Introduction
The landscape of fatty liver disease has undergone a transformative evolution with the introduction of metabolic dysfunction-associated steatotic liver disease (MASLD) as the replacement terminology for nonalcoholic fatty liver disease (NAFLD) [1]. This nomenclature change, announced in June 2023 following a rigorous multisociety Delphi consensus process involving over 200 panelists from 56 countries, reflects more than semantic refinement. It represents a fundamental reconceptualization of fatty liver disease as an intrinsically metabolic disorder with systemic manifestations that extend far beyond the hepatic parenchyma [1,2].
The impetus for this nomenclature revision arose from multiple limitations of the NAFLD terminology. First, the term was exclusionary, defined by the absence of other liver diseases rather than by positive diagnostic criteria [3,2]. Second, the terminology was perceived as stigmatizing, with terms such as fatty and nonalcoholic carrying negative connotations that could affect patient engagement and care-seeking behavior [4,3]. Third, and most critically, the previous nomenclature failed to capture the metabolic dysfunction that fundamentally drives disease pathogenesis and progression [5,1].
MASLD now affects approximately 30% of the global adult population, with prevalence rates paralleling the worldwide epidemic of obesity, type 2 diabetes mellitus, and metabolic syndrome [6,7]. What was once considered a relatively benign hepatic condition has emerged as a dynamic, progressive disorder intimately linked to multisystem injury, with the cardiovascular system representing its most frequent and fatal extrahepatic target [8,9]. Cardiovascular complications, including myocardial infarction, stroke, and heart failure, frequently manifest before significant hepatic events, underscoring the silent yet pervasive nature of the MASLD-cardiovascular disease (CVD) axis [10,8].
For internists, who serve as frontline clinicians managing patients with complex cardiometabolic disorders, understanding the new MASLD nomenclature and its implications for cardiovascular risk stratification is paramount. The liver-heart axis encompasses both a well-characterized forward pathway – wherein hepatic metabolic dysfunction promotes cardiovascular disease through shared pathophysiological mechanisms – and a clinically important but less well-studied reverse pathway – wherein primary cardiac dysfunction drives hepatic injury through hemodynamic and congestive mechanisms [11,12]. This review addresses both directions, recognizing that internists managing patients with advanced heart failure or cardiogenic shock will frequently encounter hepatic consequences that require integrated clinical reasoning.
This comprehensive review aims to provide internists with an updated understanding of MASLD nomenclature, to explore the mechanistic underpinnings of the liver-heart axis, to examine cardiovascular outcomes associated with MASLD, to discuss diagnostic and risk-stratification approaches, and to outline integrated management strategies that address both hepatic and cardiovascular manifestations of this multisystem disease.
The MASLD Nomenclature: Key Changes and Definitions
The Delphi Consensus Process
The nomenclature revision process employed a modified Delphi methodology coordinated by three major liver associations: the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL), and the Latin American Association for the Study of the Liver (ALEH) [1]. The process included four rounds of online surveys and two hybrid meetings, with participation from hepatologists, gastroenterologists, endocrinologists, primary care physicians, patient advocates, regulatory representatives, and pharmaceutical industry stakeholders [1,2].
Consensus was defined a priori as a supermajority (\documentclass[12pt]{minimal}
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\begin{document}$\geq$\end{document}≥67%) vote. Survey results demonstrated that 74% of participants supported a name change, 78% endorsed an overarching term to accommodate disease evolution, and 67% favored inclusion of a metabolic descriptor in the new nomenclature [3,1]. An independent external committee of experts made the final recommendation on the acronym and diagnostic criteria.
Core Definitions and Diagnostic Criteria
Steatotic Liver Disease (SLD)
The umbrella term encompassing all causes of hepatic steatosis, diagnosed histologically or by imaging modalities [1,2].
