Association of pan-immune inflammation value and systemic immune inflammation index with mortality in MASLD: A cohort study from NHANES 1999 to 2018

Identifying prognostic risk factors in metabolic dysfunction-associated steatotic liver disease (MASLD) remains critical. This study investigates the association of the pan-immune inflammation value (PIV) and systemic immune inflammation index (SII) with mortality in the MASLD population. This cohort study used data from the National Health and Nutrition Examination Survey 1999 to 2018, associated with the National Death Index records, including 6252 patients with MASLD. Natural logarithms of PIV and SII (lnPIV, lnSII) were analyzed due to right-skewed distributions. Kaplan–Meier survival curves and multivariate Cox proportional hazards models were employed to assess the relationships between lnPIV, lnSII, all-cause and cardiovascular disease (CVD) mortality. Restricted cubic splines were applied to explore nonlinear trends, and segmented Cox regression was used to analyze threshold effects. Model performance was evaluated using the concordance index, time-dependent receiver operating characteristic curves, and calibration plots. Subgroup analyses were conducted to assess the robustness of the findings across different populations. Over a median follow-up of 9.17 years, 1154 all-cause deaths and 373 CVD-related deaths were recorded. Compared with individuals in the lowest quartile (Q1), those in the highest quartile (Q4) of lnPIV and lnSII had multivariable-adjusted hazard ratios of 1.36 (95% confidence interval [CI], 1.08–1.70) and 1.28 (95% CI, 1.02–1.61) for all-cause mortality, and 1.59 (95% CI, 1.00–2.52) and 1.76 (95% CI, 1.18–2.62) for CVD mortality, respectively. Nonlinear associations were observed between lnPIV, lnSII, and all-cause mortality, with thresholds identified at lnPIV = 6.015 and lnSII = 6.342. No significant associations were detected ( P  > .05) below these thresholds, whereas a significant positive association was found above the thresholds ( P  < .001). In contrast, a linear relationship was observed between lnPIV, lnSII, and CVD mortality. Time-dependent receiver operating characteristic curves and calibration plots demonstrated good model discrimination and calibration. No significant interactions were found across most subgroups ( P for interaction > .05). Elevated PIV and SII are associated with an increased risk of all-cause and CVD mortality in MASLD. A significantly higher hazard of all-cause mortality was observed when lnPIV and lnSII were above specific thresholds. They are potential tools that require external validation in patients with MASLD.