ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Systemic immuno-metabolic inflammatory indices (neutrophil-to-HDL cholesterol ratio and systemic inflammation response index) are strongly associated with Metabolic Dysfunction-Associated Steatotic Liver Disease: a propensity score-matched study
Huimin Liang 1
Boqiao Wang 2
Deyuan Zhang 1
Zhongzhong Zhang 1
Xu Chen 1,3
Yijia Xu 4
Chengwei Zhang 1
Jinyang Li 1
Jie Yang 5,6
Pengjiao Xi 7
Jianwei Zhang 8
Yan Zhang 1
Haize Ge 5,6
1. School of Nursing, Tianjin Medical University, Tianjin, China
2. Office of Science, Technology and Innovation Management, Tianjin Medical College, Tianjin, China
3. The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
4. East china normal unversity, Shanghai, China
5. Tianjin University Central Hospital, Tianjin, China
6. The Third Central Hospital of Tianjin, Tianjin, China
7. Tianjin Medical University, Tianjin, China
8. Shanxi Bethune Hospital, Taiyuan, China
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Abstract
Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a systemic immuno-metabolic disorder featured by chronic low-grade inflammation and dysregulated innate immune activation. Circulating immune-related indices from routine blood tests may reflect early immuno-metabolic imbalance and provide accessible markers for disease-associated immune dysregulation. Aim: To investigate the associations of two systemic immuno-metabolic inflammatory indices (neutrophil-to-HDL cholesterol ratio [NHR] and systemic inflammation response index [SIRI]) with MASLD, and evaluate their combined discriminative performance. Methods: In this retrospective case–control study, adult participants from a tertiary hospital (November 2023–October 2024) were enrolled. After screening, 1:1 propensity score matching balanced characteristics, yielding 522 matched individuals (261 with MASLD, 261 controls). Multivariable conditional logistic regression, ROC curves, DeLong test, NRI, IDI, Hosmer-Lemeshow test, Brier score, calibration curves and 2,000 bootstrap internal validation were used. Results: After matching, NHR and SIRI were independently associated with MASLD. The combined model of NHR, SIRI and ALT showed optimal performance (AUC = 0.865, sensitivity = 72.41%, specificity = 84.30%), significantly outperforming ALT alone (Z = -8.3083, P < 0.001). Total NRI = 0.345 (95% CI: 0.245–0.438), IDI = 0.348 (95% CI: 0.282–0.424, P < 0.001). Hosmer-Lemeshow test (χ² = 11.043, df = 8, P = 0.199) and Brier score (0.151, 95% CI: 0.134–0.168) confirmed good calibration. Bootstrap validation gave corrected AUC = 0.866, mean optimism = -0.001, indicating stable performance. Conclusion: Systemic immuno-metabolic indices (NHR, SIRI) reflecting innate immune activation and lipid-related anti-inflammatory dysfunction are closely associated with MASLD. Combined assessment of NHR, SIRI and ALT offers a robust, clinically accessible approach with incremental value for identifying MASLD immuno-metabolic risk, highlighting the key role of systemic immune dysregulation in metabolic liver disease.
Summary
Keywords
Immuno-metabolic inflammation4, Metabolic dysfunction-associated steatotic liver disease1, Neutrophil-to-HDL cholesterol ratio2, Systemic immune dysregulation5, Systemic Inflammation Response Index3
Received
15 December 2025
Accepted
18 February 2026
Copyright
© 2026 Liang, Wang, Zhang, Zhang, Chen, Xu, Zhang, Li, Yang, Xi, Zhang, Zhang and Ge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Huimin Liang
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