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Defined as hepatic steatosis (\documentclass[12pt]{minimal}
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\begin{document}$\geq$\end{document}≥ 5% hepatic fat content) in the presence of at least one of five cardiometabolic risk factors, in the absence of other causes of hepatic steatosis [13,1]. The five cardiometabolic risk factors include:
Metabolic Dysfunction-Associated Steatohepatitis (MASH)
Replaces the term nonalcoholic steatohepatitis (NASH), referring to MASLD with histological evidence of steatohepatitis characterized by steatosis, hepatocellular ballooning, and lobular inflammation [14,1].
Metabolic and Alcohol-Associated Liver Disease (MetALD)
A new diagnostic category describing individuals with MASLD who consume alcohol beyond the thresholds previously used to define NAFLD (140-350 g/week for females and 210-420 g/week for males) [15,1]. This category acknowledges the synergistic effects of metabolic dysfunction and moderate alcohol consumption on liver disease progression.
Cryptogenic Steatotic Liver Disease
Reserved for individuals with hepatic steatosis who do not meet criteria for MASLD and have no other identifiable cause [1,2].
Advantages of the New Nomenclature
The transition to MASLD offers several intended clinical and research advantages. First, the affirmative, inclusion-based diagnostic criteria eliminate the need for exclusionary diagnoses, simplifying clinical practice [4,3]. Second, the terminology emphasizes the metabolic foundations of disease pathogenesis, aligning diagnostic nomenclature with therapeutic targets [5,16]. Third, non-stigmatizing language is intended to improve patient engagement, reduce psychological burden, and enhance healthcare-seeking behavior. However, prospective studies are needed to validate these anticipated benefits [17,3].
Importantly, comparative analyses demonstrate that MASLD criteria capture approximately 99% of individuals previously diagnosed with NAFLD, ensuring continuity of natural history data, clinical trial applicability, and biomarker validation [18,19]. The new nomenclature does not alter histological staging systems or modify the definition of steatohepatitis, preserving the relevance of decades of NASH-focused research [14,1].
Epidemiology and Clinical Burden of MASLD
MASLD represents the most prevalent chronic liver condition worldwide, affecting an estimated 30% of the global adult population [6,20]. Prevalence varies geographically, with the highest rates observed in South America (44.4%), the Middle East (32%), and Asia (29.6%) [21,20]. In industrialized nations, MASLD prevalence parallels obesity rates, with approximately 25-30% of adults in North America and Europe affected [21,22].
The condition demonstrates a particular predilection for individuals with metabolic syndrome components. Among patients with type 2 diabetes mellitus, MASLD prevalence reaches 55-70%, while obese individuals exhibit prevalence rates of 70-90% [23,24]. Notably, 7-20% of MASLD cases occur in non-obese or lean individuals, highlighting the complex pathophysiology beyond simple weight-related mechanisms [25,26].
Progressive fibrosis develops in approximately 20-30% of individuals with MASLD, with 10-15% advancing to cirrhosis over 10-20 years [27]. The presence of metabolic dysfunction-associated steatohepatitis (MASH) significantly accelerates fibrosis progression, with advanced fibrosis developing in 25-35% of MASH patients [28,29].
Critically, cardiovascular disease represents the leading cause of mortality in MASLD patients, accounting for approximately 40-50% of deaths, far exceeding liver-related mortality, which accounts for only 5-15% of deaths in non-cirrhotic MASLD [30,31]. This epidemiological profile underscores the primacy of cardiovascular risk management in MASLD care paradigms.
Pathophysiological Mechanisms Linking MASLD and Cardiovascular Disease
The liver-heart axis in MASLD is characterized by complex, bidirectional interactions mediated through multiple overlapping pathophysiological mechanisms [32].
