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标题: 慢性乙型肝炎患者抗病毒治疗后高水平的可溶性程序性死亡 1 [打印本页]

作者: StephenW 时间: 2021-12-22 06:58 标题: 慢性乙型肝炎患者抗病毒治疗后高水平的可溶性程序性死亡 1

慢性乙型肝炎患者抗病毒治疗后高水平的可溶性程序性死亡 1 与病毒学反应相关
谭宁、罗浩、钱康、潘佳丽、程然、奚红丽、陈宏宇、韩一凡、杨宇清、徐晓媛

PMID：34929214 DOI：10.1016/j.virusres.2021.198660

抽象的

背景：可溶性程序性细胞死亡蛋白-1（sPD-1）通过抵消程序性死亡配体-1（PD-L1）对免疫细胞的抑制作用，在慢性乙型肝炎病毒（HBV）感染中发挥重要作用。在这里，我们研究了 sPD-1 在接受核苷（酸）类似物（NA）治疗的慢性乙型肝炎（CHB）患者中预测病毒学反应（VR）的能力。

方法：本研究纳入了 2007 年 3 月在北京大学第一医院（中国）开始接受 NA 治疗的 CHB 患者 [乙型肝炎表面抗原（HBsAg）阳性≥6 个月]。 85 名 CHB 患者每 12 周进行一次随访，共随访 96 周。

结果：基线时血清 sPD-1 水平与乙型肝炎表面抗原 (HBsAg) 和 HBV DNA 呈负相关。免疫活性 CHB 患者在基线时表现出较高的血清 sPD-1 水平。在抗病毒治疗期间患有 VR 的患者在基线时表现出较高的 sPD-1 水平和较低的 HBsAg 水平。生成受试者工作特征 (ROC) 曲线以确定 sPD-1 和 HBsAg 对接受一线治疗（恩替卡韦、ETV）患者 VR 的预测价值。基线时 sPD-1 和 HBsAg 的 ROC (AUROC) 值下面积分别为 0.850 (95%CI:0.729-0.971, P=0.0005) 和 0.785 (95%CI: 0.642-0.929, P=0.005)，和最佳临界值分别为 459.46 pg/mL 和 14710 IU/mL。与单独使用 sPD-1 或 HBsAg 相比，sPD-1 和 HBsAg 的组合表现出更高的 AUROC 值（0.870,95% CI：0.748-0.983，P=0.001）。在接受二线治疗（拉米夫定、LAM/阿德福韦酯、ADV）的患者中，基线 sPD-1 水平高于 677.2 pg/mL 与 96 周抗病毒治疗后 VR 的发生率显着相关，是水平≤677.2 的 7.956 倍皮克/毫升。

结论：通过结合 sPD-1 和 HBsAg，我们获得了与 CHB 患者 VR 显着相关的生物标志物。 sPD-1水平可用于筛选抗病毒治疗预后不良的患者。

关键词：乙型肝炎病毒；核苷（酸）类似物（NA）疗法；程序性死亡配体-1；可溶性程序性细胞死亡蛋白-1；病毒学反应。

版权所有 © 2021。Elsevier B.V. 出版

作者: StephenW 时间: 2021-12-22 06:59

High Levels of Soluble Programmed Death-1 Are Associated with Virological Response in Chronic Hepatitis B patients after Antiviral Treatment
Ning Tan, Hao Luo, Qian Kang, Jiali Pan, Ran Cheng, Hongli Xi, Hongyu Chen, Yifan Han, Yuqing Yang, Xiaoyuan Xu

PMID: 34929214 DOI: 10.1016/j.virusres.2021.198660

Abstract

Background: Soluble programmed cell death protein-1 (sPD-1) plays an important role in chronic hepatitis B virus (HBV) infection by counteracting the inhibitory effect of programmed death ligand-1 (PD-L1) on immune cells. Here, we investigated the ability of sPD-1 to predict the virological response (VR) in chronic hepatitis B (CHB) patients undergoing Nucleos(t)ide analogue (NA) therapy.

Methods: CHB patients [hepatitis B surface antigen (HBsAg) positive ≥6 months] who initiated NA therapy in March 2007 at Peking University First Hospital (China) were enrolled in this study. Eighty-five CHB patients were followed-up every 12 weeks for 96 weeks.

Results: Serum sPD-1 levels at baseline were negatively correlated with hepatitis B surface antigen (HBsAg) and HBV DNA. Immune-active CHB patients exhibited higher serum sPD-1 levels at baseline. Patients with VR during the antiviral treatment exhibited higher sPD-1 levels and lower HBsAg levels at baseline. Receiver operating characteristic (ROC) curves were generated to determine the predictive value of sPD-1 and HBsAg for VR in patients who received first-line therapy (entecavir, ETV). The area under ROC (AUROC) values of sPD-1 and HBsAg at baseline were 0.850 (95%CI:0.729-0.971, P=0.0005) and 0.785 (95%CI: 0.642-0.929, P=0.005), respectively, and the optimal cut-off values were 459.46 pg/mL and 14710 IU/mL, respectively. The combination of sPD-1 and HBsAg exhibited a higher AUROC value (0.870,95% CI: 0.748-0.983, P=0.001) than did sPD-1 or HBsAg alone. In patients administered second-line therapy (lamivudine, LAM/adefovir divipoxil, ADV), baseline sPD-1 levels above 677.2 pg/mL were significantly associated with higher incidence of VR after 96 weeks of antiviral therapy, 7.956 times higher than level ≤677.2 pg/mL.

Conclusions: By combining sPD-1 and HBsAg, we obtained a biomarker significantly associated with VR in CHB patients. The sPD-1 levels could be used to screen out patients with poor prognosis of antiviral therapy.

Keywords: Hepatitis B virus; Nucleos(t)ide analogue (NA) therapy; programmed death ligand-1; soluble programmed cell death protein-1; virological response.

Copyright © 2021. Published by Elsevier B.V.

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