C区和基本核心启动子变异的干扰素诱导的HBeAg血清学转换的

StephenW

乙型肝炎病毒前C区和基本核心启动子变异的干扰素诱导的HBeAg血清学转换的不同的进化和预测值.
http://www.ncbi.nlm.nih.gov/pubmed/23112104
Hepatology. 2012 Oct 30. doi: 10.1002/hep.26121. [Epub ahead of print]
Distinct evolution and predictive value of hepatitis B virus precore and basal core promoter mutations in interferon-induced HBeAg seroconversion.Yang HC, Chen CL, Shen YC, Peng CY, Liu CJ, Tseng TC, Su TH, Chuang WL, Yu ML, Dai CY, Liu CH, Chen PJ, Chen DS, Kao JH.
SourceDepartment of Microbiology, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei; Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei.

AbstractPrecore (PC) (G1896A) and basal core promoter (BCP) (A1762T/G1764A) mutations of hepatitis B virus (HBV) genome often emerge in chronic hepatitis B (CHB) patients. Their roles in HBeAg seroconversion induced by interferon therapy remain controversial, partly because quantitative analysis for these mutants is lacking. This study aimed to develop a new assay to accurately quantify the PC and BCP mutant percentages and correlate their dynamic changes with interferon-induced HBeAg seroconversion in HBeAg-positive CHB patients. The PC and BCP mutant percentages were analyzed by PCR-pyrosequencing. Our results showed this quantitative assay for PC and BCP mutants achieved high accuracy (R(2)  >0.99) within a range between 10% and 90% mutants. We examined dynamic changes of the PC and BCP mutant percentages following interferon treatment in 203 HBeAg-positive CHB patients. By multiple logistic regression analysis, we found that the chance of HBeAg seroconversion increased by 2.2% (OR=1.022, 95% CI: 1.009-1.034, P=0.001) and 2.3% (OR=1.023, 95% CI: 1.010-1.037, P =0.001) per 1% increase of the pretreatment PC and BCP mutant percentages, respectively, after adjustment for other predictors. However, only the pretreatment PC mutation percentage was significantly associated with HBeAg seroconversion with HBV DNA < 2,000 IU/mL (OR= 1.030, 95% CI: 1.014-1.047, P<0.001) . Furthermore, the mutant percentage of PC, but not BCP, in patients achieving HBeAg seroclearance with HBV DNA < 20,000 IU/mL increased significantly during interferon treatment (P=0.039). Interestingly, patients with HBeAg seroconversion who had a high PC mutant percentage at the end of interferon treatment tended to exhibit high viremia after seroconversion. Conclusion: Quantitative analysis of PC and BCP mutants can predict interferon-induced HBeAg seroconversion and demonstrate their distinct evolution patterns during HBeAg seroconversion. (HEPATOLOGY 2012.).

StephenW

常出现在慢性乙型肝炎（CHB）患者HBV前C区（PC）（G1896A）和基本核心启动子（BCP）（A1762T/G1764A）突变的B型肝炎病毒（HBV）基因组。他们的角色，诱导干扰素治疗的HBeAg血清学转换仍然存在争议，部分原因是缺乏对这些突变体的定量分析。本研究旨在开发一种新的检测，以准确地量化PC和BCP突变体的百分比和相关性的动态变化与干扰素诱导的HBeAg阳性CHB患者的HBeAg血清学转换。 PC和BCP区突变的百分比PCR-焦磷酸测序技术进行了分析。我们的研究结果表明，这个定量测定为PC和BCP突变体实现了高准确度（R（2）> 0.99），10％和90％的突变体之间的范围内。我们研究了在203例HBeAg阳性慢性乙型肝炎患者干扰素治疗后的动态变化，PC和BCP突变的百分比。多因素logistic回归分析，我们发现，HBeAg血清转换的机会增加了2.2％（OR = 1.022，95％CI：1.009-1.034，P = 0.001）和2.3％（OR = 1.023，95％CI：1.010-1.037 ，P = 0.001）的预处理PC和BCP突变体的百分比，分别每增加1％，调整后为其他预测。但是，只有预处理PC突变率显着相关的HBeAg血清转换与HBV DNA <2000 IU /毫升（OR = 1.030，95％CI：1.014-1.047，P <0.001）。此外，突变的百分比的PC，但不是BCP，患者实现e抗原转阴，HBV DNA <20000 IU / mL的增加显着（P = 0.039），干扰素治疗过程中。有趣的是，有很高的PC突变的百分比干扰素治疗结束时HBeAg血清学转换的患者往往表现出高病毒血症后血清学转换。结论：PC和BCP突变体的定量分析，可以预测干扰素诱导的HBeAg血清转换率和HBeAg血清转换的过程中，展示其独特的进化模式。 （肝胆病2012年）。

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