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
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 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
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
Metabolic dysfunction-associated steatohepatitis(MASH)has become a leading indication for liver transplantation.Bariatric surgery is a proven intervention for weight loss and metabolic improvement in MASH but concerns...Metabolic dysfunction-associated steatohepatitis(MASH)has become a leading indication for liver transplantation.Bariatric surgery is a proven intervention for weight loss and metabolic improvement in MASH but concerns over surgical risk in patients with advanced liver disease has expanded interest in endoscopic sleeve gastroplasty(ESG)as a less invasive alternative.This review examine the efficacy,safety,and metabolic impact of ESG vs traditional bariatric surgery(Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy)in patients with MASH,with and without cirrhosis.We analyze current evidence on weight loss outcomes,histologic and biochemical improvements in MASH,resolution of metabolic syndrome,and perioperative risks associated with these procedures.Special attention is given to the feasibility of ESG in compensated cirrhosis(Child-Pugh A/B)and the potential role of bariatric interventions in delaying or avoiding liver transplantation.As the prevalence of MASH-related cirrhosis rises,refining bariatric strategies for this high-risk population is imperative.ESG may offer a lower procedural risk profile,but current data are largely limited to small,observational studies with short-term follow-up.A tailored,multidisciplinary approach is essential to optimize weight management and liver health in MASH patients,with future studies needed to clarify the long-term efficacy and safety of ESG in MASH.展开更多
Background:Metabolic dysfunction-associated steatotic liver disease(MASLD)is one of the leading causes of chronic liver disease worldwide.Recently,short-chain fatty acids(SCFAs),as metabolites of intesti-nal flora,hav...Background:Metabolic dysfunction-associated steatotic liver disease(MASLD)is one of the leading causes of chronic liver disease worldwide.Recently,short-chain fatty acids(SCFAs),as metabolites of intesti-nal flora,have been found to participate in the progression of MASLD.Sodium butyrate(NaB),one of the most important SCFAs,shows therapeutic potentials in MASLD and its mechanisms have not been fully understood.The present study aimed to investigate the effects of NaB on metabolic dysfunction-associated steatohepatitis(MASH)associated fibrosis as well as the underlying mechanisms.Methods:Male Sprague-Dawley rats were randomly assigned to three groups:(i)control group,stan-dard chow for 24 weeks;(ii)HFD group,high-fat and high-cholesterol diet(HFD)for 24 weeks;and(iii)HFD+NaB group,HFD for 24 weeks and NaB gavage for the last 16 weeks.Body weight,liver index(liver weight/body weight×100%),serum parameters,and liver histology were analyzed to evaluate MASH and fibrosis severity.AML12,RAW264.7 and LX2 cell lines were used for in vitro study.Results:Compared to MASH rats with fibrosis induced by 24-week HFD,NaB intervention alleviated the degree of hepatic steatosis,inflammation,hepatocyte ballooning,and fibrosis.Further mechanistic study showed that NaB supplementation significantly decreased miR-155-5p level in the liver and the serum of MASH rats,and the inhibition effects of miR-155-5p on suppressor of cytokine signaling 1(SOCS1)in both hepatocytes and hepatic stellate cells(HSCs)were blunted when they were treated with NaB.Fur-thermore,NaB also significantly decreased the production of platelet-derived growth factor-BB(PDGF-BB),a pro-fibrotic mediator,in hepatocytes.NaB treatment on AML12 cells markedly impaired the prolifera-tion ability of co-cultured LX2 cells.Moreover,NaB intervention or miR-155-5p mimics also interferes extracellular regulated protein kinases signaling in LX2 cells.Conclusions:NaB intervention inhibited HSCs activation via miR-155-5p/SOCS1/PDGF signaling pathway and consequently relieved fibrosis in MASH rats.NaB might be a potential agent for the treatment of fibrosis in patients with MASH.展开更多
