Association of Systemic Immune‑Inflammation Index with Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), represents a growing burden of chron-ic liver disease worldwide. Chronic low-grade inflammation is central to disease pathogenesis, but the value of systemic inflammatory biomarkers in diagnosis and risk stratification remains unclear. The systemic immune-inflammation index (SII), calculated from peripheral blood counts, has been pro-posed as a composite marker reflecting the balance between pro- and anti-inflammatory components. This study evaluates the diagnostic and predictive utility of SII in MASLD. Aim of Study: To investigate the association between the systemic immune-inflammation index (SII) and non-alcoholic fatty liver disease (NAFLD) and to explore potential factors associated with elevated SII levels in individuals with NAFLD. Patients and Methods: A matched case-control study was conducted, enrolling 174 adult Egyptian patients: 87 with ul-trasound-confirmed MASLD and 87 age- and sex-matched non-MASLD controls. Participants underwent clinical as-sessment, laboratory testing, and abdominal ultrasound with shear-wave elastography to exclude other liver diseases and stage fibrosis non-invasively. SII was calculated as platelet count × neutrophil count / lymphocyte count. The NAFLD fibrosis score (NFS) and body mass index (BMI) were also computed. Diagnostic performance was assessed with receiv-er-operating characteristic (ROC) curves, and multivariate logistic regression was used to evaluate independent predictors of MASLD. Results: Median SII values did not differ significantly be-tween MASLD and control groups (p = 0.997). In ROC analy-sis, SII alone showed poor discriminatory ability for MASLD (area under the curve (AUC) = 0.50). In multivariate regres-sion, however, lower SII emerged as an independent protective factor against MASLD (odds ratio = 0.99; p = 0.037) after ad-justing for BMI and fasting blood glucose (FBG). Higher BMI and FBG were significant risk factors. A composite model in-corporating SII, BMI and FBG improved diagnostic accuracy (AUC = 0.75), outperforming SII alone or traditional fibrosis scores. Conclusion: Although SII lacks stand-alone diagnostic value for MASLD, it contributes to risk prediction when com-bined with metabolic variables. These findings emphasize the predominance of metabolic risk factors in early disease and highlight the potential of composite scores for non-invasive screening. Further longitudinal studies using histological or magnetic resonance imaging confirmation and broader bi-omarker panels are warranted to validate the role of SII in MASLD.