Insulin Resistance and Metabolic Dysregulation
Insulin resistance is a cornerstone pathophysiological feature linking MASLD to cardiovascular disease [33,34]. Hepatic steatosis both results from and perpetuates systemic insulin resistance through the release of pro-inflammatory cytokines, altered lipoprotein metabolism, and the secretion of a diverse repertoire of hepatokines – liver-derived circulating proteins that mediate inter-organ crosstalk across the liver-heart axis. These hepatokines can be broadly organized by their predominant downstream effects. Among those with primary metabolic relevance, fibroblast growth factor 21 (FGF21) is paradoxically elevated in MASLD despite its physiological role in promoting fatty acid oxidation and insulin sensitization, a state of FGF21 resistance analogous to leptin resistance in obesity. Fetuin-A and fetuin-B, both upregulated in hepatic steatosis, impair insulin receptor signaling and promote systemic insulin resistance, with fetuin-A additionally serving as an endogenous inhibitor of the insulin receptor tyrosine kinase [35]. Selenoprotein P, a hepatokine elevated in MASLD and type 2 diabetes, impairs insulin signaling in skeletal muscle and the myocardium and has been independently associated with cardiovascular risk. Sex hormone-binding globulin (SHBG), whose hepatic synthesis is suppressed by insulin resistance and hepatic fat accumulation, serves as an inverse biomarker of metabolic syndrome severity and has been associated with incident type 2 diabetes and cardiovascular disease risk. Among hepatokines with more direct vascular and lipid-trafficking relevance, angiopoietin-like proteins 3, 4, and 8 (ANGPTL3, ANGPTL4, ANGPTL8) regulate lipoprotein lipase activity and plasma triglyceride clearance; their dysregulation in MASLD contributes to atherogenic dyslipidemia and has positioned ANGPTL3 in particular as an emerging therapeutic target in cardiometabolic disease. Hepassocin, a hepatocyte-derived growth factor, promotes hepatic steatosis by upregulating lipogenic pathways and has been associated with endothelial dysfunction and early atherosclerosis. However, its precise role in the MASLD-cardiovascular axis remains to be characterized. Collectively, this hepatokine network illustrates how the steatotic liver actively remodels systemic metabolic and vascular homeostasis, extending its pathological influence well beyond the hepatic parenchyma [35,36].
A meta-analysis involving over 500,000 participants demonstrated that insulin resistance, measured by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), significantly elevates the risk of atherosclerotic cardiovascular disease, with each 1 standard deviation increase in HOMA-IR correlating with a 1.46-fold higher risk of developing atherosclerotic cardiovascular disease [37]. Similarly, HOMA-IR scores have been independently associated with altered left ventricular relaxation and diastolic dysfunction, affecting up to 50% of patients with type 2 diabetes [38,39].
Chronic Low-Grade Inflammation
Hepatic steatosis triggers activation of innate immune pathways, particularly through Kupffer cells and hepatic stellate cells, resulting in production and systemic release of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-\documentclass[12pt]{minimal}
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\begin{document}$\beta$\end{document}β), and C-reactive protein (CRP) [40,41]. These inflammatory mediators promote endothelial dysfunction, accelerate atherosclerosis, and contribute to myocardial remodeling [42,43].
The inflammatory phase of MASLD, characterized by steatohepatitis (MASH), demonstrates particularly robust systemic inflammatory activity. Inflammatory spillover from the liver affects distant organs, including the heart, skeletal muscle, and kidneys, contributing to the multisystem impact of disease [44,45].
Oxidative Stress and Lipotoxicity
Excess reactive oxygen species generated in lipid-laden hepatocytes and activated macrophages contribute to mitochondrial dysfunction, lipid peroxidation, and cytokine release [46,47]. This oxidative milieu fosters the formation of oxidized low-density lipoprotein (LDL) and perpetuates vascular inflammation. Studies have linked markers of oxidative stress in MASLD with increased carotid intima-media thickness and coronary artery calcification, established precursors of clinical cardiovascular disease [48,49].
Lipotoxicity, resulting from the accumulation of toxic lipid species including ceramides, diacylglycerols, and free fatty acids, directly impairs cardiomyocyte function and promotes cardiac fibrosis [50,51].