Metabolic dysfunction-associated steatohepatitis(MASH)and alcoholic steatohepatitis(ASH)are severe forms of chronic liver disease,characterized by inflammation,oxidative stress,lipid dysregulation,and fibrosis.Epigene...Metabolic dysfunction-associated steatohepatitis(MASH)and alcoholic steatohepatitis(ASH)are severe forms of chronic liver disease,characterized by inflammation,oxidative stress,lipid dysregulation,and fibrosis.Epigenetic changes,including acetylation,methylation,phosphorylation,ubiquitination,sumoylation,and lactylation of histones,dynamically regulate gene expression by altering the chromatin structure.Emerging evidence highlights histone modifications as chief contributors to the pathogenesis of chronic liver diseases.Lactylation which is a novel post-translational modification(PTM)of histone,has been observed as a crucial contributor to liver physiology as well as pathobiology.This modification,characterized by the addition of lactate to lysine residues on histones,influences gene expression and cellular metabolism in the liver.Intriguingly,elevated lactate levels in the liver,resulting from either chronic alcohol consumption or a highfat/fructose-rich diet,may promote histone lactylation,particularly at histone 3 at lysine 18(H3K18),which facilitates the transcription of pro-inflammatory and fibrogenic genes.This process not only intensifies hepatic inflammation and fibrosis but also disrupts normal metabolic pathways,resulting in further liver damage.This review aims to elucidate the role of histone lactylation in MASH.Although a direct demonstration of histone lactylation in ASH has not yet been reported,the altered lactate metabolism in ASH suggests that histone lactylation may significantly contribute to its pathogenesis.Finally,we explore novel strategies targeting histone lactylation to mitigate liver injury and improve disease management in MASH and ASH.展开更多
BACKGROUND The molecular mechanisms associated with semaglutide and empagliflozin in metabolic dysfunction-associated steatotic liver disease(MASLD)still require further studies to develop precise therapeutic strategi...BACKGROUND The molecular mechanisms associated with semaglutide and empagliflozin in metabolic dysfunction-associated steatotic liver disease(MASLD)still require further studies to develop precise therapeutic strategies.AIM To investigate the effects and the mechanism of action of semaglutide and empagliflozin on MASLD in obese mice.METHODS The experimental subjects consisted of 32 mice,which were arbitrarily allocated into four distinct groups:(1)The control group;(2)The high-fat group;(3)The Sema group;and(4)The Empa group.Mice were assessed for body weight changes,glycolipid metabolic status,inflammatory oxidative stress levels,pathology and metabolomics.RESULTS Semaglutide and empagliflozin have been demonstrated to exert a substantial impact on glycolipid reduction,the amelioration of glycolipid metabolism disorders,the attenuation of inflammation and oxidative stress levels,and the restoration of the pathological structure of liver injury to a certain extent in obese mice.No statistically significant differences in the outcomes associated with MASLD were identified between the two cohorts.The results of this study demonstrated that both semaglutide and empagliflozin had the capacity to influence the levels of several lysophosphatidylcholine(LPC).CONCLUSION It has been hypothesised that the amelioration of MASLD by semaglutide and empagliflozin may be associated with a decrease in the levels of several LPCs in liver tissue.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)now affects roughly one-quarter of the world’s population,reflecting the global spread of obesity and insulin resistance.Reframing non-alcoholic fatty liver ...Metabolic dysfunction-associated fatty liver disease(MAFLD)now affects roughly one-quarter of the world’s population,reflecting the global spread of obesity and insulin resistance.Reframing non-alcoholic fatty liver disease as MAFLD emphasizes its metabolic roots and spotlights the gut-liver axis,where intestinal dysbiosis acts as a key driver of hepatic injury.Altered microbial com-munities disrupt epithelial integrity,promote bacterial translocation,and trigger endotoxin-mediated inflammation that accelerates steatosis,lipotoxicity,and fibrogenesis.Concurrent shifts in bile acid signaling and short-chain fatty acid profiles further impair glucose and lipid homeostasis,amplifying cardiometabolic risk.Epidemiological studies reveal pervasive dysbiosis in MAFLD cohorts,linked to diet quality,sedentary behavior,adiposity,and host genetics.Newly developed microbiome-derived biomarkers,advanced elastography,and integrated multi-omics panels hold promise for non-invasive diagnosis and stratification,although external validation remains limited.In early trials,interventions that re-engineer the microbiota including tailored pre-/pro-/synbiotics,rational diet patterns,next-generation fecal microbiota transplantation,and bile-acid-modulating drugs show encouraging histological and metabolic gains.Optimal care will likely couple these tools with weight-centered lifestyle programmes in a pre-cision-medicine framework.Key challenges include inter-ethnic variability in microbiome signatures,the absence of consensus treatment algorithms,and regulatory barriers to live biotherapeutics.Rigorous longitudinal studies are required to translate mechanistic insight into durable clinical benefit and improve patient-centered outcome measures.