Metabolic-associated fatty liver disease and sarcopenia:A double whammy

The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and sarcopenia.Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies.Sarcopenia can be either part of the disease process that results in MAFLD(e.g.,obesity or adiposity)or a consequence of MAFLD,especially in the advanced stages such as fibrosis and cirrhosis.Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors.Therefore,it is crucial to thoroughly understand how we deal with these diseases,especially when they coexist.We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.

From non-alcoholic fatty liver disease to metabolic-associated steatotic liver disease:Rationale and implications for the new terminology

Non-alcoholic fatty liver disease(NAFLD)was the term first used to describe hepatic steatosis in patients with the metabolic syndrome who did not consume excess amounts of alcohol.Alcoholic liver disease(ALD)has many similarities to NAFLD in both pathogenesis and histology.This entity is now the most prevalent chronic liver disease worldwide as a consequence of the epidemic of obesity.Attempts to incorporate the importance of the metabolic syndrome in the development of steatosis resulted in the renaming of NAFLD as metabolic-associated fatty liver disease.This new term,however,has the disadvantage of the use of terms that may be perceived as derogatory.The terms fatty and non-alcoholic have negative connotations in many cultures.In addition,non-alcoholic is not usually a term applicable to pediatric cases of hepatic steatosis.Recently,an international collaborative effort,with participants from 56 countries,after a global consultation process,recommended to change the nomenclature to steatotic liver disease-including metabolic dysfunction-associated steatotic liver disease,metabolic-associated steatohepatitis and metabolic dysfunction-associated ALD.The new terminology is consistent with most of the previously published epidemiological studies and will have a major impact on research into diagnosis,prognosis and treatment.

Elafibranor:A promising treatment for alcoholic liver disease,metabolic-associated fatty liver disease,and cholestatic liver disease

Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment options and improve patient outcomes.This article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease(ALD),as reported by Koizumi et al in the World Journal of Gastroenterology.We summarize the impact and mechanisms of Elafibranor on ALD,metabolic-associated fatty liver disease,and cholestatic liver disease based on current research.We also explore its potential as a dual agonist of PPARα/δ,which is undergoing Phase III clinical trials for metabolic-associated steatohepatitis.Our goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application.

Association between Serum Ferritin Levels and Metabolic-associated Fatty Liver Disease in Adults:a Cross-sectional Study Based on the NHANES

Objective Ferritin,initially acting as an iron-storage protein,was found to be associated with metabolic diseases.Our study was designed to investigate the association between serum ferritin and metabolic-associated fatty liver disease(MAFLD)using data from the National Health and Nutrition Examination Survey(NHANES)of the United State of America.Methods A cross-sectional study was conducted,enrolling a total of 2145 participants from the NHANES in the 2017–2018 cycles.Hepatic steatosis and liver fibrosis were assessed by ultrasound images and several non-invasive indexes.Multiple regression analysis was conducted to determine the associations between serum ferritin concentration and MAFLD and liver fibrosis.Results The analysis revealed that participants with higher serum ferritin levels(Q3 and Q4 groups)had a higher prevalence of MAFLD than those with the lowest serum ferritin levels[Q3 vs.Q1:OR=2.17(1.33,3.53),P<0.05 in fatty liver index(FLI);Q4 vs.Q1:OR=3.13(1.91,5.13),P<0.05 in FLI].Additionally,participants with the highest serum ferritin levels(Q4 group)displayed a higher prevalence of liver fibrosis[Q4 vs.Q1:OR=2.59(1.19,5.62),P<0.05 in liver stiffness measurement;OR=5.06(1.12,22.94),P<0.05 in fibrosis-4 index],with significantly increased risk observed in participants with concomitant diabetes[OR=7.45(1.55,35.72),P=0.012].Conclusion Our study revealed that elevated serum ferritin levels are associated with a higher prevalence of MAFLD and advanced liver fibrosis in patients.Elevated serum ferritin levels combined with diabetes are important risk factors for liver fibrosis.

Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients

BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious charac-teristics.Approximately 50%of the patients have a normal weight or are not obese.They are said to have lean-type MAFLD,and few studies of such patients are available.Because MAFLD is associated with abnormal lipid metabolism,lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis.MAFLD and analyze metabolic pathways.UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid(PA),oleic acid(OA),linoleic acid(LA),and arachidonic acid(AA)levels in lean-type MAFLD patients.RESULTS Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals(P<0.05).Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy indi-viduals(P<0.01).The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals(P<0.05)and the expression of triglycerides and fasting blood glucose were increased(P<0.01).A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P<0.05 and variable importance in projection>1.The levels of PA,OA,LA,and AA were significantly increased compared with healthy individuals.CONCLUSION The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly,yielding 65 identified biomarkers.PA,OA,LA,and AA exhibited the most significant changes,offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.

Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus

BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.

Management of metabolic-associated fatty liver disease: The diabetology perspective

The metabolic syndrome as a consequence of the obesity pandemic resulted in a substantial increase in the prevalence of metabolic-associated fatty live disease(MAFLD)and type 2 diabetes mellitus(T2DM).Because of the similarity in pathobiology shared between T2DM and MAFLD,both disorders coexist in many patients and may potentiate the disease-related outcomes with rapid progression and increased complications of the individual diseases.In fact,awareness about this coexistence and the risk of complications are often overlooked by both hepatologists and diabetologists.Management of these individual disorders in a patient should be addressed wholistically using an appropriate multidisciplinary team approach involving both the specialists and,when necessary,liaising with dieticians and surgeons.This comprehensive review is to compile the current evidence from a diabetologist's perspective on MAFLD and T2DM and to suggest optimal management strategies.

Association of non-alcoholic fatty liver and metabolic-associated fatty liver with COVID-19 outcomes:A systematic review and metaanalysis

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD)are on the rise like any other liver disease,and tend to affect 25%of the United States population.The impact of NAFLD and MAFLD on patients with coronavirus disease 2019(COVID-19)remains unclear.AIM To identify the association of NAFLD and MAFLD with mortality,hospitalization,hospital length of stay,and supplemental oxygen utilization in COVID-19 patients.METHODS A systematic review of literature on Cochrane,Embase,PubMed,ScienceDirect,and Web of Science databases was conducted from January 2019 to July 2022.Studies that evaluated NAFLD/MAFLD using laboratory methods,noninvasive imaging,or liver biopsy were included.The study protocol was registered in PROSPERO(ID CRD42022313259)and PRISMA guidelines were followed.The National Institutes of Health quality assessment tool was used to assess the quality of the studies.Pooled analysis was conducted using software Rev Man version 5.3.The stability of the results was assessed using sensitivity analysis.RESULTS Thirty-two studies with 43388 patients were included in the meta-analysis of whom 8538(20%)patients were observed to have NAFLD.There were 42254 patients from 28 studies included in the mortality analysis.A total of 2008 patients died from COVID-19;837(10.52%)in the NAFLD group and 1171(3.41%)in the non-NAFLD group.The odds ratio(OR)was 1.38 for mortality with a 95%confidence interval(95%CI)=0.97-1.95 and P=0.07.A total of 5043 patients from eight studies were included in the hospital length of stay analysis.There were 1318 patients in the NAFLD group and 3725 patients in the non-NAFLD group.A qualitative synthesis showed that the mean difference in hospital length of stay was about 2 d between the NAFLD and non-NAFLD groups with a 95%CI=0.71-3.27 and P=0.002.For hospitalization rates,the OR was 3.25 with a 95%CI of 1.73-6.10 and P=0.0002.For supplemental oxygen utilization,the OR was 2.04 with a 95%CI of 1.17-3.53 and P=0.01.CONCLUSION Our meta-analysis suggests that there are increased odds of hospitalization,longer hospital length of stay,and increased use of supplemental oxygen in NAFLD/MAFLD patients.

Gut microbiome and metabolic-associated fatty liver disease:Current status and potential applications

Metabolic-associated fatty liver disease(MAFLD)is one of the most common chronic liver diseases worldwide.In recent years,the occurrence rate of MAFLD has been on the rise,mainly due to lifestyle changes,high-calorie diets,and imbalanced dietary structures,thereby posing a threat to human health and creating heavy social and economic burdens.With the development of 16S sequencing and integrated multi-omics analysis,the role of the gut microbiota(GM)and its metabolites in MAFLD has been further recognized.The GM plays a role in digestion,energy metabolism,vitamin synthesis,the prevention of pathogenic bacteria colonisation,and immunoregulation.The gut-liver axis is one of the vital links between the GM and the liver.Toxic substances in the intestine can enter the liver through the portal vascular system when the intestinal barrier is severely damaged.The liver also influences the GM in various ways,such as bile acid circulation.The gut-liver axis is essential in maintaining the body’s normal physiological state and plays a role in the onset and prognosis of many diseases,including MAFLD.This article reviews the status of the GM and MAFLD and summarizes the GM characteristics in MAFLD.The relationship between the GM and MAFLD is discussed in terms of bile acid circulation,energy metabolism,micronutrients,and signalling pathways.Current MAFLD treat ments targeting the GM are also listed.

