Body Mass Index Subclassification and Future Risk of Metabolic Dysfunction–Associated Steatotic Liver Disease and Liver-Related Events

BACKGROUND: Recent research using a data-driven cluster approach has identified 5 discordant subclassifying body mass index (BMI) subgroups, characterized by cardiometabolic biomarkers deviated from those predicted by BMI. OBJECTIVES: This study aimed to investigate the associations of these subgroups with risks of metabolic dysfunction-associated steatotic liver disease (MASLD) and liver-related events (LREs). METHODS: This prospective cohort study included 423,091 participants. The same cluster analysis as reported by Coral et al. was performed to classify subpopulations. Incident MASLD and LREs were determined by electronic health records. Cox proportional hazards models were used to evaluate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Profiles derived from the study were similar to those identified in the work by Coral et al. Individuals with discordantly high liver transaminase [HR (95% CI): 1.72 (1.51, 1.96) for MASLD and 1.42 (1.23, 1.65) for LREs in males and 1.92 (1.61, 2.28) for MASLD and 1.68 (1.32, 2.14) for LREs in females] and hyperglycemia [HR (95% CI): 1.36 (1.06, 1.74) for MASLD and 1.31 (1.01, 1.70) for LREs in males and 1.62 (1.27, 2.08) for MASLD and 1.80 (1.31, 2.47) for LREs in females] had higher risks of liver outcomes compared with the concordant profile. In contrast, we observed a lower risk of MASLD [HR (95% CI): 0.71 (0.60, 0.84)] in females with discordantly high blood pressure relative to their BMI. For discordant adverse lipid profile and discordant inflammatory profile, no significant associations were observed. In addition, the BMI subclassification profiles had better predictive ability among males. CONCLUSIONS: Metabolically distinct BMI subgroups exhibit heterogeneous risks of MASLD and LREs.