Incidence, prevalence, and prognostic impact of sarcopenia on hepatic and cardiovascular outcomes in non-cirrhotic metabolic dysfunction–associated steatotic liver disease

What you need to know

Background and context

Sarcopenia is increasingly recognized in metabolic dysfunction–associated steatotic liver disease (MASLD), but its epidemiology and prognostic significance in non-cirrhotic populations remain incompletely characterized.

New findings

In a large nationwide cohort, sarcopenia prevalence increased over time and was independently associated with higher risks of hepatic decompensation, mortality, and major adverse cardiovascular events.

Impact on patient care

Sarcopenia identifies a high-risk phenotype in MASLD prior to cirrhosis. Routine assessment of muscle health may enhance risk stratification and support integration of exercise and nutritional interventions to improve hepatic and cardiovascular outcomes.

Introduction

Metabolic dysfunction–associated steatotic liver disease (MASLD) is currently the most prevalent chronic liver disease globally, affecting one in four adults (1). MASLD is a ubiquitous condition affecting persons across all strata, ethnicities, and regions with prevalence rising sharply since the dawn of the 21st century (2). The surge is driven by the rising tide of obesity, type 2 diabetes, and sedentary lifestyles (3, 4). It encompasses a broad spectrum from benign steatosis to hepatitis to advanced fibrosis (5). As the MASLD epidemic intensifies, clinicians face the dual challenge of addressing progressive liver pathology alongside its systemic complications and comorbidities (3). Moreover, cardiovascular disease (CVD) continues to be the leading cause of mortality in MASLD (6, 7). Thus underscoring that MASLD is not only highly prevalent but also clinically consequential, warranting urgent attention from a multisystemic perspective.

Concurrently, sarcopenia, a progressive muscle disease characterized by loss of skeletal muscle mass and strength, has emerged as an important, yet underappreciated, factor intertwined with MASLD (8). Though traditionally and metabolic abnormalities, and manifest in younger adults (9). The revised 2018 criteria of the linked to aging, it is now understood to result from chronic diseases European Working Group on Sarcopenia in Older People (EWGSOP2) and Asian Working Group (AWGS) 2019 emphasize muscle strength as the principal determinant, given its closer association with adverse outcomes compared to muscle mass alone (10). Importantly, sarcopenia is not merely physiologic declined but a pathological state driven by systemic illnesses and lifestyle (11, 12).

Mechanistically, MASLD and sarcopenia are deeply entwined. Skeletal muscle is essential for insulin-mediated glucose uptake; its depletion exacerbates insulin resistance, lipotoxicity, and systemic inflammation, hallmarks of MASLD. Conversely, hepatic steatosis impairs protein metabolism and increases myokine dysregulation, perpetuates chronic inflammation and mitochondrial dysfunction, accelerating muscle loss (13, 14). This bidirectional interplay perpetuates a cycle of metabolic deterioration affecting both liver and muscle.

Clinical data affirm this cross-link as studies have consistently shown that sarcopenia increases the risk of incident MASLD, predicts more severe steatohepatitis, and is independently associated with advanced fibrosis, irrespective of obesity or diabetes. Beyond the liver, sarcopenia portends worse outcomes in metabolic and cardiovascular health, adding to the overall morbidity burden of MASLD patients (15). While its prognostic impact is well-established in cirrhosis, emerging evidence suggests that adverse outcomes begin much earlier (9). Thus, identifying sarcopenia in non-cirrhotic MASLD may provide an opportunity for early intervention through structured exercise and nutritional strategies and alter the outcomes (9).

Despite its clinical relevance and increasing recognition of sarcopenia and MASLD, significant knowledge gaps still persist. Most epidemiological studies to date have been cross-sectional or region-specific, and few have examined long-term outcome trajectories in sarcopenic vs. non-sarcopenic non-cirrhotic MASLD on a large scale. Likewise, the combined impact of sarcopenia on cardiovascular and hepatic outcomes in these subpopulations is not fully elucidated. There is a pressing need for large, longitudinal cohort analyses to elucidate the prevalence trends of sarcopenic non-cirrhotic MASLD, its prognostic implications, and the interplay of risk factors that drive cardiovascular and liver-related outcomes. The current nationwide study intends to address this gap by stratifying MASLD patients into sarcopenic and non-sarcopenic. Through this comprehensive analysis, the current study aims to provide updated real-world evidence to inform risk stratification and management of MASLD, an increasingly recognized but still under-characterized subset of fatty liver disease.

