State Key Laboratory of Organ Failure Research, MOE Key Laboratory of Infectious Diseases Research in South China, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China; The Key Laboratory of Molecular Pathology (Hepatic Diseases) of Guangxi, Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China; Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China.
State Key Laboratory of Organ Failure Research, MOE Key Laboratory of Infectious Diseases Research in South China, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Antiviral Res. 2024 Nov;231:106005. doi: 10.1016/j.antiviral.2024.106005. Epub 2024 Sep 10.
CXC chemokine receptor 7 (CXCR7) plays pivotal roles in different virus infections. However, no research focused on the role of CXCR7 in hepatitis B virus (HBV)-infected patients. The primary aim of this study is to elucidate the role of CXCR7 in predicting the treatment response of chronic hepatitis B (CHB) patients undergoing pegylated interferon-alpha (PegIFNα) therapy.
Two cohorts with a total of 945 Chinese CHB patients (Cohort 1, n = 238; Cohort 2, n = 707) were enrolled in this retrospective study, all the patients were positive for hepatitis B e antigen (HBeAg) and received PegIFNα treatment for 48 weeks and followed-up for 24 weeks post-treatment. Nineteen tag single-nucleotide polymorphisms (SNPs) were selected within and surrounding the CXCR7 gene region. The associations of CXCR7 SNPs and polygenic score (PGS) with PegIFNα treatment response were investigated in the two cohorts.
Among the 19 candidate SNPs of CXCR7, rs2952665 (A > G) was significantly associated with combined response (CR, defined as HBeAg seroconversion and HBV DNA level <3.3logIU/mL, P = 0.002) and hepatitis B surface antigen (HBsAg) decline (P = 0.015) in the two cohorts at week 72. Furthermore, a PGS comprising CXCR7_rs2952665 and five additional SNPs, which were previously recognized as biomarkers of PegIFNα treatment response, demonstrated a robust correlation with both CR (P = 1.38 × 10) and HBsAg decline (P = 0.003) in all the patients.
This research illustrated that CXCR7_rs2952665 is a promising predictor of the PegIFNα therapy efficiency in Chinese HBeAg-positive CHB patients. A PGS consisting of CXCR7_rs2952665 and five previously reported SNPs predicts treatment response to PegIFNα better.
趋化因子 CXC 受体 7（CXCR7）在不同病毒感染中发挥关键作用。然而，目前尚无研究关注 CXCR7 在乙型肝炎病毒（HBV）感染患者中的作用。本研究的主要目的是阐明 CXCR7 在预测接受聚乙二醇干扰素-α（PegIFNα）治疗的慢性乙型肝炎（CHB）患者治疗反应中的作用。
本回顾性研究共纳入了 945 例中国 CHB 患者（队列 1，n=238；队列 2，n=707）。所有患者均为乙型肝炎 e 抗原（HBeAg）阳性，接受 PegIFNα 治疗 48 周，并在治疗后随访 24 周。在 CXCR7 基因区域内及周围选择了 19 个标签单核苷酸多态性（SNP）。在两个队列中，研究了 CXCR7 SNP 和多基因评分（PGS）与 PegIFNα 治疗反应的相关性。
在 CXCR7 的 19 个候选 SNP 中，rs2952665（A>G）在两个队列的第 72 周时，与联合应答（CR，定义为 HBeAg 血清学转换和 HBV DNA 水平<3.3logIU/mL，P=0.002）和乙型肝炎表面抗原（HBsAg）下降（P=0.015）显著相关。由 CXCR7_rs2952665 和之前被认为是 PegIFNα 治疗反应生物标志物的另外 5 个 SNP 组成的 PGS，与所有患者的 CR（P=1.38×10）和 HBsAg 下降（P=0.003）具有很强的相关性。
本研究表明，CXCR7_rs2952665 是中国 HBeAg 阳性 CHB 患者 PegIFNα 治疗效果的一个有前途的预测因子。由 CXCR7_rs2952665 和五个之前报道的 SNP 组成的 PGS 可更好地预测 PegIFNα 治疗的反应。
