Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the...Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the development of new strategies for early diagnosis and treatment is essential to improve patient outcomes.Over the past decade,the integration of artificial intelligence(AI)into gastroenterology has led to transformative advancements in medical practice.AI represents a major step towards personalized medicine,offering the potential to enhance diagnostic accuracy,refine prognostic assessments,and optimize treatment strategies.Its applications are rapidly expanding.This article explores the emerging role of AI in the management of MASLD,emphasizing its ability to improve clinical prediction,enhance the diagnostic performance of imaging modalities,and support histopathological confirmation.Additionally,it examines the development of AI-guided personalized treatments,where lifestyle modifications and close monitoring play a pivotal role in achieving therapeutic success.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is now considered to be among the most prevalent chronic liver diseases worldwide.Its comprehensive management encompasses multiple stages,including risk ...Metabolic dysfunction-associated steatotic liver disease(MASLD)is now considered to be among the most prevalent chronic liver diseases worldwide.Its comprehensive management encompasses multiple stages,including risk assessment,early detection,stratified intervention,and long-term follow-up.Among these,improving diagnostic accuracy and optimizing individualized therapeutic strategies remain key challenges in both research and clinical practice.In recent years,artificial intelligence and smart devices have developed rapidly and have gradually been applied in the medical field,offering novel tools and pathways for MASLD risk stratification,non-invasive diagnosis,therapeutic evaluation,and patient self-management.This review summarizes the current applications of artificial intelligence and smart devices in MASLD care,highlights their benefits and limitations,and discusses future directions to support precision diagnosis and treatment strategies.展开更多
Background and AimsHepatic iron deposition(HID)in the reticuloendothelial system(RES)is associated with histological severity in metabolic dysfunction-associated steatotic liver disease(MASLD).This study aimed to asse...Background and AimsHepatic iron deposition(HID)in the reticuloendothelial system(RES)is associated with histological severity in metabolic dysfunction-associated steatotic liver disease(MASLD).This study aimed to assess the interaction between the transferrin(TF)-rs1049296 C>T variant and HID patterns on the risk of significant liver fibrosis in MASLD.MethodsWe analyzed 406 adults with liver biopsy-confirmed MASLD.HID was categorized as hepatocellular,RES,or mixed,based on Perl's iron staining.The association between iron-related genetic variants and significant liver fibrosis(fibrosis stage≥F2)was analyzed,focusing on the interactions between single-nucleotide polymorphism genotypes and iron deposition patterns.Multivariable logistic regression analysis was used to adjust for potential confounders.ResultsHID was detected in 271(66.7%)patients,with hepatocellular,RES,and mixed patterns accounting for 11.1%,18.0%,and 37.7%,respectively.A significant interaction was observed between HID and the TF-rs1049296 genotype(P=0.035 for interaction).In multivariable analysis,male sex,hypertension,severe lobular inflammation,and mixed hepatocellular/RES iron deposition were independent predictors of significant liver fibrosis.RES deposition markedly increased the risk of significant liver fibrosis(adjusted odds ratio:6.65;95%confidence interval:1.84-23.97,p<0.05),particularly in men with isolated RES iron deposition(adjusted odds ratio:5.26;95%confidence interval:1.21-22.81,p<0.05).ConclusionsThe TF-rs1049296 T allele interacts with RES iron deposition to identify a MASLD subpopulation at elevated risk of progressive liver disease,providing opportunities for refined risk stratification and personalized management.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)and chronic kidney disease(CKD)have shown a marked global increase in prevalence,placing a substantial burden on public health and healthcare systems worldwid...Metabolic dysfunction-associated fatty liver disease(MAFLD)and chronic kidney disease(CKD)have shown a marked global increase in prevalence,placing a substantial burden on public health and healthcare systems worldwide.Epidemiological data demonstrate a significant overlap between these two conditions,with further evidence from research identifying common pathophysiological features,such as lipid metabolism dysregulation,disrupted energy balance,and chronic systemic inflammation.Mitochondria are central to the pathophysiology of both diseases.In addition to their role in energy production,mitochondria are involved in numerous critical cellular processes,including biosynthesis,lipid metabolism,oxidative phosphorylation,signal transduction,and apoptosis regulation.Mitochondrial dysfunction,characterized by increased reactive oxygen species,impaired adenosine triphosphate synthesis,disrupted mitophagy,and changes in mitochondrial morphology,is implicated in the progression of both MAFLDandCKD.Given the pivotal role of mitochondria in maintaining cellularmetabolism homeostasis,dysfunction of this organelle is increasingly recognized as a key mechanistic link that connects the pathophysiological processes underlying both MAFLD and CKD.This review underscores mitochondrial dysfunction as a pathogenic nexus between MAFLD and CKD and examines the mechanisms that drive their pathogenesis.展开更多
BACKGROUND Visceral fat deposition in the pancreas in the absence of significant alcohol use is termed non-alcoholic fatty pancreas disease(NAFPD)and is closely associated with metabolic dysfunction-associated steatot...BACKGROUND Visceral fat deposition in the pancreas in the absence of significant alcohol use is termed non-alcoholic fatty pancreas disease(NAFPD)and is closely associated with metabolic dysfunction-associated steatotic liver disease(MASLD).However,few studies have assessed the relationship between the severity of NAFPD and the degree of hepatic inflammation and fibrosis in patients with MASLD.AIM To evaluate how NAFPD correlates with degrees of hepatic steatosis,steatohepatitis,and hepatic fibrosis in patients with MASLD.METHODS We performed a retrospective cohort study of patients in the Yale New Haven Health System with a diagnosis of MASLD.Chart and primary imaging data were reviewed to evaluate the degree of pancreatic steatosis and its relationship to hepatic steatosis,steatohepatitis,fibrosis,and other metabolic parameters.RESULTS Ninety-nine participants were identified who met additional inclusion criteria(liver biopsy and non-contrast enhanced computed tomography scan of the abdomen).76 out of the 99 patients in our cohort met the imaging criteria for NAFPD.However,there was no association between the degree of pancreatic steatosis and hepatic steatosis(either on imaging or biopsy),or the degree of pancreatic steatosis and advanced forms of MASLD,such as the degree of metabolic dysfunction-associated steatohepatitis or stage of hepatic fibrosis.CONCLUSION MASLD and NAFPD are co-occurring diseases resulting from and contributing to metabolic dysregulation.Our study confirms this association but does not support a strong association between pancreatic steatosis and hepatic steatohepatitis or fibrosis in this cohort;larger prospective,longitudinal studies are needed in the future to better define the complex interplay of MASLD,NAFPD,and metabolic health.展开更多
