Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over a quarter of the global population, with up to 30% developing Metabolic Dysfunction-Associated Steatohepatitis (MASH), a progressive form that can silently lead to fibrosis, cirrhosis, and liver cancer. Current diagnostic methods, including blood-based scores and imaging, are insufficient for early detection, leading to late-stage diagnoses in most patients. Liver biopsy remains the diagnostic gold standard but is invasive, costly, and prone to high inter- and intra-reader variability, limiting its utility in routine care and clinical trials. Our research highlights myosteatosis-fat infiltration in skeletal muscle-as a potential early, non-invasive marker of MASH. In preclinical models and clinical studies, myosteatosis correlated with the presence of MASH and distinguished it from isolated steatosis. Notably, reductions in myosteatosis following interventions such as bariatric surgery or dietary regimens were associated with histological improvements in MASH, suggesting a potential role in predicting treatment response. In larger cohorts, myosteatosis was identified as a strong predictor of all-cause mortality. In parallel, we utilized a VCAM- 1-targeted molecular imaging technique and demonstrated a high accuracy in detecting inflammation in preclinical MASH models. This technology is now advancing to clinical trials for validation in humans. Taken together, our data support that targeted medical imaging may enable early, non-invasive diagnosis and monitoring of MASH, reducing reliance on liver biopsy and improving patient outcomes.

Background Body composition data have been limited to adults with disease or older age. The prognostic impact in otherwise asymptomatic adults is unclear. Purpose To use artificial intelligence-based body composition metrics from routine abdominal CT scans in asymptomatic adults to clarify the association between obesity, liver steatosis, myopenia, and myosteatosis and the risk of mortality. Materials and Methods In this retrospective single-center study, consecutive adult outpatients undergoing routine colorectal cancer screening from April 2004 to December 2016 were included. Using a U-Net algorithm, the following body composition metrics were extracted from low-dose, noncontrast, supine multidetector abdominal CT scans: total muscle area, muscle density, subcutaneous and visceral fat area, and volumetric liver density. Abnormal body composition was defined by the presence of liver steatosis, obesity, muscle fatty infiltration (myosteatosis), and/or low muscle mass (myopenia). The incidence of death and major adverse cardiovascular events were recorded during a median follow-up of 8.8 years. Multivariable analyses were performed accounting for age, sex, smoking status, myosteatosis, liver steatosis, myopenia, type 2 diabetes, obesity, visceral fat, and history of cardiovascular events. Results Overall, 8982 consecutive outpatients (mean age, 57 years ± 8 [SD]; 5008 female, 3974 male) were included. Abnormal body composition was found in 86% (434 of 507) of patients who died during follow-up. Myosteatosis was found in 278 of 507 patients (55%) who died (15.5% absolute risk at 10 years). Myosteatosis, obesity, liver steatosis, and myopenia were associated with increased mortality risk (hazard ratio [HR]: 4.33 [95% CI: 3.63, 5.16], 1.27 [95% CI: 1.06, 1.53], 1.86 [95% CI: 1.56, 2.21], and 1.75 [95% CI: 1.43, 2.14], respectively). In 8303 patients (excluding 679 patients without complete data), after multivariable adjustment, myosteatosis remained associated with increased mortality risk (HR, 1.89 [95% CI: 1.52, 2.35]; P < .001). Conclusion Artificial intelligence-based profiling of body composition from routine abdominal CT scans identified myosteatosis as a key predictor of mortality risk in asymptomatic adults. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Tong and Magudia in this issue.

To evaluate the association between fat infiltration in skeletal muscles (myosteatosis) and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). In a cross-sectional cohort of 72 histologically proven NAFLD patients (n = 38 with non-alcoholic steatohepatitis; NASH), among which 20 had HCC diagnosed on biopsy, we used proton density fat fraction (PDFF) at MRI to evaluate myosteatosis in skeletal muscles (mean fat fraction and first order radiomic-based pattern) at the third lumbar level, namely in erector spinae (ES), quadratus lumborum (QL), psoas, oblique, and rectus muscles. PDFFES was 70 • HCC in patients with non-alcoholic fatty liver disease, and more specifically in those with non-alcoholic steatohepatitis, is independently associated with severe fatty infiltration (myosteatosis) of paravertebral skeletal muscles. • Association between myosteatosis and HCC is independent from liver fibrosis stage. • Histogram-based radiomics features of myosteatosis predicts the risk of HCC in patients with non-alcoholic steatohepatitis.

