Metabolic dysfunction-associated steatotic liver disease:Navigating terminological evolution,diagnostic frontiers and therapeutic horizon-an editorial exploration

Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within hepatocytes.The redefinition of NAFLD in 2023 marked a significant reposition in terminology,emphasizing a broader understanding of liver steatosis and its associated risks.MASLD is now recognized as a major risk factor for liver cirrhosis,hepatocellular carcinoma,and systemic complications such as cardiovascular diseases or systemic inflammation.Diagnostic challenges arise,particularly in identifying MASLD in lean individuals,necessitating updated diagnostic protocols and investing in non-invasive diagnostic tools.Therapeutically,there is an urgent need for effective treatments targeting MASLD,with emerging pharmacological options focusing on,among others,carbohydrate and lipid metabolism.Additionally,understanding the roles of bile acid metabolism,the microbiome,and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic approaches.There is a strong need to emphasize the importance of collaborative efforts in understanding,diagnosing,and managing MASLD to improve physicians’approaches and patient outcomes.

Recent advances in age-related metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease(MASLD)affects approximately 25%of the world's population and has become a leading cause of chronic liver disease.In recent years,an increasing amount of data suggests that MASLD is associated with aging.As the population ages,age-related MASLD will become a major global health problem.Targeting an aging will become a new approach to the treatment of MASLD.This paper reviews the current studies on the role of aging-related factors and therapeutic targets in MASLD,including:Oxidative stress,autophagy,mitochondrial homeostasis,bile acid metabolism homeostasis,and dysbiosis.The aim is to identify effective therapeutic targets for age-related MASLD and its progression.

Update in lean metabolic dysfunction-associated steatotic liver disease

BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in adults.This condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase worldwide.Lean patients account for approximately 10%-15%of the MASLD population.However,the pathogenesis is complex and is not well understood.AIM To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new criteria.METHODS We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD patients.We include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.RESULTS We include 85 studies in our analysis.Our findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic response.Common risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean patients.Regarding non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients.Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser extent.However,lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart.CONCLUSION MASLD is a complex disease comprising epigenetic,genetic,and metabolic factors in its pathogenesis.Results vary across populations,gender,and age.Limited data exists on clinical practice guidelines for lean patients.Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.

Role of incretins and glucagon receptor agonists in metabolic dysfunction-associated steatotic liver disease:Opportunities and challenges

Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide,paralleling the rising pandemic of obesity and type 2 diabetes.Due to the growing global health burden and com-plex pathogenesis of MASLD,a multifaceted and innovative therapeutic approach is needed.Incretin receptor agonists,which were initially developed for diabetes management,have emerged as promising candidates for MASLD treatment.This review describes the pathophysiological mechanisms and action sites of three major classes of incretin/glucagon receptor agonists:glucagon-like peptide-1 receptor agonists,glucose-dependent insulinotropic polypeptide receptor agonists,and glucagon receptor agonists.Incretins and glucagon directly or indirectly impact various organs,including the liver,brain,pancreas,gastro-intestinal tract,and adipose tissue.Thus,these agents significantly improve glycemic control and weight management and mitigate MASLD pathogenesis.Importantly,this study provides a summary of clinical trials analyzing the effect-iveness and safety of incretin receptor agonists in MASLD management and provides an in-depth analysis highlighting their beneficial effects on improving liver function,hepatic steatosis,and intrahepatic inflammation.There are emerging challenges associated with the use of these medications in the real world,particularly adverse events,drug-drug interactions,and barriers to access,which are discussed in detail.Additionally,this review highlights the evolving role of incretin receptor agonists in MASLD management and suggests future research directions.

