Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is increasingly recognized not merely as a hepatic condition but as a multisystemic metabolic disease with wide-reaching implications. Rooted in complex disturbances such as insulin resistance, adipose tissue dysfunction, chronic low-grade inflammation, and dyslipidemia, MASLD is closely linked to a broad array of extra-hepatic complications that significantly elevate morbidity and mortality. While hepatic steatosis and inflammation remain central features, it is the systemic nature of MASLD that accounts for much of its clinical burden. Patients with MASLD face a heightened risk of cardiovascular diseases—including coronary artery disease, heart failure, and arrhythmias—which are the leading cause of death in this population. In addition, MASLD is associated with musculoskeletal disorders such as sarcopenia and osteoporosis, neurological conditions including cognitive decline and depression, and an elevated risk of certain extra-hepatic cancers. These diverse manifestations underscore the urgent need to approach MASLD as a whole-body disorder requiring interdisciplinary research and care.

This research collection aims to bring together cutting-edge studies that explore the full clinical and biological spectrum of MASLD, with a particular focus on its cardiometabolic and extra-hepatic manifestations. While MASLD originates in the liver, it is increasingly understood as a systemic disease that affects multiple organ systems and contributes significantly to all-cause morbidity and mortality.

We invite submissions that investigate the pathophysiological mechanisms, biomarkers diagnostic tools, and therapeutic strategies addressing MASLD's impact beyond the liver. This includes its well-documented association with cardiovascular disease, renal dysfunction, musculoskeletal disorders (such as sarcopenia and osteoporosis), neurological conditions (including cognitive impairment and depression), and oncologic risks, particularly extra-hepatic malignancies.

1. Cardiovascular Complications of MASLD: Mechanistic links between MASLD and atherosclerosis, heart failure, arrhythmias, or endothelial dysfunction.

2. Musculoskeletal Manifestations: Impact of MASLD on sarcopenia, osteoporosis, and muscle-liver axis dysfunction.

3. Neurological and Cognitive Implications: Associations between MASLD and cognitive impairment, neuroinflammation, depression, or Alzheimer’s disease.

4. Oncologic Risk and Extra-Hepatic Malignancies: MASLD as a risk factor for cancers outside the liver (e.g., colorectal, breast, pancreatic cancer).

5. Renal Involvement in MASLD: Interplay between MASLD and chronic kidney disease (CKD), including shared metabolic pathways.

6. Shared Pathophysiological Mechanisms: Insulin resistance, systemic inflammation, gut-liver axis, and adipose-liver crosstalk as unifying mechanisms.

7. Diagnostic and Predictive Biomarkers: Emerging imaging modalities, blood-based markers, and metabolomics for early detection of systemic complications.

8. Impact of MASLD on Quality of Life and Functional Status: Patient-reported outcomes, physical functioning, and psychosocial dimensions.

9. Multidisciplinary and Integrated Management Models: Best practices for coordinated care involving hepatology, cardiology, endocrinology, and primary care.

10. Therapeutic Strategies and Interventions: Lifestyle, pharmacologic, and surgical approaches targeting MASLD's systemic effects.

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The MASLD Spectrum: An emerging epidemic of Cardiometabolic and Extra-Hepatic Dimensions