Association Between the Neutrophil-to-Lymphocyte Ratio and Mortality Prognosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: An Analysis Based on Real-World Data From Two Cohorts

Abstract

Background: The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing, driven by the rising incidence of obesity, diabetes mellitus, and metabolic syndrome. Neutrophils are closely associated with steatotic hepatocytes and the severity of liver fibrosis. Objectives: This study aimed to investigate the association between the neutrophil-to-lymphocyte ratio (NLR) and mortality risk among individuals with MASLD in two large-scale real-world cohorts. Methods: A total of 761 participants from the US National Health and Nutrition Examination Survey (NHANES) database and 455 patients from a Chinese hospital with complete clinical information were included in this study. The association between NLR and mortality was evaluated using Kaplan-Meier (KM) survival curves, survey-weighted multivariable Cox regression analysis, and subgroup analysis. Results: In both the NHANES and Chinese cohorts, KM survival curves indicated a significantly higher mortality risk in the high-NLR group (P < 0.05). Multivariable Cox regression analyses confirmed that elevated NLR was an independent risk factor for mortality, with a significantly higher risk in the high-NLR group than in the low-NLR group (P < 0.05) after adjustment for relevant confounders. Restricted cubic spline (RCS) models did not indicate a nonlinear relationship between elevated NLR and MASLD mortality risk. Significant interaction effects were observed in the NHANES database for hyperlipidemia, smoking status, and sitting time (interaction P < 0.05). Although the association appeared more pronounced in males, older individuals, participants with a normal body mass index (BMI), individuals with hypertension, nondiabetic individuals, nonsmokers, and nondrinkers, no statistically significant interaction effects were detected in other subgroups (interaction P > 0.05). Conclusions: An elevated NLR is an independent risk factor for mortality in MASLD across both US population-based and Chinese clinical cohorts. NLR may serve as an accessible, noninvasive prognostic marker.