Abstract
OBJECTIVE: The level of systemic inflammation plays a critical role in influencing liver function. This study aims to investigate the impact of various composite inflammatory markers on the liver during the COVID-19 pandemic. METHODS: Data were sourced from the updated NHANES database, reflecting information collected during the COVID-19 pandemic between 2021 and 2023. Based on complete blood count (CBC) data, we identified six composite inflammatory markers: neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-monocyte-to-lymphocyte ratio (NMLR), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII). We described the baseline characteristics of the study population and preliminarily explored the effects of inflammation levels on liver stiffness and fatty liver using linear regression models under various fitting conditions. Furthermore, Spearman correlation analysis was performed to assess the relationships between covariates and the primary variables, and restricted cubic splines (RCS) were applied to examine the nonlinear relationships between variables. Finally, structural equation modeling (SEM) was used to investigate the mediating role of inflammatory markers in modulating the effects of different variables on liver outcomes. RESULTS: A total of 4,165 participants were included in the present study. After adjustment for a comprehensive set of covariates and potential confounders, SIRI demonstrated relatively stable associations with liver-related outcomes compared to other composite inflammatory indices, exhibiting a positive correlation with both median liver stiffness (MLS) and the controlled attenuation parameter (CAP). RCS analysis revealed a significant non-linear relationship between SIRI and CAP (P < 0.05). In the final mediation analysis, SIRI was identified as a mediator in the relationship between age, body mass index (BMI), and MLS. Similarly, SIRI mediated the effects of age, BMI, hemoglobin, and platelet count on CAP, further highlighting its central role in inflammation-related hepatic alterations. CONCLUSIONS: Our findings indicate that during the COVID-19 pandemic, SIRI exerted a significant impact on liver health, demonstrating particular utility in the early detection of hepatic fibrosis and steatosis. These results underscore the potential of SIRI as a valuable marker in the prevention and management of liver diseases, warranting greater attention in clinical and public health settings.