Methods

Study design and data source

This was a retrospective, longitudinal cohort study conducted using the U.S. Collaborative Network within TriNetX (Cambridge, MA, USA), a global multi-institutional, federated research network. TriNetX provides real-time access to de-identified electronic health records from over 110 million patients across 66 healthcare organizations in the United States, predominantly comprising large academic medical centers with both inpatient and outpatient facilities. The database captures the full patient population of participating institutions. Data de-identification is performed at the network level and certified through formal expert determination in accordance with the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule, with additional obfuscation of patient counts fewer than 10 to ensure anonymity. Clinical variables are derived directly from electronic health records of included health care organizations as well as retrieved through a built-in natural language processing system that extracts variables from clinical documents. Robust quality assurance is achieved at the time of extraction from electronic health records before inclusion in the database, in a systematic and standardised format. The process also includes data cleaning which rejects patient records that do not meet the TriNetX quality standards. The database does not include claims data or data collected from randomized clinical trials. The database includes patient data regarding demographics, diagnosis, procedures, laboratory values, and medications. The interface only provides aggregate counts and statistical summaries to protect patient health information and ensures that the data remain de-identified at all levels of data retrieval and dissemination.

Study population

Adult patients aged 18 years or older with a documented diagnosis of MASLD between January 1, 2005, and December 31, 2024, were eligible for inclusion. MASLD was identified using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for fatty (change of) liver, not elsewhere classified (K76.0), and non-alcoholic steatohepatitis (K75.81) (Supplementary Table S1). The first recorded MASLD diagnosis meeting all eligibility criteria was designated as the cohort entry point. To enhance etiologic specificity, patients with competing causes of chronic liver disease were excluded, including viral hepatitis (B15–B19), alcoholic liver disease (K70), toxic liver disease (K71), autoimmune hepatitis (K75.4), granulomatous hepatitis (K75.3), liver abscess and sequelae of chronic liver disease (ICD-9 572), Wilson disease (E83.01), hemochromatosis (E83.11), alpha-1 antitrypsin deficiency (E88.01), and other specified inflammatory, vascular, or infiltrative liver diseases (K75.0, K75.1, K75.2, K75.89, K76.1–K76.4, and K77) before cohort entry were excluded from outcome-specific analyses to ensure capture of incident events.

Exposure definitions: sarcopenia

Sarcopenia was defined using ICD-10-CM code M62.84. Patients with MASLD were categorized into sarcopenia and non-sarcopenia cohorts based on the presence or absence of this diagnosis in their longitudinal medical record, with sarcopenia required to be documented on or before the index date (16).

Index date and follow-up

The index date was defined as the first qualifying MASLD diagnosis that satisfied all inclusion and exclusion criteria. Follow-up commenced one day after the index date to minimize immortal time bias. Patients were followed longitudinally until the occurrence of the outcome of interest, death, loss to follow-up, or the end of available data, whichever occurred first. In accordance with TriNetX platform constraints, patients whose index event occurred more than 20 years prior to analysis were excluded.

Outcomes

The primary outcome included the incidence of sarcopenia in non-cirrhotic MASLD. Secondary outcomes included assessment of the risk of cardiovascular and hepatic outcomes in non-cirrhotic sarcopenic MASLD cohort compared to non-cirrhotic non-sarcopenic MASLD cohort. Hepatic decompensation was defined as a composite outcome including cirrhosis (K74.6), ascites (R18), esophageal varices (I85), gastric varices (I86.4), hepatic encephalopathy (K76.82), spontaneous bacterial peritonitis (K65.2), hepatorenal syndrome (K76.7), and hepatopulmonary syndrome (K76.81). Mortality was identified using TriNetX demographic death indicators and ICD-10-CM code R99. Cardiovascular outcomes were assessed separately and included major adverse cardiovascular events and related diagnoses, such as acute myocardial infarction (I21, I22), ischemic heart disease (I20–I25), heart failure (I50), atrial fibrillation or flutter (I48), cerebrovascular disease (I60–I69, G45), cardiac arrhythmias and arrest (I46, I47, I49), and thromboembolic events (I26, I80–I82, I81). For each outcome, patients with documented evidence of the event prior to the index date were excluded to ensure incident outcome ascertainment.

