Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similaritie...Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratifed cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD(40.3%) was significantly higher than that of NAFLD(36.9%)( P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus(T2DM)(53.8%), impaired fasting glucose(35.7%) and impaired glucose tolerance(40.9%). High risk of advanced fbrosis based on fbrosis-4 was highly prevalent(14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481(35.1%) fulflled the diagnostic criteria for MAFLD and NAFLD(MAFLD + NAFLD +), 521(5.2%) MAFLD + NAFLD-, and 181(1.8%) MAFLD-NAFLD +. The MAFLD + NAFLD-group had more signifcant metabolic disorders than those in the MAFLD + NAFLD + group(all P < 0.05). Among MAFLD-NAFLD + subjects, 82.9% had metabolic disorders. Conclusions: The new defnition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.展开更多
BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations ...BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.展开更多
Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 20...Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within hepatocytes.Th...Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within hepatocytes.The redefinition of NAFLD in 2023 marked a significant reposition in terminology,emphasizing a broader understanding of liver steatosis and its associated risks.MASLD is now recognized as a major risk factor for liver cirrhosis,hepatocellular carcinoma,and systemic complications such as cardiovascular diseases or systemic inflammation.Diagnostic challenges arise,particularly in identifying MASLD in lean individuals,necessitating updated diagnostic protocols and investing in non-invasive diagnostic tools.Therapeutically,there is an urgent need for effective treatments targeting MASLD,with emerging pharmacological options focusing on,among others,carbohydrate and lipid metabolism.Additionally,understanding the roles of bile acid metabolism,the microbiome,and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic approaches.There is a strong need to emphasize the importance of collaborative efforts in understanding,diagnosing,and managing MASLD to improve physicians’approaches and patient outcomes.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is chronic,with its progression leading to liver fibrosis and end-stage cirrhosis.Although NAFLD is increasingly common,no treatment guideline has been established.Man...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is chronic,with its progression leading to liver fibrosis and end-stage cirrhosis.Although NAFLD is increasingly common,no treatment guideline has been established.Many mechanistic studies and drug trials have been conducted for new drug development to treat NAFLD.An up-to-date overview on the knowledge structure of NAFLD through bibliometrics,focusing on research hotspots,is necessary to reveal the rational and timely directions of development in this field.AIM To research the latest literature and determine the current trends in treatment for NAFLD.METHODS Publications related to treatment for NAFLD were searched on the Web of Science Core Collection database,from 2010 to 2023.VOSviewers,CiteSpace,and R package“bibliometrix”were used to conduct this bibliometric analysis.The key information was extracted,and the results of the cluster analysis were based on network data for generating and investigating maps for country,institution,journal,and author.Historiography analysis,bursts and cluster analysis,cooccurrence analysis,and trend topic revealed the knowledge structure and research hotspots in this field.GraphPad Prism 9.5.1.733 and Microsoft Office Excel 2019 were used for data analysis and visualization.RESULTS In total,10829 articles from 120 countries(led by China and the United States)and 8785 institutions were included.The number of publications related to treatment for NAFLD increased annually.While China produced the most publications,the United States was the most cited country,and the United Kingdom collaborated the most from an international standpoint.The University of California-San Diego,Shanghai Jiao Tong University,and Shanghai University of Traditional Chinese Medicine produced the most publications of all the research institutions.The International Journal of Molecular Sciences was the most frequent journal out of the 1523 total journals,and Hepatology was the most cited and co-cited journal.Sanyal AJ was the most cited author,the most co-展开更多
The Fibroscan-AST(FAST)score was developed based on the data of patients who had a liver biopsy for non-alcoholic fatty liver disease(NAFLD)at several liver centres in England,and it was validated using data from seve...The Fibroscan-AST(FAST)score was developed based on the data of patients who had a liver biopsy for non-alcoholic fatty liver disease(NAFLD)at several liver centres in England,and it was validated using data from seven clinical studies from North America,Europe and Asia(1).The FAST score requires only controlled attenuation parameter(CAP)and liver stiffness measurement(LSM)from a vibration-controlled transient elastography(VCTE)examination and serum aspartate aminotransferase(AST)level in its calculation.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most count...Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.展开更多