Metabolic-associated fatty liver disease:New nomenclature and approach with hot debate

An international panel recently proposed an update to the terminology and diagnostic criteria for fatty liver disease.The experts proposed a change in the nomenclature from non-alcoholic fatty liver disease(NAFLD)to metabolic(dysfunction)-associated fatty liver disease(MAFLD).This single-letter change,we believe,heralds the dawn of a new era in clinical practice and in clinical and basic research as well.The new nomenclature with the easily applicable approach has stimulated the enthusiasm of the researchers worldwide,resulting in a large number of publications over the past two years.Several recent studies have provided tremendous evidence of the superiority of the MAFLD criteria over the NAFLD criteria.Many studies in different geographic areas of the world including the United States,Europe,and Asia on a large number of patients proved that the utility of MAFLD criteria was higher than that of the NAFLD criteria in different aspects of fatty liver diseases.Consequently,many societies,physician and nurse groups,health stakeholders,representatives of regulatory sciences,and others endorsed the new nomenclature.Here we highlight the endorsement of the new name by different societies and groups and the outcome of different studies on the new nomenclature in addition to a short discussion of the debate by some experts.

Classification of metabolic-associated fatty liver disease subtypes based on TCM clinical phenotype

Objective:To classify the subtypes of metabolic-associated fatty liver disease(MAFLD)and provide new insights into the heterogeneity of MAFLD.Methods:Electronic medical records(EMR)of MAFLD diagnosed in accordance with the diagnostic criteria of Hubei Provincial Hospital of Traditional Chinese Medicine from 2016-2020 were included in the study.for physical annotation,and the data on each clinical phenotype was normalized according to corresponding aspirational standards.The MAFLD heterogeneous medical record network(HEMnet)was constructed using sex,age,disease diagnosis,symptoms,and Western medicine prescriptions as nodes and the co-occurrence times between phenotypes as edges.K-means clustering was used for disease classification.Relative risk(RR)was used to assess the specificity of each phenotype.Statistical methods were used to compare differences in laboratory indicators among subtypes.Results:A total of patients(12,626)with a mean age of 55.02(±14.21)years were included in the study.MAFLD can be divided into five subtypes:digestive diseases(C0),mental disorders and gynecological diseases(C1),chronic liver diseases and decompensated complications(C2),diabetes mellitus and its complications(C3),and immune joint system diseases(C4).Conclusions:Patients with MAFLD experience various symptoms and complications.The classification of MAFLD based on the HEMnet method is highly reliable.

Lipotoxic hepatocyte-derived exosomal miR-1297 promotes hepatic stellate cell activation through the PTEN signaling pathway in metabolic-associated fatty liver disease

BACKGROUND Exosomes play an important role in metabolic-associated fatty liver disease(MAFLD),but the mechanism by which exosomes participate in MAFLD still remain unclear.AIM To figure out the function of lipotoxic exosomal miR-1297 in MAFLD.METHODS MicroRNA sequencing was used to detect differentially expressed miRNAs(DEmiR)in lipotoxic exosomes derived from primary hepatocytes.Bioinformatic tools were applied to analyze the target genes and pathways regulated by the DE-miRs.Quantitative real-time PCR(qPCR)was conducted for the verification of DEmiRs.qPCR,western blot,immunofluorescence staining and ethynyl-20-deoxyuridine assay were used to evaluate the function of lipotoxic exosomal miR-1297 on hepatic stellate cells(LX2 cells).A luciferase reporter experiment was performed to confirm the relationship of miR-1297 and its target gene PTEN.RESULTS MicroRNA sequencing revealed that there were 61 exosomal DE-miRs(P<0.05)with a fold-change>2 from palmitic acid treated primary hepatocytes compared with the vehicle control group.miR-1297 was the most highly upregulated according to the microRNA sequencing.Bioinformatic tools showed a variety of target genes and pathways regulated by these DE-miRs were related to liver fibrosis.miR-1297 was overexpressed in exosomes derived from lipotoxic hepatocytes by qPCR.Fibrosis promoting genes(α-SMA,PCNA)were altered in LX2 cells after miR-1297 overexpression or miR-1297-rich lipotoxic exosome incubation via qPCR and western blot analysis.Immunofluorescence staining and ethynyl-20-deoxyuridine staining demonstrated that the activation and proliferation of LX2 cells were also promoted after the above treatment.PTEN was found to be the target gene of miR-1297 and knocking down PTEN contributed to the activation and proliferation of LX2 cells via modulating the PI3K/AKT signaling pathway.CONCLUSION miR-1297 was overexpressed in exosomes derived from lipotoxic hepatocytes.The lipotoxic hepatocyte-derived exosomal miR-1297 could promote the activation and proliferation of hepatic stellate cells through the PTEN/PI3K/AKT signaling pathway,accelerating the progression of MAFLD.