In this editorial,author specifically focuses upon metabolic dysfunctionassociated steatotic liver disease(MASLD)and alcohol-associated liver diseases(ALD)in the current era.This editorial article is inspired by the o...In this editorial,author specifically focuses upon metabolic dysfunctionassociated steatotic liver disease(MASLD)and alcohol-associated liver diseases(ALD)in the current era.This editorial article is inspired by the observational study by Harris et al in the recent issue.Alcohol and metabolic dysfunction cause steatotic changes in the hepatic parenchyma.The ALD and MASLD are major cause of chronic liver disease.Liver cirrhosis(LC)is a result of chronic liver inflammation with many causes(e.g.,viral hepatitis,drug,alcohol and metabolic disorder).Metabolic dysfunction-associated steatohepatitis and alcohol-associated hepatitis can lead to liver fibrosis and LC.LC leads to hepatic dysfunction and can progress to eventual liver failure and death.Though chronic viral hepatitis is considered a main cause of LC for a long time,other etiologies(i.e.,ALD,MASLD)has significantly increased in the current era.From the viewpoint of carcinogenesis,LC frequently causes hepatocellular carcinoma(HCC),and HCC is the most common type of primary liver cancer worldwide.As regards major causes of HCC,chronic viral hepatitis is gradually outweighed by ALD and MASLD.Note that patients coexisting with ALD and metabolic dysfunction-associated steatohepatitis show higher occurrence of HCC.Impact of ALD and MASLD upon the development of chronic liver disease,liver fibrosis,LC,and HCC is drastically increased in the current era.Establishments of diagnostic and therapeutic strategies to overcome these hepatic disorders are still required.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease,affecting more than 30%of adults and 7%-14%of youths globally.MASLD and its advanced form of metabolic dysfunctio...Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease,affecting more than 30%of adults and 7%-14%of youths globally.MASLD and its advanced form of metabolic dysfunctionassociated steatohepatitis(MASH)can progress to liver cirrhosis and hepatocellular carcinoma.Despite its growing burden,effective therapies for MASLD and MASH remain limited.Accumulating evidence indicates that short-chain fatty acids(SCFAs)modulate the activation of hepatic innate and adaptive immune cells,influencing liver inflammation and fibrosis.Moreover,SCFAs modulate liver lipid and glucose metabolism and insulin sensitivity,affecting MASLD progression.This review summarizes the cellular and molecular mechanisms through which SCFAs impact liver inflammation,fibrosis,and energy metabolism.Several key molecular signaling pathways are discussed.Clinical trials aiming to modulate SCFA production through different treatments are reviewed.Collectively,emerging evidence supports that targeting SCFA-mediated function represents a promising therapeutic strategy for MASLD and MASH.展开更多
BACKGROUND The global incidence of metabolic dysfunction-associated steatotic liver disease(MASLD)has increased in recent years.It has already been demonstrated that exercise and weight change are associated with the ...BACKGROUND The global incidence of metabolic dysfunction-associated steatotic liver disease(MASLD)has increased in recent years.It has already been demonstrated that exercise and weight change are associated with the occurrence of MASLD;however,the association between weight fluctuation caused by different exercise intensities and the risk of MASLD remains to be studied.AIM To investigate the impact of weight fluctuation and physical activity intensity on the risk of MASLD prevalence.METHODS Data from the National Health and Nutrition Examination Survey database including five cycles from 2009 to 2018 were analyzed.The model included variables such as age,sex,and poverty income ratio.Weighted multivariate logistic regression was used to examine the influence of different weight fluctuation patterns within the two time intervals on the prevalence of MASLD.Nonparametric restricted cubic spline curves were used to analyze the non-linear relationship between net weight change and MASLD prevalence.RESULTS Among 3183 MASLD cases,the risk of MASLD increased with age for individuals transitioning from non-obese to obese or maintaining obesity,with odds ratio(OR)changing from 8.91(95%CI:7.40-10.88)and 11.87(95%CI:9.65-14.60)at 10 years before baseline to 9.58(95%CI:8.08-11.37)and 12.51(95%CI:9.33-16.78)at 25 years.Stable obesity correlated with age-dependent MASLD prevalence escalation,whereas increased physical activity attenuated MASLD risk in this group,with an OR changing from 13.64(95%CI:10.59-17.57)to 6.42(95%CI:4.24-9.72).Further analysis of the net weight changes revealed a paradoxical risk elevation with intensified physical activity during different time periods.CONCLUSION The risk of MASLD increases in individuals transitioning from non-obese to obese or maintaining obesity.Highintensity physical activity is beneficial for MASLD among individuals with stable obesity.展开更多
BACKGROUND Although epidemiological data on non-alcoholic fatty liver disease in China are available,data on cardiometabolic risk factors have not been addressed under the metabolic dysfunction-associated steatotic li...BACKGROUND Although epidemiological data on non-alcoholic fatty liver disease in China are available,data on cardiometabolic risk factors have not been addressed under the metabolic dysfunction-associated steatotic liver disease(MASLD)consensus.AIM To synthesize the epidemiological characteristics of MASLD/metabolic dysfunction-associated steatohepatitis(MASH),especially their associated cardiometabolic risk factors in China.METHODS We searched EMBASE,MEDLINE,Central Cochrane,CNKI,and Wangfan for studies from January 1,2013 to December 31,2023.Studies involving individuals with MASLD/MASH in China that reported epidemiological outcomes were included.Meta-analysis was performed to assess the prevalence of MASLD/MASH.Exploratory outcomes included extrahepatic comorbidities and genetic variants related to MASLD.RESULTS In total,561 studies involving 6632718 participants were included in this analysis.The prevalence of MASLD and MASH and the annual incidence of MASLD were 30.4%[95%confidence interval(CI):29.4-31.3],6.7%(95%CI:2.2-13.4),and 37 cases per 1000 person-years(95%CI:28-47),respectively.In addition,the prevalence rates of MASLD in individuals with dyslipidemia,obesity,and hypertension were 59.9%(95%CI:52.6-67.0),53.9%(95%CI:47.9-59.9),and 44.3%(95%CI:41.1-47.6),respectively.The prevalence of lean MASLD(body mass index<24 kg/m2)was 12.0%(95%CI:10.0-14.0),and 21.7%of the total MASLD population in China had lean MASLD.CONCLUSION This study provides a comprehensive overview of the epidemiology and disease burden of MASLD/MASH in China,providing additional evidence for optimizing MASLD/MASH management in China and a reference for the global understanding of MASLD/MASH epidemiology.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)poses a sub-stantial global health burden,progressing from simple steatosis to metabolic dysfunction-associated steatohepatitis and cirrhosis.A deeper und...Metabolic dysfunction-associated steatotic liver disease(MASLD)poses a sub-stantial global health burden,progressing from simple steatosis to metabolic dysfunction-associated steatohepatitis and cirrhosis.A deeper understanding of the underlying mechanisms and associated complications is crucial for developing effective therapies.Extracellular vesicles(EVs),nanoscale membrane-enclosed particles carrying bioactive cargoes such as proteins and noncoding RNAs,including microRNAs and long noncoding RNAs,play crucial roles in intercel-lular communication and have emerged as critical mediators of MASLD patho-genesis.This article details the current understanding of the function of EVs in MASLD progression,emphasizing specific cell-derived EVs implicated in disease development.We elucidate how EVs facilitate intercellular communication and influence key pathological processes,including lipotoxicity,inflammation,and fibrosis.Furthermore,we examine the involvement of EVs in MASLD-associated complications and evaluate their potential as minimally invasive tools for disease diagnosis,staging,and prognosis.We also explore EV-based therapeutic stra-tegies,encompassing preclinical studies,while acknowledging current challenges and future opportunities.Finally,we discuss emerging research trends,the po-tential for personalized medicine,and areas necessitating further investigation,particularly the utilization of EVs as therapeutic targets or delivery vehicles.This review underscores the pivotal role of EVs in MASLD,providing insights into their translational potential for improved patient outcomes.展开更多
The growing global burden of metabolic dysfunction-associated steatohepatitis(MASH)demands a deeper understanding of its underlying mechanisms and risk factors.Recent studies,such as the large population-based case-co...The growing global burden of metabolic dysfunction-associated steatohepatitis(MASH)demands a deeper understanding of its underlying mechanisms and risk factors.Recent studies,such as the large population-based case-control analysis by Abdel-Razeq et al,suggest a significant association between Helicobacter pylori(H.pylori)infection and an increased risk of developing MASH.This study provides compelling data supporting this association,even after adjusting for confounders such as obesity,diabetes,and hyperlipidemia.However,the complexity of this relationship remains unresolved,requiring further investigation into the biological,genetic,and environmental pathways that connect these two conditions.This article critically reviews the study’s findings and identifies its limitations,offering innovative research directions for the future.Key areas of focus include integrating genomic and microbiome analyses,exploring the impact of H.pylori eradication on MASH progression,studying molecular mechanisms at the intersection of infection and liver disease,and developing personalized therapeutic strategies.展开更多
BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is exp...BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is expected when both diseases co-exist.Therefore,thorough risk stratification is important to inform better clinical practice decisions based on good quality evidence for patient with MAFLD and T2DM.AIM To identify the CVD and cardiovascular event(CVE)risk in a systematic review when MAFLD and T2DM co-exist to inform better clinical practice decisions.METHODS A systematic review was performed by compiling data by searching PubMed,EMBASE and Cochrane Library databases.Quality appraisal of retrieved studies and the meta-analysis were performed using Joanna Briggs Institute(JBI)tool and RevMan 5.4 software respectively.The effect indicators for CVE and CVD risk were expressed as odds ratios(OR)and 95%CI with P-values<0.05 as significant.RESULTS Fourteen(5 cohort and 9 cross-sectional)studies with 370013 participants were included in this review.The metaanalysis of CVE showed that the risk of CVE in T2DM was higher in the MAFLD group when compared to the non-MAFLD group[OR 1.28(95%CI,1.04-1.56)P=0.02]with follow up duration ranging between 5-6 years.The prevalence of CVD in the metanalysis of cross-sectional studies was found to be higher[OR 1.47(95%CI,1.21-1.78)P=0.0001]in T2DM with MAFLD when compared to T2DM without MAFLD.Significant heterogeneity exists due to variations in study design,methodologies,and MAFLD diagnostic criteria,which may have influenced the study's findings.CONCLUSION The presence of MAFLD in T2DM increased the risk of CVE.The prevalence of CVD is higher in T2DM with MAFLD as compared to T2DM without MAFLD.Large well-designed multicentric long-term prospective studies are necessary to appropriately risk stratify the cardiovascular effect of the MAFLD in T2DM patients.展开更多
BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diag...BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diagnosed via imaging or biopsy with metabolic criteria and may progress to metabolic dysfunction–asso-ciated steatohepatitis,potentially leading to fibrosis,cirrhosis,or cancer.The coexistence of hepatic steatosis with chronic hepatitis B(CHB)is mainly related to metabolic factors and increases mortality and cancer risks.As a noninvasive method,attenuation imaging(ATI)shows promise in quantifying liver fat,demonstrating strong correlation with liver biopsy.AIM To investigate the disparity of ATI for assessing biopsy-based hepatic steatosis in CHB patients and MASLD patients.METHODS The study enrolled 249 patients who underwent both ATI and liver biopsy,including 78 with CHB and 171 with MASLD.Hepatic steatosis was classified into grades S0 to S3 according to the proportion of fat cells present.Liver fibrosis was staged from 0 to 4 according to the meta-analysis of histological data in viral hepatitis scoring system.The diagnostic performance of attenuation coefficient(AC)values across different groups was compared for each grade of steatosis.Factors associated with the AC values were determined through linear regression analysis.A multivariate logistic regression model was established to predict≥S2 within the MASLD group.RESULTS In both the CHB and the MASLD groups,AC values increased significantly with higher steatosis grade(P<0.001).In the CHB group,the areas under the curve(AUCs)of AC for predicting steatosis grades≥S1,≥S2 and S3 were 0.918,0.960 and 0.987,respectively.In contrast,the MASLD group showed AUCs of 0.836,0.774,and 0.688 for the same steatosis grades.The diagnostic performance of AC for detecting≥S2 and S3 indicated significant differences between the two groups(both P<0.001).Multivariate linear regression analysis identified body mass index,trigly-cerides,and steatosis grade as significant factors for AC.When the steatosis grade is≥S2,it can progress to more serious liver conditions.A clinical model integrating blood biochemical parameters and AC was developed in the MASLD group to enhance the prediction of≥S2,achieving an AUC of 0.848.CONCLUSION The AC could effectively discriminate the degree of steatosis in both the CHB and MASLD groups.In the MASLD group,when combined with blood biochemical parameters,AC exhibited better predictive ability for moderate to severe steatosis.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease worldwide.Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseas...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease worldwide.Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseases.MASLD exhibits a progressive trajectory that may culminate in development of hepatic cirrhosis,thereby predisposing affected individuals to an elevated likelihood of hepatocarcinogenesis.Diet,especially dietary fatty acids,serves as a key link between nutrient intake and MASLD pathogenesis.AIM To explore the impact of various omega-6 fatty acid subtypes on the pathogenesis and therapeutic strategies of MASLD.METHODS A systematic literature search was conducted across Web of Science,PubMed,Cochrane Central,Scopus,and Embase databases from inception through June 2024 to identify all original studies linking different subtypes of omega-6 polyunsaturated fatty acids to the pathogenesis and management of MASLD.The search strategy explored the linkage between omega-6 polyunsaturated fatty acids and their subtypes,including linoleic acid(LA),gamma-linolenic acid(GLA),arachidonic acid,conjugated LA,and docosapentaenoic acid,in relation to MASLD and cardiometabolic risk.RESULTS By employing the specified search strategy,a total of 83 articles were identified as potentially eligible.During the title,abstract,and full-text screening phases,27 duplicate records were removed,leaving 56 records for relevance screening.Of these,43 records were excluded for reasons such as irrelevance and language restrictions(limited to English),resulting in 13 full-text articles being included for detailed assessment(10 human studies,1 animal study,and 2 review articles).Although certain subtypes,as GLA,dihomo-GLA,omega-6-derived oxylipins,and most arachidonic acid-derived eicosanoids,exhibit pro-inflammatory effects,our findings suggest that other subtypes such as LA,cis-9,trans-11 conjugated LA,and docosapentaenoic acid have beneficial effects on fatty liver,cardiometabolic risk factors,and inflammation,even at high intake levels.CONCLUSION The varying health effects of omega-6 fatty acids,ranging from anti-inflammatory to pro-inflammatory impacts on the liver,leave the question of their recommendation for MASLD patients unresolved.This underscores the importance of careful selection when considering omega-6 supplementation.展开更多
Background:In recent years,the rising prevalence of obesity and metabolic syndrome has led to an increased number of individuals developing metabolic dysfunction-associated steatotic liver disease(MASLD).Furthermore,g...Background:In recent years,the rising prevalence of obesity and metabolic syndrome has led to an increased number of individuals developing metabolic dysfunction-associated steatotic liver disease(MASLD).Furthermore,given the substantial global prevalence of chronic hepatitis B(CHB),instances of MASLD coexisting with CHB are becoming increasingly commonplace in clinical scenarios.Both conditions can lead to liver fibrosis,cirrhosis,and potentially hepatocellular carcinoma(HCC).However,the intrica-cies of the dual etiology,consequential outcomes,and associated risks of CHB concurrent with MASLD are still not fully understood.Data sources:A literature search was conducted on PubMed for articles published up to March 2024.The search keywords included nonalcoholic fatty liver disease,nonalcoholic steatohepatitis,chronic hepatitis B,liver fibrosis,hepatocellular carcinoma,nuclear factor erythroid 2-related factor 2,and oxidative stress.Results:This review examined recent studies on the interplay between MASLD and CHB.The coexis-tence of these conditions may facilitate the clearance of hepatitis B surface antigen from the serum and impede hepatitis B virus(HBV)replication.Conversely,individuals with coexisting CHB tend to exhibit a lower rate of hypertriglyceridemia and reduced serum triglyceride levels compared with those only having NAFLD.Nevertheless,these observations do not necessarily indicate universally positive outcomes.Indeed,MASLD and CHB may synergistically act as“co-conspirators”to exacerbate clinical manifestations,particularly liver fibrosis and HCC.Conclusions:As our understanding of the interaction between steatosis and HBV infection becomes clearer,we can better assess the risk of advanced liver disease in patients with concurrent CHB and MASLD.These insights will support the exploration of potential underlying mechanisms and may provide recommendations for improving patient outcomes.展开更多
BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in the...BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.展开更多
Skeletal muscle alterations(SMA)are increasingly recognized as both contributors and consequences of metabolic dysfunction-associated steatotic liver disease(MASLD),affecting disease progression and outcomes.Sarcopeni...Skeletal muscle alterations(SMA)are increasingly recognized as both contributors and consequences of metabolic dysfunction-associated steatotic liver disease(MASLD),affecting disease progression and outcomes.Sarcopenia is common in patients with MASLD,with a prevalence ranging from 20%to 40%depending on the population and diagnostic criteria used.In advanced stages,such as metabolic dysfunction-associated steatohepatitis and fibrosis,its prevalence is even higher.Sarcopenia exacerbates insulin resistance,systemic inflammation,and oxidative stress,all of which worsen MASLD.It is an independent risk factor for fibrosis progression and poor outcomes including mortality.Myosteatosis refers to the abnormal accumulation of fat within muscle tissue,leading to decreased muscle quality.Myosteatosis is prevalent(>30%)in patients with MASLD,especially those with obesity or type 2 diabetes,although this can vary with the imaging techniques used.It reduces muscle strength and metabolic efficiency,further contributing to insulin resistance and is usually associated with advanced liver disease,cardiovascular complications,and lower levels of physical activity.Altered muscle metabolism,which includes mitochondrial dysfunction and impaired amino acid metabolism,has been reported in metabolic syndromes,including MASLD,although its actual prevalence is unknown.Altered muscle metabolism limits glucose uptake and oxidation,worsening hyperglycemia and lipotoxicity.Reduced muscle perfusion and oxygenation due to endothelial dysfunction and systemic metabolic alterations are common in MASLD associated with comorbidities,such as obesity,hypertension,and atherosclerosis.It decrea-ses the muscle capacity for aerobic metabolism,leading to fatigue and reduced physical activity in patients with MASLD,aggravating metabolic dysfunction.Various SMA in MASLD worsen insulin resistance and hepatic fat accumulation,may accelerate progression to fibrosis and cirrhosis,and increase the risk of cardiovascular disease and mortality.Management strategies for SMA include resistance training,aerobic exercise,and nutritional support(e.g.,high-protein diets,vitamin D,and omega-3 fatty acids),which are essential for mitigating skeletal muscle loss and improving outcomes.However,pharmacological agents that target the muscle and liver(such as glucagon-like peptide-1 receptor agonists)show promise but have not yet been approved for the treatment of MASLD.展开更多
Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has no...Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has not been explored yet.This study aimed to investigate KIF13B’s role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target.Methods:We assessed KIF13B expression in MAFLD patients and rodent models.The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice,hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets.The underlying mechanisms by which Kif13bgoverned hepatic lipid homeostasis and MAFLD progression were explored in vitro.Finally,the Kif13b’s impact on atherosclerotic development was studied in the context of MAFLD.Results:KIF13B expression was reduced in patients and murine models with MAFLD.Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis,which is further exacerbated by different overnutrition diets.Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis(MASH)in methionine-choline-deficient diet(MCD)-fed mice.Furthermore,Kif13b deficiency accelerates atherosclerosis in the context of MAFLD.Mechanistically,Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation.Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1(AMPKα1)to regulate the phosphorylation of AMPKα1,governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1(Srebp1)-mediated denovo lipogenesis in the liver.Conclusion:This work establishes a causal relationship between KIF13B deficiency and MAFLD,emphasizing KIF13B as a potential therapeutic target for treating MAFLD.展开更多
Fatigue is among the most common,albeit underestimated,symptoms in patients with metabolic dysfunction-associated steatotic liver disease.It affects quality of life and reduces the effectiveness of non-pharmacological...Fatigue is among the most common,albeit underestimated,symptoms in patients with metabolic dysfunction-associated steatotic liver disease.It affects quality of life and reduces the effectiveness of non-pharmacological interventions,thereby negatively affecting the prognosis.This review discusses the clinical problems associated with increased fatigue,explores diagnostic methods,considers key pathogenetic mechanisms of this symptom development(including neuroinflammation,hyperammonemia,mitochondrial and muscle dysfunction,sleep disorders,changes in the composition of gut microbiota),and describes the role of interorgan communication(the liver-brain and gut-brain axes)in the formation of the central link of fatigue.The presented data emphasize the need for an integrated approach to the diagnosis and correction of fatigue,which would include not only the impact on metabolic disorders,but also on neurophysiological and behavioral factors.Early assessment of fatigue and targeted interventions on key pathogenetic links can increase the effectiveness of non-pharmacological intervention(which currently form the basis of metabolic dysfunction-associated steatotic liver disease therapy)and improve the prognosis of patients with this chronic liver disease.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as a silent epidemic having substantial clinical implications,with liver transplantation being one of the areas most impacted.The increasing p...Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as a silent epidemic having substantial clinical implications,with liver transplantation being one of the areas most impacted.The increasing prevalence of metabolic fatty liver disease has reduced the quality of available donor organs.While noninvasive methods are increasingly applied to evaluate liver steatosis in deceased donors,liver biopsy remains the gold standard.Many aspects of liver biopsies are not yet fully standardized.Macrovesicular hepatic steatosis is associated with decreased allograft quality and poorer short-and long-term transplant outcomes,especially in moderate and severe steatotic cases.Donation after cardiac arrest further exacerbates these poor outcomes.Matching marginal allografts with suitable recipients based on recipient characteristics is crucial for improving transplant outcomes.Living donor liver transplant is a feasible option for addressing organ shortages.Noninvasive evaluation is preferred for assessing liver health;however,when the results are inconclusive,a liver biopsy is recommended.Lifestyle modifications can improve graft,living donor and recipient outcomes.Analysis of the impact of MASLD on the donor pool and the implementation of new optimization strategies are essential to ensure the sustainability of transplantation as a curative treatment for advanced liver cirrhosis.The aim of this review was to summarize the effect of MASLD on the liver donor population,highlighting how to evaluate steatosis in donors,and to discuss its clinical implications as well as strategies to optimize organ allocation in the MASLD era.展开更多
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the development of new strategies for early diagnosis and treatment is essential to improve patient outcomes.Over the past decade,the integration of artificial intelligence(AI)into gastroenterology has led to transformative advancements in medical practice.AI represents a major step towards personalized medicine,offering the potential to enhance diagnostic accuracy,refine prognostic assessments,and optimize treatment strategies.Its applications are rapidly expanding.This article explores the emerging role of AI in the management of MASLD,emphasizing its ability to improve clinical prediction,enhance the diagnostic performance of imaging modalities,and support histopathological confirmation.Additionally,it examines the development of AI-guided personalized treatments,where lifestyle modifications and close monitoring play a pivotal role in achieving therapeutic success.
