代谢功能障碍相关脂肪性肝病全谱中的血清LEAP2水平：一种用于严重程度分层的潜在非侵入性生物标志物。

Serum LEAP2 Levels Across the Spectrum of Metabolic Dysfunction-Associated Fatty Liver Disease: A Potential Noninvasive Biomarker for Severity Stratification.

作者信息

Huang Xinyang, Deng Zihao, Li Xiaozhou, Yan Songxin, Zhong Kunjiang, Yuan Fengning, Liu Ligang, Deng Chaolin, Liu Tingting, Zhao Ruizhao, Buhe Amin, Li Tianxiong, Zhao Hao

机构信息

Capital Medical University, Beijing, People's Republic of China.

Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2025 Jul 22;18:2439-2450. doi: 10.2147/DMSO.S536270. eCollection 2025.

DOI:10.2147/DMSO.S536270

PMID:40726500

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12301118/

Abstract

PURPOSE

To evaluate circulating liver-expressed antimicrobial peptide 2 (LEAP2) as a potential noninvasive biomarker for the presence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its progression to metabolic dysfunction-associated steatohepatitis (MASH).

PATIENTS AND METHODS

This prospective observational study enrolled obese patients with MAFLD, categorized into simple steatosis (SS) or MASH based on liver histopathology, along with healthy controls (HC). Serum levels LEAP2 were quantified using enzyme-linked immunosorbent assay (ELISA). Baseline characteristics were compared among groups, followed by univariable and multivariate ordinary logistic regression to identify MAFLD predictors. The diagnostic performance of LEAP2 was evaluated through receiver operating characteristic (ROC) curve analysis. Additionally, Hepatic LEAP2 transcriptomic data from public Gene Expression Omnibus (GEO) datasets (GSE126848, GSE135251) were analyzed for validation.

RESULTS

Seventy-four participants (24 HC, 24 SS, 26 MASH) were analyzed. Serum LEAP2 levels significantly and progressively increased with MAFLD severity (median ng/mL: HC 11.54, SS 13.62, MASH 18.34; P<0.001), correlating positively with disease stage (Spearman's =0.526, P<0.001). This pattern was validated using hepatic LEAP2 transcript data from GEO datasets (P<0.001; Spearman's =0.317, P<0.001). Multivariate logistic regression identified serum LEAP2 as an independent factor associated with MAFLD presence (OR=1.14, 95% CI 1.03-1.26; P=0.014), alongside BMI and ALT, while HDL was protective. ROC analysis demonstrated good diagnostic performance for distinguishing MASH from HC (AUC=0.86) and moderate performance for adjacent stages (HC vs SS, AUC=0.70; SS vs MASH, AUC=0.70).

CONCLUSION

Serum LEAP2 levels progressively increase with MAFLD severity and are independently associated with the disease. LEAP2 demonstrates potential as a noninvasive biomarker for assessing MAFLD severity, particularly in distinguishing MASH from healthy individuals. These findings warrant further investigation into LEAP2's pathophysiological role and therapeutic potential.

摘要

目的

评估循环中的肝脏表达抗菌肽2（LEAP2）作为代谢功能障碍相关脂肪性肝病（MAFLD）及其进展为代谢功能障碍相关脂肪性肝炎（MASH）的潜在非侵入性生物标志物。

患者和方法

这项前瞻性观察性研究纳入了患有MAFLD的肥胖患者，根据肝脏组织病理学分为单纯性脂肪变性（SS）或MASH，以及健康对照（HC）。使用酶联免疫吸附测定（ELISA）对血清LEAP2水平进行定量。比较各组的基线特征，然后进行单变量和多变量普通逻辑回归以确定MAFLD的预测因素。通过受试者工作特征（ROC）曲线分析评估LEAP2的诊断性能。此外，还分析了来自公共基因表达综合数据库（GEO）数据集（GSE126848、GSE135251）的肝脏LEAP2转录组数据进行验证。

结果

对74名参与者（24名HC、24名SS、26名MASH）进行了分析。血清LEAP2水平随着MAFLD严重程度显著且逐渐升高（中位数ng/mL：HC为11.54，SS为13.62，MASH为18.34；P<0.001），与疾病阶段呈正相关（Spearman相关系数=0.526，P<0.001）。使用来自GEO数据集的肝脏LEAP2转录数据验证了这种模式（P<0.001；Spearman相关系数=0.317，P<0.001）。多变量逻辑回归确定血清LEAP2是与MAFLD存在相关的独立因素（OR=1.14，95%CI 1.03 - 1.26；P=0.014），与BMI和ALT一起，而HDL具有保护作用。ROC分析表明，LEAP2在区分MASH与HC方面具有良好的诊断性能（AUC=0.86），在相邻阶段（HC与SS，AUC=0.70；SS与MASH，AUC=0.70）具有中等性能。