Association of Life's Crucial 9 Score With Liver Fibrosis and Mortality in U.S. Adults With MASLD: Evidence From NHANES and the Mediating Role of Systemic Inflammation.

BACKGROUND

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent. Life's Crucial 9 (LC9) combines cardiometabolic and mental health metrics linked to MASLD pathogenesis, but its association with liver fibrosis and prognosis in MASLD remains unknown.

METHODS

Using National Health and Nutrition Examination Survey (NHANES) data, we performed a prospective cohort analysis for mortality (2005-2016, n = 2524) and a cross-sectional analysis for liver fibrosis (2017-2018, n = 1277). Significant fibrosis was defined as liver stiffness measurement (LSM) ≥8.0 kPa by vibration-controlled transient elastography. Systemic inflammation was assessed using the systemic immune-inflammation index (SII) and pan-immune-inflammation value (PIV). Multivariable regression and mediation analyses were conducted.

RESULTS

Higher LC9 scores were associated with lower liver stiffness (β = -0.07, 95% CI: -0.12 to -0.01). Each 1-point increase in LC9 reduced fibrosis risk by 5% (OR = 0.95), with the highest quartile showing the lowest risk (OR = 0.21). Over a median follow-up of 98 months, each 1-point LC9 increase was associated with a 3% reduction in all-cause mortality (HR = 0.97). Lower systemic inflammation partially mediated the LC9-mortality relationship (SII: 5%, PIV: 6.3%).

CONCLUSION

Higher LC9 scores are associated with reduced liver fibrosis and improved survival in MASLD, with systemic inflammation partially mediating the mortality association.