Metabolic dysfunction-associated steatotic liver disease and type 2 diabetes: A dual threat to cardiac dysfunction progression

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), particularly in patients with type 2 diabetes mellitus (T2DM), is increasingly recognized as a multi-system disease that affects both hepatic and cardiovascular health. This study explores the association between MASLD-related liver fibrosis and cardiac dysfunction, focusing on how liver fibrosis contributes to cardiac remodeling and dysfunction. Cernea et al’s research highlights the strong correlation between liver fibrosis and changes in left ventricular mass, left atrial dimensions, and systolic and diastolic function in diabetic patients. Notably, the study suggests a protective role of sex-hormone binding protein against cardiac remodeling. These findings underline the importance of early detection of liver fibrosis using non-invasive markers like fibrosis-4 index and nonalcoholic fatty liver disease fibrosis scores, which may offer dual protection for both liver and heart health in T2DM patients. Moreover, this study calls for further research into the shared pathogenic mechanisms, including inflammation and fibrosis pathways, between the liver and heart. It advocates for the integration of liver fibrosis screening into cardiovascular risk management, urging clinicians to adopt a more holistic approach in treating patients with MASLD and T2DM. The research has broad implications for preventing cardiovascular complications and improving outcomes in this high-risk population.

Key Words: Metabolic dysfunction-associated steatotic liver disease; Type 2 diabetes; Cardiac dysfunction; Left ventricular mass; Sex-hormone binding protein; Fibrosis-4 index scores

Core Tip: Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM), both components of metabolic syndrome, are increasingly recognized for their synergistic impact on cardiovascular health. The intertwined relationship between these conditions amplifies the risk of cardiovascular disease, highlighting the need for integrated management strategies to mitigate this dual threat. Through a comprehensive evaluation of Cernea et al’s study on the combination of MASLD and T2DM in promoting cardiac dysfunction, this editorial provides a comprehensive review of the current research on MASLD and cardiovascular disease, a discussion of the progress made in this field, and the potential directions for future research.

TO THE EDITOR

Metabolic dysfunction-associated steatotic liver disease (MASLD), a recently reclassified condition, presents a complex interplay between the liver and metabolic systems, notably in patients with type 2 diabetes mellitus (T2DM). While MASLD has long been recognized for its detrimental hepatic consequences, recent investigations, including the study by Cernea et al[1], have illuminated its significant cardiovascular impact, particularly through the progression of liver fibrosis.

RELATIONSHIP BETWEEN MASLD-ASSOCIATED LIVER FIBROSIS AND CARDIAC DYSFUNCTION

The association between MASLD-related liver fibrosis and cardiac dysfunction represents a critical, though understudied, area of metabolic research[2,3]. Cernea et al’s study[1] explores this interaction, revealing that patients with advanced MASLD-related fibrosis exhibit signs of systolic and diastolic dysfunction as well as increased left ventricular mass (LVM) and left atrial dimensions. The study’s findings raise important clinical questions: How does liver fibrosis exacerbate cardiac dysfunction? Could early detection of fibrosis through non-invasive markers like fibrosis-4 index and nonalcoholic fatty liver disease fibrosis scores offer a dual-protective strategy for both liver and heart health in diabetic populations?

This study’s novelty lies in its investigation of how liver fibrosis contributes to cardiac remodeling, a phenomenon observed through alterations in left ventricular function and structure. With over 60% of the patients in the study displaying increased LVM index, the question of shared pathogenic mechanisms between MASLD and cardiovascular disease (CVD) becomes crucial. The results are particularly striking in their implication of sex-hormone binding protein, which correlates negatively with LVM and left atrial dimensions, suggesting a potentially protective role for this protein in cardiac remodeling. However, the underlying mechanisms remain to be elucidated, warranting further research. Such findings have far-reaching implications, especially in the context of diastolic dysfunction, a precursor to heart failure with preserved ejection fraction. Given the established link between insulin resistance and the progression of MASLD, clinicians should consider MASLD-related fibrosis as a contributing factor in diabetic heart failure, particularly in the early stages of CVD risk stratification[2]. On the other hand, the inclusion of T2DM adds complexity to the interpretation of the results. T2DM itself is a well-known risk factor for CVD, and distinguishing the independent effects of MASLD-related fibrosis on cardiac dysfunction from the pre-existing cardiovascular risks inherent to diabetes is challenging. While the authors did adjust for several confounders, the contribution of hyperglycemia, insulin resistance, and diabetic cardiomyopathy might confound the true impact of MASLD-related fibrosis on cardiac outcomes. Future studies should carefully dissect whether fibrosis exacerbates or merely coincides with the natural history of diabetes-related heart disease.

Another limitation lies in the reliance on non-invasive fibrosis scores like fibrosis-4 index and nonalcoholic fatty liver disease fibrosis scores. While these tools are widely used and recommended by clinical guidelines, they may have limited specificity in certain populations and can misclassify fibrosis severity. Given the heterogeneity of MASLD and the varying degrees of liver damage seen in different patients, liver biopsy or advanced imaging techniques (e.g., elastography) might offer a more precise evaluation of fibrosis and its relationship with cardiac remodeling[4]. Future studies incorporating more definitive diagnostic tools could yield even more robust associations.

CONCLUSION

In conclusion, recent studies open new avenues of inquiry into the cardio-hepatic interaction, urging both researchers and clinicians to adopt a dual-organ perspective in managing MASLD. By acknowledging the cardiac risks associated with advanced liver fibrosis, we can develop more holistic and effective treatment strategies, improving both hepatic and cardiac outcomes for patients with T2DM.