Norbert Stefan

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease worldwide. People with MASLD can progress to cirrhosis and have an increased risk of developing hepatic decompensation and hepatocellular carcinoma. People with MASLD are also at increased risk of type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), chronic kidney disease, and extrahepatic cancers and most people with MASLD die from CVD. With a prevalence of about 65%, MASLD is very common among adults with T2DM. This close link between MASLD and cardiometabolic diseases suggests that the conditions share common causes, e.g., insulin resistance, hyperglycaemia, subclinical inflammation, and dysfunctional adipose tissue, and that they also influence each other. In this respect, important insights have been gained in recent years, particularly regarding the heterogeneity of MASLD pathophysiology. In this review we address this heterogeneity and discuss its impact on MASLD-related outcomes. Since successful treatment of MASLD often resembles an effective treatment regimen for T2DM, we discuss how metabolism-based treatment approaches, accounting for the heterogeneity of the pathogenesis of MASLD, might enable personalized treatment of this disease in the future.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is recognized as a systemic metabolic disorder with marked cardiovascular implications, as cardiovascular disease is a leading cause of death. Despite non-invasive diagnostic tests, such as the fibrosis-4 index and vibration-controlled transient elastography, and the availability of resmetirom and emerging pharmacotherapies with dual liver and cardiovascular benefits (for example, glucagon-like peptide 1 receptor agonists and sodium–glucose cotransporter 2 inhibitors), substantial gaps in coordinated clinical management remain. MASLD is often under-recognized in cardiology, and the cardiovascular risk associated with MASLD is similarly under-appreciated in hepatology practice, resulting in fragmented care and a lack of integrated management pathways. This discrepancy leads to missed opportunities for early intervention and suboptimal outcomes in the progression of both hepatic and cardiovascular diseases. To address these gaps, a more collaborative, multidisciplinary approach is needed, integrating early screening, risk stratification and coordinated management across specialities. In this Expert Recommendation, we outline key considerations for heart–liver co-management in MASLD, propose practical strategies for screening and risk stratification, and discuss pathways to implement coordinated multidisciplinary care in clinical practice within a structured metabolic care framework.

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