Association of LE8 defined health behaviors with MASLD and the mediating role of inflammation and oxidative stress: A cross-sectional study

In 2022, the American Heart Association updated "Life's Simple 7" to "Life's Essential 8" (LE8). In June 2023, the Delphi consensus proposed that metabolic dysfunction-associated steatotic liver disease (MASLD) should be the new successor of the term nonalcoholic fatty liver disease. We aimed to explore the association of 4 health behaviors defined by LE8 with MASLD and to systematically investigate the mediating role of inflammatory markers and oxidative stress. This study investigated cross-sectional data from 3691 adults in the 2017 to 2018 National Health and Nutrition Examination Survey. The health behavior score (ranging from 0-100) was calculated as the unweighted average of 4 indicators (diet, physical activity, smoking, and sleep) based on the definition of LE8. The association between health behaviors and MASLD was explored through multiple logistic regression. Restricted cubic splines were used to explore nonlinear correlations and inflection points were determined through 2-piecewise linear regression. In addition, mediation analysis was conducted to systematically investigate the role of oxidative stress and inflammatory markers. In the multiple logistic regression that adjusted for confounders, we estimated the odds ratio (OR) of MASLD with per 10 score increase in health behavior was 0.95 (95% confidence interval [CI]: 0.91-0.98; P = .004); and compared to individuals with Low health behavior (0-49), those with high health behavior (80-100) had a reduced risk of MASLD (OR: 0.72, 95% CI: 0.58-0.88, P = .002). Restricted cubic spline depicted a nonlinear association (P for nonlinear = 0.043), and a 2-piecewise linear regression identified an inflection point at 80. Further segmented regression demonstrated that health behavior predicted the risk of MASLD only when the score > 80 (OR: 0.75, 95% CI: 0.59-0.94, P = .01). Moreover, mediation analysis revealed that 3 oxidative stress markers (gamma-glutamyltransferase, 25(OH)D, bilirubin) and neutrophil count primarily mediated the effect of health behavior on MASLD (P < .001). The inverse association of health behaviors with MASLD showed a threshold effect with an inflection point of 80, and oxidative stress biomarkers (gamma-glutamyltransferase, 25(OH)D, bilirubin) and neutrophils were the main mediators.