Red blood cell distribution width derivatives in alcohol-related liver cirrhosis and metabolic-associated fatty liver disease

BACKGROUND Looking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring.There are still plenty of unresolved issues related to the actual role of hematological indices as potential markers of liver function.AIM To study red blood cell distribution width(RDW),RDW-to-platelet ratio(RPR)and RDW-to-lymphocyte ratio(RLR) in alcohol-related liver cirrhosis(ALC) and metabolic-associated fatty liver disease(MAFLD).METHODS The study group was composed of 302 people:142 patients with ALC and 92 with MAFLD;68 persons were included as controls.RDW,RPR and RLR were measured in each person.Indirect and direct parameters of liver fibrosis were also assessed [aspartate transaminase to alkaline transaminase ratio,aspartate transaminase to platelet ratio index(APRI),fibrosis-4(FIB-4),gamma-glutamyl transpeptidase to platelet ratio(GPR),procollagen I carboxyterminal propeptide,procollagen Ⅲ aminoterminal propeptide,transforming growth factor-α,plateletderived growth factor AB,laminin].MELD score in ALC patients and nonalcoholic fatty liver disease(NAFLD) fibrosis score together with BARD score were obtained in the MAFLD group.The achieved results were compared to controls.Then a correlation between assessed markers was done.Diagnostic value of each investigated parameter and its suggested cut-off in the research group RESULTS RDW,RPR and RLR values turned out to be significantly higher in ALC and MAFLD groups compared to controls(ALC:P<0.0001;NAFLD:P<0.05,P<0.0001 and P<0.0001,respectively).RPR correlated positively with MELD score(P<0.01) and indirect indices of liver fibrosis(FIB-4 and GPR;P<0.0001) in ALC patients;negative correlations were found between PDGF-AB and both:RDW and RPR(P<0.01 and P<0.0001,respectively).RPR correlated positively with NAFLD fibrosis score and APRI(P<0.0001) in the MAFLD group;a positive relationship was observed between RDW and FIB-4,too(P<0.05).AUC values and suggested cut-offs for RDW,RPR and RLR in ALC patients were:0.912(>14.2%),0.965(>0.075) and 0.914(>8.684),respectively.AUC values and suggested cut-offs for RDW,RPR and RLR in MAFLD patients were:0.606(>12.8%),0.724(>0.047) and 0.691(>6.25),respectively.CONCLUSION RDW with its derivatives appear to be valuable diagnostic markers in patients with ALC.They can also be associated with a deterioration of liver function in this group.

Atherogenic index of plasma combined with waist circumference and body mass index to predict metabolic-associated fatty liver disease

BACKGROUND Early identification of metabolic-associated fatty liver disease(MAFLD)is urgent.Atherogenic index of plasma(AIP)is a reference predictor of obesity-related diseases,but its predictive value for MAFLD remains unclear.No studies have reported whether its combination with waist circumference(WC)and body mass index(BMI)can improve the predictive performance for MAFLD.AIM To systematically explore the relationship between AIP and MAFLD and evaluate its predictive value for MAFLD and to pioneer a novel noninvasive predictive model combining AIP,WC,and BMI while validating its predictive performance for MAFLD.METHODS This cross-sectional study consecutively enrolled 864 participants.Multivariate logistic regression analysis and receiver operating characteristic curve were used to evaluate the relationship between AIP and MAFLD and its predictive power for MAFLD.The novel prediction model A-W-B combining AIP,WC,and BMI to predict MAFLD was established,and internal verification was completed by magnetic resonance imaging diagnosis.RESULTS Subjects with higher AIP exhibited a significantly increased risk of MAFLD,with an odds ratio of 12.420(6.008-25.675)for AIP after adjusting for various confounding factors.The area under receiver operating characteristic curve of the A-W-B model was 0.833(0.807-0.858),which was significantly higher than that of AIP,WC,and BMI(all P<0.05).Subgroup analysis illustrated that the A-W-B model had significantly higher area under receiver operating characteristic curves in female,young and nonobese subgroups(all P<0.05).The best cutoff values for the A-W-B model to predict MAFLD in males and females were 0.5932 and 0.4105,respectively.Additionally,in the validation set,the area under receiver operating characteristic curve of the A-W-B model to predict MAFLD was 0.862(0.791-0.916).The A-W-B level was strongly and positively associated with the liver proton density fat fraction(r=0.630,P<0.001)and significantly increased with the severity of MAFLD(P<0.05).CONCLUSION AIP was strongly and positively associated with the risk of MAFLD and can be a reference predictor for MAFLD.The novel prediction model A-W-B combining AIP,WC,and BMI can significantly improve the predictive ability of MAFLD and provide better services for clinical prediction and screening of MAFLD.

