Association of healthy lifestyles with risk of all-cause and cause-specific mortality among individuals with metabolic dysfunction-associated steatotic liver disease: results from the DFTJ cohort

To examine the associations of healthy lifestyles with risk of all-cause and cause-specific mortality among adults with metabolic dysfunction-associated steatotic liver disease (MASLD), and whether the association was mediated by systemic immune-inflammatory biomarkers (SIIBs). The study included 10,347 subjects with MASLD, who were enrolled in the Dongfeng-Tongji cohort study. The healthy lifestyles referred to non-smoking, being physically active (≥7.5 metabolic equivalents-hours/week), low-risk alcohol consumption (1-14 g/day for women and 1-28 g/day for men), and optimal sleep duration (≥6 to ≤8 h/day). Cox proportional hazard models were used to examine the relationship between each lifestyle and SIIBs with the risk of all-cause and cause-specific mortality. A mediation analysis was conducted to investigate the role of SIIBs on the association between healthy lifestyles and mortality. There were 418 MASLD subjects dead till the follow-up of 2018, including 259 deaths from cardiovascular disease (CVD). Compared to MASLD participants with 0-1 healthy lifestyle score (HLS), those with 3-4 HLS had the lowest risk of all-cause mortality [hazard ratio (HR), 0.46; 95% CI, (0.36-0.60)], and CVD mortality [HR (95%CI), 0.41 (0.29-0.58)]. Mediation analyses indicated that SIIBs mediated the association between healthy lifestyles and mortality, with proportions ranging from 2.5% to 6.1%. These findings suggest that adherence to healthy lifestyles can significantly reduce mortality for MASLD patients, and the decreased SIIBs may partially explain the protection mechanism of healthy lifestyles.