Comprehensive management of modifiable factors and all-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease

Background and aims To assess the association between comprehensive control of modifiable factors and all-cause mortality in metabolic dysfunction–associated steatotic liver disease (MASLD) patients, explore effect modification by liver fibrosis, sex, and age, and compare mortality risk between MASLD patients with different control levels and the non-MASLD population. Methods This retrospective cohort study included 15 802 MASLD patients from US National Health and Nutrition Examination Survey 2003–2018. A comprehensive management score was constructed based on seven modifiable factors (blood pressure, glucose, lipids, inflammation, smoking, alcohol, physical activity). Patients were categorized into low, intermediate, and high control groups. Multivariable Cox models, likelihood ratio tests, and stratified analyses were used to assess associations and effect modifications. Results Over 7.8 years median follow-up, 1524 deaths occurred. Compared with low control, high control was associated with 34% lower mortality hazard ratio = 0.66, 95% confidence interval (CI): 0.54–0.81, with a 21% risk reduction per control level increment (hazard ratio = 0.79, 95% CI: 0.72–0.86). The effect was not modified by liver fibrosis ( P -interaction = 0.75) but was significantly modified by sex ( P < 0.001): risk reduction was 46% in females (hazard ratio = 0.54, 95% CI: 0.37–0.79) and 21% in males (hazard ratio = 0.79, 95% CI: 0.62–0.99). No age interaction was found ( P = 0.14). Compared with non-MASLD population, high-control MASLD patients had 32% lower mortality (hazard ratio = 0.68, 95% CI: 0.61–0.76). Sensitivity analyses confirmed robustness. Conclusion Comprehensive management of modifiable factors was significantly associated with lower mortality in MASLD patients, independent of liver fibrosis and more pronounced in females. High-level control may enable survival outcomes superior to the general population.