Atherogenic Dyslipidemia
MASLD is characterized by a distinctive atherogenic lipid profile including elevated triglycerides, increased small dense LDL particles, reduced HDL cholesterol, and elevated apolipoprotein B [52,53]. This dyslipidemia results from hepatic overproduction of very-low-density lipoproteins (VLDL), impaired lipoprotein clearance, and altered apolipoprotein metabolism [54,55].
The atherogenic dyslipidemia associated with MASLD independently predicts cardiovascular events beyond traditional Framingham risk factors [56,57].
Gut-Liver-Heart Axis
Emerging evidence highlights the roles of gut microbiome dysbiosis, increased intestinal permeability, and bacterial translocation in the pathogenesis of MASLD and cardiovascular disease [58,59]. Patients with MASLD exhibit altered gut microbial composition, with increased abundance of pro-inflammatory taxa, including Enterobacteriaceae and Proteobacteria, and decreased abundance of beneficial commensals, including Faecalibacterium prausnitzii and Akkermansia muciniphila [60,61].
Lipopolysaccharides (LPS) derived from gut bacteria traverse the compromised intestinal barrier, reach the liver via portal circulation, and activate toll-like receptor 4 (TLR4) signaling, triggering hepatic and systemic inflammation [62,63]. Elevated circulating LPS levels have been associated with both MASLD severity and cardiovascular events [64,65]. A particularly well-characterized gut-derived metabolite linking hepatic and cardiovascular pathology is trimethylamine N-oxide (TMAO). Generated when gut bacteria metabolize dietary choline, phosphatidylcholine, and L-carnitine to trimethylamine (TMA), which is subsequently oxidized to TMAO by hepatic flavin-containing monooxygenase 3 (FMO3), circulating TMAO levels reflect the combined influence of dietary substrate availability, gut microbial composition, and hepatic oxidative capacity – all of which are altered in MASLD [59]. Elevated TMAO has been independently associated with accelerated atherosclerosis through promotion of macrophage foam cell formation and impaired reverse cholesterol transport, with enhanced platelet hyperreactivity and thrombotic risk, and with adverse cardiac remodeling and incident heart failure, including heart failure with preserved ejection fraction [64]. Patients with MASLD demonstrate elevated circulating TMAO levels compared to matched controls, and TMAO concentrations correlate with hepatic fibrosis severity, suggesting that progressive liver dysfunction amplifies TMAO generation and systemic vascular exposure [62]. While direct interventional data in MASLD remain limited, TMAO biology provides a mechanistically coherent link between gut dysbiosis, hepatic metabolic dysfunction, and the full spectrum of cardiovascular manifestations observed in this population – spanning atherosclerosis, thrombosis, and heart failure – reinforcing the clinical importance of the gut-liver-heart axis.
Hepatic Fibrosis and Cardiovascular Risk
Hepatic fibrosis stage has emerged as a critical determinant of cardiovascular risk in MASLD, often surpassing the predictive value of steatosis or steatohepatitis alone [66,67]. Advanced fibrosis (stage F3-F4) is independently associated with increased cardiovascular events, cardiovascular mortality, and all-cause mortality [68,69].
The mechanisms linking hepatic fibrosis to cardiovascular disease remain incompletely understood but likely involve persistent systemic inflammation, endothelial dysfunction, enhanced platelet activation, and altered hepatic synthesis of cardiovascular-protective proteins [70,71].
Genetic Determinants and the Discordant Phenotype Problem
Common genetic variants exert substantial influence on MASLD susceptibility, fibrosis progression, and – critically – cardiovascular risk profiles, often in discordant directions, with direct clinical relevance for internists. The most studied variant, PNPLA3 I148M (rs738409), encodes a gain-of-function substitution in patatin-like phospholipase domain-containing protein 3 that impairs hepatic lipid droplet remodeling. Carriers of the G allele demonstrate accelerated hepatic steatosis, steatohepatitis, fibrosis, and hepatocellular carcinoma risk, yet paradoxically do not appear to carry a proportionally elevated cardiovascular risk, possibly because the variant promotes hepatic lipid retention rather than dyslipidemic spillover into the systemic circulation [72,73].
