Temporal comorbidity patterns preceding MASLD-related major adverse liver outcomes: a nationwide population-based case-control study in Sweden.

Background: The patterns of comorbidities preceding major adverse liver outcomes (MALOs) in metabolic dysfunction-associated steatotic liver disease (MASLD) are unclear. Methods: All patients from the Swedish National Patient Register with MASLD-related MALO between 2006 and 2022 were identified, and matched for age, sex and diagnosis year, with individuals having MASLD without MALO, and population controls. Hierarchical clustering using International Classification of Diseases-10 codes was employed for identifying comorbidities, with comparison between the groups. Median times of comorbidities until MALO were calculated. Results: 996 patients with MASLD-related MALO and median age of 67 years (IQR=60-73), of which 49% men, were matched with 3921 individuals with MASLD without MALO and 9056 population controls. A median of nine comorbidity categories was observed in patients with MALO, who exhibited a cardiometabolic cluster with type 2 diabetes (49%) and hypertension (56%), which were diagnosed 6 years before MALO. Heart failure and atrial fibrillation/flutter preceded MALO in 13% and 14% and were diagnosed 4 years beforehand. Myocardial infarction occurred 6 years prior to MALO in 8%, while angina pectoris developed 8 years prior in 14% of patients. Sleep disorders were seen 8 years before MALO in 14% of patients. All identified comorbidities were present at lower rates in individuals with MASLD without MALO and population controls (p<0.001). Conclusions: Patients with MASLD-related MALO are frequently multimorbid. Cardiac disease and sleep disorders, with cardiometabolic risk factors, characterise individuals developing MALO. These patterns may simplify case finding and earlier interventions.