Gestational diabetes mellitus may predispose to metabolic dysfunction-associated steatotic liver disease

The development of type 2 diabetes mellitus is a major contributing factor to the worldwide health burden of metabolic dysfunction-associated steatotic liver disease(MASLD).Insulin resistance,subclinical inflammation,dyslipidemia,obesity,and hypertension are all factors in this reciprocal interaction that contribute to the development of MASLD,which includes hepatocellular carci-noma,advanced fibrosis/cirrhosis,and non-alcoholic steatohepatitis(NASH).A new risk factor for MASLD/NASH that affects the course of the disease independently throughout life is gestational diabetes mellitus(GDM).Women with a history of GDM had a higher chance of developing NASH,according to a recent study that used a large-scale database.Although the precise etiology is yet unknown,temporary disruption of pancreatic beta cell activity during pregnancy may set off systemic inflammation,affecting distant organs including the liver.Early screening and management strategies are crucial in mitigating MASLD progression and preventing adverse cardiovascular events in affected individuals.

Impact of metabolic dysfunction-associated steatotic liver disease on COVID-19 hospitalizations:A propensity-matched analysis of the United States

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),formally known as nonalcoholic fatty liver disease,is the most common chronic liver disease in the United States.Patients with MASLD have been reported to be at a higher risk of developing severe coronavirus disease 2019(COVID-19)and death.However,most studies are single-center studies,and nationwide data in the AIM To study the influence of MASLD on COVID-19 hospitalizations during the initial phase of the pandemic.METHODS We retrospectively analyzed the 2020 National Inpatient Sample(NIS)database to identify primary COVID-19 hospitalizations based on an underlying diagnosis of MASLD.A matched comparison cohort of COVID-19 hospit-alizations without MASLD was identified from NIS after 1:N propensity score matching based on gender,race,and comorbidities,including hypertension,heart failure,diabetes,and cirrhosis.The primary outcomes included inpatient mortality,length of stay,and hospitalization costs.Secondary outcomes included the prevalence of systemic complications.RESULTS A total of 2210 hospitalizations with MASLD were matched to 2210 hospitalizations without MASLD,with a good comorbidity balance.Overall,there was a higher prevalence of severe disease with more intensive care unit admissions(9.5%vs 7.2%,P=0.007),mechanical ventilation(7.2%vs 5.7%,P=0.03),and septic shock(5.2%vs 2.7%,P<0.001)in the MASLD cohort than in the non-MASLD cohort.However,there was no difference in mortality(8.6%vs 10%,P=0.49),length of stay(5 d vs 5 d,P=0.25),and hospitalization costs(42081.5$vs 38614$,P=0.15)between the MASLD and non-MASLD cohorts.CONCLUSION The presence of MAFLD with or without liver cirrhosis was not associated with increased mortality in COVID-19 hospitalizations;however,there was an increased incidence of severe COVID-19 infection.This data(2020)predates the availability of COVID-19 vaccines,and many MASLD patients have since been vaccinated.It will be interesting to see if these trends are present in the subsequent years of the pandemic.

Metabolic dysfunction-associated steatotic liver disease heterogeneity: Need of subtyping

Metabolic dysfunction-associated steatotic liver disease(MASLD)is a widespread global disease with significant health burden.Unhealthy lifestyle,obesity,diabetes mellitus(DM),insulin resistance,and genetics have been implicated in the pathogenesis of MASLD.A significant degree of heterogeneity exists among each of above-mentioned risk factors.Heterogeneity of these risk factors translates into the heterogeneity of MASLD.On the other hand,MASLD can itself lead to insulin resistance and DM.Such heterogeneity makes it difficult to assess the natural course of an individual with MASLD in clinical practice.At present MASLD is considered as one disease despite the variability of etiopathogenic processes,and we lack the consensus definitions of unique subtypes of MASLD.In this review,pathogenic processes of MASLD are discussed and a need of subtyping is recommended.

