Abstract
BACKGROUND: Neutrophil-associated inflammatory markers (NPR, NHR, SII, and SIRI) have been implicated in various metabolic diseases. However, studies on these markers with metabolic dysfunction-associated steatotic liver disease (MASLD) and advanced liver fibrosis (ALF), as well as their impact on all-cause mortality, remain limited. METHODS: In this historical cohort study, data from 8051 adults aged 20 years and older were analysed. Weighted logistic regression was used to investigate the associations of neutrophil-associated inflammatory markers with MASLD and ALF. Nonlinear associations were described via restricted cubic spline regression. The diagnostic utility was assessed via receiver operating characteristic (ROC) curves. Furthermore, weighted Kaplan‒Meier survival curves and Cox proportional hazards models were employed to assess all-cause mortality risk. Sensitivity analyses were employed to guarantee the robustness of the findings. RESULTS: Following adjustment for confounding factors, there was a significant positive association between the ln-transformed NPR, NHR, SII, and SIRI and the risk of MASLD (P < 0.001). Conversely, an inverse association was noted between the ln-transformed SII, SIRI and ALF (P < 0.05). Nonlinear relationships were identified between ln-transformed NPR, NHR, and SIRI and the risk of MASLD (P < 0.001), as well as between ln-transformed NPR, SII, and SIRI and the risk of ALF (P < 0.001). Furthermore, the ln-transformed NHR (cut-off value: - 2.571) exhibited the highest diagnostic accuracy for MASLD (AUC 0.71, 95% CI = 0.70, 0.72), whereas the NPR (cut-off value: - 3.857) demonstrated the highest diagnostic value for ALF (AUC 0.73, 95% CI = 0.70, 0.75). The results of the present study revealed an independent association between the ln-transformed NPR and an elevated risk of all-cause mortality in subjects diagnosed with MASLD. Subgroup analyses highlighted the underrepresentation of neutrophil-associated inflammatory markers in lean individuals with MASLD and ALF (BMI < 25 kg/m(2)). CONCLUSIONS: Neutrophil-associated inflammatory markers are independently associated with MASLD and ALF. Specifically, the ln-transformed NHR and SII show promise as diagnostic markers for MASLD and ALF, respectively. Moreover, elevated ln-transformed NPR is independently associated with an increased risk of all-cause mortality in individuals with MASLD, highlighting the potential clinical relevance of these inflammatory markers in the context of steatotic liver disease.