外周血单个核细胞中LY6E和TRIM6表达的改变与HBeAg阴性慢性乙型肝炎患者的HBsAg清除及对聚乙二醇干扰素-α治疗的反应相关。

Altered LY6E and TRIM6 expression in PBMCs correlated with HBsAg clearance and response to Peg-IFN-α treatment in HBeAg-negative chronic hepatitis B patients.

作者信息

Shan Yiru, Pang Hao, Tang Yao, Yang Na, Wang Rui, Yang Fan, Qin Bo

机构信息

Department of Infectious Diseases, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Central Laboratory, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Virol J. 2025 Mar 15;22(1):74. doi: 10.1186/s12985-025-02689-8.

DOI:10.1186/s12985-025-02689-8

PMID:40089754

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11909810/

Abstract

BACKGROUND

Pegylated interferon alpha (Peg-IFN-α) has the potential to eradicate hepatitis B surface antigen (HBsAg). This study aimed to investigate whether the expression levels of lymphocyte antigen 6 family member E (LY6E) and tripartite motif-containing protein 6 (TRIM6) mRNAs in peripheral blood mononuclear cells (PBMCs) of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) patients is associated with the response to Peg-IFN-α treatment and HBsAg clearance.

METHODS

In this prospective study, HBeAg-negative chronic HBV patients treated with Peg-IFN-α were followed for 48 weeks. The participants were classified into two groups, the virological response (VR) group and nonvirological response (NVR) group, according to the changes in HBV DNA and HBsAg levels observed at week 48 of treatment. Furthermore, these patients were divided into a serological response (SR) group and a nonserological response (NSR) group, depending on whether they exhibited a loss of serum HBsAg or evidence of seroconversion. The expression levels of LY6E and TRIM6 mRNAs in PBMCs were evaluated using real-time quantitative PCR with fluorescence detection. The diagnostic performance of LY6E and TRIM6 was assessed by analyzing the receiver operating characteristic (ROC) curve and calculating the area under the ROC curve (AUC).

RESULTS

After the treatment period, the observed VR and SR rates were 44.64% and 28.57%, respectively. Dynamic changes in LY6E and TRIM6 mRNA levels were significantly different between the VR and NVR groups and between the SR and NSR groups. Multivariate analysis revealed that TRIM6 was independently associated with VR at weeks 12 and 24 of Peg-IFN-α therapy and with SR at week 12; in addition, LY6E was independently associated with VR at week 12 and SR at week 24. At week 24, the area under the curve (AUC) for LY6E in the prediction of VR was 0.6942, and the AUC for the prediction of SR was 0.7766; at week 12, TRIM6 had AUCs of 0.7600 for the prediction of VR and 0.8469 for the prediction of SR.

CONCLUSIONS

LY6E and TRIM6 are important biomarkers for early therapeutic responses to Peg-IFN-α and HBsAg clearance.

TRIAL REGISTRATION

Registration number: 2023 - 311. Date of registration: 1 October 2023.

摘要

背景

聚乙二醇化干扰素α（Peg-IFN-α）有根除乙肝表面抗原（HBsAg）的潜力。本研究旨在探讨乙肝e抗原（HBeAg）阴性的慢性乙型肝炎病毒（HBV）患者外周血单个核细胞（PBMC）中淋巴细胞抗原6家族成员E（LY6E）和含三联基序蛋白6（TRIM6）mRNA的表达水平是否与Peg-IFN-α治疗反应及HBsAg清除相关。

方法

在这项前瞻性研究中，对接受Peg-IFN-α治疗的HBeAg阴性慢性HBV患者进行了48周的随访。根据治疗第48周时观察到的HBV DNA和HBsAg水平变化，将参与者分为两组，即病毒学应答（VR）组和非病毒学应答（NVR）组。此外，根据患者是否出现血清HBsAg消失或血清学转换证据，将这些患者分为血清学应答（SR）组和非血清学应答（NSR）组。采用荧光检测实时定量PCR评估PBMC中LY6E和TRIM6 mRNA的表达水平。通过分析受试者工作特征（ROC）曲线并计算ROC曲线下面积（AUC）来评估LY6E和TRIM6的诊断性能。

结果

治疗期结束后，观察到的VR率和SR率分别为44.64%和28.57%。LY6E和TRIM6 mRNA水平的动态变化在VR组和NVR组之间以及SR组和NSR组之间存在显著差异。多因素分析显示，TRIM6在Peg-IFN-α治疗的第12周和第24周与VR独立相关，在第12周与SR独立相关；此外，LY6E在第12周与VR独立相关，在第24周与SR独立相关。在第24周时，LY6E预测VR的曲线下面积（AUC）为0.6942，预测SR的AUC为0.7766；在第12周时TRIM6预测VR的AUC为0.7600，预测SR的AUC为0.8469。