To date, a biopsy is mandatory to evaluate parenchymal inflammation in the liver. Here, we evaluated whether molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) could be used as an alternative non-invasive tool to detect liver inflammation in the setting of chronic liver disease. To do so, we radiolabeled anti-VCAM-1 nanobody (99mTc-cAbVCAM1-5) and used single-photon emission computed tomography (SPECT) to quantify liver uptake in preclinical models of non-alcoholic fatty liver disease (NAFLD) with various degree of liver inflammation: wild-type mice fed a normal or high-fat diet (HFD), FOZ fed a HFD and C57BL6/J fed a choline-deficient or -supplemented HFD. 99mTc-cAbVCAM1-5 uptake strongly correlates with liver histological inflammatory score and with molecular inflammatory markers. The diagnostic power to detect any degree of liver inflammation is excellent (AUROC 0.85-0.99). These data build the rationale to investigate 99mTc-cAbVCAM1-5 imaging to detect liver inflammation in patients with NAFLD, a largely unmet medical need.

Background:Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in the world. Progression toward non-alcoholic steatohepatitis (NASH) is associated with alterations of skeletal muscle. One plausible mechanism for altered muscle compartment in liver disease is changes in ammonia metabolism. In the present study, we explored the hypothesis that NASH-associated hyperammonemia drives muscle changes as well as liver disease progression.Materials and methods:In Alms1-mutant mice (foz/foz) fed a 60% fat diet (HFD) for 12 weeks; we investigated hepatic and muscular ammonia detoxification efficiency. We then tested the effect of an 8 week-long supplementation with L-ornithine L-aspartate (LOLA), a known ammonia-lowering treatment, given after either 4 or 12 weeks of HFD for a preventive or a curative intervention, respectively. We monitored body composition, liver and muscle state by micro computed tomography (micro-CT) as well as muscle strength by four-limb grip test.Results:According to previous studies, 12 weeks of HFD induced NASH in all foz/foz mice. Increase of hepatic ammonia production and alterations of urea cycle efficiency were observed, leading to hyperammonemia. Concomitantly mice developed marked myosteatosis. First signs of myopenia occurred after 20 weeks of diet. Early LOLA treatment given during NASH development, but not its administration in a curative regimen, efficiently prevented myosteatosis and muscle quality, but barely impacted liver disease or, surprisingly, ammonia detoxification.Conclusion:Our study confirms the perturbation of hepatic ammonia detoxification pathways in NASH. Results from the interventional experiments suggest a direct beneficial impact of LOLA on skeletal muscle during NASH development, though it does not improve ammonia metabolism or liver disease.

BACKGROUND & AIMS:Through FXR and TGR5 signaling, bile acids (BAs) modulate lipid and glucose metabolism, inflammation and fibrosis. Hence, BAs returning to the liver after enteric secretion, modification and reabsorption may contribute to the pathogenesis of non-alcoholic steatohepatitis (NASH). Herein, we characterized the enterohepatic profile and signaling of BAs in preclinical models of NASH, and explored the consequences of experimental manipulation of BA composition.METHODS:We used high-fat diet (HFD)-fed foz/foz and high-fructose western diet-fed C57BL/6J mice, and compared them to their respective controls. Mice received a diet supplemented with deoxycholic acid (DCA) to modulate BA composition.RESULTS:Compared to controls, mice with NASH had lower concentrations of BAs in their portal blood and bile, while systemic BA concentrations were not significantly altered. Notably, the concentrations of secondary BAs, and especially of DCA, and the ratio of secondary to primary BAs were strikingly lower in bile and portal blood of mice with NASH. Hence, portal blood was poor in FXR and TGR5 ligands, and conferred poor anti-inflammatory protection in mice with NASH. Enhanced primary BAs synthesis and conversion of secondary to primary BAs in NASH livers contributed to the depletion in secondary BAs. Dietary DCA supplementation in HFD-fed foz/foz mice restored the BA concentrations in portal blood, increased TGR5 and FXR signaling, improved the dysmetabolic status, protected from steatosis and hepatocellular ballooning, and reduced macrophage infiltration.CONCLUSIONS:BA composition in the enterohepatic cycle, but not in systemic circulation, is profoundly altered in preclinical models of NASH, with specific depletion in secondary BAs. Dietary correction of the BA profile protected from NASH, supporting a role for enterohepatic BAs in the pathogenesis of NASH.LAY SUMMARY:This study clearly demonstrates that the alterations of enterohepatic bile acids significantly contribute to the development of non-alcoholic steatohepatitis in relevant preclinical models. Indeed, experimental modulation of bile acid composition restored perturbed FXR and TGR5 signaling and prevented non-alcoholic steatohepatitis and associated metabolic disorders.