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is a progressive metabolic disorder that is pathologically characterized by abnormal lipid deposition in the liver and metabolic inflammation.The current ...Metabolic dysfunction-associated steatotic liver disease(MASLD)is a progressive metabolic disorder that is pathologically characterized by abnormal lipid deposition in the liver and metabolic inflammation.The current clinical mana-gement of MASLD largely involves generalized lifestyle modifications including diet and broad-spectrum metabolic interventions such as insulin sensitizers.These approaches often yield suboptimal outcomes because of poor long-term adhe-rence,heterogeneous patient responses,and limited efficacy in advanced disease stages.Crucially,they fail to address disease-specific molecular drivers,such as aging-associated pathways exemplified by vitamin D receptor dysregulation.Given the complexity and progressive nature of MASLD,it is crucial to further elucidate its mechanisms,develop precise therapeutic strategies,and raise awareness of the disease among the public and medical community.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease with a continually rising global prevalence and significant mortality rates.Emerging evidence suggests a strong a...Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease with a continually rising global prevalence and significant mortality rates.Emerging evidence suggests a strong association between MASLD and mental health disorders such as depression and anxiety.In addition to the shared risk factors such as obesity,type 2 diabetes and insulin resistance which contribute to this relationship through mechanisms involving systemic inflammation and oxidative stress;other pathophysiological mechanisms such as dysregulation of hypothalamic-pituitary-adrenal axis,neurotransmitter imbalances and gut dysbiosis have also been proposed to play a significant role.The current paper aims to review the pathophysiological mechanisms underlying the association between MASLD and mood disorders such as depression and anxiety.We note a bidirectional relationship between these two disorders,and the dual burden of both these disease processes can be alleviated by early detection and encouraging a more proactive and holistic approach through diet and lifestyle changes.This review summarizes the existing literature on association between MASLD and depression.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohe...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohepatitis,which is characterized by inflammation,hepatocyte injury,and fibrosis,increasing the risk of cirrhosis and liver failure.Recent studies suggest that neutrophil extracellular traps(NETs)and extracellular DNA(ecDNA)contribute to liver inflammation and fibrogenesis.However,their role in MASLD pathogenesis remains incompletely understood.AIM To investigate the dynamics of circulating NETs and ecDNA as potential biomarkers of liver injury in MASLD.METHODS Using three complementary mouse models,thioacetamide(TAA)-induced fibrosis,choline-deficient L-amino acid-defined(CDAA)diet-induced metabolic dysfunction-associated steatohepatitis,and cafeteria(CAF)diet-induced MASLD,we assessed the association between NET-related markers and liver damage.Blood samples were collected biweekly to analyze ecDNA and NET markers,including myeloperoxidase(MPO)and MPO-DNA complexes,using ELISA and real-time PCR.Liver histopathology was assessed for inflammation,fibrosis,and neutrophil infiltration.RESULTS The TAA and CDAA models exhibited significant liver injury,characterized by increased plasma alanine aminotransferase and aspartate aminotransferase levels,hepatocellular damage,and fibrosis.Elevated circulating NET markers(MPO and ecDNA)were observed in these models,with a strong correlation between NET formation and liver pathology.The CAF diet model induced steatosis but failed to elicit significant liver fibrosis or an increase in NET markers,suggesting that NETosis is associated with more severe liver damage.Notably,ecDNA and MPO levels correlated with neutrophil infiltration and fibrosis scores,indicating their potential as biomarkers of MASLD progression.CONCLUSION NETosis and ecDNA levels reflect liver injury severity in MASLD.NET markers and liver fibrosis were strongly associated in TAA and CDAA models,whereas CAF model showed minimal NET involvement.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.