Incidence and prevalence analyses

To evaluate the temporal burden of sarcopenia among patients with MASLD, annual incidence and prevalence estimates were generated using the TriNetX Incidence and Prevalence Tool. These analyses were restricted to the period from 2010 through 2024 to reflect contemporary diagnostic and coding practices. Incidence was defined as the number of new sarcopenia diagnoses per calendar year among MASLD patients without prior sarcopenia, while prevalence was defined as the proportion of MASLD patients with an existing sarcopenia diagnosis in a given year.

Propensity score matching

To mitigate confounding and balance baseline characteristics between cohorts, 1:1 propensity score matching was performed between MASLD patients with sarcopenia and those without sarcopenia using a greedy nearest-neighbor algorithm with a caliper width of 0.1 pooled standard deviations. Covariates included demographic characteristics, metabolic comorbidities such as obesity, type 2 diabetes mellitus, hypertension, hyperlipidemia, chronic kidney disease, cardiovascular comorbidities, smoking or nicotine dependence, medication use including antihypertensive agents, lipid-lowering therapies, beta-blockers, diuretics, and renin–angiotensin system inhibitors, as well as baseline laboratory values when available. Covariate balance before and after matching was assessed using standardized mean differences, with values below 0.1 indicating adequate balance.

Statistical analysis

All analyses were performed using the TriNetX browser-based real-time analytics platform (TriNetX Live; TriNetX LLC, Cambridge, MA). Baseline characteristics were summarized using means with standard deviations for continuous variables and proportions for categorical variables. Pre-specified covariates included demographics, metabolic comorbidities, cardiovascular risk factors, smoking status, medication exposures, and relevant laboratory parameters when available.

To minimize confounding, 1:1 propensity score matching was conducted between MASLD patients with and without sarcopenia. Propensity scores were estimated using logistic regression incorporating age, sex, race and ethnicity, obesity, type 2 diabetes, hypertension, dyslipidemia, chronic kidney disease, baseline cardiovascular disease, smoking status, and cardiometabolic medication use. The TriNetX platform applied greedy nearest-neighbor matching with a caliper width of 0.1 pooled standard deviations and randomized observation order to reduce matching bias. Covariate balance was assessed using standardized mean differences, with values <0.1 indicating adequate balance. Separate propensity score models were constructed for hepatic and cardiovascular outcome cohorts, reflecting differences in eligibility criteria and baseline populations

After matching, time-to-event outcomes were evaluated using Kaplan–Meier methods with log-rank testing. Hazard ratios with 95% confidence intervals were estimated using Cox proportional hazards models, and proportionality assumptions were satisfied for all analyses. Continuous variables were compared using the Student's t test. All statistical tests were two-sided, and p-values <0.05 were considered statistically significant.

Results

A total of 1,859,498 adult patients with a diagnosis of metabolic dysfunction–associated steatotic liver disease (MASLD) were identified within the TriNetX U.S. Collaborative Network during the study period (2015–2024). Among these, 714 patients had a documented diagnosis of sarcopenia (ICD M62.84). Cohort construction and exclusions are detailed in the study flow diagram (Figure 1). The annual incidence proportion of sarcopenia among MASLD patients increased steadily from 0.001% in 2015 to 0.022% in 2024, while prevalence rose from 0.001% to 0.064% over the same period (Figure 2; Supplementary Table S2). Both male and female patients exhibited parallel increases in sarcopenia incidence and prevalence over time. By 2024, prevalence was comparable between sexes, reaching 0.064% in males and 0.065% in females, indicating no substantial sex-based divergence in sarcopenia burden within the MASLD population (Figure 3; Supplementary Table S3).

Sarcopenia and hepatic outcomes

Baseline characteristics for hepatic outcomes

Baseline characteristics for the hepatic outcomes cohort before and after propensity score matching are summarized in Table 1. Before matching, sarcopenic MASLD patients were significantly older and exhibited a higher burden of metabolic comorbidities, cardiovascular disease, chronic kidney disease, and inflammatory markers compared with non-sarcopenic controls. After matching, baseline characteristics were well balanced across cohorts, with standardized mean differences below 0.1 for all included variables.

Table 1. Baseline characteristics before and after propensity score matching (for hepatic outcomes).

INR, international normalized ratio; MASLD, metabolic dysfunction-associated steatotic liver disease; SD, standard deviation.

