Inflammation, nutrition, and biological aging: The prognostic role of Naples prognostic score in nonalcoholic fatty liver disease outcomes

[Display omitted] •NPS predicts all-cause and cancer mortality in NAFLD patients, similar to FIB-4 and NFS.•Combining NPS with FIB-4 or NFS improves mortality prediction.•Biological aging partially mediates the link between NPS and mortality.•NPS is a cost-effective and reliable prognostic tool for NAFLD. This study aimed to evaluate the prognostic value of the Naples Prognostic Score (NPS) for predicting mortality in patients with nonalcoholic fatty liver disease (NAFLD) and compare its performance with established non-invasive fibrosis scores, including the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS). Data from 10,035 NAFLD patients identified within the 1999–2018 National Health and Nutrition Examination Survey (NHANES) were analyzed. Cox regression models assessed the association between NPS and all-cause mortality, while time-dependent ROC analysis compared its predictive accuracy with FIB-4 and NFS. Mediation analysis explored the role of phenotypic age acceleration (PhenoAgeAccel). NPS was significantly associated with all-cause mortality, with each point increase corresponding to a 26 % increased risk (HR = 1.26, 95 % CI: 1.19–1.34). NPS demonstrated comparable predictive performance to FIB-4 and NFS, with further improvement when combined with either score (HRs of 2.03 and 2.11 for NPS + FIB-4 and NPS + NFS, respectively). PhenoAgeAccel mediated 31.5 % of the effect of NPS on mortality. This study found that NPS has the potential to be an independent, cost-effective, and reliable novel prognostic indicator for NAFLD that may complement existing tools and help improve risk stratification and management strategies for NAFLD, thereby preventing adverse outcomes.