The TM6SF2 E167K variant (rs58542926) illustrates this dissociation most strikingly. Loss-of-function of transmembrane 6 superfamily member 2 reduces hepatic VLDL secretion, resulting in hepatic lipid accumulation and accelerated fibrosis, while simultaneously lowering circulating triglycerides and LDL cholesterol – a profile associated with reduced atherosclerotic cardiovascular disease risk despite more severe liver disease [70,73]. This TM6SF2 paradox exemplifies why genetic background can uncouple the liver-heart axis, and why cardiovascular risk cannot be assumed to track linearly with hepatic disease severity in all patients.
HSD17B13 loss-of-function variants confer hepatoprotection by reducing hepatic inflammatory activity and fibrosis progression, and have attracted interest as therapeutic targets, though their effect on cardiovascular risk remains under investigation [73,74]. MBOAT7 variants similarly promote hepatic steatosis and fibrosis through altered phosphatidylinositol remodeling, with an emerging but incompletely characterized cardiometabolic profile [73].
For internists, the practical implication is that patients with discordant phenotypes – severe liver disease but favorable lipid profiles, or vice versa – may harbor underlying genetic architecture that modifies standard cardiovascular risk predictions. While routine genetic testing is not currently recommended in clinical practice, awareness of these variants helps explain phenotypic heterogeneity among patients with MASLD. It underscores the need for individualized rather than uniform cardiovascular risk assessment.
The Reverse Pathway: Cardiac Dysfunction and Congestive Hepatopathy
While the predominant focus of the liver-heart axis in MASLD literature is the forward pathway from hepatic metabolic dysfunction to cardiovascular disease, the reverse pathway – wherein primary cardiac dysfunction drives progressive hepatic injury – is of equal clinical importance for internists and represents a distinct but intersecting disease process [11,71].
Hemodynamic Mechanisms
Right-sided heart failure, whether arising de novo or as a consequence of advanced left ventricular dysfunction, generates sustained elevation of central venous and hepatic venous pressures. This increased back-pressure is transmitted directly to the hepatic sinusoids via the inferior vena cava and hepatic veins, resulting in sinusoidal congestion, hepatocellular hypoxia, and zone 3 (centrilobular) necrosis – the histological hallmark of congestive hepatopathy [11,71]. In parallel, reduced cardiac output impairs hepatic arterial perfusion, creating a dual insult of venous congestion and arterial ischemia that is particularly injurious in the setting of acute decompensation. Elevated right atrial pressure also impairs portal venous return, contributing to splanchnic congestion, gut barrier dysfunction, and bacterial translocation, which may further amplify systemic inflammation [58,63].
Congestive Hepatopathy and Cardiac Cirrhosis
Chronic, sustained hepatic venous hypertension – most commonly seen in patients with heart failure with reduced ejection fraction, constrictive pericarditis, severe tricuspid regurgitation, or Fontan circulation – drives progressive hepatic fibrosis by activating hepatic stellate cells in response to persistent sinusoidal pressure and hypoxia [70,71]. This process, termed congestive hepatopathy, exists on a spectrum from mild centrilobular fibrosis to frank cardiac cirrhosis, the latter carrying its own risks of portal hypertension, hepatic synthetic dysfunction, variceal bleeding, and hepatocellular carcinoma [71]. The fibrosis pattern of cardiac cirrhosis is characteristically reversed to that of MASLD – beginning in zone 3 (centrilobular) rather than zone 1 (periportal) – a distinction of diagnostic importance when evaluating liver biopsy specimens in patients with coexisting cardiac and metabolic disease [70].