Hepatic outcomes after propensity score matching

Over a mean follow-up of 757.78 ± 669.04 days in the sarcopenia cohort and 1342.95 ± 1,086.83 days in matched controls, sarcopenic MASLD patients experienced significantly higher rates of adverse hepatic outcomes (Table 2). Cirrhosis developed in 75 sarcopenic MASLD patients compared with 18 non-sarcopenic MASLD patients, corresponding to an OR of 4.46 (95% CI 2.64–7.52). Hepatic decompensation occurred in 120 sarcopenic patients vs. 26 controls (OR 5.18, 95% CI 3.35–8.80). Moreover, all-cause mortality was significantly higher among sarcopenic patients (231 vs. 115 events; OR 2.36, 95% CI 1.85–3.02). Thus demonstrating a marked increase in liver-related morbidity and mortality associated with sarcopenia (Figure 4).

Table 2. Hepatic outcomes after propensity score matching.

CI, confidence interval; MASLD, metabolic dysfunction-associated steatotic liver disease; SD, standard deviation.

Predictors of hepatic outcomes

On Cox Proportional analysis, sarcopenia was strongly associated with an increased hazard of adverse hepatic outcomes (HR 5.03, 95% CI 4.21–6.02; p < 0.0001) (Table 3). On further Cox Proportional analysis of hepatic outcomes in the sarcopenic MASLD cohort, significant predictors included older age, type 2 diabetes mellitus, elevated HbA1c, lean BMI, and anemia. Higher HDL cholesterol levels, Asian, and African-American ethnicity were associated with lower hepatic risk.

Table 3. COX proportionality for hepatic outcomes (MASLD with sarcopenia vs. MASLD without Sarcopenia).

CI, confidence interval; dL, deciliter; g, gram; HDL, high density lipoprotein; Kg, kilogram; LDL, low density lipoprotein; MASLD, metabolic dysfunction-associated steatotic liver disease; mg- milligram).

Sarcopenia and cardiovascular outcomes

Baseline characteristics for cardiovascular outcomes

For cardiovascular outcome analyses, patients with baseline cardiovascular disease or insufficient follow-up were excluded, resulting in a reduced cohort (610 sarcopenic and 998,642 non-sarcopenic MASLD patients) prior to propensity score matching (Table 4). Baseline characteristics for the CV outcomes cohort before and after propensity score matching are summarized in Table 4. Prior to matching, MASLD patients with sarcopenia were significantly older and had a higher prevalence of metabolic comorbidities, cardiovascular disease, chronic kidney disease, and greater use of cardiometabolic medications compared with non-sarcopenic MASLD patients. Laboratory parameters, including inflammatory markers and lipid indices, also differed significantly between groups. After propensity score matching, all baseline demographic, clinical, medication, and laboratory variables were well balanced between cohorts, with standardized mean differences below 0.1 for all covariates, indicating successful matching.

Table 4. Baseline characteristics before and after propensity score matching (for cardiovascular outcomes).

dL, deciliter; g, gram; HDL, high density lipoprotein; Kg, kilogram; LDL, low density lipoprotein; INR, international normalized ratio; MASLD, metabolic dysfunction-associated steatotic liver disease; uL, microliter; RAS, renin-angiotensin system; SD, standard deviation.

Cardiovascular outcomes after propensity score matching

Following propensity score matching, MASLD patients with sarcopenia demonstrated significantly higher rates of adverse cardiovascular outcomes compared with matched non-sarcopenic controls (Table 5). Over a mean follow-up of 762.5 ± 722.5 days in the sarcopenia cohort and 1,308.1 ± 1,108.9 days in matched controls, MASLD patients with sarcopenia experienced significantly higher rates of adverse CV outcomes (Table 5). All-cause mortality occurred more frequently in sarcopenic patients [166 vs. 69 events; odds ratio (OR) 2.94, 95% CI 2.16–3.99]. Major adverse CV events were also more common in the sarcopenia cohort (162 vs. 103 events; OR 1.78, 95% CI 1.35–2.35). Sarcopenia was associated with increased odds of atrial fibrillation/flutter (OR 1.99, 95% CI 1.18–3.33), ischemic heart disease (OR 1.60, 95% CI 1.17–2.19), and heart failure (OR 2.06, 95% CI 1.34–3.16). Furthermore, significantly increased risk of cerebrovascular events (OR 1.64, 95% CI 1.07–2.54), and thrombotic disorders (OR 2.84, 95% CI 1.77–4.57) was observed in sarcopenic MASLD cohorts (Figure 5).

Table 5. Cardiovascular outcomes after propensity score matching.