Abstract Background Obesity among older adults has increased tremendously. Obesity accelerates ageing and predisposes to age‐related conditions and diseases, such as loss of endurance capacity, insulin resistance and features of the metabolic syndrome. Namely, ectopic lipids play a key role in the development of nonalcoholic fatty liver disease (NAFLD) and myosteatosis, two severe burdens of ageing and metabolic diseases. Adiponectin (ApN) is a hormone, mainly secreted by adipocytes, which exerts insulin‐sensitizing and fat‐burning properties in several tissues including the liver and the muscle. Its overexpression also increases lifespan in mice. In this study, we investigated whether an ApN receptor agonist, AdipoRon (AR), could slow muscle dysfunction, myosteatosis and degenerative muscle markers in middle‐aged obese mice. The effects on myosteatosis were compared with those on NAFLD. Methods Three groups of mice were studied up to 62 weeks of age: One group received normal diet (ND), another, high‐fat diet (HFD); and the last, HFD combined with AR given orally for almost 1 year. An additional group of young mice under an ND was used. Treadmill tests and micro‐computed tomography (CT) were carried out in vivo. Histological, biochemical and molecular analyses were performed on tissues ex vivo. Bodipy staining was used to assess intramyocellular lipid (IMCL) and lipid droplet morphology. Results AR did not markedly alter diet‐induced obesity. Yet, this treatment rescued exercise endurance in obese mice (up to 2.4‐fold, P < 0.05), an event that preceded the improvement of insulin sensitivity. Dorsal muscles and liver densities, measured by CT, were reduced in obese mice (−42% and −109%, respectively, P < 0.0001), suggesting fatty infiltration. This reduction tended to be attenuated by AR. Accordingly, AR significantly mitigated steatosis and cellular ballooning at liver histology, thereby decreasing the NALFD activity score (−30%, P < 0.05). AR also strikingly reversed IMCL accumulation either due to ageing in oxidative fibres (types 1/2a, soleus) or to HFD in glycolytic ones (types 2x/2b, extensor digitorum longus) (−50% to −85%, P < 0.05 or less). Size of subsarcolemmal lipid droplets, known to be associated with adverse metabolic outcomes, was reduced as well. Alleviation of myosteatosis resulted from improved mitochondrial function and lipid oxidation. Meanwhile, AR halved aged‐related accumulation of dysfunctional proteins identified as tubular aggregates and cylindrical spirals by electron microscopy (P < 0.05). Conclusions Long‐term AdipoRon treatment promotes ‘healthy ageing’ in obese middle‐aged mice by enhancing endurance and protecting skeletal muscle and liver against the adverse metabolic and degenerative effects of ageing and caloric excess.