Liver disease in patients with transfusion-dependentβ-thalassemia:The emerging role of metabolism dysfunction-associated steatotic liver disease

In this Editorial,we highlight the possible role that metabolism dysfunction-associated steatotic liver disease(MASLD)may play in the future,regarding liver disease in patients with transfusion-dependent β-thalassemia(TDBT).MASLD is characterized by excessive accumulation of fat in the liver(hepatic steatosis),in the presence of cardiometabolic factors.There is a strong correlation between the occurrence of MASLD and insulin resistance,while its increased prevalence parallels the global epidemic of diabetes mellitus(DM)and obesity.Patients with TDBT need regular transfusions for life to ensure their survival.Through these transfusions,a large amount of iron is accumulated,which causes saturation of transferrin and leads to the circulation of free iron molecules,which cause damage to vital organs(primarily the liver and myocardium).Over the past,the main mechanisms for the development of liver disease in these patients have been the toxic effect of iron on the liver and chronic hepatitis C,for which modern and effective treatments have been found,resulting in successful treatment.Additional advances in the treatment and monitoring of these patients have led to a reduction in deaths,and an increase in their life expectancy.This increased survival makes them vulnerable to the onset of diseases,which until recently were mainly related to the non-thalassemic general population,such as obesity and DM.There is insufficient data in the literature regarding the prevalence of MASLD in this population or on the risk factors for its occurrence.However,it was recently shown by a study of 45 heavily transfused patients with beta-thalassemia(Padeniya et al,BJH),that the presence of steatosis is a factor influencing the value of liver elastography and thus liver fibrosis.These findings suggest that future research in the field of liver disease in patients with TDBT should be focused on the occurrence,the risk factors,and the effect of MASLD on these patients.

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease

Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.

Omics-based biomarkers as useful tools in metabolic dysfunctionassociated steatotic liver disease clinical practice:How far are we?

Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.

Disparate outcomes in Hispanic patients with metabolic dysfunctionassociated steatotic liver disease/steatohepatitis and type 2 diabetes: Large cohort study

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH)are a growing health burden across a significant portion of the global patient population.However,these conditions seem to have disparate rates and outcomes between different ethnic populations.The combination of MASLD/MASH and type 2 diabetes increases the risk of hepatocellular carcinoma(HCC),and Hispanic patients experience the greatest burden,particularly those in South Texas.AIM To compare outcomes between Hispanic and non-Hispanic patients in the United States,while further focusing on the Hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a function of geographical circumstance or if there is a more widespread reason that all clinicians must account for in prognostic consideration.METHODS This cohort analysis was conducted with data obtained from TriNetX,LLC(“TriNetX”),a global federated health research network that provides access to deidentified medical records from healthcare organizations worldwide.Two cohort networks were used:University of Texas Medical Branch(UTMB)hospital and the United States national database collective to determine whether disparities were related to geographic regions,like Southeast Texas.RESULTS This study findings revealed Hispanics/Latinos have a statistically significant higher occurrence of HCC,type 2 diabetes mellitus,and liver fibrosis/cirrhosis in both the United States and the UTMB Hispanic/Latino groups.Allcause mortality in Hispanics/Latinos was lower within the United States group and not statistically elevated in the UTMB cohort.CONCLUSION This would appear to support that Hispanic patients in Southeast Texas are not uniquely affected compared to the national Hispanic population.

Screening for metabolic dysfunction-associated fatty liver disease:Time to discard the emperor’s clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

Current remarks and future directions on the interactions between metabolic dysfunction-associated fatty liver disease and COVID-19

During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Several studies highlighted the fact that individuals with MAFLD had higher probability of severe acute respiratory syndrome coronavirus 2 infection and more severe adverse clinical outcomes.One of the proposed mechanisms is the inflammatory response pathway,especially the one involving cytokines,such as interleukin 6,which appeared particularly elevated in those patients and was deemed responsible for additional insult to the already damaged liver.This should increase our vigilance in terms of early detection,close follow up and early treatment for individuals with MAFLD and COVID-19 infection.In the direction of early diagnosis,biomarkers such as cytokeratin-18 and scoring systems such as Fibrosis-4 index score are proposed.COVID-19 is a newly described entity,expected to be of concern for the years to come,and MAFLD is a condition with an ever-increasing impact.Delineating the interaction between these two entities should be brought into the focus of research.Reducing morbidity and mortality of patients with COVID-19 and MAFLD should be the ultimate objective,and the optimal way to achieve this is by designing evidence-based prevention and treatment policies.

Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in animals.METHODS Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained.RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop HCC.Comparing animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the HCC-group.The opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-protein.Comparing with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P<0.05).Carm1 was lower in HCC compared to RIF(P<0.05).Hepatic expression of Mmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(P<0.05).Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and Mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P<0.05).miR-26b was lower in HCC compared to RIF,and the inverse was observed for miR-224(P<0.05).There was no difference among groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.

Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

Predictive value of angiopoietin-like protein 8 in metabolic dysfunction-associated fatty liver disease and its progression:A case-control study

BACKGROUND The prevalence of metabolic dysfunction-associated fatty liver disease(MAFLD)is rapidly increasing,currently affecting approximately 25%of the global population.Liver fibrosis represents a crucial stage in the development of MAFLD,with advanced liver fibrosis elevating the risks of cirrhosis and hepatocellular carcinoma.Simple serum markers are less effective in diagnosing liver fibrosis compared to more complex markers.However,imaging techniques like transient elastography face limitations in clinical application due to equipment and technical constraints.Consequently,it is imperative to identify a straightforward yet effective method for assessing MAFLD-associated liver fibrosis.AIM To investigate the predictive value of angiopoietin-like protein 8(ANGPTL8)in MAFLD and its progression.METHODS We analyzed 160 patients who underwent abdominal ultrasonography in the Endocrinology Department,Xiaogan Central Hospital affiliated to Wuhan University of Science and Technology,during September 2021-July 2022.Using abdominal ultrasonography and MAFLD diagnostic criteria,among the 160 patients,80 patients(50%)were diagnosed with MAFLD.The MAFLD group was divided into the liver fibrosis group(n=23)and non-liver fibrosis group(n=57)by using a cut-off fibrosis-4 index≥1.45.Logistical regression was used to analyze the risk of MAFLD and the risk factors for its progression.Receiver operating characteristic curves were used to evaluate the predictive value of serum ANGPTL8 in MAFLD and its progression.RESULTS Compared with non-MAFLD patients,MAFLD patients had higher serum ANGPTL8 and triglyceride-glucose(TyG)index(both P<0.05).Serum ANGPTL8(r=0.576,P<0.001)and TyG index(r=0.473,P<0.001)were positively correlated with MAFLD.Serum ANGPTL8 was a risk factor for MAFLD[odds ratio(OR):1.123,95%confidence interval(CI):1.066-1.184,P<0.001).Serum ANGPTL8 and ANGPTL8+TyG index predicted MAFLD[area under the curve(AUC):0.832 and 0.886,respectively;both P<0.05].Compared with MAFLD patients without fibrosis,those with fibrosis had higher serum ANGPTL8 and TyG index(both P<0.05),and both parameters were positively correlated with MAFLD-associated fibrosis.Elevated serum ANGPTL8(OR:1.093,95%CI:1.044-1.144,P<0.001)and TyG index(OR:2.383,95%CI:1.199-4.736,P<0.013)were risk factors for MAFLD-associated fibrosis.Serum ANGPTL8 and ANGPTL8+TyG index predicted MAFLD-associated fibrosis(AUC:0.812 and 0.835,respectively;both P<0.05).CONCLUSION The serum levels of ANGPTL8 are elevated and positively correlated with MAFLD.They can serve as predictors for the risk of MAFLD and liver fibrosis,with the ANGPTL8+TyG index potentially exhibiting even higher predictive value.