CI, confidence interval; MACE, major adverse cardiovascular event; MASLD, metabolic dysfunction-associated steatotic liver disease; SD, standard deviation.

*MACE includes non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death.

Predictors of cardiovascular outcomes

On Cox Proportional analysis, sarcopenia was strongly associated with an increased hazard of adverse cardiovascular outcomes (HR 2.24, 95% CI 1.91–2.62; p < 0.0001) (Table 6). On further Cox Proportional analysis of hepatic outcomes in sarcopenic MASLD cohort, increasing age, male sex, type 2 diabetes mellitus, hypertension, elevated HbA1c, lean BMI range (18–24.9 kg/m²), and anemia were also associated with higher cardiovascular risk. Higher HDL cholesterol levels and Asian ethnicity were associated with a reduced hazard of cardiovascular outcomes (Figure 6).

Table 6. COX proportionality for cardiovascular outcomes (MASLD with sarcopenia vs. MASLD without Sarcopenia).

CI, confidence interval; dL, deciliter; g, gram; HDL, high density lipoprotein; Kg, kilogram; LDL, low density lipoprotein; MASLD, metabolic dysfunction-associated steatotic liver disease; mg, milligram.

Discussion

The current large, nationwide, real-world cohort study spanning more than a decade demonstrated a steadily rising burden of sarcopenia among MASLD patients, accompanied by a profound and independent association with adverse hepatic and cardiovascular outcomes. Using robust propensity-matched analyses, sarcopenia emerged as a powerful predictor of cirrhosis, hepatic decompensation, and all-cause mortality, conferring more than five-fold higher hazards for hepatic events and nearly three-fold higher odds of death. Importantly, sarcopenia was also independently associated with a broad spectrum of cardiovascular complications, including major adverse cardiovascular events, heart failure, cerebrovascular disease, and thrombotic disorders, underscoring its role as a systemic risk modifier rather than a mere musculoskeletal comorbidity. These findings position sarcopenia as a critical co-factor in MASLD prognosis.

Our results align with a growing body of literature linking low muscle mass i.e., sarcopenia to worse clinical outcomes in MASLD. Prior cohort studies have shown that MASLD patients with sarcopenia are significantly more prone to advanced liver disease (17). A study demonstrated that sarcopenia doubled the odds of significant fibrosis, independent of obesity and insulin resistance (18). Similarly, a nationwide analysis ∼1.8-fold higher odds of significant fibrosis in sarcopenic MASLD patients, an association that persisted across BMI categories and after adjusting for metabolic confounders (19). This was further concluded by a recent meta-analysis with sarcopenic MASLD patients have pooled OR ∼1.5 of advanced fibrosis than those without sarcopenia (20). While the prognostic impact of sarcopenia in cirrhosis is well established (predicting higher mortality and complications), our study extends this risk to non-cirrhotic populations, underscoring that adverse outcomes begin to accrue at earlier disease stages (21). Perhaps the most novel aspect of our findings is the strong link between sarcopenia and cardiovascular events in MASLD. Cardiovascular disease is the leading cause of mortality in MASLD, and emerging evidence suggests that coexisting sarcopenia exacerbates this risk (15, 21). Sarcopenia was associated with a 320% increase in cardiovascular mortality among individuals with MASLD (21). Studies also reported roughly four-fold higher odds of an elevated 10-year ASCVD risk score in sarcopenic MASLD than metabolically healthy controls, and in patients with type 2 diabetes, sarcopenic MASLD was significantly associated with accelerated carotid atherosclerosis progression (adjusted OR ∼2.2 over 6–8 years) (22, 23). Taken together, these data highlight a synergistic interaction between poor muscle status and fatty liver in driving both liver-related and cardiovascular morbidity. Notably, most prior studies were cross-sectional or included patients with advanced fibrosis, whereas our cohort was limited to non-cirrhotic MASLD; this strengthens the evidence that sarcopenia confers excess risk even before cirrhosis has developed.

