Metabolic dysfunction-associated steatotic liver disease, known as MASLD, affects roughly a third of adults worldwide and has long been treated as a liver problem first and foremost. A new expert recommendation published in Nature Reviews Gastroenterology & Hepatology argues that this framing is dangerously incomplete. Led by Xiao-Dong Zhou and Ming-Hua Zheng of Wenzhou Medical University, together with an international team spanning hepatology, cardiology, endocrinology and epidemiology, the paper calls for MASLD to be recognised as a systemic cardiometabolic disorder that demands coordinated heart–liver management across medical specialities. Cardiovascular disease, the authors note, is a leading cause of death in people with MASLD, yet the condition remains chronically under-recognised in cardiology clinics, while cardiovascular risk is under-appreciated in hepatology practice.
The scale of the blind spot is considerable. Population studies and meta-analyses cited by the group show that MASLD increases the risk of fatal and non-fatal cardiovascular events, new-onset heart failure, and atrial fibrillation. One recent meta-analysis of around 11 million individuals linked fatty liver disease to a significantly elevated risk of incident heart failure, and biopsy-proven cohorts have revealed that incident heart failure is both common and frequently missed in these patients. The group describes a global cardiovascular–liver–metabolic ‘syndemic’, in which shared risk factors such as obesity, type 2 diabetes and dyslipidaemia drive parallel epidemics of liver fibrosis and cardiovascular disease. When each speciality manages only its own organ, patients fall through the gaps, interventions arrive late, and outcomes suffer on both fronts.
At the mechanistic level, the liver and the heart are locked in bidirectional dialogue. The steatotic liver acts as an endocrine and inflammatory organ, exporting excess very-low-density lipoproteins, pro-inflammatory cytokines and other mediators that promote endothelial dysfunction, atherosclerosis and myocardial remodelling. Hepatic insulin resistance aggravates systemic metabolic dysfunction, while emerging proteomic work suggests that distinct organ-damage signatures can flag MASLD patients at risk of systemic complications before overt disease develops. Conversely, cardiac dysfunction feeds back on the liver: elevated central venous pressure in heart failure congests the hepatic circulation, and experimental evidence shows that myocardial infarction can accelerate steatohepatitis by triggering immunoinflammatory responses. Recent research also suggests that low-to-moderate alcohol intake and hypertension both amplify fibrosis progression in MASLD, tightening the links between metabolic, hepatic and cardiac trajectories.
A central tenet of the recommendation is that liver fibrosis, rather than simple steatosis, is the pivotal risk stratifier. Fat in the liver alone carries a more modest prognostic signal; the accumulation of fibrous scar tissue is what tracks with hepatic decompensation, cardiovascular events and mortality. The authors therefore propose that the degree of fibrosis should guide not only hepatological monitoring but also cardiovascular risk assessment, effectively serving as a shared currency between the two disciplines. Data from the global burden of disease project and longitudinal cohort analyses indicate that fibrosis stage predicts clinical events across the MASLD spectrum, including in so-called lean individuals, and that patients with coexisting cardiovascular–kidney–metabolic syndrome progress to advanced fibrosis and liver-related events more rapidly.
To operationalise this insight, the paper lays out a stepwise screening algorithm designed for real-world efficiency. First-line assessment uses the fibrosis-4 index, a simple calculation from age, aminotransferases, platelet count and aspartate aminotransferase that can be computed in any clinic. Patients flagged by this inexpensive test proceed to vibration-controlled transient elastography, a non-invasive ultrasound-based measurement of liver stiffness, and those with concerning results are referred for specialist evaluation. This cascade, the authors argue, enables identification of clinically significant fibrosis and high-risk metabolic phenotypes without resorting to liver biopsy in most patients, and it aligns with recent European screening studies that found previously unrecognised liver fibrosis to be common in the general population. The same non-invasive tools can be deployed longitudinally, since changes in stiffness and fibrosis markers over time carry prognostic information for both organ systems.