We read with great interest the recent paper by Linge and colleagues[1]Linge J. Ekstedt M. Dahlqvist Leinhard O. Adverse muscle composition is linked to poor functional performance and metabolic comorbidities in NAFLD.JHEP Rep. October 2020; : 100197PubMed Google Scholar wherein the prevalence and implication of adverse muscle composition (AMC) are evaluated in patients with NAFLD. AMC is defined here as low muscle volume and high muscle fat infiltration (MFI). Muscle data are gained from MRI-derived acquisition2Ross R. Goodpaster B.H. Kelley D. Boada F. Magnetic resonance imaging in human body composition Research: from quantitative to qualitative tissue measurement.Ann N Y Acad Sci. 2006; 904: 12-17Crossref Scopus (56) Google Scholar, 3Shen W. Punyanitya M. Wang Z. Gallagher D. St.-Onge M-P Albu J. et al.Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image.J Appl Physiol. 2004; 97: 2333-2338Crossref PubMed Scopus (997) Google Scholar, 4Brennan D.D. Whelan P.F. Robinson K. Ghita O. O’Brien J.M. Sadleir R. et al.Rapid automated measurement of body fat distribution from whole-body MRI.AJR Am J Roentgenol. 2005; 185: 418-423Crossref PubMed Scopus (67) Google Scholar using automated analyses developed by the authors.[5]West J. Dahlqvist Leinhard O. Romu T. Collins R. Garratt S. Bell J.D. et al.Feasibility of MR-based body composition analysis in large scale population studies.PLoS One. 2016; 11 (Gonzalez-Bulnes A, ed.)e0163332Crossref PubMed Scopus (53) Google Scholar,[6]https://patentscope.wipo.int/. References: WO2020161274 and WO2019081656.Google Scholar The study supports that a poor muscle health status (or AMC) is associated with poor function and a high prevalence of metabolic comorbidities in patients with NAFLD. We fully share the interest in evaluating how the muscle compartment is alterated in NAFLD, however we are puzzled by the authors’ reading and interpretation of some of the data. The authors report that fat free muscle volume, whether expressed as a raw value, normalized to height or to a virtual control group, was higher or similar in patients with NAFLD compared to those without NAFLD. Further, the authors found that the proportion of patients with a low handgrip strength was not different between patients with or without NAFLD. Handgrip strength, whose values were regretfully not reported by the authors, is, in the disease context, perhaps the most relevant marker for skeletal muscle function, as it is not directly modulated by obesity-induced mechanical overload. Thus, in the population described, the prevalence of low muscle volume, of low muscle strength, or of sarcopenia (adequately defined by the authors[7]Cruz-Jentoft A.J. Bahat G. Bauer J. Boirie Y. Bruyère O. Cederholm T. et al.Sarcopenia: revised European consensus on definition and diagnosis.Age Ageing. 2019; 48: 16-31Crossref PubMed Scopus (3534) Google Scholar) is lower (or not different) in patients with NAFLD than in those without NAFLD. In the cohort, the degree of MFI was higher in patients with NAFLD compared to patients without, a finding that corroborates data from another large study.[8]Chen V.L. Wright A.P. Halligan B. Chen Y. Du X. Handelman S.K. et al.Body composition and genetic lipodystrophy risk score associate with nonalcoholic fatty liver disease and liver fibrosis.Hepatol Commun. 2019; 3: 1073-1084Crossref PubMed Scopus (10) Google Scholar Hence, MFI, rather than low muscle volume or low muscle strength, was associated with NAFLD. Disconcertingly, the authors suggest that muscle volume should be combined with MFI to delineate an AMC group within the NAFLD population, reported here to be at a higher risk for adverse metabolic and functional outcomes. They suggest that this combination of muscle parameters could “strengthen pre-established sarcopenia guidelines” even though muscle strength (the key determinant of sarcopenia[7]Cruz-Jentoft A.J. Bahat G. Bauer J. Boirie Y. Bruyère O. Cederholm T. et al.Sarcopenia: revised European consensus on definition and diagnosis.Age Ageing. 2019; 48: 16-31Crossref PubMed Scopus (3534) Google Scholar) is discarded from the equation. In our view, there is another reading for the data; hence, we have a proposition for future developments that we would like to share with the authors. First, in the AMC group (n = 169), sarcopenia was scarce (prevalence of 5.9%, 10/169) whereas high MFI was a defining parameter (prevalence of 100%, 169/169). Besides, muscle volume was higher in patients with NAFLD. Therefore, the higher proportion of patients with “AMC” in the NAFLD population compared to the non-NAFLD population is preponderantly driven by the greater prevalence of high MFI and not by low muscle volume and/or sarcopenia. A case for considering MFI. Second, the authors mention that patients with AMC represent an at-risk subgroup (in particular for coronary heart disease events) within NAFLD. The possibility of identifying at-risk patients is highly clinically relevant as cardiovascular events are consistently reported as the first cause of death in patients with NAFLD.