Liver function tests and metabolic-associated fatty liver disease:Changes in upper normal limits,does it really matter?

BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is the commonest cause of abnormal liver function tests(LFTs).Current upper normal of limit(UNL)of LFTs was derived from a“healthy”population,where undiagnosed MAFLD and viral hepatitis might be suspected.AIM To evaluated potential implications of changes in UNL of alanine aminotransferase(ALT)in MAFLD.METHODS We retrospectively assessed consecutive first referrals with a diagnosis of MAFLD from 2010 to 2017.The conventional UNL of ALT was 45 IU/L for men and 34 IU/L for women,while a low UNL of ALT was 30 IU/L for men and 19 IU/L for women.The UNL of aspartate aminotransferase(AST)was 40 IU/L.RESULTS Total 436 patients were enrolled;of these,288 underwent liver biopsy.Setting a lower UNL reduced the percentage of those with significant disease despite normal ALT;specifically,patients with advanced fibrosis(F≥F3)or definite“metabolic-associated steato-hepatitis(MASH)”(NAS≥5)within normal ALT decreased from 10%to 1%and from 28%to 4%respectively.However,the proportion of those with elevated ALT and no evidence of advanced fibrosis or“definite MASH”increased from 39%to 47%and from 3%to 19%.Overall,LFTs performed poorly in distinguishing“definite MASH”from simple steatosis(receiver operating characteristic areas under the curves 0.59 for ALT and 0.55 for AST).CONCLUSION Liver function tests might both under-and overestimate MASH-related liver disease.Reducing the UNL might not be beneficial and imply an increase in healthcare burden.Risk stratification in MAFLD should rely on a combination of risk factors,not on LFTs alone.

Research progress on the correlation between metabolic-associated fatty liver disease and metabolic diseases

Metabolic-associated fatty liver disease(MAFLD)is a positive diagnostic criterion and metabolic dysfunction is listed as an important cause of hepatic liver disease.MAFLD is a liver manifestation of metabolic syndrome and a key driver of metabolic syndrome.Glucose and lipid metabolism are disordered in MAFLD,which leads to extrahepatic complications through cytokines,genetic variation,visceral fat accumulation,dietary intake,and complex intestinal microbiome.Extensive clinical evidence suggests that MAFLD is independently associated with various metabolic diseases.With its renaming,the epidemiology,pathogenesis,and treatment of MAFLD and metabolic-related diseases need to be reassessed and studied to lay out a foundation for effective prevention and treatment strategies in the future.

Research progress on the correlation between metabolic-associated fatty liver disease and cardiovascular disease

Metabolisc-associated fatty liver disease(MAFLD)is a multi-system disease in which cardiovascular disease plays an important role and is considered the main cause of death.Notably,cardiovascular disease events in young patients with MAFLD have attracted extensive attention.This article reviews the research progress on the correlation between MAFLD and cardiovascular disease.

Muscle strength and non-alcoholic fatty liver disease/metabolicassociated fatty liver disease

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.

Recent developments in non-invasive methods for assessing metabolic dysfunction-associated fatty liver disease

The prevalence of metabolic dysfunction-associated fatty liver disease(MAFLD)is increasing,affecting over one-third of the global population and contributing to significant morbidity and mortality.Diagnosing MAFLD,especially with advan-ced fibrosis,remains challenging due to the limitations of liver biopsy,the current gold standard.Non-invasive tests are crucial for early detection and management.Among these,the fibrosis-4 index(Fib-4)is widely recommended as a first-line test for screening for liver fibrosis.Advanced imaging techniques,including ultrasound-based elastography and magnetic resonance elastography,offer high accuracy but are limited by cost and availability.Combining biomarkers,such as in the enhanced liver fibrosis score and FibroScan-AST score,enhances diagnostic precision and is recommended to further stratify patients who are considered to be intermediate or high risk from the Fib-4 score.We believe that the future lies in the combined use of biomarkers to improve diagnostic accuracy.

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.