/sample sequenced). Sequences excluding overlapping regions were aligned using ClustalX and the viral diversity was accessed using Pebble 1.0. Statistical analysis was performed with SPSSv18 using Mann Whitney U test, Chi squared test and multivariate Cox regression. RESULTS: Thirty-four of 42 seroconverters were non-genotype C compared to 11/25 non-seroconverters (p=0.005). Seroconverters compared to non-seroconverters had fewer males, 55% v 88%)(p=0.007), lower HBeAg titres 675 v 1846 PE IU/ml (p=0.006), higher viral diversity, 1.1x10-2 v 5.8x10-3 substitutions/site (p=0.001), more precore stop codon mutants 27.3% v 1.3% (p<0.001), lower HBV DNA, 6.9 v 7.7 log10copies/ml (p=0.013). Using multivariate Cox regression to correct for the differences in time before seroconversion, HBeAg titre was the only significant independent predictor of HBeAg seroconversion, hazard ratio 1.75 (95%CI 1.2 – 2.6, p=0.006).
CONCLUSION: Of all the virological factors examined, HBeAg titre was the only independent predictor of HBeAg seroconversion. Validation in larger studies would be important before this marker could be utilised in the clinic.




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StephenW

定量e抗原HBeAg血清转换的最好的预测
S. LIM 1，2，A.妙OO1 Y.程2 B. Seet 2
1。胃肠病学和肝病学系，新加坡，新加坡国立大学健康系统。
2。医学部，林勇柳医学院，新加坡国立大学，新加坡，新加坡。


简介：我们推测，乙肝病毒准种发挥发病机制的基础上，我们发现接受HBeAg血清转换的患者有显著增加乙肝病毒准种的演变和HBeAg血清转换前的病毒多样性（LIM伊特尔胃肠病学2007年的HBeAg血清转换的重要作用; 133：951 - 8）。在这项研究中，我们试图确定病毒学因素，可以预测血清转换。因此，我们探讨病毒的多样性和其他病毒标志物作为基线预测HBeAg血清转换（HBeAg的水平，前C区终止密码子频率，病毒载量及基因型）的潜力。
方法：共有42 HBeAg的seroconverters和25个非HBeAg的seroconverters的前血清转换血清可用。用限制性片段长度多态性进行基因分型。 HBeAg的水平进行了量化使用的e抗原检测试剂盒（建筑师，雅培）和保罗 - 埃利希（PE）的参考标准，和保罗 - 埃利希国际单位（PE IU /毫升）表示。进行PCR扩增，克隆和前C /核心基因从这些患者的HBV DNA测序（> 20个克隆/样本测序）。排除重叠区域的序列对齐使用ClustalX和病毒的多样性是用卵石1.0访问。使用曼惠特尼U检验，卡方检验和多变量Cox回归进行统计分析与SPSSv18。
结果：42 seroconverters三十四个非C基因型相比，11/25非seroconverters（P = 0.005）。非- seroconverters Seroconverters相比较少的男性，55％对88％）（P = 0.007），HBeAg的滴度降低675 V 1846 PE IU /毫升（P = 0.006），较高的病毒多样性，5.8x10 1.1x10 - 2 V -网站3个换人/（P = 0.001），前C区终止密码子突变体27.3％比1.3％（P <0.001），降低乙肝病毒DNA，6.9 v 7.7 log10copies/ml（P = 0.013）。使用多变量Cox回归到正确的时间在血清转换前的差异，HBeAg的滴度是唯一显著的独立预测HBeAg血清转换，危险比为1.75（95％CI，1.2 - 2.6，P = 0.006）。
结论：所有的病毒学因素的研究，HBeAg的滴度，HBeAg血清转换的唯一独立预测因素。验证更多的研究将是重要的，在此之前的标记可在诊所使用。