[9]Francque S.M. van der Graaff D. Kwanten W.J. Non-alcoholic fatty liver disease and cardiovascular risk: pathophysiological mechanisms and implications.J Hepatol. 2016; 65: 425-443Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar Thus, it would have been very informative to provide data about the relative cardiovascular risk in the AMC or high MFI group in the NAFLD population (1,204 patients) when compared to subjects with AMC or high MFI in the non-NAFLD population (4,122 patients). Indeed, about 10% of the latter vs. 14% of patients with NAFLD have an AMC. Such investigations would have provided insights on whether an AMC or a high MFI per se is related to increased cardiovascular risk (as suggested elsewhere[10]Miljkovic I. Kuipers A.L. Cauley J.A. Prasad T. Lee C.G. Ensrud K.E. et al.Greater skeletal muscle fat infiltration is associated with higher all-cause and cardiovascular mortality in older men.J Gerontol A Biol Sci Med Sci. 2015; 70: 1133-1140Crossref PubMed Scopus (75) Google Scholar) and how NAFLD presence truly affects the risk. Third, we understand that the patients included in the AMC group were systematically excluded from the “low muscle mass only” or “high muscle fat only” group and were never accounted for in analysis comparing a “low muscle mass” or a “high muscle fat” group to the “normal muscle composition” group. Considering that (a) a high MFI or a low muscle strength was far more prevalent (37.8%; 455/1,204 and 6.64%; 80/1,204, respectively) than sarcopenia (1.58%, 19/1,204) in the whole NAFLD population when compared to the non-NAFLD population and (b) the degree of MFI was, by itself, associated with higher cardiovascular and type II diabetes risk (Table S2), we question whether the evaluation of MFI alone, or next to muscle strength (EWGSOP[7]Cruz-Jentoft A.J. Bahat G. Bauer J. Boirie Y. Bruyère O. Cederholm T. et al.Sarcopenia: revised European consensus on definition and diagnosis.Age Ageing. 2019; 48: 16-31Crossref PubMed Scopus (3534) Google Scholar or percentile-based definition), might better identify patients with adverse metabolic outcome than the proposed AMC criteria based on muscle volume and fat infiltration. Further, this stratified analysis according to MFI and/or muscle strength may help in defining appropriate read-outs, with a non-negligible impact on study designs and recruitment of participating centers: while an MRI-based measure of muscle volume is time consuming or costly, handgrip strength is performed at the bedside using a cheap hand dynamometer and MFI is easily measured by post hoc analysis of MRI-derived acquisitions with tools available on any clinically used pictures archiving and communication system (PACS). Taken together, based on the data presented, the rationale or the scientific value of adding muscle volume to MFI in the definition of an AMC (indicative of an adverse metabolic outcome) appears unclear to us. M.N is supported by the PhD fellowship from FRIA ( FNRS , Belgium) [grant number 31618719 ] and I.L by the Fund for Scientific Medical Research (FNRS Belgium) [grant number T.0141.19 ]. Maxime Nachit drafted the manuscript. Yves Horsmans and Isabelle Leclercq have critically revised and finalized the manuscript. All authors have approved the final version of the manuscript. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. The following is/are the supplementary data to this article: Download .pdf (.16 MB) Help with pdf files Multimedia component 1 Adverse muscle composition is linked to poor functional performance and metabolic comorbidities in NAFLDJHEP ReportsVol. 3Issue 1PreviewSarcopenia and frailty are recognised as important factors in later stages of liver disease. However, their role in non-alcoholic fatty liver disease (NAFLD) is not yet fully understood. In this study we investigate the associations of MRI-measured adverse muscle composition (AMC: low muscle volume and high muscle fat) with poor function, sarcopenia, and metabolic comorbidity within NAFLD in the large UK Biobank imaging study. Full-Text PDF Open AccessReply to: "Rationale of adding muscle volume to muscle fat infiltration in the definition of an adverse muscle composition is unclear"JHEP ReportsVol. 3Issue 2PreviewWe thank Dr. Leclerq and colleagues for their interest in our paper and for taking the time to express their concerns.1 The discussion of potential sarcopenia biomarkers is important; herein, we reply to authors’ concerns. Full-Text PDF Open Access