Portal Hemodynamics and Clinical Consequences
As congestive hepatopathy progresses, portal hypertension may develop even in the absence of advanced parenchymal fibrosis, driven primarily by elevated hepatic venous outflow resistance rather than intrahepatic architectural distortion [71]. Clinically, this manifests as ascites, peripheral edema, and splenomegaly – findings that may be incorrectly attributed to cardiac failure alone, delaying recognition of the hepatic contribution. Hepatic synthetic function, reflected by prolonged prothrombin time, hypoalbuminemia, and hyperbilirubinemia, is impaired in advanced congestive hepatopathy and carries independent prognostic significance in heart failure patients beyond standard cardiac biomarkers [11,71]. Serum aminotransferases are typically mildly elevated in chronic congestive hepatopathy. Still, they may rise sharply – occasionally mimicking acute hepatitis – during episodes of acute hemodynamic decompensation, a pattern sometimes termed ischemic hepatitis or shock liver [70,71].
Clinical Implications for Internists
For internists, several practical points follow from recognition of the reverse pathway. First, liver function abnormalities in patients with known heart failure should not be reflexively attributed to medications or incidental hepatic disease; a hemodynamic contribution should be systematically considered, particularly when right-sided pressures are elevated [11,71]. Second, the coexistence of MASLD and congestive hepatopathy in the same patient – increasingly common given the shared cardiometabolic substrate – creates diagnostic complexity, as fibrosis on non-invasive testing or biopsy may reflect both metabolic and congestive mechanisms [70]. Third, optimization of cardiac hemodynamics – through guideline-directed medical therapy, diuresis, device therapy, or valve intervention – represents the primary therapeutic lever for congestive hepatopathy, and hepatic parameters frequently improve with successful cardiac management [71]. Fourth, in patients being evaluated for advanced heart failure therapies, including left ventricular assist devices or cardiac transplantation, accurate hepatic assessment is essential, as significant hepatic fibrosis or cardiac cirrhosis may influence candidacy and post-procedural outcomes [11,71].
Cardiovascular Manifestations of MASLD
Coronary artery disease and Myocardial Infarction
Multiple epidemiological studies demonstrate robust associations between MASLD and coronary artery disease [75,76]. Meta-analyses report that MASLD increases the risk of coronary artery disease by 1.5-2.0-fold after adjustment for traditional cardiovascular risk factors [77,32]. The association strengthens with disease severity, with MASH and advanced fibrosis conferring a higher risk than simple steatosis [78,79].
MASLD patients exhibit increased coronary artery calcification scores, higher prevalence of vulnerable plaque morphology, and greater extent of multivessel coronary disease compared to matched controls [80,81]. Importantly, myocardial infarction risk increases progressively with the stage of hepatic fibrosis, underscoring the importance of fibrosis assessment in cardiovascular risk stratification [82,68].
Heart Failure
MASLD demonstrates particularly strong associations with heart failure, especially heart failure with preserved ejection fraction (HFpEF) [83,84]. Meta-analytic evidence indicates that MASLD increases heart failure risk by approximately 1.5-fold, with higher relative risks for HFpEF compared to heart failure with reduced ejection fraction (HFrEF) [85,86].
Magnetic resonance imaging studies reveal structural and functional cardiac alterations in MASLD patients, including increased left ventricular mass, concentric remodeling, impaired diastolic relaxation, and reduced myocardial strain, even in the absence of clinically evident cardiac disease [87,88]. Increased epicardial adipose tissue thickness, commonly observed in MASLD, promotes cardiac dysfunction through pro-inflammatory cytokine production and direct lipotoxic effects on myocardium [89,90].
Atrial Fibrillation
Emerging evidence links MASLD to increased atrial fibrillation prevalence and incidence [91,92]. The inflammatory milieu characteristic of MASH may foster atrial electrical remodeling, promoting arrhythmogenesis [93,72]. Meta-analyses demonstrate that MASLD increases atrial fibrillation risk by approximately 1.4-fold, with risk amplification in patients with more severe hepatic disease [94,95].
Stroke
Several observational studies report associations between MASLD and increased stroke risk, both ischemic and hemorrhagic subtypes [96,97]. MASLD patients demonstrate higher carotid intima-media thickness, increased carotid plaque prevalence, and greater plaque vulnerability compared to controls. Meta-analytic estimates suggest MASLD increases stroke risk by approximately 1.3-1.5-fold [98,99].