On the therapeutic front, the framework recommends pairing intensive lifestyle intervention with cardiometabolic drug classes that deliver dual liver and cardiovascular benefits. Glucagon-like peptide 1 receptor agonists have now demonstrated histological improvement in steatohepatitis in phase 3 trials of semaglutide and tirzepatide, alongside established reductions in major adverse cardiovascular events, heart failure hospitalisation and, for tirzepatide, benefit in obesity-related heart failure with preserved ejection fraction. Sodium–glucose cotransporter 2 inhibitors similarly combine cardiovascular and renal protection with emerging evidence of reduced liver-related events and mortality in patients with MASH cirrhosis. Meanwhile, resmetirom, the first approved liver-directed therapy for MASH with moderate to advanced fibrosis, addresses the hepatic side of the equation and has gained regulatory approval in both the United States and Europe. Statins, the authors add, remain underused in MASLD despite evidence of multisystem benefit and reassuring hepatic safety.
The recommendation does not stop at individual drugs; it embeds them within a structured metabolic care framework that treats the patient as a cardiometabolic whole. Data-driven cluster analyses and polygenic risk scores now identify biologically distinct MASLD subtypes, some predisposed to severe fibrosis and others to cardiometabolic complications, offering a route to precision-matched therapy. The authors argue that cardiovascular risk calculators such as SCORE2 and the American Heart Association’s PREVENT equations should be complemented by markers that capture the MASLD-specific burden, including high-sensitivity C-reactive protein, lipoprotein(a), inflammation indices and non-invasive fibrosis measures. They also stress aggressive management of hypertension, diabetes and dyslipidaemia, careful attention to alcohol consumption, and recognition that cardiovascular events themselves accelerate liver disease progression.
Implementation, the group acknowledges, is the hardest part. Quality-standards audits in the United Kingdom have documented wide variation in fatty liver disease care delivery, and therapeutic inertia remains endemic in cardiovascular prevention. The paper therefore proposes concrete pathways: bidirectional referral arrangements in which cardiologists screen for MASLD using FIB-4 and hepatologists routinely assess cardiovascular risk; shared care clinics and multidisciplinary teams; embedded non-invasive liver measures in both cardiology and hepatology workflows; and co-management protocols that specify who monitors what, and when. Clinical trials, they contend, should likewise embed dual hepatic and cardiovascular endpoints, a roadmap recently elaborated for multiorgan trial design spanning the MASLD–MASH–cardiovascular–kidney–metabolic spectrum. Without such integration, the benefits of newly available therapies risk accruing to the minority of patients who already navigate both specialities successfully.
The paper’s broader message is a reframing of MASLD itself: from an incidental imaging finding, or a condition waiting for cirrhosis, to a systemic metabolic disease whose most lethal complication is often cardiac. With global projections suggesting the MASLD burden will continue to climb through 2050, and cause-specific mortality data showing cardiovascular death outpacing liver-related death in these patients, the stakes of getting co-management right are high. The authors, whose work is supported by the CHAIN Consortium, position their expert recommendation as a practical bridge between cardiology and hepatology, one built on existing tools rather than speculative technology. If adopted, the framework could convert a fragmented two-organ problem into a single, coherent cardiometabolic care pathway, closing screening gaps, sequencing therapies by fibrosis stage and cardiovascular risk, and ultimately reducing the twin burdens of heart disease and liver failure in one of the world’s most common chronic conditions.
The shift in terminology itself reflects the evolving understanding of the disease. The multisociety Delphi consensus that introduced the MASLD nomenclature in 2023 deliberately replaced older terms to emphasise metabolic dysfunction as the unifying mechanism, and to allow coexistence with other hepatic conditions such as alcohol-associated liver disease. This reframing matters clinically, because the metabolic cluster that defines MASLD overlaps almost completely with the risk factors tracked by cardiovascular prevention guidelines, making the liver a natural target organ for cardiometabolic screening programmes.
Epidemiological data underpinning the recommendation are substantial. The Global Burden of Disease Study 2023 analysis projected continued growth in MASLD prevalence through mid-century, and systematic reviews have documented that hepatic and extrahepatic cancers, cardiovascular events and chronic kidney disease collectively account for a large share of adverse outcomes, with liver-related mortality no longer dominating the natural history except in advanced fibrosis. This changing pattern of mortality is precisely why the authors argue that risk stratification must serve two organ systems simultaneously.
