基线HBsAg和HBCRAG滴度ALLOW聚乙二醇干扰素为主的“精密药”HBeA

StephenW

BASELINE HBSAG AND HBCRAG TITERS ALLOW PEGINTERFERON BASED “PRECISION MEDICINE” IN HBEAG-NEGATIVE CHRONIC HEPATITIS B.
Author(s): Michelle Martinot Peignoux
, Martine Lapalus
, Nathalie Boyer
, Corinne Castelnau
, Nathalie Giuily
, Michelle Pouteau
, Tarik Asselah
, Patrick Marcellin

FRI-133

Topic: Hepatitis B & D - clinical (therapy, new compounds, resistance)

Background and aims
Quantitative Hepatitis B core-related-antigen (qHBcrAg) has been evaluated as additional marker to quantitative HBsAg (qHBsAg), for management of chronic hepatitis B. We aimed evaluating baseline combination of qHBsAg and qHBcrAg for identification of patients that could benefit from peginterferon alfa-2a (PegIFN) based therapy.

Methods
62 HBeAg-negative patients treated with PegIFN or PegIFN plus Tenofovir-disoproxil-fumarate (PegIFN+TDF). HBsAg and HBcrAg titers were measured at baseline.

Results
30 patients received PegIFN and 32 PegIFN+TDF. SVR was 33% and 53% in PegIFN and PegIFN+TDF patients, respectively. AUC(95%CI) was 0.716(0.578-0.855) for HBsAg and 0.668(0.524-0.811) for HBcrAg (p=0.554). Cut-off selected at the predictor threshold that maximizes Youden’s index for identifying patients likely to respond were: 3.141(2.941-3.592) log10 IU/mL and 3.450(2.150-5.050) log10 U/mL for HBsAg and HBcrAg, respectively. Titers below these cut-offs were observed in 15/27 (56%) and 4/35 (11%) patients with and without SVR, respectively for qHBsAg, and 14/27 (52%) and 6/35 (17%) patients with and without SVR, respectively for qHBcrAg. Combination of HBsAg and HBcrAg in 1 predictive score showed AUC(95%CI) of 0.745(0.612-0.878). PPVs were: 0.762(0.590-0.947), 0.714(0.533-1.000) and 0.800(0.611-1.000) and NPVs were 0.756(0.660-0.889) 0.718(0.630-0.857) and 0.765(0.675-0.889) for HBsAg, HBcrAg and the combination of both markers, respectively. The logistic regressions showed high performances. Results were not different regardless treatment regimens ROC curves for HBsAg loss showed AUC(95%CI): 0.771(0.576-0.965) and 0.552(0.324-0.779) for qHBsAg, qHBcrAg respectively (p=0.0304).

Conclusions
Baseline qHBsAg 3.141 log10 IU/mL and qHBcrAg 3.450 log10 U/mL thresholds used separately or in combination allow prediction of response, prior PegIFN based therapy, with PPV 80.0% and NPV 76.5%. Both markers could be used, separately or in combination, for PegIFN based 'precision therapy'. Higher SVR rates are observed with the combination of 48 weeks PegIFN+TDF (53%) in comparison to 48 weeks of PegIFN monotherapy (33%), emphasizing that the combination of PegIFN alfa-2a plus TDF might be an interesting alternative of finite therapy allowing individualizing treatment and ultimately improves clinical practice.

StephenW

基线HBsAg和HBCRAG滴度ALLOW聚乙二醇干扰素为主的“精密药”HBeAg阴性慢性乙型肝炎
作者（S）：米歇尔马丁诺特Peignoux
，马丁Lapalus
，娜塔莉·博耶
科琳娜卡斯泰尔诺
，娜塔莉Giuily
米歇尔Pouteau
，塔里克Asselah
帕特里克Marcellin

FRI-133

主题：乙型肝炎＆D - 临床（治疗，新的化合物，电阻）

背景和目的
定量乙型肝炎核心相关抗原（qHBcrAg）已被评为额外的标记到定量的乙肝表面抗原（qHBsAg），用于治疗慢性乙型肝炎的管理我们的目的为评估患者的识别和qHBsAg的qHBcrAg基线组合，可以从聚乙二醇干扰素α受益-2a（PegIFN）为基础的治疗。

方法
与PegIFN或PegIFN加替诺福韦-诺福韦富马酸酯（PegIFN + TDF）治疗的62例HBeAg阴性患者。在基线测定HBsAg和HBcrAg滴度。

结果
30例患者接受PegIFN和32 PegIFN + TDF。 SVR分别为33％和在PegIFN和PegIFN + TDF患者53％。 AUC（95％CI）为0.716（0.578-0.855）为HBsAg和0.668（0.524-0.811）为HBcrAg（P = 0.554）。在最大化约登指数识别可能反应的患者预测门槛所选截止分别为：3.141（2.941-3.592）日志10 IU / mL和3.450（2.150-5.050）日志10 U / mL的乙型肝炎表面抗原和HBcrAg分别。在15/27（56％）和4/35（11％）的患者中观察到低于这些截止值滴度有和没有SVR分别为qHBsAg，和14/27（52％）和6/35（17％）患者和无SVR分别为qHBcrAg。在1比分预测HBsAg和HBcrAg的组合显示AUC的0.745（0.612-0.878）（95％CI）。阳性预测值分别为：0.762（0.590-0.947），0.714（0.533-1.000）和0.800（0.611-1.000）和净现值分别为乙肝表面抗原，HBcrAg 0.756（0.660-0.889）0.718（0.630-0.857）和0.765（0.675-0.889）和两种标记的分别的组合。后勤回归分析表明高性能。结果并没有考虑不同的治疗方案对HBsAg消失ROC曲线显示AUC（95％CI）：0.771分别为（0.576-0.965）和0.552（0.324-0.779）为qHBsAg，qHBcrAg（P = 0.0304）。

结论
基线qHBsAg 3.141日志10 IU / mL和qHBcrAg 3.450 log10的单独使用或组合使用U / ml的阈值允许响应的预测，事先PegIFN基础的治疗，与PPV 80.0％和NPV 76.5％。两标记可被使用，单独或组合，对于基于PegIFN'精度疗法“。较高的SVR率都使用48周PegIFN + TDF（53％）的比较48周PegIFN单一治疗（33％）的组合观察到的，强调PegIFNα-2a联合TDF的组合可能是有限的治疗的一个有趣的选择允许个体化治疗和最终提高临床实践。