In this editorial,we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology(2024;30:1346-1357).The study highlights a noteworthy association between persiste...In this editorial,we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology(2024;30:1346-1357).The study highlights a noteworthy association between persistently elevated,yet highnormal levels of alanine transaminase(ALT)and an escalated cumulative risk of developing metabolic dysfunction-associated fatty liver disease(MAFLD).MAFLD has emerged as a globally prevalent chronic liver condition,whose incidence is steadily rising in parallel with improvements in living standards.Left unchecked,MAFLD can progress from hepatic steatosis to liver fibrosis,cirrhosis,and even hepatocellular carcinoma,underscoring the importance of early screening and diagnosis.ALT is widely recognized as a reliable biomarker for assessing the extent of hepatocellular damage.While ALT levels demonstrate a significant correlation with the severity of fatty liver disease,they lack specificity.The article by Chen et al contributes to our understanding of the development of MAFLD by investigating the long-term implications of high-normal ALT levels.Their findings suggest that sustained elevation within the normal range is linked to an increased likelihood of developing MAFLD,emphasizing the need for closer monitoring and potential intervention in such cases.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)with hepatic histological NAFLD activity score≥4 and fibrosis stage F≥2 is regarded as“at risk”non-alcoholic steatohepatitis(NASH).Based on an international conse...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)with hepatic histological NAFLD activity score≥4 and fibrosis stage F≥2 is regarded as“at risk”non-alcoholic steatohepatitis(NASH).Based on an international consensus,NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH),respectively;hence,we introduced the term“high-risk MASH”.Diagnostic values of seven non-invasive models,including FibroScan-aspartate transaminase(FAST),fibrosis-4(FIB-4),aspartate transaminase to platelet ratio index(APRI),etc.for high-risk MASH have rarely been studied and compared in MASLD.AIM To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH.METHODS A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital,between January 2012 and December 2020.After screening for MASLD and the exclusion criteria,279 patients wereincluded and categorized into high-risk and non-high-risk MASH groups.Utilizing threshold values of each model,sensitivity,specificity,positive predictive value(PPV),and negative predictive values(NPV),were calculated.Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve(AUROC).RESULTS MASLD diagnostic criteria were met by 99.4%patients with NAFLD.The MASLD population was analyzed in two cohorts:Overall population(279 patients)and the subgroup(117 patients)who underwent liver transient elastography(FibroScan).In the overall population,FIB-4 showed better diagnostic efficacy and higher PPV,with sensitivity,specificity,PPV,NPV,and AUROC of 26.9%,95.2%,73.5%,72.2%,and 0.75.APRI,Forns index,and aspartate transaminase to alanine transaminase ratio(ARR)showed moderate diagnostic efficacy,whereas S index and gamma-glutamyl transpeptidase to platelet ratio(GPR)were relatively weaker.In the subgroup,FAST had the highest diagnosti展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH)are a growing health burden across a significant portion of the global patient popula...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH)are a growing health burden across a significant portion of the global patient population.However,these conditions seem to have disparate rates and outcomes between different ethnic populations.The combination of MASLD/MASH and type 2 diabetes increases the risk of hepatocellular carcinoma(HCC),and Hispanic patients experience the greatest burden,particularly those in South Texas.AIM To compare outcomes between Hispanic and non-Hispanic patients in the United States,while further focusing on the Hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a function of geographical circumstance or if there is a more widespread reason that all clinicians must account for in prognostic consideration.METHODS This cohort analysis was conducted with data obtained from TriNetX,LLC(“TriNetX”),a global federated health research network that provides access to deidentified medical records from healthcare organizations worldwide.Two cohort networks were used:University of Texas Medical Branch(UTMB)hospital and the United States national database collective to determine whether disparities were related to geographic regions,like Southeast Texas.RESULTS This study findings revealed Hispanics/Latinos have a statistically significant higher occurrence of HCC,type 2 diabetes mellitus,and liver fibrosis/cirrhosis in both the United States and the UTMB Hispanic/Latino groups.Allcause mortality in Hispanics/Latinos was lower within the United States group and not statistically elevated in the UTMB cohort.CONCLUSION This would appear to support that Hispanic patients in Southeast Texas are not uniquely affected compared to the national Hispanic population.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide,paralleling the rising pandemic of obesity and type 2 diabetes.Due to the growing global health...Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide,paralleling the rising pandemic of obesity and type 2 diabetes.Due to the growing global health burden and com-plex pathogenesis of MASLD,a multifaceted and innovative therapeutic approach is needed.Incretin receptor agonists,which were initially developed for diabetes management,have emerged as promising candidates for MASLD treatment.This review describes the pathophysiological mechanisms and action sites of three major classes of incretin/glucagon receptor agonists:glucagon-like peptide-1 receptor agonists,glucose-dependent insulinotropic polypeptide receptor agonists,and glucagon receptor agonists.Incretins and glucagon directly or indirectly impact various organs,including the liver,brain,pancreas,gastro-intestinal tract,and adipose tissue.Thus,these agents significantly improve glycemic control and weight management and mitigate MASLD pathogenesis.Importantly,this study provides a summary of clinical trials analyzing the effect-iveness and safety of incretin receptor agonists in MASLD management and provides an in-depth analysis highlighting their beneficial effects on improving liver function,hepatic steatosis,and intrahepatic inflammation.There are emerging challenges associated with the use of these medications in the real world,particularly adverse events,drug-drug interactions,and barriers to access,which are discussed in detail.Additionally,this review highlights the evolving role of incretin receptor agonists in MASLD management and suggests future research directions.展开更多
BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now...BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in adults.This condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase worldwide.Lean patients account for approximately 10%-15%of the MASLD population.However,the pathogenesis is complex and is not well understood.AIM To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new criteria.METHODS We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD patients.We include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.RESULTS We include 85 studies in our analysis.Our findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic response.Common risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean patients.Regarding non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients.Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser extent.However,lean NAFLD patients exhibited a worse prognosis compared to the obese 展开更多
The onset of metabolic dysfunction-associated steatohepatitis(MASH)or non-alcoholic steatohepatitis(NASH)represents a tipping point leading to liver injury and subsequent hepatic complications in the natural progressi...The onset of metabolic dysfunction-associated steatohepatitis(MASH)or non-alcoholic steatohepatitis(NASH)represents a tipping point leading to liver injury and subsequent hepatic complications in the natural progression of what is now termed metabolic dysfunction-associated steatotic liver diseases(MASLD),formerly known as non-alcoholic fatty liver disease(NAFLD).With no pharmacological treat-ment currently available for MASH/NASH,the race is on to develop drugs targeting multiple facets of hepatic metabolism,inflammation,and pro-fibrotic events,which are major drivers of MASH.Nuclear receptors(NRs)regulate genomic transcription upon binding to lipophilic ligands and govern multiple aspects of liver metabolism and inflammation.Ligands of NRs may include hormones,lipids,bile acids,and synthetic ligands,which upon binding to NRs regulate the transcriptional activities of target genes.NR ligands are presently the most promising drug candidates expected to receive approval from the United States Food and Drug Administration as a pharmacological treatment for MASH.This review aims to cover the current understanding of NRs,including nuclear hormone receptors,non-steroid hormone receptors,circadian NRs,and orphan NRs,which are currently undergoing clinical trials for MASH treatment,along with NRs that have shown promising results in preclinical studies.展开更多
With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn pu...With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.展开更多
BACKGROUND There is limited evidence regarding the association between muscle strength and metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the association between muscle strength and MAF...BACKGROUND There is limited evidence regarding the association between muscle strength and metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the association between muscle strength and MAFLD in the general population in Korea.METHODS This nationwide representative cross-sectional study included 31649 individuals aged≥19 years who participated in the Korea National Health and Nutrition Examination Survey between 2015 and 2018.Odds ratios(ORs)and 95%confidence intervals(95%CIs)for MAFLD according to sex-specific quartiles of muscle strength,defined by relative handgrip strength,were calculated using multivariable logistic regression analysis.Additionally,multivariable logistic regression analysis was used to assess the association between muscle strength and probable liver fibrosis in patients with MAFLD.RESULTS Of all the participants,29.3%had MAFLD.The prevalence of MAFLD was significantly higher in the lower muscle strength quartile groups for all participants,sexes,and age groups(P<0.001).A 1.92-fold(OR=1.92,95%CI:1.70–2.16)and 3.12-fold(OR=3.12,95%CI:2.64–3.69)higher risk of MAFLD was observed in the lowest quartile(Q1)group than in the other groups(Q2–Q4)and the highest quartile(Q4)group,respectively.The ORs of MAFLD were significantly increased in the lower muscle strength quartile groups in a dose-dependent manner(P for trend<0.001).These associations persisted in both sexes.An inverse association between muscle strength and the risk of MAFLD was observed in all subgroups according to age,obesity,and diabetes mellitus.In patients with MAFLD,the odds of severe liver fibrosis were higher in Q1(OR=1.83,95%CI:1.25–2.69)than in other groups(Q2–Q4).CONCLUSION Among Korean adults,low muscle strength was associated with an increased risk of MAFLD and liver fibrosis in patients with MAFLD.展开更多
Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is sti...Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)i...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 pa展开更多
