Background: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver condition globally, spanning a spectrum from simple steatosis to non-alcoholic steatohepatitis (NASH) and progressive fibrosis. Inflammation and metabolic dysregulation play key roles in its pathogenesis. Accordingly, inflammatory and metabolic biomarkers have gained increasing attention as potential tools for non-invasive diagnosis and disease staging.Objective: This scoping review aimed to synthesize current evidence on the diagnostic performance of inflammatory and metabolic biomarkers for NAFLD, with a focus on their potential application in early screening and disease stratification.Methods: We systematically searched PubMed and CNKI databases for relevant peer-reviewed literature published up to August 2024. The search strategy combined MeSH terms and free-text keywords, and study selection was guided by the Population–Concept–Context (PCC) framework. Methodological quality was assessed using the Newcastle–Ottawa Scale and AHRQ criteria.Results: Fifteen eligible studies (11 case-control, 2 cohort, 1 cross-sectional, and 1 retrospective study) were included, yielding 18 candidate biomarkers. The triglyceride-glucose (TyG) index was commonly associated with early-stage NAFLD screening; cytokeratin-18 (CK18) was linked to NASH detection, while adiponectin and osteopontin (OPN) were related to liver fibrosis. Additionally, inflammatory indices such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII) showed clinical promise due to their accessibility and low cost.Conclusion: Inflammatory and metabolic biomarkers provide valuable non-invasive insights into the diagnosis and staging of NAFLD. The integration of multiple biomarkers may enhance diagnostic accuracy and support stratified management strategies. However, further validation is needed to establish standardized thresholds and confirm clinical utility across diverse populations.

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is increasingly recognized as a systemic immuno-metabolic disorder characterized by chronic low-grade inflammation and dysregulated innate immune activation. Circulating immune-related indices derived from routine blood tests may reflect early immuno-metabolic imbalance and provide accessible markers for identifying disease-associated immune dysregulation. Aim: To investigate the associations of two systemic immuno-metabolic inflammatory indices, namely the neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) and the systemic inflammation response index (SIRI) with MASLD, and to evaluate their combined discriminative performance. Methods: In this retrospective case–control study, adult participants attending a tertiary hospital between November 2023 and October 2024 were enrolled. After strict eligibility screening, propensity score matching (1:1) was applied to balance demographic characteristics and comorbidities, yielding 522 matched individuals (261 with MASLD and 261 without MASLD). Multivariable conditional logistic regression was used to assess associations between immuno-metabolic inflammatory indices and MASLD. Discriminatory performance was assessed using receiver operating characteristic (ROC) curves. The DeLong test, Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI) were used to evaluate discriminative ability. Model calibration was evaluated using the Hosmer-Lemeshow test, Brier score, and calibration curves. Internal validation was performed using 2,000 bootstrap resamples. Results: After propensity score matching, both NHR and SIRI were independently associated with MASLD in multivariable analysis. The combined model integrating NHR, SIRI, and alanine aminotransferase (ALT) demonstrated optimal discriminative performance (AUC = 0.865, sensitivity = 72.41%, specificity = 84.30%), significantly outperforming the ALT-only model (DeLong test, Z = -8.3083, P < 0.001). The total Net Reclassification Improvement (NRI) was 0.345 (95% CI: 0.245–0.438), and the total Integrated Discrimination Improvement (IDI) was 0.348 (95% CI: 0.282–0.424, P < 0.001). The Hosmer-Lemeshow test (χ² = 11.043, df = 8, P = 0.199) and Brier score (0.151, 95% CI: 0.134–0.168) confirmed good model calibration, and the calibration curve showed excellent agreement between predicted probabilities and actual incidence. Internal validation through 2,000 bootstrap resamples resulted in a corrected AUC of 0.866 (95% CI: 0.836–0.897), with an average optimism of -0.001, indicating good model stability and minimal risk of overfitting. Conclusion: Systemic immuno-metabolic inflammatory indices reflecting innate immune activation and lipid-related anti-inflammatory dysfunction (NHR and SIRI) are closely associated with MASLD. The combined assessment of NHR, SIRI, and ALT provides a robust, clinically accessible approach with significant incremental value for identifying immuno-metabolic risk in MASLD, highlighting the central role of systemic immune dysregulation in metabolic liver disease.