Scholarlink

Background <p>Early identification of significant liver pathology is crucial for timely antiviral intervention in individuals with chronic hepatitis B (CHB) infection. Current non-invasive methods show limited accuracy in detecting occult liver damage, particularly in those with normal ALT. This study evaluated serum N-glycan profiles for diagnosing significant liver pathology in treatment-naïve CHB patients across clinical phases.</p> Methods <p>This cross-sectional study analyzed 626 treatment-naïve CHB patients confirmed by liver biopsy, classified according to 2025 EASL guidelines. Serum N-glycan profiles were determined using DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis. Significant liver pathology was defined as inflammation grade ≥ G2 and/or fibrosis stage ≥ S2 (per Scheuer scoring system). Multivariate logistic regression models were developed and compared with traditional non-invasive markers.</p> Results <p>Among 626 CHB patients, 66.0% had significant inflammation and 58.9% had significant fibrosis. Patients with significant pathology showed characteristic alterations, with elevated P1, P3, P6, P7, P11 peaks and decreased P0, P5, P8, P10 peaks (all <i>p</i> &lt; 0.0001). Compared to respective infection phases, hepatitis phases showed P1 increases of 19.6% and 36% in HBeAg(+) and HBeAg(-) patients, with P11 increases of 82.4% and 73.4%, while P0 decreased by 20.3% and 27.6%, and P10 by 21.6% and 20.3%. Relative to mild pathology (G and S &lt; 2), P1 increased by 27% in significant pathology (G and/or S ≥ 2), reaching 58.7%/48.7% in G4/S4 stages (vs. G0/S0). In ALT-normal HBeAg(+) infection phase, P1 increased by 80.2%/65.8% in G4/S4 stages (vs. G0/S0), with P2 also increasing by 54.1%/45.2%. Multivariate analysis identified P11 as strongest risk factor (OR = 3.84, 95%CI: 1.74–8.45, <i>p</i> = 0.0008), followed by P1 (OR = 2.04, 95%CI: 1.57–2.64, <i>p</i> &lt; 0.0001) and P7 (OR = 1.75, 95%CI: 1.31–2.34, <i>p</i> = 0.0002), while P2 (OR = 0.07, 95%CI: 0.02–0.26, <i>p</i> &lt; 0.0001) and P0 (OR = 0.30, 95%CI: 0.12–0.79, <i>p</i> = 0.0140) served as protective factors. The glycomics combined model (AUC = 0.876 (0.844–0.908)) achieved superior performance and outperformed the clinical model (AUC = 0.818 (0.779–0.857)), LSM (AUC = 0.817 (0.775–0.858)), APRI (AUC = 0.830 (0.792–0.867)), and FIB-4 (AUC = 0.672 (0.621–0.723)) (all <i>p</i> &lt; 0.001), with 78.7% sensitivity and 83.2% specificity. The optimized model reached AUC = 0.917 (0.891–0.942) with accuracy 84.2%, with 78.7% sensitivity and 94.6% specificity. Both glycomics-based models maintained diagnostic capability in ALT-normal patients particularly in HBeAg(+) infection.</p> Conclusions <p>Serum N-glycomics demonstrates promising potential for non-invasive identification of significant liver pathology in treatment-naïve CHB patients, providing an alternative approach for early treatment decisions, especially in ALT-normal patients with occult liver damage.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Serum N-glycomics for non-invasive detection of significant liver pathology across clinical phases of treatment-naïve chronic hepatitis B

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月25日

查看全文
  • Xinjie Li,
  • Meijie Shi,
  • Hao Yu,
  • Jinbao Huang,
  • Shanshan Ji,
  • Bo Han,
  • Yan Zhong,
  • Pengyuan Kang,
  • Yuqi Zhang,
  • Cuiying Chen,
  • Chao Zhang,
  • Lei Xu,
  • Xiaoling Chi,
  • Tao Shen

摘要

Background

Early identification of significant liver pathology is crucial for timely antiviral intervention in individuals with chronic hepatitis B (CHB) infection. Current non-invasive methods show limited accuracy in detecting occult liver damage, particularly in those with normal ALT. This study evaluated serum N-glycan profiles for diagnosing significant liver pathology in treatment-naïve CHB patients across clinical phases.

Methods

This cross-sectional study analyzed 626 treatment-naïve CHB patients confirmed by liver biopsy, classified according to 2025 EASL guidelines. Serum N-glycan profiles were determined using DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis. Significant liver pathology was defined as inflammation grade ≥ G2 and/or fibrosis stage ≥ S2 (per Scheuer scoring system). Multivariate logistic regression models were developed and compared with traditional non-invasive markers.

Results

Among 626 CHB patients, 66.0% had significant inflammation and 58.9% had significant fibrosis. Patients with significant pathology showed characteristic alterations, with elevated P1, P3, P6, P7, P11 peaks and decreased P0, P5, P8, P10 peaks (all p < 0.0001). Compared to respective infection phases, hepatitis phases showed P1 increases of 19.6% and 36% in HBeAg(+) and HBeAg(-) patients, with P11 increases of 82.4% and 73.4%, while P0 decreased by 20.3% and 27.6%, and P10 by 21.6% and 20.3%. Relative to mild pathology (G and S < 2), P1 increased by 27% in significant pathology (G and/or S ≥ 2), reaching 58.7%/48.7% in G4/S4 stages (vs. G0/S0). In ALT-normal HBeAg(+) infection phase, P1 increased by 80.2%/65.8% in G4/S4 stages (vs. G0/S0), with P2 also increasing by 54.1%/45.2%. Multivariate analysis identified P11 as strongest risk factor (OR = 3.84, 95%CI: 1.74–8.45, p = 0.0008), followed by P1 (OR = 2.04, 95%CI: 1.57–2.64, p < 0.0001) and P7 (OR = 1.75, 95%CI: 1.31–2.34, p = 0.0002), while P2 (OR = 0.07, 95%CI: 0.02–0.26, p < 0.0001) and P0 (OR = 0.30, 95%CI: 0.12–0.79, p = 0.0140) served as protective factors. The glycomics combined model (AUC = 0.876 (0.844–0.908)) achieved superior performance and outperformed the clinical model (AUC = 0.818 (0.779–0.857)), LSM (AUC = 0.817 (0.775–0.858)), APRI (AUC = 0.830 (0.792–0.867)), and FIB-4 (AUC = 0.672 (0.621–0.723)) (all p < 0.001), with 78.7% sensitivity and 83.2% specificity. The optimized model reached AUC = 0.917 (0.891–0.942) with accuracy 84.2%, with 78.7% sensitivity and 94.6% specificity. Both glycomics-based models maintained diagnostic capability in ALT-normal patients particularly in HBeAg(+) infection.

Conclusions

Serum N-glycomics demonstrates promising potential for non-invasive identification of significant liver pathology in treatment-naïve CHB patients, providing an alternative approach for early treatment decisions, especially in ALT-normal patients with occult liver damage.