基金supported by the National Key Research and Development Program(2024YFA1307101).
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is now considered to be among the most prevalent chronic liver diseases worldwide.Its comprehensive management encompasses multiple stages,including risk assessment,early detection,stratified intervention,and long-term follow-up.Among these,improving diagnostic accuracy and optimizing individualized therapeutic strategies remain key challenges in both research and clinical practice.In recent years,artificial intelligence and smart devices have developed rapidly and have gradually been applied in the medical field,offering novel tools and pathways for MASLD risk stratification,non-invasive diagnosis,therapeutic evaluation,and patient self-management.This review summarizes the current applications of artificial intelligence and smart devices in MASLD care,highlights their benefits and limitations,and discusses future directions to support precision diagnosis and treatment strategies.
基金funded by grants from the National Natural Science Foundation of China(82070588)High-Level Creative Talents from the Department of Public Health in Zhejiang Province(S2032102600032)+2 种基金the Project of New Century 551 Talent Nurturing in WenzhouGT is supported in part by grants from the School of Medicine,University of Verona,Verona,Italy.CDB is supported in part by the Southampton NIHR Biomedical Research Centre(NIHR203319),UKCDB has received research grant support from Echosens,the manufacturer of the Fibroscan device used to assess liver fat and fibrosis in chronic liver diseases.
文摘Background and AimsHepatic iron deposition(HID)in the reticuloendothelial system(RES)is associated with histological severity in metabolic dysfunction-associated steatotic liver disease(MASLD).This study aimed to assess the interaction between the transferrin(TF)-rs1049296 C>T variant and HID patterns on the risk of significant liver fibrosis in MASLD.MethodsWe analyzed 406 adults with liver biopsy-confirmed MASLD.HID was categorized as hepatocellular,RES,or mixed,based on Perl's iron staining.The association between iron-related genetic variants and significant liver fibrosis(fibrosis stage≥F2)was analyzed,focusing on the interactions between single-nucleotide polymorphism genotypes and iron deposition patterns.Multivariable logistic regression analysis was used to adjust for potential confounders.ResultsHID was detected in 271(66.7%)patients,with hepatocellular,RES,and mixed patterns accounting for 11.1%,18.0%,and 37.7%,respectively.A significant interaction was observed between HID and the TF-rs1049296 genotype(P=0.035 for interaction).In multivariable analysis,male sex,hypertension,severe lobular inflammation,and mixed hepatocellular/RES iron deposition were independent predictors of significant liver fibrosis.RES deposition markedly increased the risk of significant liver fibrosis(adjusted odds ratio:6.65;95%confidence interval:1.84-23.97,p<0.05),particularly in men with isolated RES iron deposition(adjusted odds ratio:5.26;95%confidence interval:1.21-22.81,p<0.05).ConclusionsThe TF-rs1049296 T allele interacts with RES iron deposition to identify a MASLD subpopulation at elevated risk of progressive liver disease,providing opportunities for refined risk stratification and personalized management.
基金supported by Top Talent Support Program for young and middle-aged people of Wuxi Health Committee(Grant No.HB2023008)Top Medical Expert Team of Wuxi Taihu Talent Plan(Grant Nos.DJTD202106,GDTD202105 and YXTD202101)+2 种基金Medical Key Discipline Program ofWuxi Health.Commission(Grant Nos.ZDXK2021007 and CXTD2021005)Top Talent Support Program for Young and Middle-Aged People of Wuxi Health Committee(Grant No.BJ2023090)Scientific Research Program of Wuxi Health Commission(Grant Nos.Z20210 and M202208).
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)and chronic kidney disease(CKD)have shown a marked global increase in prevalence,placing a substantial burden on public health and healthcare systems worldwide.Epidemiological data demonstrate a significant overlap between these two conditions,with further evidence from research identifying common pathophysiological features,such as lipid metabolism dysregulation,disrupted energy balance,and chronic systemic inflammation.Mitochondria are central to the pathophysiology of both diseases.In addition to their role in energy production,mitochondria are involved in numerous critical cellular processes,including biosynthesis,lipid metabolism,oxidative phosphorylation,signal transduction,and apoptosis regulation.Mitochondrial dysfunction,characterized by increased reactive oxygen species,impaired adenosine triphosphate synthesis,disrupted mitophagy,and changes in mitochondrial morphology,is implicated in the progression of both MAFLDandCKD.Given the pivotal role of mitochondria in maintaining cellularmetabolism homeostasis,dysfunction of this organelle is increasingly recognized as a key mechanistic link that connects the pathophysiological processes underlying both MAFLD and CKD.This review underscores mitochondrial dysfunction as a pathogenic nexus between MAFLD and CKD and examines the mechanisms that drive their pathogenesis.
文摘BACKGROUND Visceral fat deposition in the pancreas in the absence of significant alcohol use is termed non-alcoholic fatty pancreas disease(NAFPD)and is closely associated with metabolic dysfunction-associated steatotic liver disease(MASLD).However,few studies have assessed the relationship between the severity of NAFPD and the degree of hepatic inflammation and fibrosis in patients with MASLD.AIM To evaluate how NAFPD correlates with degrees of hepatic steatosis,steatohepatitis,and hepatic fibrosis in patients with MASLD.METHODS We performed a retrospective cohort study of patients in the Yale New Haven Health System with a diagnosis of MASLD.Chart and primary imaging data were reviewed to evaluate the degree of pancreatic steatosis and its relationship to hepatic steatosis,steatohepatitis,fibrosis,and other metabolic parameters.RESULTS Ninety-nine participants were identified who met additional inclusion criteria(liver biopsy and non-contrast enhanced computed tomography scan of the abdomen).76 out of the 99 patients in our cohort met the imaging criteria for NAFPD.However,there was no association between the degree of pancreatic steatosis and hepatic steatosis(either on imaging or biopsy),or the degree of pancreatic steatosis and advanced forms of MASLD,such as the degree of metabolic dysfunction-associated steatohepatitis or stage of hepatic fibrosis.CONCLUSION MASLD and NAFPD are co-occurring diseases resulting from and contributing to metabolic dysregulation.Our study confirms this association but does not support a strong association between pancreatic steatosis and hepatic steatohepatitis or fibrosis in this cohort;larger prospective,longitudinal studies are needed in the future to better define the complex interplay of MASLD,NAFPD,and metabolic health.
