Abstract
BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) affects up to one-third of the global population. Since no approved pharmacotherapy for MAFLD is available, lifestyle modification remains the cornerstone of clinical care. Our study aims to evaluate the association of an overall healthy lifestyle with MAFLD risk. METHODS: We conducted an analysis of 327,387 participants from UK biobank. An overall healthy lifestyle score including six evidence-based lifestyles (diet, alcohol consumption, physical activity, sedentary behavior, sleep, and smoking) was assessed by questionnaires. MAFLD and its subtypes were diagnosed by blood biochemistry, ICD codes, and medication information from touchscreen and verbal interview. The prevalence ratios (PRs) and risk ratios (RRs) were estimated by Poisson regression models with robust variance. RESULTS: In the cross-sectional analysis, the PR (95% CI) was 0.83 (0.83 to 0.84) for MAFLD, and 0.83 (0.83 to 0.84) for MAFLD-overweight/obesity (MAFLD-O), 0.68 (0.66 to 0.70) for MAFLD-lean/normal weight and metabolic dysfunction (P-value for heterogeneity < 0.001), and 0.71 (0.71 to 0.72) for MAFLD-type 2 diabetes mellitus (MAFLD-T2D); and 0.68 (0.66 to 0.71) for dual (or more) etiology fatty liver disease (MAFLD-dual) and 0.83 (0.83 to 0.84) for single etiology MAFLD (MAFLD-single) (P-value for heterogeneity < 0.001) for one additional point in the overall healthy lifestyle score. During a median follow-up of 4.4 years, the RR (95% CI) was 0.83 (0.81 to 0.85) for MAFLD, and 0.83 (0.81 to 0.85) for MAFLD-O, 0.71 (0.62 to 0.81) for MAFLD-L, and 0.68 (0.64 to 0.72) for MAFLD-T2D (P-value for heterogeneity < 0.001); and 0.83 (0.81 to 0.85) for MAFLD-dual and 0.70 (0.58 to 0.85) for MAFLD-single (P-value for heterogeneity = 0.08) for one additional point in the overall healthy lifestyle score. These findings were validated in a prospective analysis among 15,721 participants with revisit data, and also supported by fatty liver index and proton density fat fraction data. CONCLUSIONS: An overall healthy lifestyle that includes six evidence-based factors was strongly associated with lower MAFLD risk, especially the subtypes with multiple etiologies.