The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease...The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and sarcopenia.Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies.Sarcopenia can be either part of the disease process that results in MAFLD(e.g.,obesity or adiposity)or a consequence of MAFLD,especially in the advanced stages such as fibrosis and cirrhosis.Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors.Therefore,it is crucial to thoroughly understand how we deal with these diseases,especially when they coexist.We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.展开更多
Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment ...Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment options and improve patient outcomes.This article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease(ALD),as reported by Koizumi et al in the World Journal of Gastroenterology.We summarize the impact and mechanisms of Elafibranor on ALD,metabolic-associated fatty liver disease,and cholestatic liver disease based on current research.We also explore its potential as a dual agonist of PPARα/δ,which is undergoing Phase III clinical trials for metabolic-associated steatohepatitis.Our goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application.展开更多
Non-alcoholic fatty liver disease(NAFLD)was the term first used to describe hepatic steatosis in patients with the metabolic syndrome who did not consume excess amounts of alcohol.Alcoholic liver disease(ALD)has many ...Non-alcoholic fatty liver disease(NAFLD)was the term first used to describe hepatic steatosis in patients with the metabolic syndrome who did not consume excess amounts of alcohol.Alcoholic liver disease(ALD)has many similarities to NAFLD in both pathogenesis and histology.This entity is now the most prevalent chronic liver disease worldwide as a consequence of the epidemic of obesity.Attempts to incorporate the importance of the metabolic syndrome in the development of steatosis resulted in the renaming of NAFLD as metabolic-associated fatty liver disease.This new term,however,has the disadvantage of the use of terms that may be perceived as derogatory.The terms fatty and non-alcoholic have negative connotations in many cultures.In addition,non-alcoholic is not usually a term applicable to pediatric cases of hepatic steatosis.Recently,an international collaborative effort,with participants from 56 countries,after a global consultation process,recommended to change the nomenclature to steatotic liver disease-including metabolic dysfunction-associated steatotic liver disease,metabolic-associated steatohepatitis and metabolic dysfunction-associated ALD.The new terminology is consistent with most of the previously published epidemiological studies and will have a major impact on research into diagnosis,prognosis and treatment.展开更多
BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious charac-teristics.Approximately 50%of the patients have a no...BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious charac-teristics.Approximately 50%of the patients have a normal weight or are not obese.They are said to have lean-type MAFLD,and few studies of such patients are available.Because MAFLD is associated with abnormal lipid metabolism,lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis.MAFLD and analyze metabolic pathways.UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid(PA),oleic acid(OA),linoleic acid(LA),and arachidonic acid(AA)levels in lean-type MAFLD patients.RESULTS Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals(P<0.05).Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy indi-viduals(P<0.01).The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals(P<0.05)and the expression of triglycerides and fasting blood glucose were increased(P<0.01).A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P<0.05 and variable importance in projection>1.The levels of PA,OA,LA,and AA were significantly increased compared with healthy individuals.CONCLUSION The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly,yielding 65 identified biomarkers.PA,OA,LA,and AA exhibited the most significant changes,offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.展开更多