文摘In this editorial,author specifically focuses upon metabolic dysfunctionassociated steatotic liver disease(MASLD)and alcohol-associated liver diseases(ALD)in the current era.This editorial article is inspired by the observational study by Harris et al in the recent issue.Alcohol and metabolic dysfunction cause steatotic changes in the hepatic parenchyma.The ALD and MASLD are major cause of chronic liver disease.Liver cirrhosis(LC)is a result of chronic liver inflammation with many causes(e.g.,viral hepatitis,drug,alcohol and metabolic disorder).Metabolic dysfunction-associated steatohepatitis and alcohol-associated hepatitis can lead to liver fibrosis and LC.LC leads to hepatic dysfunction and can progress to eventual liver failure and death.Though chronic viral hepatitis is considered a main cause of LC for a long time,other etiologies(i.e.,ALD,MASLD)has significantly increased in the current era.From the viewpoint of carcinogenesis,LC frequently causes hepatocellular carcinoma(HCC),and HCC is the most common type of primary liver cancer worldwide.As regards major causes of HCC,chronic viral hepatitis is gradually outweighed by ALD and MASLD.Note that patients coexisting with ALD and metabolic dysfunction-associated steatohepatitis show higher occurrence of HCC.Impact of ALD and MASLD upon the development of chronic liver disease,liver fibrosis,LC,and HCC is drastically increased in the current era.Establishments of diagnostic and therapeutic strategies to overcome these hepatic disorders are still required.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease,affecting more than 30%of adults and 7%-14%of youths globally.MASLD and its advanced form of metabolic dysfunctionassociated steatohepatitis(MASH)can progress to liver cirrhosis and hepatocellular carcinoma.Despite its growing burden,effective therapies for MASLD and MASH remain limited.Accumulating evidence indicates that short-chain fatty acids(SCFAs)modulate the activation of hepatic innate and adaptive immune cells,influencing liver inflammation and fibrosis.Moreover,SCFAs modulate liver lipid and glucose metabolism and insulin sensitivity,affecting MASLD progression.This review summarizes the cellular and molecular mechanisms through which SCFAs impact liver inflammation,fibrosis,and energy metabolism.Several key molecular signaling pathways are discussed.Clinical trials aiming to modulate SCFA production through different treatments are reviewed.Collectively,emerging evidence supports that targeting SCFA-mediated function represents a promising therapeutic strategy for MASLD and MASH.
基金Supported by National Natural Science Foundation of China,No.82474378Shanghai Natural Science Foundation,No.22ZR1455900+4 种基金Shanghai Municipal Health Planning Commission Clinical Research Specialized Face Project,No.201940449Key Project of Science and Technology Innovation Program of Shanghai Putuo District Health and Health System,No.ptkwws202201Reserve Excellent Chinese Medicine Talent Program of Shanghai University of Traditional Chinese Medicine,No.20D-RC-02Apricot Grove,Shanghai Putuo District Excellent Young Talent Training Program,No.ptxlyq2201Shanghai Putuo District Health and Health System Characteristic Specialty Disease Construction Project,No.2023tszb01.
文摘BACKGROUND The global incidence of metabolic dysfunction-associated steatotic liver disease(MASLD)has increased in recent years.It has already been demonstrated that exercise and weight change are associated with the occurrence of MASLD;however,the association between weight fluctuation caused by different exercise intensities and the risk of MASLD remains to be studied.AIM To investigate the impact of weight fluctuation and physical activity intensity on the risk of MASLD prevalence.METHODS Data from the National Health and Nutrition Examination Survey database including five cycles from 2009 to 2018 were analyzed.The model included variables such as age,sex,and poverty income ratio.Weighted multivariate logistic regression was used to examine the influence of different weight fluctuation patterns within the two time intervals on the prevalence of MASLD.Nonparametric restricted cubic spline curves were used to analyze the non-linear relationship between net weight change and MASLD prevalence.RESULTS Among 3183 MASLD cases,the risk of MASLD increased with age for individuals transitioning from non-obese to obese or maintaining obesity,with odds ratio(OR)changing from 8.91(95%CI:7.40-10.88)and 11.87(95%CI:9.65-14.60)at 10 years before baseline to 9.58(95%CI:8.08-11.37)and 12.51(95%CI:9.33-16.78)at 25 years.Stable obesity correlated with age-dependent MASLD prevalence escalation,whereas increased physical activity attenuated MASLD risk in this group,with an OR changing from 13.64(95%CI:10.59-17.57)to 6.42(95%CI:4.24-9.72).Further analysis of the net weight changes revealed a paradoxical risk elevation with intensified physical activity during different time periods.CONCLUSION The risk of MASLD increases in individuals transitioning from non-obese to obese or maintaining obesity.Highintensity physical activity is beneficial for MASLD among individuals with stable obesity.
文摘BACKGROUND Although epidemiological data on non-alcoholic fatty liver disease in China are available,data on cardiometabolic risk factors have not been addressed under the metabolic dysfunction-associated steatotic liver disease(MASLD)consensus.AIM To synthesize the epidemiological characteristics of MASLD/metabolic dysfunction-associated steatohepatitis(MASH),especially their associated cardiometabolic risk factors in China.METHODS We searched EMBASE,MEDLINE,Central Cochrane,CNKI,and Wangfan for studies from January 1,2013 to December 31,2023.Studies involving individuals with MASLD/MASH in China that reported epidemiological outcomes were included.Meta-analysis was performed to assess the prevalence of MASLD/MASH.Exploratory outcomes included extrahepatic comorbidities and genetic variants related to MASLD.RESULTS In total,561 studies involving 6632718 participants were included in this analysis.The prevalence of MASLD and MASH and the annual incidence of MASLD were 30.4%[95%confidence interval(CI):29.4-31.3],6.7%(95%CI:2.2-13.4),and 37 cases per 1000 person-years(95%CI:28-47),respectively.In addition,the prevalence rates of MASLD in individuals with dyslipidemia,obesity,and hypertension were 59.9%(95%CI:52.6-67.0),53.9%(95%CI:47.9-59.9),and 44.3%(95%CI:41.1-47.6),respectively.The prevalence of lean MASLD(body mass index<24 kg/m2)was 12.0%(95%CI:10.0-14.0),and 21.7%of the total MASLD population in China had lean MASLD.CONCLUSION This study provides a comprehensive overview of the epidemiology and disease burden of MASLD/MASH in China,providing additional evidence for optimizing MASLD/MASH management in China and a reference for the global understanding of MASLD/MASH epidemiology.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)poses a sub-stantial global health burden,progressing from simple steatosis to metabolic dysfunction-associated steatohepatitis and cirrhosis.A deeper understanding of the underlying mechanisms and associated complications is crucial for developing effective therapies.Extracellular vesicles(EVs),nanoscale membrane-enclosed particles carrying bioactive cargoes such as proteins and noncoding RNAs,including microRNAs and long noncoding RNAs,play crucial roles in intercel-lular communication and have emerged as critical mediators of MASLD patho-genesis.This article details the current understanding of the function of EVs in MASLD progression,emphasizing specific cell-derived EVs implicated in disease development.We elucidate how EVs facilitate intercellular communication and influence key pathological processes,including lipotoxicity,inflammation,and fibrosis.Furthermore,we examine the involvement of EVs in MASLD-associated complications and evaluate their potential as minimally invasive tools for disease diagnosis,staging,and prognosis.We also explore EV-based therapeutic stra-tegies,encompassing preclinical studies,while acknowledging current challenges and future opportunities.Finally,we discuss emerging research trends,the po-tential for personalized medicine,and areas necessitating further investigation,particularly the utilization of EVs as therapeutic targets or delivery vehicles.This review underscores the pivotal role of EVs in MASLD,providing insights into their translational potential for improved patient outcomes.
