EASL2012:Wildtype virus strongest determinant of good results treat peginterfero

StephenW

Abstract               
                                

Title	Presence of only wildtype virus is the strongest determinant of HBV DNA undetectability and HBsAg clearance in HBeAg-positive chronic hepatitis B patients treated with peginterferon
Speaker:	Milan   Sonneveld
Author:	M.J. Sonneveld1*, V. Rijckborst2, S. Zeuzem3, E.J. Heathcote4, K. Simon5, H. Senturk6, S.D. Pas2, B.E. Hansen2, H.L. Janssen2
Affiliation:	1Gastroenterology and Hepatology, 2Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands, 3Johann Wolfgang Goethe University Medical Center, Frankfurt/Main, Germany, 4University of Toronto, Toronto, ON, Canada, 5Medical University Wroclaw, Wroclaw, Poland, 6Bezm-i Alem University, Istanbul, Turkey. *[email protected]
Introduction: Peginterferon (PEG-IFN) may result in HBeAg clearance, but persistence of viral replication due to presence of precore (PC) and/or core promoter (BCP) mutant virus is frequently observed. Methods: 214 HBeAg-positive patients treated with PEG-IFN±lamivudine for 52 weeks were classified at baseline as wildtype (WT) or non-WT (detectable mutants at PC or BCP) by line-probe assay. Response was assessed at 6 months post-treatment (week 78). Results: Patients harboured HBV genotypes A(35%), B(9%), C(14%), D(40%) or other(3%). PC and/or BCP mutants were detected in 64% of patients in varying frequencies across genotypes A-D. Patients with only WT had higher baseline HBV DNA levels (9.20 versus 8.86 log copies/mL, p=0.015), higher HBeAg levels (2.81 versus 2.33 log IU/mL, p< 0.001) and higher HBsAg levels (4.53 versus 4.28 log IU/mL, p=0.007) than patients with detectable mutants after adjustment for HBV genotype. Patients with WT were more likely to achieve a combined response (HBeAg loss with HBV DNA < 10,000 c/mL, 34% vs 11%, p< 0.001), HBV DNA undetectability (< 400 c/mL, 20% vs 2%, p< 0.001) and HBsAg clearance (18% vs 2%, p< 0.001) at week 78. WT at baseline was associated with combined response (OR 2.67, p=0.028), and was the strongest pre-treatment predictor of HBV DNA undetectability (OR 7.93, p=0.002) and HBsAg (OR 4.64, p=0.031) clearance at week 78, when adjusting for HBV genotype A, baseline HBV DNA and ALT and age. After stratification by HBV genotype and baseline HBV DNA and ALT, presence of only WT virus was associated with HBeAg loss with HBV DNA < 10,000 copies/mL (combined response), but not with HBeAg clearance alone (table). Conclusions: Presence of only WT virus is a strong predictor of viral clearance in HBeAg-positive patients treated with PEG-IFN and selective use of PEG-IFN in only patients with WT virus may help optimize the use of this agent in clinical practice. [Probability of response to PEG-IFN by WT/non-WT]

StephenW

标题只野生型病毒的存在，是最强的HBV DNA不可检测的决定因素，HBsAg和HBeAg阳性慢性乙型肝炎聚乙二醇干扰素治疗的患者中的间隙
主讲人：米兰Sonneveld
作者：兆焦耳Sonneveld1，S. Zeuzem3，EJ，五Rijckborst2 heathcote4，Simon5光，H. Senturk6，S.D. pas2，B.E. hansen2，H.L. Janssen2
联系：鹿特丹2Erasmus MC大学医学中心，鹿特丹，荷兰，3Johann·沃尔夫冈·歌德大学医学中心，多伦多，多伦多，德国，法兰克福/ 4University，作者，加拿大，大学弗罗茨瓦夫5Medical，弗罗茨瓦夫，波兰，6Bezm 1Gastroenterology和肝病我阿莱姆大学，伊斯坦布尔，土耳其。 * m.j.sonneveld @ erasmusmc.nl
简介：聚乙二醇干扰素（PEG-干扰素）可能会导致HBeAg阴转，但由于存在前C（PC）和/或核心启动子（BCP）突变病毒病毒复制的持久性，经常观察。
方法：214与PEG-干扰素±拉米夫定治疗52周的HBeAg阳性患者在基线划分为野生型（WT），或由线探针法（检测在PC或BCP突变）非WT。响应在6个月的治疗后（78周）进行了评估。
结果：患者窝藏HBV基因型一（35％），乙（9％），C（14％），D类（40％）或其他（3％）。 PC和/或BCP突变检测在通过基因型公元不同频率的患者在64％。只有野生型的患者有较高的基线HBV DNA水平（9.20与8.86日志拷贝/毫升，P = 0.015），HBeAg的水平更高（2.81比2.33日志IU /毫升，P <0.001）和较高的HBsAg水平（4.53与4.28日志国际单位/毫升，P = 0.007），比调整后的HBV基因型的检测突变的患者。与野生型的患者更容易实现了合并后的反应（e抗原与HBV DNA的损失<10000 C /毫升，34％和11％，P <0.001），HBV DNA的不可检测（<400 /毫升，20％和2％， P <0.001）和78周（HBsAg清除18％和2％，P <0.001）。野生基线与联合反应（OR 2.67，P = 0.028），是最强的预测治疗前HBV DNA的不可检测（OR 7.93，P = 0.002）和HBsAg（OR 4.64，P = 0.031）周间隙78，当HBV基因型A，基线HBV DNA和ALT和年龄调整。乙型肝炎病毒基因型和基线HBV DNA和ALT，只有野生型病毒的存在分层后的HBeAg与HBV DNA <10,000拷贝/毫升（结合反应）的损失，但不单独HBeAg阴转（表）。
结论：只有野生型病毒的存在是一个强有力的预测PEG-干扰素和选择性只与野生型病毒的患者使用PEG-干扰素可能有助于优化使用本剂在临床实践中治疗的HBeAg阳性患者的病毒清除。


PEG-干扰素的概率由野生型/非野生
[概率响应PEG-干扰素聚/非野生

咬牙硬挺

就是说变异的病毒对长效干扰素应答不好吧？

StephenW

回复 咬牙硬挺 的帖子

不如野生型病毒一样好。奇怪的结果。

咬牙硬挺

回复 StephenW 的帖子

骆抗先也是这种观点，变异病毒使用干扰素容易生效但停针后易复发，派罗欣复发率70％