•Muscle fat content is higher in patients with obesity and NASH than in those with obesity and NAFL.•There is no low muscle mass in patients with obesity-associated NASH.•Muscle fat content is strongly associated with cardinal histological features of NASH.•NASH improvement is associated with a significant decrease of muscle fat content.

BACKGROUND & AIMS:Retrospective cross-sectional studies linked sarcopenia and myosteatosis with metabolic dysfunction-associated fatty liver disease (MAFLD). Here, we wanted to clarify the dynamic relationship between sarcopenia, myosteatosis, and MAFLD. METHODS:A cohort of 48 obese patients was randomised for a dietary intervention consisting of 16 g/day of inulin (prebiotic) or maltodextrin (placebo) supplementation. Before and after the intervention, we evaluated liver steatosis and stiffness with transient elastography (TE); we assessed skeletal muscle index (SMI) and skeletal muscle fat index (SMFI) (a surrogate for absolute fat content in muscle) using computed tomography (CT) and bioelectrical impedance analysis (BIA). RESULTS:At baseline, sarcopenia was uncommon in patients with MAFLD (4/48, 8.3%). SMFI was higher in patients with high liver stiffness than in those with low liver stiffness (640.6 ± 114.3 cm2/ Hounsfield unit [HU] vs. 507.9 ± 103.0 cm2/HU, p = 0.001). In multivariate analysis, SMFI was robustly associated with liver stiffness even when adjusted for multiple confounders (binary logistic regression, p <0.05). After intervention, patients with inulin supplementation lost weight, but this was not associated with a decrease in liver stiffness. Remarkably, upon intervention (being inulin or maltodextrin), patients who lowered their SMFI, but not those who increased SMI, had a 12.7% decrease in liver stiffness (before = 6.36 ± 2.15 vs. after = 5.55 ± 1.97 kPa, p = 0.04). CONCLUSIONS:Myosteatosis, but not sarcopenia, is strongly and independently associated with liver stiffness in obese patients with MAFLD. After intervention, patients in which the degree of myosteatosis decreased reduced their liver stiffness, irrespective of body weight loss or prebiotic treatment. The potential contribution of myosteatosis to liver disease progression should be investigated. CLINICAL TRIALS REGISTRATION NUMBER:NCT03852069. LAY SUMMARY:The fat content in skeletal muscles (or myosteatosis) is strongly associated with liver stiffness in obese patients with MAFLD. After a dietary intervention, patients in which the degree of myosteatosis decreased also reduced their liver stiffness. The potential contribution of myosteatosis to liver disease progression should be investigated.

Obesity could lead to metabolic dysfunction-associated fatty liver disease (MAFLD), which severity could be linked to muscle and gut microbiota disturbances. Our prospective study enrolled 52 obese patients whose MAFLD severity was estimated by transient elastography. Patients with severe steatosis (n = 36) had higher ALAT values, fasting blood glucose levels as well as higher visceral adipose tissue area and skeletal muscle index evaluated by computed tomography. Patients with fibrosis (n = 13) had higher ASAT values, increased whole muscle area and lower skeletal muscle density index. In a multivariate logistic regression analysis, myosteatosis was the strongest factor associated with fibrosis. Illumina sequencing of 16S rRNA gene amplicon was performed on fecal samples. The relative abundance of fecal Clostridium sensu stricto was significantly decreased with the presence of liver fibrosis and was negatively associated with liver stiffness measurement and myosteatosis. In addition, 19 amplicon sequence variants were regulated according to the severity of the disease. Linear discriminant analysis effect size (LEfSe) also highlighted discriminant microbes in patients with fibrosis, such as an enrichment of Enterobacteriaceae and Escherichia/Shigella compared to patients with severe steatosis without fibrosis. All those data suggest a gut-liver-muscle axis in the pathogenesis of MAFLD complications.

Fat accumulation in skeletal muscle was recently established as a major risk factor for cardiovascular disease (CVD) in the general population, but its relevance for patients with kidney failure is unknown. Here we examined the potential association between muscle radiation attenuation (MRA), a non-invasive indicator of fat deposits in muscle, and cardiovascular events in patients with kidney failure treated with peritoneal dialysis (PD) and investigated dynamic changes and determinants of MRA in this population. We retrospectively assessed MRA on computed tomography images collected yearly in 101 incident patients with kidney failure starting PD between January 2006 and December 2015. After a median of 21 months on dialysis, 34 patients had 58 non-fatal cardiovascular events, and 22 patients had died. Baseline MRA was associated with cardiovascular events during time on dialysis, and patients with higher MRA (reflecting lower amounts of fat in muscle) showed a reduced incidence of CVD, independently of traditional risk factors (adjusted HR, 0.91; 95% CI, 0.86–0.97, P = 0.006). Multivariate regression analysis identified old age, female gender, visceral fat area, and low residual urine volume as independent determinants of MRA. As compared with reference values from a healthy population, patients with kidney failure had lower MRA (i.e., increased fat accumulation), independently of age, gender, and body-mass index. The subset of patients who underwent kidney transplantation showed a significant increase in MRA after restoration of kidney function. These observations expand the association between ectopic fat accumulation and CVD to the population on dialysis, and suggest that kidney failure is reversibly associated with fatty muscle infiltration.