Bile acids(BAs)play important roles in the digestion of dietary fats and molecular signal transduction,and modulation of the BA composition usually affects the progression of metabolic diseases.While the liver produce...Bile acids(BAs)play important roles in the digestion of dietary fats and molecular signal transduction,and modulation of the BA composition usually affects the progression of metabolic diseases.While the liver produces primary BAs,the gut microbiota modifies these products into various forms that greatly increase their diversity and biological functions.Mechanistically,BAs can regulate their own metabolism and transport as well as other key aspects of metabolic processes via dedicated BA receptors.Disruption of BA transport and homeostasis leads to the progression of liver diseases,including metabolic dysfunction-associated steatotic liver disease(MASLD)and hepatocellular carcinoma(HCC).Here,we summarize the microbial transformations of BAs and their downstream signaling in the development of metabolic diseases and present new insights into novel therapeutic strategies targeting BA pathways that may contribute to these diseases.展开更多
The newly released nomenclature of metabolic dysfunction-associated steatotic liver disease(MASLD)in the 2023 European Association for the Study of the Liver Congress has raised great clinical concerns.This marks the ...The newly released nomenclature of metabolic dysfunction-associated steatotic liver disease(MASLD)in the 2023 European Association for the Study of the Liver Congress has raised great clinical concerns.This marks the second instance of significant renaming of non-alcoholic fatty liver disease since the introduction of metabolic dysfunction-associated fatty liver disease(MAFLD)in 2020.The nomenclature and definitions of MASLD and MAFLD exhibit significant disparities as well as substantial consensus.The disparities regarding the framework of nomenclature,the definitions,the clinical management,and the impact on the clinical outcomes between MASLD and MAFLD were comprehensively compared in this editorial.Additionally,the consensus reached by the MASLD and MAFLD definitions also emphasizes positive diagnosis rather than negative diagnosis within the framework of establishing a diagnostic approach.Furthermore,they acknowledged the pivotal role of metabolic dysfunction in the pathogenesis of MAFLD or MASLD and the positive role of increasing the awareness of the disease in public.Fortunately,the non-invasive tests remains effective in the MASLD and MAFLD era.Elucidating these disparities would contribute to a more comprehensive comprehension of the nature of steatotic liver disease and enhance clinical practice.Thus,more efforts are required to reach more consensus about these important topics.展开更多
Liver transplantation(LT)for metabolic dysfunction-associated steatotic liver disease(MASLD)is increasing globally due to rising rates of obesity and metabolic syndrome,posing significant challenges.MASLD patients typ...Liver transplantation(LT)for metabolic dysfunction-associated steatotic liver disease(MASLD)is increasing globally due to rising rates of obesity and metabolic syndrome,posing significant challenges.MASLD patients typically present with advanced age,higher body mass index(BMI),and metabolic com-orbidities such as diabetes,hypertension,and dyslipidemia.Comprehensive pre-transplant evaluations are crucial for assessing surgical risks and preparing patients for transplantation.MASLD patients with higher BMI may experience longer operative times,potentially affecting intraoperative outcomes.In the months following LT,MASLD recipients face persistent challenges,including a higher incidence of metabolic syndrome and cardiovascular events compared to non-MASLD recipients.However,survival rates at 1-,3-,and 5-years post-LT do not markedly differ from other etiologies,indicating comparable surgical outcomes.Optimizing outcomes in MASLD patients undergoing LT demands a multidisciplinary approach from pre-transplant assessment to post-transplant care.Strategies must address metabolic comorbidities,manage cardiovascular health,and monitor steatosis recurrence,which can be exacerbated by obesity and diabetes.This approach aims to mitigate long-term graft complications and mortality risks,ultimately enhancing transplant success and patient well-being.Continued research is essential to refine these approaches and meet the evolving challenges posed by MASLD as a leading indication for LT worldwide.展开更多
基金supported by grants from the Collaborative Innovation Program of Shanghai Municipal Health Commission (2020CXJQ01)the National Natural Science Foundation of China (81873565 and 82100605)+2 种基金Shanghai Jiao Tong University Transmed Awards Research (20190104)Star Program of Shanghai Jiao Tong University (YG2021QN54)Hospital Funded Clinical Research,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (17CSK04 and 15LC06)。
文摘Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratifed cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD(40.3%) was significantly higher than that of NAFLD(36.9%)( P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus(T2DM)(53.8%), impaired fasting glucose(35.7%) and impaired glucose tolerance(40.9%). High risk of advanced fbrosis based on fbrosis-4 was highly prevalent(14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481(35.1%) fulflled the diagnostic criteria for MAFLD and NAFLD(MAFLD + NAFLD +), 521(5.2%) MAFLD + NAFLD-, and 181(1.8%) MAFLD-NAFLD +. The MAFLD + NAFLD-group had more signifcant metabolic disorders than those in the MAFLD + NAFLD + group(all P < 0.05). Among MAFLD-NAFLD + subjects, 82.9% had metabolic disorders. Conclusions: The new defnition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.
