Cumulative Exposure to High Systemic Inflammation and Incident Metabolic Dysfunction-Associated Steatotic Liver...

This study aimed to examine the association between cumulative exposure to systemic inflammation and incident metabolic dysfunction-associated steatotic liver disease (MASLD) and related liver fibrosis in mainland China.

This study used data from an ongoing longitudinal physical examination cohort. We enrolled 9,725 participants (aged ≥18 years) who completed three consecutive biennial health examinations between 2018 and 2022, with complete follow-up in 2024. Systemic inflammation was quantified using three established biomarkers: neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). Cumulative exposure was calculated from baseline to the third examination by multiplying biomarker values by the time (years) between consecutive examinations. The primary outcome was MASLD development at the fourth examination, and advanced liver fibrosis among incident MASLD cases was further evaluated using the fibrosis-4 index (≥2.67). Multivariable logistic regression models were used to explore the associations between cumulative exposure to inflammation and MASLD incidence and fibrosis severity.

At the fourth examination, 939 incident MASLD cases (9.66%) were identified. In fully adjusted models, participants in the highest quartile of cumulative NC exposure had 2.20-fold higher odds of MASLD (95% confidence interval [CI], 1.81 to 2.69; P for trend <0.001) than those in the lowest quartile. Similarly, the highest quartile of cumulative SII exposure had 1.32-fold higher odds (95% CI, 1.09 to 1.59; P for trend=0.003). Conversely, cumulative NLR exposure showed no significant association with MASLD incidence. The addition of cumulative NC or SII to the basic model comprising traditional risk factors improved the ability to predict MASLD. Furthermore, among participants who developed MASLD, the highest quartile of cumulative NC (odds ratio [OR], 4.74; 95% CI, 1.76 to 12.75; P for trend <0.001) and cumulative SII (OR, 3.74; 95% CI, 1.48 to 9.45; P for trend=0.006), but not cumulative NLR, were significantly associated with an elevated risk of advanced liver fibrosis.

Greater NC exposure and excessive SII exposure were each independently associated with incident MASLD and related advanced liver fibrosis. Whether reducing inflammation can help prevent MASLD requires further investigation.