Association of Change in Healthy Lifestyle in Early Adulthood With Steatotic Liver Disease Risk in Midlife

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.