Exploring the Systemic Immune-Inflammation Index as a novel biomarker for nonalcoholic fatty liver disease: a systematic review and meta-analysis.

Background: Nonalcoholic fatty liver disease (NAFLD) represents one of the most prevalent chronic hepatic disorders globally and is intricately associated with metabolic dysregulation and persistent systemic inflammation. The Systemic Immune-Inflammation Index (SII) has emerged as a promising noninvasive indicator for various inflammation-mediated conditions, including NAFLD. This meta-analysis was undertaken to assess the association between SII and NAFLD. Methods: Observational studies identified through a systematic search of PubMed, Web of Science, Embase, and Scopus up to February 2025 that examined the association between SII and NAFLD were considered eligible for inclusion. Quantitative synthesis of the data was conducted through meta-analytic techniques employing a random-effects model to derive pooled effect estimates, thereby accounting for potential heterogeneity across studies. Results: The meta-analysis demonstrated a statistically significant association between higher SII levels and NAFLD. When SII was analyzed as a continuous variable, the pooled effect size was significant (Hedges' g = 0.11, 95% CI: 0.04-0.18, P < 0.01), indicating elevated SII levels in individuals with NAFLD compared to controls. When evaluated categorically, individuals with high SII values had increased odds of having NAFLD (OR = 1.45, 95% CI: 1.18-1.78, P < 0.01). Statistical power was sufficient to support the validity of the observed associations. Conclusions: SII shows a significant association with NAFLD and may serve as a valuable, noninvasive biomarker for early detection and risk stratification. Despite promising results, the presence of heterogeneity and possible publication bias highlights the need for more standardized and longitudinal research to validate SII's clinical utility in NAFLD.