Serum LEAP2 Levels Across the Spectrum of Metabolic Dysfunction-Associated Fatty Liver Disease: A Potential Noninvasive Biomarker for Severity Stratification.
{"title":"Serum LEAP2 Levels Across the Spectrum of Metabolic Dysfunction-Associated Fatty Liver Disease: A Potential Noninvasive Biomarker for Severity Stratification.","authors":"Xinyang Huang, Zihao Deng, Xiaozhou Li, Songxin Yan, Kunjiang Zhong, Fengning Yuan, Ligang Liu, Chaolin Deng, Tingting Liu, Ruizhao Zhao, Amin Buhe, Tianxiong Li, Hao Zhao","doi":"10.2147/DMSO.S536270","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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).</p><p><strong>Patients and methods: </strong>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.</p><p><strong>Results: </strong>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 <i>ρ</i>=0.526, P<0.001). This pattern was validated using hepatic LEAP2 transcript data from GEO datasets (P<0.001; Spearman's <i>ρ</i>=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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"2439-2450"},"PeriodicalIF":3.0000,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301118/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DMSO.S536270","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
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 ρ=0.526, P<0.001). This pattern was validated using hepatic LEAP2 transcript data from GEO datasets (P<0.001; Spearman's ρ=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.
目的:评估循环肝脏表达的抗菌肽2 (LEAP2)作为代谢功能障碍相关脂肪性肝病(MAFLD)存在及其进展为代谢功能障碍相关脂肪性肝炎(MASH)的潜在无创生物标志物。患者和方法:这项前瞻性观察性研究纳入了肥胖的MAFLD患者,根据肝脏组织病理学分为单纯性脂肪变性(SS)或MASH,以及健康对照组(HC)。采用酶联免疫吸附法(ELISA)定量测定血清LEAP2水平。比较各组之间的基线特征,然后进行单变量和多变量普通逻辑回归以确定MAFLD的预测因子。通过受试者工作特征(ROC)曲线分析评价LEAP2的诊断效能。此外,还分析了来自公共基因表达综合(GEO)数据集(GSE126848, GSE135251)的肝脏LEAP2转录组数据进行验证。结果: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严重程度的增加而显著递增(中位ng/mL: HC 11.54, SS 13.62, MASH 18.34;p =0.526, p =0.317, p结论:血清LEAP2水平随MAFLD严重程度逐渐升高,且与疾病独立相关。LEAP2显示了作为评估mald严重程度的非侵入性生物标志物的潜力,特别是在区分MASH与健康个体方面。这些发现为进一步研究LEAP2的病理生理作用和治疗潜力提供了依据。
期刊介绍:
An international, peer-reviewed, open access, online journal. The journal is committed to the rapid publication of the latest laboratory and clinical findings in the fields of diabetes, metabolic syndrome and obesity research. Original research, review, case reports, hypothesis formation, expert opinion and commentaries are all considered for publication.