基金National Natural Science Foundation of China,No.72101236China Postdoctoral Science Foundation,No.2022M722900+1 种基金Collaborative Innovation Project of Zhengzhou City,No.XTCX2023006Nursing Team Project of the First Affiliated Hospital of Zhengzhou University,No.HLKY2023005.
文摘BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.
文摘Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within hepatocytes.The redefinition of NAFLD in 2023 marked a significant reposition in terminology,emphasizing a broader understanding of liver steatosis and its associated risks.MASLD is now recognized as a major risk factor for liver cirrhosis,hepatocellular carcinoma,and systemic complications such as cardiovascular diseases or systemic inflammation.Diagnostic challenges arise,particularly in identifying MASLD in lean individuals,necessitating updated diagnostic protocols and investing in non-invasive diagnostic tools.Therapeutically,there is an urgent need for effective treatments targeting MASLD,with emerging pharmacological options focusing on,among others,carbohydrate and lipid metabolism.Additionally,understanding the roles of bile acid metabolism,the microbiome,and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic approaches.There is a strong need to emphasize the importance of collaborative efforts in understanding,diagnosing,and managing MASLD to improve physicians’approaches and patient outcomes.
基金National Science Foundation of China,No.81273142Anhui Provincial Natural Science Foundation,No.2108085MH298+3 种基金University Scientific Research Project of Anhui Provincial Education Department,No.KJ2021A0323Fund of Anhui Medical University,No.2021xkj196Clinical Medicine project of Anhui Medical University,No.2021LCXK027The Second Hospital of Anhui Medical University Natural Science Foundation,No.2019GMFY02。
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is chronic,with its progression leading to liver fibrosis and end-stage cirrhosis.Although NAFLD is increasingly common,no treatment guideline has been established.Many mechanistic studies and drug trials have been conducted for new drug development to treat NAFLD.An up-to-date overview on the knowledge structure of NAFLD through bibliometrics,focusing on research hotspots,is necessary to reveal the rational and timely directions of development in this field.AIM To research the latest literature and determine the current trends in treatment for NAFLD.METHODS Publications related to treatment for NAFLD were searched on the Web of Science Core Collection database,from 2010 to 2023.VOSviewers,CiteSpace,and R package“bibliometrix”were used to conduct this bibliometric analysis.The key information was extracted,and the results of the cluster analysis were based on network data for generating and investigating maps for country,institution,journal,and author.Historiography analysis,bursts and cluster analysis,cooccurrence analysis,and trend topic revealed the knowledge structure and research hotspots in this field.GraphPad Prism 9.5.1.733 and Microsoft Office Excel 2019 were used for data analysis and visualization.RESULTS In total,10829 articles from 120 countries(led by China and the United States)and 8785 institutions were included.The number of publications related to treatment for NAFLD increased annually.While China produced the most publications,the United States was the most cited country,and the United Kingdom collaborated the most from an international standpoint.The University of California-San Diego,Shanghai Jiao Tong University,and Shanghai University of Traditional Chinese Medicine produced the most publications of all the research institutions.The International Journal of Molecular Sciences was the most frequent journal out of the 1523 total journals,and Hepatology was the most cited and co-cited journal.Sanyal AJ was the most cited author,the most co-
文摘The Fibroscan-AST(FAST)score was developed based on the data of patients who had a liver biopsy for non-alcoholic fatty liver disease(NAFLD)at several liver centres in England,and it was validated using data from seven clinical studies from North America,Europe and Asia(1).The FAST score requires only controlled attenuation parameter(CAP)and liver stiffness measurement(LSM)from a vibration-controlled transient elastography(VCTE)examination and serum aspartate aminotransferase(AST)level in its calculation.
