Metabolic-dysfunction associated steatotic liver disease and atrial fibrillation: A review of pathogenesis

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) significantly contributes to cardiovascular morbidity, with cardiovascular disease being the leading cause of mortality among affected individuals. Atrial fibrillation (AF), the most common cardiac arrhythmia, is frequently observed in patients with MASLD. While shared metabolic risk factors such as obesity, diabetes, dyslipidemia, and hypertension are implicated, underlying pathophysiological mechanisms that include systemic inflammation, oxidative stress, insulin resistance, endothelial dysfunction, and activation of the renin-angiotensin-aldosterone system (RAAS) are proposed to play significant part in the increased risk of AF in MASLD. The aim is to review the pathogenesis linking MASLD and AF. A comprehensive literature review was conducted, focusing on studies that explore the epidemiology, pathogenesis, and clinical implications of MASLD and AF. Databases searched included PubMed, Scopus, and Web of Science, with keywords such as “metabolic associated steatotic liver disease”, “non fibrotic metabolic associated steatohepatitis”, “Nonalcoholic fatty liver disease”, “metabolic syndrome”, “atrial fibrillation”, “antifibrotic therapies”, "pathogenesis", and "cardiovascular risk". Chronic low-grade inflammation and oxidative stress in MASLD contribute to atrial structural and electrical remodeling, fostering an arrhythmogenic substrate. Insulin resistance, a hallmark of MASLD, exacerbates metabolic dysfunction and promotes atrial fibrosis. Dysregulated lipid metabolism and gut microbiota alterations further compound cardiovascular risk. Aldosterone dysregulation and systemic inflammation stemming from RAAS activation contributes to the shared pathophysiology. The severity of MASLD does not seem to directly influence the risk of AF, suggesting that even early stages of liver disease can increase susceptibility to this arrhythmia. Effective management of MASLD requires targeted risk-factor modification strategies, including weight management, glycemic control, and pharmacological interventions. A multidisciplinary approach is essential for comprehensive assessment and management of MASLD patients, with a focus on cardiovascular risk assessment and arrhythmia prevention. Future research should explore the impact of emerging MASLD therapeutic agents on the incidence and recurrence of cardiac arrhythmias. Early detection and comprehensive management of MASLD and AF are crucial to mitigate the dual burden of these conditions.

Keywords: Metabolic-dysfunction associated steatotic liver disease; Non-alcoholic fatty liver disease; Atrial fibrillation; Non-alcoholic steatohepatitis; Insulin resistance; Oxidative stress; Dyslipidemia; Obesity

Core Tip: Metabolic dysfunction-associated steatotic liver disease (MASLD) and atrial fibrillation (AF) share common metabolic risk factors, including obesity, diabetes, dyslipidemia, and hypertension. Pathophysiological mechanisms such as systemic inflammation, oxidative stress, insulin resistance, and renin-angiotensin-aldosterone system activation link MASLD to AF. Chronic inflammation and oxidative stress in MASLD lead to atrial remodeling, creating an arrhythmogenic substrate. Effective management of MASLD requires targeted risk-factor modification strategies and a multidisciplinary approach to reduce cardiovascular risk and prevent arrhythmias. Early detection and comprehensive management are crucial to mitigate the dual burden of MASLD and AF.