State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University , Guangzhou, China.
Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University , Guangzhou, China.
J Clin Microbiol. 2024 Feb 14;62(2):e0139623. doi: 10.1128/jcm.01396-23. Epub 2024 Jan 23.
Chemokine receptor 4 (CXCR4) plays a vital role in immunoregulation during hepatitis B virus (HBV) infection. This study aimed to screen single-nucleotide polymorphisms (SNPs) of for predicting pegylated interferon-alpha (PegIFNα) therapy response in chronic hepatitis B (CHB) patients. This retrospective cohort study enrolled a total of 945 CHB patients in two cohorts (Cohort 1, = 238; Cohort 2, = 707), and all the patients were hepatitis B e antigen (HBeAg)-positive and treated with PegIFNα for 48 weeks and followed up for 24 weeks. Twenty-two tag SNPs were selected in and its flanking region. A polygenic score (PGS) was utilized to evaluate the cumulative effect of multiple SNPs. The relationships between SNPs and PGS and PegIFNα treatment response were explored in the two cohorts. Among the 22 candidate SNPs of , rs28367495 (T > C) was significantly linked to PegIFNα treatment response in both cohorts. In patients with more number of rs28367495 C allele, a higher rate of combined response (CR, defined as HBeAg seroconversion and HBV DNA level < 3.3 log IU/mL; = 1.51 × 10), a lower mean hepatitis B surface antigen (HBsAg) level ( = 4.76 × 10), and a higher mean HBsAg decline ( = 3.88 × 10) at Week 72 were achieved. Moreover, a PGS integrating _rs28367495 and five previously reported SNPs was strongly correlated with CR ( = 1.26 × 10), HBsAg level ( = 4.90 × 10), and HBsAg decline ( = 0.005) in all the patients of the two cohorts. _rs28367495 is a promising indicator for predicting the responsiveness to PegIFNα treatment for HBeAg-positive CHB patients. The new PGS may further improve the prediction performance.
趋化因子受体 4（CXCR4）在乙型肝炎病毒（HBV）感染期间的免疫调节中发挥重要作用。本研究旨在筛选 中的单核苷酸多态性（SNP），以预测慢性乙型肝炎（CHB）患者接受聚乙二醇干扰素-α（PegIFNα）治疗的反应。这项回顾性队列研究共纳入了两批队列的 945 名 CHB 患者（队列 1， = 238；队列 2， = 707），所有患者均为乙型肝炎 e 抗原（HBeAg）阳性，接受 PegIFNα治疗 48 周，并随访 24 周。在 及其侧翼区域中选择了 22 个标签 SNP。多基因评分（PGS）用于评估多个 SNP 的累积效应。在两个队列中探讨了 SNPs 与 PGS 以及 PegIFNα 治疗反应之间的关系。在 的 22 个候选 SNP 中，rs28367495（T > C）在两个队列中均与 PegIFNα 治疗反应显著相关。在具有更多 rs28367495 C 等位基因的患者中，联合应答（CR，定义为 HBeAg 血清学转换和 HBV DNA 水平 < 3.3 log IU/mL； = 1.51 × 10）的比率更高，乙型肝炎表面抗原（HBsAg）水平的平均值更低（ = 4.76 × 10），HBsAg 下降的平均值更高（ = 3.88 × 10），在第 72 周时。此外，整合 _rs28367495 和五个先前报道的 SNP 的 PGS 与两个队列中所有患者的 CR（ = 1.26 × 10）、HBsAg 水平（ = 4.90 × 10）和 HBsAg 下降（ = 0.005）呈强烈相关。rs28367495 是预测 HBeAg 阳性 CHB 患者对 PegIFNα 治疗反应的有希望的指标。新的 PGS 可能进一步提高预测性能。