Several biological mechanisms plausibly underlie the observed bidirectional link between sarcopenia and MASLD (Figures 7, 8). Chronic low-grade inflammation is a central driver: excess visceral adiposity in MASLD releases pro-inflammatory cytokines such as TNF-α and IL-6, which can trigger muscle protein catabolism and functional decline (24). Hepatic steatosis itself contributes to systemic inflammation and disrupts protein metabolism, leading to myocyte mitochondrial dysfunction and accelerated muscle loss (25). Reciprocally, loss of skeletal muscle mass exacerbates insulin resistance—since muscle is the principal site of insulin-mediated glucose disposal—thereby promoting hyperglycemia and increased hepatic lipogenesis (26). This creates a vicious cycle where sarcopenia worsens the metabolic milieu that drives steatohepatitis. Hormonal dysregulation is also implicated: patients with metabolic syndrome often exhibit reduced growth hormone/IGF-1 and testosterone levels, which impairs muscle anabolism and may exacerbate hepatic fat accumulation (27). At the same time, the fatty liver secretes hepatokines (e.g., fetuin-A) and induces hyperinsulinemia, both of which can further promote muscle wasting, while the loss of myokines from muscle (such as irisin or IL-15) removes signals that normally help attenuate liver fat and inflammation (28). Thus, inflammation, insulin resistance, and endocrine alterations form an integrated muscle–liver cross-talk network that fuels both sarcopenia and MASLD progression in tandem (29, 30).

The current study has several strengths, including the large sample size drawn from a nationwide multi-center database and a long observation period of up to 15 years. The use of a real-world EHR network (TriNetX) enhances generalizability, capturing a diverse MASLD population across academic and community settings. The study rigorously excluded other chronic liver diseases and applied propensity score matching to balance key confounders, lending credibility to the observed associations. Nevertheless, important limitations must be acknowledged. First, our exposure and outcomes were ascertained via ICD codes, which may be subject to misclassification. Sarcopenia in particular is likely underdiagnosed and under-coded in practice, meaning our “sarcopenia” cohort probably represents more severe cases where the condition was recognized clinically. As a result, some MASLD patients with mild to moderate muscle loss might have been misclassified in the non-sarcopenia group, potentially biasing our estimates toward the null. Moreover, the ICD code for sarcopenia does not capture muscle function or strength. We lacked direct measurements of muscle mass or performance (e.g., DEXA scans, CT muscle area, grip strength), which are now considered the gold-standard for sarcopenia assessment. Additionally, there may be selection bias in healthcare utilization: patients with more health issues (either sarcopenia or metabolic comorbidities) might undergo more frequent visits and thus have more opportunities for outcome detection. The median follow-up was shorter in the sarcopenia group than in controls, partly due to higher mortality, which might affect the observed incidence rates. Finally, as an observational study, our findings show association but cannot prove causation. It remains possible that more aggressive MASLD drives muscle loss (reverse causality) or that a third factor (e.g., systemic inflammation burden) independently worsens both muscle and liver health.

From a clinical perspective, our findings have important implications and highlight avenues for future research. They underscore the need to screen for sarcopenia in patients with MASLD—particularly older individuals and those with coexisting metabolic disease—even before the onset of cirrhosis. Simple assessments such as grip strength, gait speed, or body composition analysis could be feasibly incorporated into routine MASLD clinics to enable early detection. This risk stratification is clinically relevant, as emerging evidence suggests that sarcopenia identifies patients at higher risk of fibrosis progression and cardiovascular events (23).

Importantly, sarcopenia is a modifiable risk factor. Unlike fixed genetic determinants, muscle mass and function can be improved through targeted interventions. Lifestyle modification remains the cornerstone of management, with structured exercise—particularly resistance training combined with aerobic activity—and adequate protein intake shown to improve muscle strength and mass while also conferring metabolic and hepatic benefits, independent of weight loss. Our findings support integrating exercise physiology services and nutritional counselling into MASLD care, thereby addressing both liver-related outcomes and cardiovascular risk.

Although several pharmacologic strategies aimed at muscle preservation such as anabolic agents (testosterone, GH supplement), myostatin inhibitors, and selective androgen receptor modulators, etc. are not currently approved for sarcopenia in MASLD, and lifestyle interventions remain the most evidence-based approach. Looking ahead, prospective studies and randomized trials are needed to determine whether targeted treatment of sarcopenia can translate into reductions in cirrhosis and cardiovascular events. Incorporating quantitative muscle assessments into MASLD risk models may further refine prognostication. Overall, our findings support a more integrated approach to MASLD management that recognizes muscle health as a key determinant of long-term outcomes.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fepid.2026.1779600/full#supplementary-material

Supplementary material Supplementary material at the source

Footnotes

Edited by: Xiaotao Zhang, Icahn School of Medicine at Mount Sinai, United States

Reviewed by: Navin Suthahar, Erasmus Medical Center, Netherlands

Nelson Lu, United States Food and Drug Administration, United States