Systemic Immune-Inflammation Index (SII) vs. The De Ritis Ratio in Subclinical Metabolic Stress

Background Metabolic dysfunction-associated fatty liver disease (MAFLD/MASLD) is an escalating public health issue due to its protracted progression and systemic metabolic ramifications. Thyroid-stimulating hormone (TSH) mediated mechanisms that facilitate hepatic fat accumulation can represent a pathway through which subclinical hypothyroidism (SCH) exerts its influence. The De Ritis ratio (AST/ALT) and the systemic immune-inflammation index (SII) are new signs of inflammation in the body and stress on the liver. This review synthesizes the current clinical evidence exploring the interlink between SCH, inflammation, and hepatocellular injury in MASLD. Methods A structured perspective review was conducted utilizing the PubMed, Embase, Web of Science, and Cochrane Library databases (up to February 2026) to identify studies examining the relationships between MAFLD/MASLD, inflammatory and endocrine biomarkers, including the SII and De Ritis ratio, and subclinical hepatic and vascular outcomes; the findings were summarized narratively. Results A combination of data from SII and De Ritis ratio studies shows that systemic inflammation and hepatocellular injury are both good predictors of MASLD severity and its effects outside the liver. SCH may act as an upstream endocrine driver, elevating the risk of fibrosis and cardiovascular disease by enhancing hepatic lipid accumulation, systemic inflammation (SII), and AST/ALT imbalance (De Ritis ratio). Conclusion Understanding the combined predictive value of the De Ritis ratio and SII may improve early risk assessment, guide targeted therapies, and reduce cardiometabolic consequences. To validate these biomarkers, elucidate causality, and enhance endocrine-metabolic therapy in both adult and paediatric populations, future research should prioritize longitudinal and interventional studies.