Abstract
BACKGROUND & AIMS: Although benefits of healthy behaviors are well-recognized, it remains unclear whether change in healthy lifestyle in early adulthood influences steatotic liver disease (SLD) development in midlife, and to what extent genetic predisposition might modify these associations. METHODS: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, we constructed a healthy lifestyle score comprising smoking, alcohol intake, physical activity, and dietary quality in young adults aged 18 to 30 years at Year 0 (Y0: 1985-1986) and Y7. A score of 0 or 1 indicated an unhealthy lifestyle, whereas 2 to 4 indicated healthy. A 7-year healthy lifestyle change was classified as persistently unhealthy, worsened, improved, or persistently healthy. SLD at Y25 was identified by non-contrast abdominal computed tomography. RESULTS: Among 2401 participants, 545 had SLD at Y25. Compared with those who maintained a persistently unhealthy lifestyle over a 7-year period (absolute risk: 28.2%; 95% confidence interval [CI], 24.1%-32.4%), participants with an initially unhealthy lifestyle at Y0 who subsequently improved had reduced absolute risks of SLD (17.7%; 95% CI, 13.1%-22.3%), with the multivariable adjusted relative risk (RR) of 0.64 (95% CI, 0.48-0.85). Similarly, those who with a persistently healthy lifestyle had lower SLD risk (RR, 0.79; 95% CI, 0.67-0.94). A 1-point increase in healthy lifestyle score over 7 years was associated with a 13% (95% CI, 6%-20%) reduced risk. The observed associations remained consistent, regardless of genetic risk (eg, >median vs ≤median of polygenic risk score, PNPLA3 rs738409 G allele carriers vs non-carriers). CONCLUSIONS: Maintaining or improving healthy behaviors during early adulthood was associated with a reduced risk of midlife SLD, regardless of genetic predisposition.