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 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 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.
文摘Metabolic dysfunction-associated steatohepatitis(MASH)has become a leading indication for liver transplantation.Bariatric surgery is a proven intervention for weight loss and metabolic improvement in MASH but concerns over surgical risk in patients with advanced liver disease has expanded interest in endoscopic sleeve gastroplasty(ESG)as a less invasive alternative.This review examine the efficacy,safety,and metabolic impact of ESG vs traditional bariatric surgery(Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy)in patients with MASH,with and without cirrhosis.We analyze current evidence on weight loss outcomes,histologic and biochemical improvements in MASH,resolution of metabolic syndrome,and perioperative risks associated with these procedures.Special attention is given to the feasibility of ESG in compensated cirrhosis(Child-Pugh A/B)and the potential role of bariatric interventions in delaying or avoiding liver transplantation.As the prevalence of MASH-related cirrhosis rises,refining bariatric strategies for this high-risk population is imperative.ESG may offer a lower procedural risk profile,but current data are largely limited to small,observational studies with short-term follow-up.A tailored,multidisciplinary approach is essential to optimize weight management and liver health in MASH patients,with future studies needed to clarify the long-term efficacy and safety of ESG in MASH.
基金supported by grants from the National Natural Science Foundation of China(81873565 and 81900507).
文摘Background:Metabolic dysfunction-associated steatotic liver disease(MASLD)is one of the leading causes of chronic liver disease worldwide.Recently,short-chain fatty acids(SCFAs),as metabolites of intesti-nal flora,have been found to participate in the progression of MASLD.Sodium butyrate(NaB),one of the most important SCFAs,shows therapeutic potentials in MASLD and its mechanisms have not been fully understood.The present study aimed to investigate the effects of NaB on metabolic dysfunction-associated steatohepatitis(MASH)associated fibrosis as well as the underlying mechanisms.Methods:Male Sprague-Dawley rats were randomly assigned to three groups:(i)control group,stan-dard chow for 24 weeks;(ii)HFD group,high-fat and high-cholesterol diet(HFD)for 24 weeks;and(iii)HFD+NaB group,HFD for 24 weeks and NaB gavage for the last 16 weeks.Body weight,liver index(liver weight/body weight×100%),serum parameters,and liver histology were analyzed to evaluate MASH and fibrosis severity.AML12,RAW264.7 and LX2 cell lines were used for in vitro study.Results:Compared to MASH rats with fibrosis induced by 24-week HFD,NaB intervention alleviated the degree of hepatic steatosis,inflammation,hepatocyte ballooning,and fibrosis.Further mechanistic study showed that NaB supplementation significantly decreased miR-155-5p level in the liver and the serum of MASH rats,and the inhibition effects of miR-155-5p on suppressor of cytokine signaling 1(SOCS1)in both hepatocytes and hepatic stellate cells(HSCs)were blunted when they were treated with NaB.Fur-thermore,NaB also significantly decreased the production of platelet-derived growth factor-BB(PDGF-BB),a pro-fibrotic mediator,in hepatocytes.NaB treatment on AML12 cells markedly impaired the prolifera-tion ability of co-cultured LX2 cells.Moreover,NaB intervention or miR-155-5p mimics also interferes extracellular regulated protein kinases signaling in LX2 cells.Conclusions:NaB intervention inhibited HSCs activation via miR-155-5p/SOCS1/PDGF signaling pathway and consequently relieved fibrosis in MASH rats.NaB might be a potential agent for the treatment of fibrosis in patients with MASH.
基金Supported by the Science and Engineering Research Board,No.CRG/2022/002149the Indian Council of Medical Research,No.ICMR/02/833/IGP-2024 and No.R.12016/12/2023-HR.