基金Supported by Scientific Research Project of Putian University,No.2022059.
文摘The growing global burden of metabolic dysfunction-associated steatohepatitis(MASH)demands a deeper understanding of its underlying mechanisms and risk factors.Recent studies,such as the large population-based case-control analysis by Abdel-Razeq et al,suggest a significant association between Helicobacter pylori(H.pylori)infection and an increased risk of developing MASH.This study provides compelling data supporting this association,even after adjusting for confounders such as obesity,diabetes,and hyperlipidemia.However,the complexity of this relationship remains unresolved,requiring further investigation into the biological,genetic,and environmental pathways that connect these two conditions.This article critically reviews the study’s findings and identifies its limitations,offering innovative research directions for the future.Key areas of focus include integrating genomic and microbiome analyses,exploring the impact of H.pylori eradication on MASH progression,studying molecular mechanisms at the intersection of infection and liver disease,and developing personalized therapeutic strategies.
文摘BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is expected when both diseases co-exist.Therefore,thorough risk stratification is important to inform better clinical practice decisions based on good quality evidence for patient with MAFLD and T2DM.AIM To identify the CVD and cardiovascular event(CVE)risk in a systematic review when MAFLD and T2DM co-exist to inform better clinical practice decisions.METHODS A systematic review was performed by compiling data by searching PubMed,EMBASE and Cochrane Library databases.Quality appraisal of retrieved studies and the meta-analysis were performed using Joanna Briggs Institute(JBI)tool and RevMan 5.4 software respectively.The effect indicators for CVE and CVD risk were expressed as odds ratios(OR)and 95%CI with P-values<0.05 as significant.RESULTS Fourteen(5 cohort and 9 cross-sectional)studies with 370013 participants were included in this review.The metaanalysis of CVE showed that the risk of CVE in T2DM was higher in the MAFLD group when compared to the non-MAFLD group[OR 1.28(95%CI,1.04-1.56)P=0.02]with follow up duration ranging between 5-6 years.The prevalence of CVD in the metanalysis of cross-sectional studies was found to be higher[OR 1.47(95%CI,1.21-1.78)P=0.0001]in T2DM with MAFLD when compared to T2DM without MAFLD.Significant heterogeneity exists due to variations in study design,methodologies,and MAFLD diagnostic criteria,which may have influenced the study's findings.CONCLUSION The presence of MAFLD in T2DM increased the risk of CVE.The prevalence of CVD is higher in T2DM with MAFLD as compared to T2DM without MAFLD.Large well-designed multicentric long-term prospective studies are necessary to appropriately risk stratify the cardiovascular effect of the MAFLD in T2DM patients.
基金Supported by the National Natural Science Foundation of China,No.82202185and Shanghai Science and Technology Development Foundation,No.22Y11911500.
文摘BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diagnosed via imaging or biopsy with metabolic criteria and may progress to metabolic dysfunction–asso-ciated steatohepatitis,potentially leading to fibrosis,cirrhosis,or cancer.The coexistence of hepatic steatosis with chronic hepatitis B(CHB)is mainly related to metabolic factors and increases mortality and cancer risks.As a noninvasive method,attenuation imaging(ATI)shows promise in quantifying liver fat,demonstrating strong correlation with liver biopsy.AIM To investigate the disparity of ATI for assessing biopsy-based hepatic steatosis in CHB patients and MASLD patients.METHODS The study enrolled 249 patients who underwent both ATI and liver biopsy,including 78 with CHB and 171 with MASLD.Hepatic steatosis was classified into grades S0 to S3 according to the proportion of fat cells present.Liver fibrosis was staged from 0 to 4 according to the meta-analysis of histological data in viral hepatitis scoring system.The diagnostic performance of attenuation coefficient(AC)values across different groups was compared for each grade of steatosis.Factors associated with the AC values were determined through linear regression analysis.A multivariate logistic regression model was established to predict≥S2 within the MASLD group.RESULTS In both the CHB and the MASLD groups,AC values increased significantly with higher steatosis grade(P<0.001).In the CHB group,the areas under the curve(AUCs)of AC for predicting steatosis grades≥S1,≥S2 and S3 were 0.918,0.960 and 0.987,respectively.In contrast,the MASLD group showed AUCs of 0.836,0.774,and 0.688 for the same steatosis grades.The diagnostic performance of AC for detecting≥S2 and S3 indicated significant differences between the two groups(both P<0.001).Multivariate linear regression analysis identified body mass index,trigly-cerides,and steatosis grade as significant factors for AC.When the steatosis grade is≥S2,it can progress to more serious liver conditions.A clinical model integrating blood biochemical parameters and AC was developed in the MASLD group to enhance the prediction of≥S2,achieving an AUC of 0.848.CONCLUSION The AC could effectively discriminate the degree of steatosis in both the CHB and MASLD groups.In the MASLD group,when combined with blood biochemical parameters,AC exhibited better predictive ability for moderate to severe steatosis.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease worldwide.Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseases.MASLD exhibits a progressive trajectory that may culminate in development of hepatic cirrhosis,thereby predisposing affected individuals to an elevated likelihood of hepatocarcinogenesis.Diet,especially dietary fatty acids,serves as a key link between nutrient intake and MASLD pathogenesis.AIM To explore the impact of various omega-6 fatty acid subtypes on the pathogenesis and therapeutic strategies of MASLD.METHODS A systematic literature search was conducted across Web of Science,PubMed,Cochrane Central,Scopus,and Embase databases from inception through June 2024 to identify all original studies linking different subtypes of omega-6 polyunsaturated fatty acids to the pathogenesis and management of MASLD.The search strategy explored the linkage between omega-6 polyunsaturated fatty acids and their subtypes,including linoleic acid(LA),gamma-linolenic acid(GLA),arachidonic acid,conjugated LA,and docosapentaenoic acid,in relation to MASLD and cardiometabolic risk.RESULTS By employing the specified search strategy,a total of 83 articles were identified as potentially eligible.During the title,abstract,and full-text screening phases,27 duplicate records were removed,leaving 56 records for relevance screening.Of these,43 records were excluded for reasons such as irrelevance and language restrictions(limited to English),resulting in 13 full-text articles being included for detailed assessment(10 human studies,1 animal study,and 2 review articles).Although certain subtypes,as GLA,dihomo-GLA,omega-6-derived oxylipins,and most arachidonic acid-derived eicosanoids,exhibit pro-inflammatory effects,our findings suggest that other subtypes such as LA,cis-9,trans-11 conjugated LA,and docosapentaenoic acid have beneficial effects on fatty liver,cardiometabolic risk factors,and inflammation,even at high intake levels.CONCLUSION The varying health effects of omega-6 fatty acids,ranging from anti-inflammatory to pro-inflammatory impacts on the liver,leave the question of their recommendation for MASLD patients unresolved.This underscores the importance of careful selection when considering omega-6 supplementation.
基金supported by a grant from the Scientific Re-search Program of Furong Laboratory(No.2023SK2108).