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.
基金Supported by the Natural Science Foundation of Sichuan Province,No.24NSFSC0163State Key Clinical Department of Oral&Maxillofacial Surgery。
文摘In this editorial,we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology(2024;30:1346-1357).The study highlights a noteworthy association between persistently elevated,yet highnormal levels of alanine transaminase(ALT)and an escalated cumulative risk of developing metabolic dysfunction-associated fatty liver disease(MAFLD).MAFLD has emerged as a globally prevalent chronic liver condition,whose incidence is steadily rising in parallel with improvements in living standards.Left unchecked,MAFLD can progress from hepatic steatosis to liver fibrosis,cirrhosis,and even hepatocellular carcinoma,underscoring the importance of early screening and diagnosis.ALT is widely recognized as a reliable biomarker for assessing the extent of hepatocellular damage.While ALT levels demonstrate a significant correlation with the severity of fatty liver disease,they lack specificity.The article by Chen et al contributes to our understanding of the development of MAFLD by investigating the long-term implications of high-normal ALT levels.Their findings suggest that sustained elevation within the normal range is linked to an increased likelihood of developing MAFLD,emphasizing the need for closer monitoring and potential intervention in such cases.
基金Supported by National Natural Science Foundation of China,No.82170591Natural Science Foundation of Beijing,No.7222097.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)with hepatic histological NAFLD activity score≥4 and fibrosis stage F≥2 is regarded as“at risk”non-alcoholic steatohepatitis(NASH).Based on an international consensus,NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH),respectively;hence,we introduced the term“high-risk MASH”.Diagnostic values of seven non-invasive models,including FibroScan-aspartate transaminase(FAST),fibrosis-4(FIB-4),aspartate transaminase to platelet ratio index(APRI),etc.for high-risk MASH have rarely been studied and compared in MASLD.AIM To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH.METHODS A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital,between January 2012 and December 2020.After screening for MASLD and the exclusion criteria,279 patients wereincluded and categorized into high-risk and non-high-risk MASH groups.Utilizing threshold values of each model,sensitivity,specificity,positive predictive value(PPV),and negative predictive values(NPV),were calculated.Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve(AUROC).RESULTS MASLD diagnostic criteria were met by 99.4%patients with NAFLD.The MASLD population was analyzed in two cohorts:Overall population(279 patients)and the subgroup(117 patients)who underwent liver transient elastography(FibroScan).In the overall population,FIB-4 showed better diagnostic efficacy and higher PPV,with sensitivity,specificity,PPV,NPV,and AUROC of 26.9%,95.2%,73.5%,72.2%,and 0.75.APRI,Forns index,and aspartate transaminase to alanine transaminase ratio(ARR)showed moderate diagnostic efficacy,whereas S index and gamma-glutamyl transpeptidase to platelet ratio(GPR)were relatively weaker.In the subgroup,FAST had the highest diagnosti
基金Supported by Institute for Translational Sciences at the University of Texas Medical Branch,supported in part by a Clinical and Translational Science Award from the National Center for Advancing Translational Sciences at the National Institutes of Health,UL1TR001439Moody Endowment Grant,2014-07.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH)are a growing health burden across a significant portion of the global patient population.However,these conditions seem to have disparate rates and outcomes between different ethnic populations.The combination of MASLD/MASH and type 2 diabetes increases the risk of hepatocellular carcinoma(HCC),and Hispanic patients experience the greatest burden,particularly those in South Texas.AIM To compare outcomes between Hispanic and non-Hispanic patients in the United States,while further focusing on the Hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a function of geographical circumstance or if there is a more widespread reason that all clinicians must account for in prognostic consideration.METHODS This cohort analysis was conducted with data obtained from TriNetX,LLC(“TriNetX”),a global federated health research network that provides access to deidentified medical records from healthcare organizations worldwide.Two cohort networks were used:University of Texas Medical Branch(UTMB)hospital and the United States national database collective to determine whether disparities were related to geographic regions,like Southeast Texas.RESULTS This study findings revealed Hispanics/Latinos have a statistically significant higher occurrence of HCC,type 2 diabetes mellitus,and liver fibrosis/cirrhosis in both the United States and the UTMB Hispanic/Latino groups.Allcause mortality in Hispanics/Latinos was lower within the United States group and not statistically elevated in the UTMB cohort.CONCLUSION This would appear to support that Hispanic patients in Southeast Texas are not uniquely affected compared to the national Hispanic population.