Abstract P402: Association of an Overall Healthy Lifestyle With Different Types of Metabolic Dysfunction-Associated Fatty Liver Disease

Background & Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) affects up to one-third of the global population and increases the risk of cardiometabolic disease. 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 different types of MAFLD. Methods: We conducted a prospective analysis of 15,721 participants from UK biobank. An overall healthy lifestyle including six evidence-based lifestyles (diet, alcohol consumption, physical activity, sedentary behavior, sleep, and smoking) was assessed by questionnaires. MALFD and its typing were diagnosed by blood biochemistry, ICD codes, and medication information from touchscreen and verbal interview. The risk ratios (RRs) were estimated by Poisson regression models with robust variance. Results: During a median follow-up of 4.4 years, 5,522 participants had MAFLD diagnosed. Compared with those with zero to two healthy lifestyles, the RRs (95% CIs) of those with six healthy lifestyles were 0.41 (0.36 to 0.47) for MAFLD; 0.41 (0.35 to 0.46) for MAFLD-overweight/obesity (MAFLD-O), 0.27 (0.12 to 0.60) for MAFLD-lean/normal weight and metabolic dysfunction (MAFLD-L), 0.17 (0.11 to 0.26) for MAFLD-type 2 diabetes mellitus(MAFLD-T2D) (P-value for heterogeneity < 0.001); and the RRs (95% CIs) of those with five healthy lifestyles were 0.53 (0.49 to 0.58) for single etiology MAFLD (MAFLD-single) and 0.23 (0.10 to 0.55) for dual (or more) etiology fatty liver disease (MAFLD-dual) (P-value for heterogeneity = 0.08). For one additional point in the overall healthy lifestyle, 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). Meanwhile, significant differences in the correlations of individual lifestyles with subtypes of MAFLD were discovered for sufficient physical activity, low sedentary time, adequate sleep, and never smoking, and with different etiology MAFLD were discovered for low sedentary time. Conclusions: An overall healthy lifestyle that includes six evidence-based factors were strongly associated with lower MAFLD risk, especially MAFLD-L and MAFLD-dual. Our findings support the potential benefits of an integrated healthy lifestyle for MAFLD management and suggest differences in the impact of lifestyle on different types of MAFLD but warrant confirmation by well-designed prospective studies and clinical trials.