Systemic Inflammatory Response Index (SIRI) is associated with all-cause mortality and cardiovascular mortality among individuals with Nonalcoholic Fatty Liver Disease (NAFLD): evidence from NHANES (1999-2018)

Background: Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent global health concern, with systemic inflammation significantly contributing to disease progression and related cardiovascular complications. The systemic inflammatory response index (SIRI), which combines neutrophil, monocyte, and lymphocyte counts, has been associated with negative outcomes in various diseases. Nevertheless, the connection between the SIRI and mortality in NAFLD patients has yet to be thoroughly investigated. Objective: This study aimed to examine the associations between the SIRI and all-cause and cardiovascular disease (CVD) mortality in a large cohort of NAFLD patients. Methods: Data were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, including 5,179 individuals diagnosed with NAFLD. Kaplan-Meier (KM) survival curves, restricted cubic spline (RCS) analysis and Cox proportional hazard models were used to assess the relationship between the SIRI and mortality. Receiver operating characteristic (ROC) curves were used to explore the prognostic value of SIRI. Sensitivity analysis was performed to enhance the robustness of the results. Results: Over a median follow-up of 109 months, 898 participants died, 310 of whom died from CVD. Participants who experienced mortality had higher levels of SIRI in the baseline. KM survival analysis revealed that participants in the highest SIRI quartile (Q4) had significantly worse survival outcomes than those in Q1 (log-rank test, P < 0.001). The multivariable-adjusted Cox regression models demonstrated that higher SIRI levels were independently associated with increased risks of all-cause mortality (HR per unit increase = 1.20; 95% CI: 1.09-1.32) and CVD mortality (HR per unit increase = 1.17; 95% CI: 1.02-1.35). Compared with those SIRI levels in Q1, participants in Q4 had a 57% higher risk of all-cause mortality (HR = 1.57; 95% CI: 1.17-2.10) and an 81% greater risk of CVD mortality (HR = 1.81; 95% CI: 1.07-3.07) compared to those in Q1. ROC curve analysis yielded an area under the curve (AUC) of 0.622 for predicting all-cause mortality and 0.625 for predicting CVD mortality. Conclusion: The SIRI is a robust and independent predictor of all-cause and CVD mortality in NAFLD patients. These findings underscore the importance of systemic inflammation in NAFLD progression.