Yangxuan He,1,2,* Manling Hu,1,2,* Xinlei Miao,1 Fei Xu,1,3 Jiayi Deng,1,2 Ziping Song,1,2 Meng Li,1,3 Yunxiang Ming,1,2 Song Leng1,3 

1Health Management Center, the Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Department of Gastroenterology,the Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 3School of Public Health. Dalian Medical University, Dalian, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Song Leng, The Second Affiliated Hospital of Dalian Medical University, No. 467, Zhongshan Road, Shahekou District, Dalian, Liaoning, 116023, People’s Republic of China, Tel +86-0411-84686593, Email dllengsong@163.com

Objective: Previous research studies have linked the systemic immune inflammation index (SII), derived from a complete blood count, to metabolic dysfunction-associated steatotic liver disease (MASLD). However, evidence on the relationship between longitudinal changes in SII and MASLD remains limited. This study aimed to explore distinct SII trajectories and their association with MASLD incidence.
Methods: A longitudinal study analyzed 25,600 individuals who underwent periodic health assessments at a Dalian City hospital between 2014 and 2023. MASLD was diagnosed via ultrasound. The SII was calculated using the formula SII = (platelet count × neutrophil count) / lymphocyte count. Group-based trajectory modeling was used to identify SII trajectories, and restricted cubic spline (RCS) analysis was employed to assesse the dose-response relationship. Stratified analyses and sensitivity analyses were also conducted.
Results: Three SII trajectories were identified: “low stable” (50.6%), “moderate stable” (35.1%), and “high stable” (8.9%). After adjustments, the hazard ratios (HR) for MASLD incidence were 1.118 (95% CI: 1.057– 1.182, P< 0.001) for the “moderate stable” group and 1.284 (95% CI: 1.172– 1.408, P< 0.001) for the “high stable” group. These associations persisted after adjusting for lifestyle factors. A significant non-linear relationship between SII and MASLD risk was found in both the overall population and among different genders. Subgroup and sensitivity analyses consistently confirmed these findings.
Conclusion: Elevated SII levels are significantly associated with an increased risk of MASLD, particularly among individuals under 45 and women. Regular SII monitoring may improve risk stratification and facilitate targeted prevention strategies for those at higher risk of MASLD.

Keywords: systemic inflammation, dynamic status, long-term trajectories, metabolic dysfunction-associated steatotic liver disease, prospective cohort