Sarcopenia and metabolic dysfunction associated steatotic liver disease:Time to address both

Sarcopenia and metabolic dysfunction associated steatotic liver disease(MASLD)are closely intertwined.Sarcopenia,traditionally a disease of the older adult and chronic disease population,has been closely studied as one of the pathophysiologic conditions at play in the development of MASLD.They share similar risk factors of insulin resistance and physical inactivity.Given similar pathophysiology along the liver-muscle axis,sarcopenia has been studied as a risk factor for MASLD,and vice versa.Current research suggests a bidirectional relationship.Given the chronicity of MASLD as a chronic inflammatory liver disease,it can break down muscle mass and lead to sarcopenia,while sarcopenia promotes intramuscular lipid accumulation that releases cytokines that can aggravate inflammation in the liver.However,for the longest time,a lack of consensus definition for MASLD and sarcopenia made it difficult to study their relationship and outcomes.A recent nomenclature update to diagnosing MASLD has made it easier for researchers to identify cohorts for study.However,no gold standard technique to measure muscle mass or consensus sarcopenia definition has been identified yet.Future studies are needed to reach a consensus and reduce diagnostic variation.With similar pathophysiology and shared risk factors between the two diseases,future research may also identify potential therapeutic targets along the liver-muscle axis that would benefit both sarcopenia and MASLD in order to maximize their outcomes.

Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease

BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD.METHODS Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were collected.Following fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™system.RESULTS Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides distasonis.The functional prediction provided two different metabolic profiles between MASLD and LOLA.The 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis.The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis.CONCLUSION Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.

From metabolic dysfunction-associated fatty liver disease to metabolic dysfunction-associated steatotic liver disease:Controversy and consensus

The newly released nomenclature of metabolic dysfunction-associated steatotic liver disease(MASLD)in the 2023 European Association for the Study of the Liver Congress has raised great clinical concerns.This marks the second instance of significant renaming of non-alcoholic fatty liver disease since the introduction of metabolic dysfunction-associated fatty liver disease(MAFLD)in 2020.The nomenclature and definitions of MASLD and MAFLD exhibit significant disparities as well as substantial consensus.The disparities regarding the framework of nomenclature,the definitions,the clinical management,and the impact on the clinical outcomes between MASLD and MAFLD were comprehensively compared in this editorial.Additionally,the consensus reached by the MASLD and MAFLD definitions also emphasizes positive diagnosis rather than negative diagnosis within the framework of establishing a diagnostic approach.Furthermore,they acknowledged the pivotal role of metabolic dysfunction in the pathogenesis of MAFLD or MASLD and the positive role of increasing the awareness of the disease in public.Fortunately,the non-invasive tests remains effective in the MASLD and MAFLD era.Elucidating these disparities would contribute to a more comprehensive comprehension of the nature of steatotic liver disease and enhance clinical practice.Thus,more efforts are required to reach more consensus about these important topics.

The impact of metabolic dysfunction-associated fatty liver disease on the prognosis of patients with hepatocellular carcinoma after radical resection

Background:Metabolic dysfunction-associated fatty liver disease(MAFLD)is recently proposed an entity by a group of international experts.However,the impact of MAFLD on the prognosis of patients with hepatocellular carcinoma(HCC)is not clear.The aim of this study was to explore the influence of MAFLD for the prognosis of HCC after radical resection.Methods:HCC patients who received radical resection were enrolled.The recurrence-free survival(RFS)and overall survival(OS)were compared between MAFLD and non-MAFLD.Results:A total of 576 HCC patients were included,and among them 114(19.8%)met the diagnostic criteria of MAFLD.The median RFS was 34.0 months in the MAFLD group and 19.0 months in the non-MAFLD group.The 1-,3-,and 5-year RFS rates were 64.9%,49.1%and 36.1%in the MAFLD group,which were higher than those of the non-MAFLD group(59.4%,35.3%and 26.5%,respectively,P=0.01).The mean OS was 57.0 months in the MAFLD group and 52.2 months in the non-MAFLD group.There was no statistical difference in OS rate between the MAFLD group and non-MAFLD group.Similar results were found in HBV-related HCC patients in the subgroup analysis.Univariate analysis revealed that MAFLD was a protective factor for RFS in HCC patients after radical resection(P<0.05),and there was no association between MAFLD and OS rate(P>0.05).Multivariate analysis demonstrated that MAFLD was not an independent protective factor for HCC patients with radical resection.Conclusions:MAFLD improves RFS rate in HCC patients with radical resection,but is not an independent protective factor and not associated with OS rate.