EASL2012:WEEK 12 HBsAg titer decline is predictive of SVR in chronic hepatitis B

StephenW

Abstract               
                                

Title	WEEK 12 HBsAg titer decline is predictive of SVR in chronic hepatitis B patients receiving pegylated interferon plus tenofovir combination therapy
Speaker:	Patrick   Marcellin
Author:	P. Marcellin1*, M. Martinot-Peignoux2, M. Lapalus2, O. Lada2, Q. Zhang2, N. Boyer1, T. Asselah1
Affiliation:	1Service d'Hépatologie, 2INSERM U773/CRB3 Université Paris-Diderot, Clichy, France. *[email protected]
Background: HBsAg loss isconsidered as the ultimate therapeutic end point for chronic hepatitis B (CHB)patients. The combination of pegylated interferon (PEG-IFN) with a potentanalogue might accelerate HBsAg decline and clearance. Our aim was to assessthe predictive value of HBsAg decline during combination therapy of PEG-IFNplus tenofovir. Patients and methods: 36 CHB patients receiving48 weeks of the combination of PEG-IFN plus tenofovir were included. HBsAg andHBV-DNA levels were measured at baseline, week 12, week 24, end of therapy and24 weeks after treatment cessation (W+24). Sustained virological response (SVR)defined as HBV-DNA < 2000 IU/ml at the end of follow-up. Results: Among the 36 patients,69% were HBeAg-negative, 97% had virological response at end of treatment,11/36 (30%) had a SVR and 4/36 (11%) had an HBsAg loss at the end follow-up. 9/11(82%)SVR, 4/4 (100%) HBsAg loss were HBeAg-negative. At baseline HBsAg titer ≤ 2000log IU/ml was observed in 12 patients, 6/12 (PPV:50%) were SVR; HBsAgtiter > 2000 IU/ml was observed in 24 patients 19/24 were non responders(NPV:79%). A decline in HBsAg titer < 0.5 log IU/ml or< 10% was observed in 29 and 25 patients at week 12, 20/29 (NPV:69%) and20/25 (NPV:80%) were NR. A decline in HBsAg titer < 0.5 log IU/ml or < 10% was observed in 22 and 20 patients at week 24, 18/22 (NPV:82%) and 16/20(NPV:80%) were NR. Among the 4 patients with HBsAg loss: 4/4 (100%) had baselineHBsAg titer ≤ 2000 IU/ml; 3/4 (75%) and 4/4 (100%). showed a decline in HBsAgtiter > 10% at week 12 and week 24, respectively. Conclusions: In patients receivingPEG-IFN plus tenofovir, a SVR was observed in 30% and an HBsAg loss in 11%.Baseline HBsAg titer was predictive of: ≤ 2000 IU/ml HBsAg loss (100%) and SVR(PPV 50%); > 2000 IU/ml non-response (NPV 80%). A lack of ≥ 10% decline inHBsAg level at week 12 or week 24 allows identifying non-responders with a highNPV 80%. An early (week 12) HBsAg level decline is associated with HBsAg loss.

StephenW

标题12周的HBsAg滴度下降是在慢性乙型肝炎患者接受聚乙二醇干扰素加替诺福韦联合治疗的SVR预测
主讲人：帕特里克Marcellin
作者：P. Marcellin1 *，M.马天瑞-Peignoux2，M. Lapalus2，澳Lada2，Zhang2问N. Boyer1，T. Asselah1
单位：1SERVICE D'Hépatologie2INSERM U773/CRB3巴黎大学的狄德罗，克利希，法国。 * michelle.martinot @ inserm.fr
背景：HBsAg消失，最终为慢性乙型肝炎（CHB）患者的治疗终点。一个强有力的模拟组合的聚乙二醇干扰素（PEG-干扰素）可能会加速HBsAg的下降和清理。我们的目的是评估乙肝表面抗原结合PEG-干扰素加替诺福韦治疗期间下降的预测值。
患者和方法：36例慢性乙型肝炎患者接受48周PEG-干扰素加替诺福韦组合都包括在内。 HBsAg和HBV-DNA水平测定在基线，12周，24周，治疗24周后停止治疗（宽+24）结束。定义为持续病毒学应答（SVR），HBV-DNA <2000 IU /毫升的后续结束。
结果：36例患者中，69％为HBeAg阴性，97％在治疗结束时病毒学应答，11/36（30％）有SVR和4/36（11％），HBsAg消失在年底跟进行动。 9/11（82％），4/4（100％）HBsAg消失SVR的HBeAg阴性。在基线表面抗原滴度≤2000日志国际单位/毫升，观察12例，6/12（PPV的：50％），SVR;乙肝表面抗原滴度> 2000 IU / ml的24例19/24（净现值非应答：79 ％）。一个表面抗原滴度下降<0.5日志或IU / ml <10％，在29日和25例观察12周，20/29（净现值：69％）和20/25（净现值：80％）是星期日。一个表面抗原滴度下降<0.5日志IU / ml或<10％，于22日和20例患者在24周，18/22（净现值：82％）和16/20（净现值：80％）是星期日。基线表面抗原滴度HBsAg消失4例：4/4（100％）≤2000 IU / ml的3/4（75％）和4/4（100％）。在表面抗原滴度下降> 10％在12周和24周，分别显示。
结论：在接受PEG-干扰素加替诺福韦的患者，SVR的30％和11％的HBsAg消失在观察。表面抗原滴度基线预测：≤2000 IU / ml的HBsAg消失（100％），SVR（PPV的50％）;> 2000 IU / ml的无反应（净现值80％）。缺乏乙肝表面抗原的水平在12周或24周下降≥10％，可确定无反应，具有很高的净现值80％。早期（12周）HBsAg水平下降与HBsAg消失。

咬牙硬挺

以前说联合治疗预后无显著优势，现在看来又有新进展了啊

tonychant

抗病毒治疗12周之后，高血清IL-21水平预测慢性乙肝HBeAg血清转化
High serum IL-21 levels after 12weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B
Background & Aims
Interleukin-21 (IL-21) stimulates T cell and B cell responses and plays a role in control of chronic viral infections. The role of IL-21 in chronic hepatitis B virus (HBV) infection is not understood.

Methods
Serum IL-21 levels were measured by enzyme immunoassay in 75 HBeAg-positive chronic hepatitis B (CHB) patients undergoing telbivudine treatment. The findings were validated in 103 patients from a separate clinical trial of telbivudine. A complete response to telbivudine was defined as having both HBeAg seroconversion and serum HBV-DNA level <300copies/ml by treatment week 52. The proportions of T-cells producing IL-21 and/or expressing programmed death 1 (PD-1) in peripheral blood mononuclear cells were assessed longitudinally during treatment by intracellular cytokine staining and flow cytometry.

Results
Median serum IL-21 levels at treatment week 12 were significantly higher in patients who did achieve vs. patients who did not achieve a complete response in both the initial (128.4 vs. 69.2pg/ml, p=0.003) and the validation (142.2 vs. 89.9pg/ml,p=0.004) trials. Serum levels of IL-21 (p=0.005) or HBV-DNA (p=0.003) levels at treatment week 12 independently predicted HBeAg seroconversion in the first year of treatment. The decrease in PD-1 expression on CD4+ and CD8+ T cells during the first 12weeks on telbivudine treatment was not correlated with changes in IL-21 concentrations.

Conclusions
Serum IL-21 levels may be a biomarker for HBeAg seroconversion, and may contribute to individualization of antiviral therapy in HBeAg-positive CHB. IL-21 may also have a role in immunotherapy for CHB.