Presence of precore and core promoter mutants limits the probability of response

StephenW

Hepatology. 2012 Feb 6. doi: 10.1002/hep.25636. [Epub ahead of print]
Presence of precore and core promoter mutants limits the probability of response to peginterferon in HBeAg-positive chronic hepatitis B.Sonneveld MJ, Rijckborst V, Zeuzem S, Heathcote EJ, Simon K, Senturk H, Pas SD, Hansen BE, Janssen HL.
SourceDepartment of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

AbstractPeginterferon (PEG-IFN) treatment of HBeAg-positive chronic hepatitis B (CHB) results in HBeAg loss in 30% of patients, but clearance of HBV DNA and HBsAg from serum is less often achieved. We investigated whether the presence of precore (PC) and basal core promoter (BCP) mutants before PEG-IFN treatment affects serological and virological response. A total of 214 HBeAg-positive CHB patients treated with PEG-IFN±lamivudine for 52 weeks in a global randomized trial were classified at baseline as wildtype (WT) or non-WT (detectable mutants at PC/BCP) by line-probe assay. Response was assessed at 6 months post-treatment and through long-term follow-up(LTFU). Mutants were detected in 64% of patients, in varying frequencies across HBV genotypes A through D. Patients with WT had higher baseline HBV DNA, HBeAg and HBsAg levels than patients with non-WT. Patients with WT were more likely to achieve HBeAg loss with HBV DNA<10,000 copies/mL (response, 34 versus 11%,p<0.001) and HBsAg clearance (18 versus 2%,p<0.001) at week 78 than non-WT patients. Among WT patients who achieved HBeAg clearance at week 78, 78% had undetectable HBV DNA and 61% achieved HBsAg clearance at LTFU (versus 26% and 15% in non-WT patients,p<0.001 for both). Presence of WT virus at baseline was an independent predictor of response (OR 2.90, 95%CI:1.15-7.31,p=0.023) and HBsAg clearance (OR 5.58, 95%CI:1.26-24.63,p=0.013) and patients with non-A genotypes with detectable mutants had a low probability of response. CONCLUSION: Presence of only WT virus at baseline is a strong predictor of response (HBeAg loss with HBV DNA <10,000 copies/mL) to PEG-IFN for HBeAg-positive CHB. Patients with detectable PC and/or BCP mutants have a lower probability of response and are less optimal candidates for PEG-IFN therapy. (HEPATOLOGY 2012.).




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StephenW

肝病。 2012年二月6。 DOI：10.1002/hep.25636。 [出处提前打印]
在HBeAg阳性慢性乙型肝炎前C区和核心启动子突变体的存在限制反应的概率聚乙二醇
sonneveld，Rijckborst至五兆焦耳，Zeuzem希思科特EJ，西蒙ķ，SenturkĤ，PAS SD，汉森，扬森红莲。
源

胃肠病学和肝病，Erasmus MC大学医学中心，鹿特丹，荷兰。
抽象

聚乙二醇（PEG-干扰素）治疗HBeAg阳性慢性乙型肝炎（CHB）的结果在30％的患者在HBeAg的损失，但是从血清HBV DNA和HBsAg清除是不太经常取得。我们调查是否存在前C（PC）和基本核心启动子（BCP）突变体的聚乙二醇干扰素治疗前，会影响血清学和病毒学应答。共有214例HBeAg阳性CHB患者在一个全球性的随机试验，52周PEG-干扰素±拉米夫定治疗基线被列为野生型（WT）或野生型（非检测到突变的PC / BCP）线探针法。在6个月治疗后，并通过长期随访（LTFU）反应评估。 64％的患者，在跨HBV基因型的不同频率突变检测通过D.与WT患者有较高的基线HBV DNA，与非野生型患者HBeAg和HBsAg水平。与野生型的患者更可能比非野生实现与乙型肝炎病毒DNA <10,000拷贝/毫升（反应，34％对11％，P <0.001）和HBsAg清除HBeAg消失，78周（​​18比2％，P <0.001）患者。在野生型患者78周时达到HBeAg的间隙中，有78％不到的HBV DNA和61％在LTFU取得HBsAg清除（相对于26％和15％，在非野生型的患者，P <0.001）。野生型病毒存在于基线反应的独立预测因素（OR 2.90，95％CI :1.15-7 0.31，P = 0.023）和乙肝表面抗原清除率（OR 5.58，95％CI :1.2​​6-24 0.63，P = 0.013）与患者非A基因型检测突变的概率很低的响应。结论：只有野生型病毒存在于基线是强烈的反应预测HBeAg阳性慢性乙型肝炎（HBeAg消失与HBV DNA <10,000拷贝/毫升）PEG-干扰素。检测PC和/或BCP突变的患者有反应的机率较低，PEG-干扰素治​​疗的最佳候选人。 （2012年肝病。）。

版权所有©2012美国肝病研究协会。

javeping

检测PC和/或BCP突变的患者!!是什么的检查

StephenW

回复 javeping 的帖子

我不知道。在这篇论文中，它被简单地描述为“line-probe线探针”检测。
此法似乎能告诉你，你是否有任何突变的乙肝病毒及野生型病毒.

咬牙硬挺

没看懂啊

StephenW

回复 咬牙硬挺 的帖子

1. 病毒会变异(mutate)
2. 在乙型肝炎病毒感染的肝，我们可能有100％野生型(wild type)病毒，野生型和变异病毒
混合，或100％变异病毒.

这篇论文建议在HBeAg阳性患者, 如果他们是100％野生型病毒，有更好的干扰素治疗响应.