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide,paralleling the rising pandemic of obesity and type 2 diabetes.Due to the growing global health burden and com-plex pathogenesis of MASLD,a multifaceted and innovative therapeutic approach is needed.Incretin receptor agonists,which were initially developed for diabetes management,have emerged as promising candidates for MASLD treatment.This review describes the pathophysiological mechanisms and action sites of three major classes of incretin/glucagon receptor agonists:glucagon-like peptide-1 receptor agonists,glucose-dependent insulinotropic polypeptide receptor agonists,and glucagon receptor agonists.Incretins and glucagon directly or indirectly impact various organs,including the liver,brain,pancreas,gastro-intestinal tract,and adipose tissue.Thus,these agents significantly improve glycemic control and weight management and mitigate MASLD pathogenesis.Importantly,this study provides a summary of clinical trials analyzing the effect-iveness and safety of incretin receptor agonists in MASLD management and provides an in-depth analysis highlighting their beneficial effects on improving liver function,hepatic steatosis,and intrahepatic inflammation.There are emerging challenges associated with the use of these medications in the real world,particularly adverse events,drug-drug interactions,and barriers to access,which are discussed in detail.Additionally,this review highlights the evolving role of incretin receptor agonists in MASLD management and suggests future research directions.
文摘BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in adults.This condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase worldwide.Lean patients account for approximately 10%-15%of the MASLD population.However,the pathogenesis is complex and is not well understood.AIM To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new criteria.METHODS We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD patients.We include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.RESULTS We include 85 studies in our analysis.Our findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic response.Common risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean patients.Regarding non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients.Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser extent.However,lean NAFLD patients exhibited a worse prognosis compared to the obese
基金supported by the SERB(CRC/2022/002149)Wellcome Trust/DBT India Alliance Fellowship[IA/I/16/2/502691].
文摘The onset of metabolic dysfunction-associated steatohepatitis(MASH)or non-alcoholic steatohepatitis(NASH)represents a tipping point leading to liver injury and subsequent hepatic complications in the natural progression of what is now termed metabolic dysfunction-associated steatotic liver diseases(MASLD),formerly known as non-alcoholic fatty liver disease(NAFLD).With no pharmacological treat-ment currently available for MASH/NASH,the race is on to develop drugs targeting multiple facets of hepatic metabolism,inflammation,and pro-fibrotic events,which are major drivers of MASH.Nuclear receptors(NRs)regulate genomic transcription upon binding to lipophilic ligands and govern multiple aspects of liver metabolism and inflammation.Ligands of NRs may include hormones,lipids,bile acids,and synthetic ligands,which upon binding to NRs regulate the transcriptional activities of target genes.NR ligands are presently the most promising drug candidates expected to receive approval from the United States Food and Drug Administration as a pharmacological treatment for MASH.This review aims to cover the current understanding of NRs,including nuclear hormone receptors,non-steroid hormone receptors,circadian NRs,and orphan NRs,which are currently undergoing clinical trials for MASH treatment,along with NRs that have shown promising results in preclinical studies.
文摘With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.
文摘BACKGROUND There is limited evidence regarding the association between muscle strength and metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the association between muscle strength and MAFLD in the general population in Korea.METHODS This nationwide representative cross-sectional study included 31649 individuals aged≥19 years who participated in the Korea National Health and Nutrition Examination Survey between 2015 and 2018.Odds ratios(ORs)and 95%confidence intervals(95%CIs)for MAFLD according to sex-specific quartiles of muscle strength,defined by relative handgrip strength,were calculated using multivariable logistic regression analysis.Additionally,multivariable logistic regression analysis was used to assess the association between muscle strength and probable liver fibrosis in patients with MAFLD.RESULTS Of all the participants,29.3%had MAFLD.The prevalence of MAFLD was significantly higher in the lower muscle strength quartile groups for all participants,sexes,and age groups(P<0.001).A 1.92-fold(OR=1.92,95%CI:1.70–2.16)and 3.12-fold(OR=3.12,95%CI:2.64–3.69)higher risk of MAFLD was observed in the lowest quartile(Q1)group than in the other groups(Q2–Q4)and the highest quartile(Q4)group,respectively.The ORs of MAFLD were significantly increased in the lower muscle strength quartile groups in a dose-dependent manner(P for trend<0.001).These associations persisted in both sexes.An inverse association between muscle strength and the risk of MAFLD was observed in all subgroups according to age,obesity,and diabetes mellitus.In patients with MAFLD,the odds of severe liver fibrosis were higher in Q1(OR=1.83,95%CI:1.25–2.69)than in other groups(Q2–Q4).CONCLUSION Among Korean adults,low muscle strength was associated with an increased risk of MAFLD and liver fibrosis in patients with MAFLD.
