Diet composition impacts the natural history of steatotic liver disease.

Background: Metabolic-associated steatotic liver disease (MASLD), caused by insulin resistance and the metabolic syndrome, may result in progressive liver fibrosis. Animal studies suggest that dietary content modulates liver fibrosis progression. Our aim was to identify dietary components and food-related behaviors that may be associated with fibrosis progression and liver-related outcomes in a well-characterized human MASLD cohort.

Methods: Patients with MASLD who had completed a detailed Lifestyle Survey, including a semiquantitative Food Frequency Questionnaire in the Veterans Health Administration Million Veteran Program, were included. The primary outcome was liver fibrosis progression using the Fibrosis-4 slope; the secondary outcome was time to cirrhosis by ICD9/10 codes. Key baseline covariates included: race/ethnicity, body mass index, diabetes mellitus, AUDIT-C score, and baseline Fibrosis-4 score. Using bootstrapped Elastic Net regression in R, self-reported food intake and scaled nutrient variables of interest associated with the outcomes were identified and then validated using multivariable Generalized Linear Model and Cox models.

Results: A total of 84,024 individuals with MASLD with nutritional data were included in this study. Median age at MASLD diagnosis was 56 years (IQR 49-63). Frequency of consumption of coffee, tea, vegetables (broccoli, spinach/collard greens), legumes, nuts, modest alcohol, white meat, rice/pasta, dairy, and intakes of specific nutrients including nitrate/vitamin K, caffeine, betaine, amino acids, and beta carotene were associated with reduced fibrosis progression. Consumption of white bread, cookies, breakfast cereals, and specific nutrients such as iron (non-heme), B vitamins, and flavanones were all significantly associated with increased fibrosis progression in MASLD (p<0.05).

Conclusions: Dietary choices such as intake of processed foods, high-fructose foods, and refined carbohydrates may be associated with MASLD progression, while intake of vegetables, nuts, whole grains, and caffeine may be protective.