文摘Background:In recent years,the rising prevalence of obesity and metabolic syndrome has led to an increased number of individuals developing metabolic dysfunction-associated steatotic liver disease(MASLD).Furthermore,given the substantial global prevalence of chronic hepatitis B(CHB),instances of MASLD coexisting with CHB are becoming increasingly commonplace in clinical scenarios.Both conditions can lead to liver fibrosis,cirrhosis,and potentially hepatocellular carcinoma(HCC).However,the intrica-cies of the dual etiology,consequential outcomes,and associated risks of CHB concurrent with MASLD are still not fully understood.Data sources:A literature search was conducted on PubMed for articles published up to March 2024.The search keywords included nonalcoholic fatty liver disease,nonalcoholic steatohepatitis,chronic hepatitis B,liver fibrosis,hepatocellular carcinoma,nuclear factor erythroid 2-related factor 2,and oxidative stress.Results:This review examined recent studies on the interplay between MASLD and CHB.The coexis-tence of these conditions may facilitate the clearance of hepatitis B surface antigen from the serum and impede hepatitis B virus(HBV)replication.Conversely,individuals with coexisting CHB tend to exhibit a lower rate of hypertriglyceridemia and reduced serum triglyceride levels compared with those only having NAFLD.Nevertheless,these observations do not necessarily indicate universally positive outcomes.Indeed,MASLD and CHB may synergistically act as“co-conspirators”to exacerbate clinical manifestations,particularly liver fibrosis and HCC.Conclusions:As our understanding of the interaction between steatosis and HBV infection becomes clearer,we can better assess the risk of advanced liver disease in patients with concurrent CHB and MASLD.These insights will support the exploration of potential underlying mechanisms and may provide recommendations for improving patient outcomes.
文摘BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.
基金Supported by Russian Science Foundation,No.19-76-30014.
文摘Skeletal muscle alterations(SMA)are increasingly recognized as both contributors and consequences of metabolic dysfunction-associated steatotic liver disease(MASLD),affecting disease progression and outcomes.Sarcopenia is common in patients with MASLD,with a prevalence ranging from 20%to 40%depending on the population and diagnostic criteria used.In advanced stages,such as metabolic dysfunction-associated steatohepatitis and fibrosis,its prevalence is even higher.Sarcopenia exacerbates insulin resistance,systemic inflammation,and oxidative stress,all of which worsen MASLD.It is an independent risk factor for fibrosis progression and poor outcomes including mortality.Myosteatosis refers to the abnormal accumulation of fat within muscle tissue,leading to decreased muscle quality.Myosteatosis is prevalent(>30%)in patients with MASLD,especially those with obesity or type 2 diabetes,although this can vary with the imaging techniques used.It reduces muscle strength and metabolic efficiency,further contributing to insulin resistance and is usually associated with advanced liver disease,cardiovascular complications,and lower levels of physical activity.Altered muscle metabolism,which includes mitochondrial dysfunction and impaired amino acid metabolism,has been reported in metabolic syndromes,including MASLD,although its actual prevalence is unknown.Altered muscle metabolism limits glucose uptake and oxidation,worsening hyperglycemia and lipotoxicity.Reduced muscle perfusion and oxygenation due to endothelial dysfunction and systemic metabolic alterations are common in MASLD associated with comorbidities,such as obesity,hypertension,and atherosclerosis.It decrea-ses the muscle capacity for aerobic metabolism,leading to fatigue and reduced physical activity in patients with MASLD,aggravating metabolic dysfunction.Various SMA in MASLD worsen insulin resistance and hepatic fat accumulation,may accelerate progression to fibrosis and cirrhosis,and increase the risk of cardiovascular disease and mortality.Management strategies for SMA include resistance training,aerobic exercise,and nutritional support(e.g.,high-protein diets,vitamin D,and omega-3 fatty acids),which are essential for mitigating skeletal muscle loss and improving outcomes.However,pharmacological agents that target the muscle and liver(such as glucagon-like peptide-1 receptor agonists)show promise but have not yet been approved for the treatment of MASLD.
基金supported by the National Natural Science Foundation of China(82270479,82070460)the Beijing Natural Science Foundation(7242084 to Xun-De Xian)the National Key Research and Development Program of China from the Ministry of Science and Technology(2021YFF0702802 to Yu-Hui Wang).
文摘Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has not been explored yet.This study aimed to investigate KIF13B’s role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target.Methods:We assessed KIF13B expression in MAFLD patients and rodent models.The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice,hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets.The underlying mechanisms by which Kif13bgoverned hepatic lipid homeostasis and MAFLD progression were explored in vitro.Finally,the Kif13b’s impact on atherosclerotic development was studied in the context of MAFLD.Results:KIF13B expression was reduced in patients and murine models with MAFLD.Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis,which is further exacerbated by different overnutrition diets.Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis(MASH)in methionine-choline-deficient diet(MCD)-fed mice.Furthermore,Kif13b deficiency accelerates atherosclerosis in the context of MAFLD.Mechanistically,Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation.Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1(AMPKα1)to regulate the phosphorylation of AMPKα1,governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1(Srebp1)-mediated denovo lipogenesis in the liver.Conclusion:This work establishes a causal relationship between KIF13B deficiency and MAFLD,emphasizing KIF13B as a potential therapeutic target for treating MAFLD.
基金Supported by Russian Science Foundation,No.23-45-10030.
文摘Fatigue is among the most common,albeit underestimated,symptoms in patients with metabolic dysfunction-associated steatotic liver disease.It affects quality of life and reduces the effectiveness of non-pharmacological interventions,thereby negatively affecting the prognosis.This review discusses the clinical problems associated with increased fatigue,explores diagnostic methods,considers key pathogenetic mechanisms of this symptom development(including neuroinflammation,hyperammonemia,mitochondrial and muscle dysfunction,sleep disorders,changes in the composition of gut microbiota),and describes the role of interorgan communication(the liver-brain and gut-brain axes)in the formation of the central link of fatigue.The presented data emphasize the need for an integrated approach to the diagnosis and correction of fatigue,which would include not only the impact on metabolic disorders,but also on neurophysiological and behavioral factors.Early assessment of fatigue and targeted interventions on key pathogenetic links can increase the effectiveness of non-pharmacological intervention(which currently form the basis of metabolic dysfunction-associated steatotic liver disease therapy)and improve the prognosis of patients with this chronic liver disease.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as a silent epidemic having substantial clinical implications,with liver transplantation being one of the areas most impacted.The increasing prevalence of metabolic fatty liver disease has reduced the quality of available donor organs.While noninvasive methods are increasingly applied to evaluate liver steatosis in deceased donors,liver biopsy remains the gold standard.Many aspects of liver biopsies are not yet fully standardized.Macrovesicular hepatic steatosis is associated with decreased allograft quality and poorer short-and long-term transplant outcomes,especially in moderate and severe steatotic cases.Donation after cardiac arrest further exacerbates these poor outcomes.Matching marginal allografts with suitable recipients based on recipient characteristics is crucial for improving transplant outcomes.Living donor liver transplant is a feasible option for addressing organ shortages.Noninvasive evaluation is preferred for assessing liver health;however,when the results are inconclusive,a liver biopsy is recommended.Lifestyle modifications can improve graft,living donor and recipient outcomes.Analysis of the impact of MASLD on the donor pool and the implementation of new optimization strategies are essential to ensure the sustainability of transplantation as a curative treatment for advanced liver cirrhosis.The aim of this review was to summarize the effect of MASLD on the liver donor population,highlighting how to evaluate steatosis in donors,and to discuss its clinical implications as well as strategies to optimize organ allocation in the MASLD era.