The screening tools proposed also carry caveats worth noting. The fibrosis-4 index performs well at ruling out advanced fibrosis but has limited specificity, particularly in middle-aged patients with obesity or diabetes, where false positives are common and can drive unnecessary referrals. Vibration-controlled transient elastography offers better discrimination but can be unreliable in obesity and in acute hepatic inflammation, and access remains uneven across health systems. The stepwise algorithm therefore functions best as a triage instrument, reserving liver biopsy for indeterminate cases where the result would change management.
On the pharmacological side, the dual-benefit argument is supported by an expanding evidence base. Incretin-based therapies act on hepatic, adipose and central nervous system pathways that influence appetite, insulin sensitivity and hepatic fat flux, while sodium–glucose cotransporter 2 inhibitors shift myocardial metabolism and reduce cardiac congestion. Resmetirom, a selective thyroid hormone receptor-beta agonist, targets hepatic mitochondrial function and fat oxidation, complementing rather than replacing systemic metabolic therapy. The authors emphasise that sequencing these agents according to fibrosis stage and cardiovascular risk profile remains an open question that only trials with dual endpoints can resolve, reinforcing their call for co-management pathways embedded in routine practice.
Subject of Research: Heart–liver co-management and multidisciplinary cardiometabolic care in metabolic dysfunction-associated steatotic liver disease (MASLD)
Article Title: Heart–liver co-management in MASLD: expert perspectives and recommendations from a multidisciplinary cardiometabolic framework
Article References: Zhou, X.-D., Jeong, S., Chen, Q.-F., Targher, G., Byrne, C. D., Chew, N. W. S., Younossi, Z. M., Lip, G. Y. H., Tilg, H., George, J., Stefan, N., Sperling, L. S., Luu, H. N., Fudim, M., Loomba, R., & Zheng, M.-H. (2026). Heart–liver co-management in MASLD: expert perspectives and recommendations from a multidisciplinary cardiometabolic framework. Nature Reviews Gastroenterology & Hepatology. https://doi.org/10.1038/s41575-026-01255-z
Image Credits: AI Generated
DOI: 10.1038/s41575-026-01255-z
Keywords: MASLD, cardiovascular disease, liver fibrosis, heart–liver co-management, FIB-4, transient elastography, GLP-1 receptor agonists, SGLT2 inhibitors, resmetirom, cardiometabolic syndrome, risk stratification, multidisciplinary care
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Frances Kline. (September 12, 2026). Fatty Liver Disease Is a Heart Problem Too: Experts Call for Joined-Up Care. Scienmag. https://scienmag.com/fatty-liver-disease-is-a-heart-problem-too-experts-call-for-joined-up-care/
Frances Kline. “Fatty Liver Disease Is a Heart Problem Too: Experts Call for Joined-Up Care.” Scienmag, 12 September 2026, https://scienmag.com/fatty-liver-disease-is-a-heart-problem-too-experts-call-for-joined-up-care/. Accessed 12 September 2026.
Frances Kline. “Fatty Liver Disease Is a Heart Problem Too: Experts Call for Joined-Up Care.” Scienmag. September 12, 2026. https://scienmag.com/fatty-liver-disease-is-a-heart-problem-too-experts-call-for-joined-up-care/
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Tags: Cardiometabolic Disordercardiometabolic syndromecardiovascular diseaseCardiovascular Risks in Liver DiseaseFatty Liver and Heart Failurefatty liver diseaseFatty Liver Disease and Atrial FibrillationFIB-4Global Syndemic of Liver and Heart DiseaseGLP-1 receptor agonistsHeart-Liver Disease Connectionheart–liver co-managementIntegrated Heart and Liver CareLiver fibrosisMASLDMetabolic Dysfunction and Cardiovascular Diseasemultidisciplinary careresmetiromrisk stratificationSGLT2 inhibitorsSystemic Approach to MASLDtransient elastographyUnder-recognition of Cardio-Liver Conditions
