Martinot-Peignoux M, Lapalus M, Maylin S, Boyer N, Castelnau C, Giuily N, Pouteau M, Moucari R, Asselah T, Marcellin P
INSERM, UMR1149, Centre de Recherche sur l'Inflammation, Paris, France.
Université Denis Diderot Paris 7, Paris, France.
J Viral Hepat. 2016 Nov;23(11):905-911. doi: 10.1111/jvh.12565. Epub 2016 Jul 4.
Quantitative hepatitis B core-related antigen (qHBcrAg) has been proposed as an additional marker to quantitative HBsAg (qHBsAg), for management of chronic hepatitis B. Evaluate baseline combination of qHBsAg and qHBcrAg for identification of patients that could benefit from pegylated interferon-alpha-2a (PegIFN)-based therapy. Sixty-two HBeAg-negative patients treated with PegIFN or PegIFN plus tenofovir disoproxil fumarate (PegIFN+TDF). HBsAg and HBcrAg titres were evaluated at baseline. Thirty patients received PegIFN and 32 PegIFN+TDF. SR was 10 of 30 and 17 of 32 in PegIFN and PegIFN+TDF patients, respectively. Cut-offs determined by maximized Youden's index for identifying patients likely to respond to therapy were as follows: 3.141 log IU/mL and 3.450 log U/mL for HBsAg and HBcrAg, respectively. At the end of 3 years post-treatment follow-up, HBsAg loss was observed in 7 of 30 and 6 of 32 in PegIFN and PegIFN+TDF patients, respectively. The AUC was estimated to be 0.716 (95% CI [0.578, 0.855]) for HBsAg and 0.668 (95% CI [0.524, 0.811]) for HBcrAg (P=.5541). PPVs for AUCs(95%CI) were 0.762(0.590-0.947), 0.714(0.533-1.000) and 0.800(0.611-1.000), and NPVs for AUCs(95%CI) were 0.756(0.660-0.899), 0.718(0.630-0.857) and 0.765(0.675-0.889) for qHBsAg, qHBcrAg and the combination of both markers, respectively. Baseline qHBsAg 3.141 log IU/mL and qHBcrAg 3.450 log U/mL thresholds used separately or in combination allow prediction of response, prior to PegIFN-based therapy, with a PPV of 80.3% and NPV of 76.5%. Baseline qHBsAg is predictive of HBsAg loss. Both markers could be used, separately or in combination, for PegIFN-based 'precision therapy'. Our results emphasize that the combination of PegIFN alpha-2a plus TDF with 53% of SR might be an alternative to finite therapy.
定量乙肝核心相关抗原（qHBcrAg）已被提议作为定量乙肝表面抗原（qHBsAg）之外的另一种标志物，用于慢性乙型肝炎的管理。评估qHBsAg和qHBcrAg的基线组合，以识别可能从聚乙二醇化干扰素-α-2a（PegIFN）治疗中获益的患者。62例HBeAg阴性患者接受了PegIFN或PegIFN联合替诺福韦酯（PegIFN+TDF）治疗。在基线时评估HBsAg和HBcrAg滴度。30例患者接受PegIFN治疗，32例接受PegIFN+TDF治疗。PegIFN组和PegIFN+TDF组的持续病毒学应答（SR）分别为3者中的10例和32者中的17例。通过最大化约登指数确定的用于识别可能对治疗有反应的患者的临界值如下：HBsAg为3.141 log IU/mL，HBcrAg为3.450 log U/mL。在治疗后3年随访结束时，PegIFN组30例患者中有7例出现HBsAg消失，PegIFN+TDF组32例患者中有6例出现HBsAg消失。HBsAg的曲线下面积（AUC）估计为0.716（95%可信区间[0.578, 0.855]），HBcrAg的AUC为0.668（95%可信区间[0.524, 0.811]）（P=0.5541）。AUCs（95%可信区间）的阳性预测值（PPV）分别为0.762（0.590 - 0.947）、0.714（0.533 - 1.000）和0.800（0.611 - 1.000），AUCs（95%可信区间）的阴性预测值（NPV）分别为0.756（0.660 - 0.899）、0.718（0.630 - 0.857）和0.765（0.675 - 0.889），分别对应qHBsAg、qHBcrAg以及两种标志物的组合。单独或联合使用的基线qHBsAg 3.141 log IU/mL和qHBcrAg 3.450 log U/mL阈值能够在基于PegIFN的治疗前预测反应，PPV为80.3%，NPV为76.5%。基线qHBsAg可预测HBsAg消失。两种标志物可单独或联合用于基于PegIFN的“精准治疗”。我们的结果强调，PegIFNα-2a联合TDF且持续病毒学应答率为53%可能是有限疗程治疗的一种替代方案。