文摘Metabolic dysfunction-associated steatohepatitis(MASH)and alcoholic steatohepatitis(ASH)are severe forms of chronic liver disease,characterized by inflammation,oxidative stress,lipid dysregulation,and fibrosis.Epigenetic changes,including acetylation,methylation,phosphorylation,ubiquitination,sumoylation,and lactylation of histones,dynamically regulate gene expression by altering the chromatin structure.Emerging evidence highlights histone modifications as chief contributors to the pathogenesis of chronic liver diseases.Lactylation which is a novel post-translational modification(PTM)of histone,has been observed as a crucial contributor to liver physiology as well as pathobiology.This modification,characterized by the addition of lactate to lysine residues on histones,influences gene expression and cellular metabolism in the liver.Intriguingly,elevated lactate levels in the liver,resulting from either chronic alcohol consumption or a highfat/fructose-rich diet,may promote histone lactylation,particularly at histone 3 at lysine 18(H3K18),which facilitates the transcription of pro-inflammatory and fibrogenic genes.This process not only intensifies hepatic inflammation and fibrosis but also disrupts normal metabolic pathways,resulting in further liver damage.This review aims to elucidate the role of histone lactylation in MASH.Although a direct demonstration of histone lactylation in ASH has not yet been reported,the altered lactate metabolism in ASH suggests that histone lactylation may significantly contribute to its pathogenesis.Finally,we explore novel strategies targeting histone lactylation to mitigate liver injury and improve disease management in MASH and ASH.
基金Supported by The Scientific Research Programme on Traditional Chinese Medicine in Hebei Province,No.2024127.
文摘BACKGROUND The molecular mechanisms associated with semaglutide and empagliflozin in metabolic dysfunction-associated steatotic liver disease(MASLD)still require further studies to develop precise therapeutic strategies.AIM To investigate the effects and the mechanism of action of semaglutide and empagliflozin on MASLD in obese mice.METHODS The experimental subjects consisted of 32 mice,which were arbitrarily allocated into four distinct groups:(1)The control group;(2)The high-fat group;(3)The Sema group;and(4)The Empa group.Mice were assessed for body weight changes,glycolipid metabolic status,inflammatory oxidative stress levels,pathology and metabolomics.RESULTS Semaglutide and empagliflozin have been demonstrated to exert a substantial impact on glycolipid reduction,the amelioration of glycolipid metabolism disorders,the attenuation of inflammation and oxidative stress levels,and the restoration of the pathological structure of liver injury to a certain extent in obese mice.No statistically significant differences in the outcomes associated with MASLD were identified between the two cohorts.The results of this study demonstrated that both semaglutide and empagliflozin had the capacity to influence the levels of several lysophosphatidylcholine(LPC).CONCLUSION It has been hypothesised that the amelioration of MASLD by semaglutide and empagliflozin may be associated with a decrease in the levels of several LPCs in liver tissue.