基金Supported by PIP-CONICET 2021-2023 grant,No.11220200100875COPICT-2020-Serie,No.A-00788and“Florencio Fiorini Foundation”grants.
文摘Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.
基金Supported by University of Edinburgh Hepatology Laboratory Internal Fundingthe Liver Endowment Funds of the Edinburgh&Lothian Health Foundation.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 pa
基金supported by the National Natural Science Foundation of China(No.82130022,31925021)the National Key Research and Development Program of China(No.2018YFA0800700 and 2022YFC3401500).
文摘Bile acids(BAs)play important roles in the digestion of dietary fats and molecular signal transduction,and modulation of the BA composition usually affects the progression of metabolic diseases.While the liver produces primary BAs,the gut microbiota modifies these products into various forms that greatly increase their diversity and biological functions.Mechanistically,BAs can regulate their own metabolism and transport as well as other key aspects of metabolic processes via dedicated BA receptors.Disruption of BA transport and homeostasis leads to the progression of liver diseases,including metabolic dysfunction-associated steatotic liver disease(MASLD)and hepatocellular carcinoma(HCC).Here,we summarize the microbial transformations of BAs and their downstream signaling in the development of metabolic diseases and present new insights into novel therapeutic strategies targeting BA pathways that may contribute to these diseases.
文摘The newly released nomenclature of metabolic dysfunction-associated steatotic liver disease(MASLD)in the 2023 European Association for the Study of the Liver Congress has raised great clinical concerns.This marks the second instance of significant renaming of non-alcoholic fatty liver disease since the introduction of metabolic dysfunction-associated fatty liver disease(MAFLD)in 2020.The nomenclature and definitions of MASLD and MAFLD exhibit significant disparities as well as substantial consensus.The disparities regarding the framework of nomenclature,the definitions,the clinical management,and the impact on the clinical outcomes between MASLD and MAFLD were comprehensively compared in this editorial.Additionally,the consensus reached by the MASLD and MAFLD definitions also emphasizes positive diagnosis rather than negative diagnosis within the framework of establishing a diagnostic approach.Furthermore,they acknowledged the pivotal role of metabolic dysfunction in the pathogenesis of MAFLD or MASLD and the positive role of increasing the awareness of the disease in public.Fortunately,the non-invasive tests remains effective in the MASLD and MAFLD era.Elucidating these disparities would contribute to a more comprehensive comprehension of the nature of steatotic liver disease and enhance clinical practice.Thus,more efforts are required to reach more consensus about these important topics.
文摘Liver transplantation(LT)for metabolic dysfunction-associated steatotic liver disease(MASLD)is increasing globally due to rising rates of obesity and metabolic syndrome,posing significant challenges.MASLD patients typically present with advanced age,higher body mass index(BMI),and metabolic com-orbidities such as diabetes,hypertension,and dyslipidemia.Comprehensive pre-transplant evaluations are crucial for assessing surgical risks and preparing patients for transplantation.MASLD patients with higher BMI may experience longer operative times,potentially affecting intraoperative outcomes.In the months following LT,MASLD recipients face persistent challenges,including a higher incidence of metabolic syndrome and cardiovascular events compared to non-MASLD recipients.However,survival rates at 1-,3-,and 5-years post-LT do not markedly differ from other etiologies,indicating comparable surgical outcomes.Optimizing outcomes in MASLD patients undergoing LT demands a multidisciplinary approach from pre-transplant assessment to post-transplant care.Strategies must address metabolic comorbidities,manage cardiovascular health,and monitor steatosis recurrence,which can be exacerbated by obesity and diabetes.This approach aims to mitigate long-term graft complications and mortality risks,ultimately enhancing transplant success and patient well-being.Continued research is essential to refine these approaches and meet the evolving challenges posed by MASLD as a leading indication for LT worldwide.
