The Basics of Metabolic Dysfunction Associated Steatotic Liver Disease for the Cardiologist: Pathophysiological Links, Diagnostics, and Treatment Considerations (JACC November 2025-1)-Article: The Basics of Metabolic Dysfunction Associated Steatotic Liver Disease for the Cardiologist: Pathophysiological Links, Diagnostics, and Treatment Considerations

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This state-of-the-art review from the Journal of the American College of Cardiology (2025) provides cardiologists with a comprehensive overview of Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). MASLD affects about one-third of the global population and is a leading cause of liver transplantation in the U.S., but is increasingly recognized as a multisystem disorder with strong links to cardiovascular disease (CVD)—the primary cause of death in this population.<br /><br />MASLD and CVD share overlapping risk factors and pathophysiologic mechanisms, including insulin resistance, chronic inflammation, oxidative stress, endothelial dysfunction, ectopic fat accumulation, and genetic predisposition (notably PNPLA3 and TM6SF2 variants). These mechanisms not only drive progression of liver disease—from simple steatosis to steatohepatitis (MASH), fibrosis, and cirrhosis—but also potentiate cardiovascular complications such as coronary artery disease, hypertension, heart failure, cardiac arrhythmias, and valvular heart disease.<br /><br />Prevalence varies by region and ethnicity, with highest rates in Latin America and among Mexican Americans in the U.S. MASLD remains underdiagnosed due to asymptomatic nature, lack of screening, and nonspecific diagnostic coding. Cardiologists frequently care for patients with cardiometabolic comorbidities (e.g., obesity, diabetes, dyslipidemia) that overlap with MASLD risk.<br /><br />Diagnosis in cardiology involves initial hepatic steatosis detection by imaging (ultrasound, CT, MRI), but risk stratification focuses on fibrosis assessment using noninvasive tests such as the Fibrosis-4 (FIB-4) index, NAFLD Fibrosis Score, vibration-controlled transient elastography (VCTE), and the Enhanced Liver Fibrosis (ELF) test. Liver biopsy remains the gold standard but is reserved for complex cases. Cardiologists should screen high-risk patients (e.g., those with obesity, type 2 diabetes) and refer those with intermediate or high fibrosis risk to hepatology.<br /><br />Management centers on lifestyle interventions—weight loss, Mediterranean diet, regular aerobic and resistance exercise, smoking cessation, and moderated alcohol intake—and cardiometabolic risk control. Pharmacotherapy options are expanding: the FDA recently approved resmetirom for MASH with fibrosis, and cardiometabolic agents such as statins, GLP-1 receptor agonists, SGLT2 inhibitors, and thiazolidinediones show benefits on both liver and cardiovascular outcomes. Bariatric surgery offers histologic and cardiovascular improvements in select obese patients.<br /><br />The review emphasizes the pivotal role of cardiologists in multidisciplinary MASLD care: screening, risk stratification, management of overlapping metabolic risk factors, prescribing evidence-based therapies, and coordinating referrals to liver specialists. This integrated approach addresses a growing public health burden and limited hepatology workforce, improving early detection and patient-centered care to reduce morbidity and mortality from both liver and cardiovascular disease.

Meta Tag

Concept Metabolic Dysfunction-Associated Steatotic Liver Disease

Concept Fibrosis Risk Stratification

Concept FIB-4 Score

Concept Metabolic Dysfunction-Associated Steatohepatitis

Concept Insulin Resistance

Keywords

Metabolic Dysfunction–Associated Steatotic Liver Disease

MASLD

nonalcoholic fatty liver disease

cardiovascular disease

insulin resistance

fibrosis assessment

liver transplantation

cardiometabolic risk factors

pharmacotherapy

lifestyle interventions

Metabolic Dysfunction-Associated Steatotic Liver Disease

Fibrosis Risk Stratification

FIB-4 Score

Metabolic Dysfunction-Associated Steatohepatitis

Insulin Resistance