Liver fibrosis burden and risk of incident arrhythmia in metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent condition associated with increased cardiometabolic risk. While hepatic fibrosis is a determinant of prognosis in MASLD, its relationship with incident arrhythmic outcomes, particularly atrial fibrillation (AF), remains incompletely defined. We investigated whether liver fibrosis burden assessed by noninvasive fibrosis scores is associated with incident electrocardiogram (ECG)-detected arrhythmia in a population-based cohort. We analyzed data from the Lifelines prospective cohort study in the Netherlands. MASLD was defined using the hepatic steatosis index, cardiometabolic risk factors, and exclusion of excess alcohol intake. Liver fibrosis was assessed using the fibrosis-4 (FIB-4) index and the aspartate aminotransferase-to-platelet ratio index (APRI). Incident arrhythmia and AF were identified exclusively by follow-up ECG recordings. Cox proportional hazards models were used to evaluate associations, with sequential adjustment for cardiometabolic confounders and age-stratified analyses. Among 10,263 participants with MASLD, elevated fibrosis burden defined by FIB-4 ≥ 1.45 was consistently associated with a higher risk of incident ECG-detected arrhythmia and AF. This association remained significant after adjustment for major metabolic risk factors and was observed within the MASLD cohort. Notably, the excess arrhythmic risk was age dependent, with associations limited to participants aged ≥ 50 years, whereas no incident events occurred among younger individuals with elevated FIB-4. Elevated liver fibrosis burden assessed by FIB-4 is independently associated with increased risk of incident ECG-detected arrhythmia, particularly AF, among individuals with MASLD.