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)now affects roughly one-quarter of the world’s population,reflecting the global spread of obesity and insulin resistance.Reframing non-alcoholic fatty liver disease as MAFLD emphasizes its metabolic roots and spotlights the gut-liver axis,where intestinal dysbiosis acts as a key driver of hepatic injury.Altered microbial com-munities disrupt epithelial integrity,promote bacterial translocation,and trigger endotoxin-mediated inflammation that accelerates steatosis,lipotoxicity,and fibrogenesis.Concurrent shifts in bile acid signaling and short-chain fatty acid profiles further impair glucose and lipid homeostasis,amplifying cardiometabolic risk.Epidemiological studies reveal pervasive dysbiosis in MAFLD cohorts,linked to diet quality,sedentary behavior,adiposity,and host genetics.Newly developed microbiome-derived biomarkers,advanced elastography,and integrated multi-omics panels hold promise for non-invasive diagnosis and stratification,although external validation remains limited.In early trials,interventions that re-engineer the microbiota including tailored pre-/pro-/synbiotics,rational diet patterns,next-generation fecal microbiota transplantation,and bile-acid-modulating drugs show encouraging histological and metabolic gains.Optimal care will likely couple these tools with weight-centered lifestyle programmes in a pre-cision-medicine framework.Key challenges include inter-ethnic variability in microbiome signatures,the absence of consensus treatment algorithms,and regulatory barriers to live biotherapeutics.Rigorous longitudinal studies are required to translate mechanistic insight into durable clinical benefit and improve patient-centered outcome measures.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is a progressive metabolic disorder that is pathologically characterized by abnormal lipid deposition in the liver and metabolic inflammation.The current clinical mana-gement of MASLD largely involves generalized lifestyle modifications including diet and broad-spectrum metabolic interventions such as insulin sensitizers.These approaches often yield suboptimal outcomes because of poor long-term adhe-rence,heterogeneous patient responses,and limited efficacy in advanced disease stages.Crucially,they fail to address disease-specific molecular drivers,such as aging-associated pathways exemplified by vitamin D receptor dysregulation.Given the complexity and progressive nature of MASLD,it is crucial to further elucidate its mechanisms,develop precise therapeutic strategies,and raise awareness of the disease among the public and medical community.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease with a continually rising global prevalence and significant mortality rates.Emerging evidence suggests a strong association between MASLD and mental health disorders such as depression and anxiety.In addition to the shared risk factors such as obesity,type 2 diabetes and insulin resistance which contribute to this relationship through mechanisms involving systemic inflammation and oxidative stress;other pathophysiological mechanisms such as dysregulation of hypothalamic-pituitary-adrenal axis,neurotransmitter imbalances and gut dysbiosis have also been proposed to play a significant role.The current paper aims to review the pathophysiological mechanisms underlying the association between MASLD and mood disorders such as depression and anxiety.We note a bidirectional relationship between these two disorders,and the dual burden of both these disease processes can be alleviated by early detection and encouraging a more proactive and holistic approach through diet and lifestyle changes.This review summarizes the existing literature on association between MASLD and depression.
基金Supported by Slovak Research and Development Agency,No.APVV-21-0370Ministry of Education,Science,Research and Sport of the Slovak Republic,No.VEGA 1/0706/25 and No.VEGA 1/0341/23.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohepatitis,which is characterized by inflammation,hepatocyte injury,and fibrosis,increasing the risk of cirrhosis and liver failure.Recent studies suggest that neutrophil extracellular traps(NETs)and extracellular DNA(ecDNA)contribute to liver inflammation and fibrogenesis.However,their role in MASLD pathogenesis remains incompletely understood.AIM To investigate the dynamics of circulating NETs and ecDNA as potential biomarkers of liver injury in MASLD.METHODS Using three complementary mouse models,thioacetamide(TAA)-induced fibrosis,choline-deficient L-amino acid-defined(CDAA)diet-induced metabolic dysfunction-associated steatohepatitis,and cafeteria(CAF)diet-induced MASLD,we assessed the association between NET-related markers and liver damage.Blood samples were collected biweekly to analyze ecDNA and NET markers,including myeloperoxidase(MPO)and MPO-DNA complexes,using ELISA and real-time PCR.Liver histopathology was assessed for inflammation,fibrosis,and neutrophil infiltration.RESULTS The TAA and CDAA models exhibited significant liver injury,characterized by increased plasma alanine aminotransferase and aspartate aminotransferase levels,hepatocellular damage,and fibrosis.Elevated circulating NET markers(MPO and ecDNA)were observed in these models,with a strong correlation between NET formation and liver pathology.The CAF diet model induced steatosis but failed to elicit significant liver fibrosis or an increase in NET markers,suggesting that NETosis is associated with more severe liver damage.Notably,ecDNA and MPO levels correlated with neutrophil infiltration and fibrosis scores,indicating their potential as biomarkers of MASLD progression.CONCLUSION NETosis and ecDNA levels reflect liver injury severity in MASLD.NET markers and liver fibrosis were strongly associated in TAA and CDAA models,whereas CAF model showed minimal NET involvement.