Cardiovascular Mortality
Critically, MASLD significantly increases cardiovascular mortality risk, which represents the leading cause of death in this population [100,68]. Meta-analyses including over 9 million participants demonstrate that MASLD increases cardiovascular mortality risk by approximately 1.6-fold compared to individuals without MASLD [101,102]. Risk escalates with disease severity, with MASH and advanced fibrosis conferring substantially higher cardiovascular mortality compared to simple steatosis [103,104].
Limitations and Future Directions
Several limitations merit acknowledgment. First, the majority of outcome data cited in this review derive from studies conducted under NAFLD/NASH terminology. However, the 99% diagnostic overlap supports continuity of evidence; prospective validation of cardiovascular outcomes specifically under MASLD criteria remains limited. Second, substantial residual confounding by shared cardiometabolic risk factors – including obesity, type 2 diabetes, hypertension, and dyslipidemia – persists across observational studies linking MASLD to cardiovascular disease, and causality cannot be firmly established from available data. Third, diagnostic heterogeneity is considerable; studies vary widely in how hepatic steatosis was ascertained (ultrasound, MRI-PDFF, histology, or liver enzymes), how fibrosis was staged, and which cardiovascular endpoints were captured, limiting direct comparability across cohorts. Fourth, prospective data generated specifically within the MASLD nomenclature framework are scarce, and the anticipated benefits of the new terminology – including improved disease recognition, reduced stigma, and enhanced patient engagement – have not yet been validated in longitudinal studies.
Despite substantial progress in understanding the MASLD-cardiovascular axis, important knowledge gaps persist. These include elucidating the precise molecular mechanisms linking hepatic fibrosis to cardiovascular outcomes, developing integrated risk prediction models incorporating fibrosis stage alongside traditional cardiovascular risk factors, identifying therapies that simultaneously address hepatic and cardiovascular disease, characterizing ethnic and racial disparities in MASLD prevalence and treatment response, and conducting long-term studies assessing the real-world impact of nomenclature change on diagnosis rates and patient outcomes. Cost-effectiveness analyses of screening strategies and emerging pharmacotherapies also remain an important area for future investigation [180,181].
Conclusion
The redefinition of fatty liver disease as MASLD represents more than nomenclature revision; it embodies a conceptual transformation recognizing the disease as a systemic metabolic disorder with significant cardiovascular implications. The liver-heart axis in MASLD is characterized by complex bidirectional interactions mediated by insulin resistance, chronic inflammation, oxidative stress, atherogenic dyslipidemia, and dysregulation of the gut-liver-heart axis. MASLD significantly increases risks of coronary artery disease, myocardial infarction, heart failure, particularly HFpEF, atrial fibrillation, stroke, and cardiovascular mortality, with hepatic fibrosis stage serving as a critical risk amplifier.
For internists managing patients across the cardiometabolic spectrum, the new MASLD nomenclature underscores the imperative for integrated care that addresses both hepatic and cardiovascular manifestations. Early identification through appropriate case-finding, accurate fibrosis assessment using non-invasive tools, comprehensive cardiovascular risk evaluation, and implementation of intensive lifestyle modifications form the foundation of management. Judicious use of cardiometabolic medications, including GLP-1 receptor agonists, SGLT2 inhibitors, statins, and antihypertensives, provides synergistic benefits for hepatic and cardiovascular health.
The transition to MASLD nomenclature is intended to facilitate better disease recognition, and may reduce stigmatization while aligning diagnostic criteria with pathophysiological understanding and therapeutic targets. As the field advances with emerging MASLD-specific pharmacotherapies and refined risk stratification tools, multidisciplinary collaboration will remain essential to optimize patient outcomes. Internists must embrace their central role in the comprehensive, integrated management of MASLD and its cardiovascular complications, recognizing that successful care requires addressing the liver-heart axis as an interconnected system rather than isolated organ dysfunction. Prospective validation of these anticipated benefits remains an important priority for future research.