Objective Ferritin,initially acting as an iron-storage protein,was found to be associated with metabolic diseases.Our study was designed to investigate the association between serum ferritin and metabolic-associated f...Objective Ferritin,initially acting as an iron-storage protein,was found to be associated with metabolic diseases.Our study was designed to investigate the association between serum ferritin and metabolic-associated fatty liver disease(MAFLD)using data from the National Health and Nutrition Examination Survey(NHANES)of the United State of America.Methods A cross-sectional study was conducted,enrolling a total of 2145 participants from the NHANES in the 2017–2018 cycles.Hepatic steatosis and liver fibrosis were assessed by ultrasound images and several non-invasive indexes.Multiple regression analysis was conducted to determine the associations between serum ferritin concentration and MAFLD and liver fibrosis.Results The analysis revealed that participants with higher serum ferritin levels(Q3 and Q4 groups)had a higher prevalence of MAFLD than those with the lowest serum ferritin levels[Q3 vs.Q1:OR=2.17(1.33,3.53),P<0.05 in fatty liver index(FLI);Q4 vs.Q1:OR=3.13(1.91,5.13),P<0.05 in FLI].Additionally,participants with the highest serum ferritin levels(Q4 group)displayed a higher prevalence of liver fibrosis[Q4 vs.Q1:OR=2.59(1.19,5.62),P<0.05 in liver stiffness measurement;OR=5.06(1.12,22.94),P<0.05 in fibrosis-4 index],with significantly increased risk observed in participants with concomitant diabetes[OR=7.45(1.55,35.72),P=0.012].Conclusion Our study revealed that elevated serum ferritin levels are associated with a higher prevalence of MAFLD and advanced liver fibrosis in patients.Elevated serum ferritin levels combined with diabetes are important risk factors for liver fibrosis.展开更多
BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unkno...BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.展开更多
The metabolic syndrome as a consequence of the obesity pandemic resulted in a substantial increase in the prevalence of metabolic-associated fatty live disease(MAFLD)and type 2 diabetes mellitus(T2DM).Because of the s...The metabolic syndrome as a consequence of the obesity pandemic resulted in a substantial increase in the prevalence of metabolic-associated fatty live disease(MAFLD)and type 2 diabetes mellitus(T2DM).Because of the similarity in pathobiology shared between T2DM and MAFLD,both disorders coexist in many patients and may potentiate the disease-related outcomes with rapid progression and increased complications of the individual diseases.In fact,awareness about this coexistence and the risk of complications are often overlooked by both hepatologists and diabetologists.Management of these individual disorders in a patient should be addressed wholistically using an appropriate multidisciplinary team approach involving both the specialists and,when necessary,liaising with dieticians and surgeons.This comprehensive review is to compile the current evidence from a diabetologist's perspective on MAFLD and T2DM and to suggest optimal management strategies.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD)are on the rise like any other liver disease,and tend to affect 25%of the United States population.The impact of NA...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD)are on the rise like any other liver disease,and tend to affect 25%of the United States population.The impact of NAFLD and MAFLD on patients with coronavirus disease 2019(COVID-19)remains unclear.AIM To identify the association of NAFLD and MAFLD with mortality,hospitalization,hospital length of stay,and supplemental oxygen utilization in COVID-19 patients.METHODS A systematic review of literature on Cochrane,Embase,PubMed,ScienceDirect,and Web of Science databases was conducted from January 2019 to July 2022.Studies that evaluated NAFLD/MAFLD using laboratory methods,noninvasive imaging,or liver biopsy were included.The study protocol was registered in PROSPERO(ID CRD42022313259)and PRISMA guidelines were followed.The National Institutes of Health quality assessment tool was used to assess the quality of the studies.Pooled analysis was conducted using software Rev Man version 5.3.The stability of the results was assessed using sensitivity analysis.RESULTS Thirty-two studies with 43388 patients were included in the meta-analysis of whom 8538(20%)patients were observed to have NAFLD.There were 42254 patients from 28 studies included in the mortality analysis.A total of 2008 patients died from COVID-19;837(10.52%)in the NAFLD group and 1171(3.41%)in the non-NAFLD group.The odds ratio(OR)was 1.38 for mortality with a 95%confidence interval(95%CI)=0.97-1.95 and P=0.07.A total of 5043 patients from eight studies were included in the hospital length of stay analysis.There were 1318 patients in the NAFLD group and 3725 patients in the non-NAFLD group.A qualitative synthesis showed that the mean difference in hospital length of stay was about 2 d between the NAFLD and non-NAFLD groups with a 95%CI=0.71-3.27 and P=0.002.For hospitalization rates,the OR was 3.25 with a 95%CI of 1.73-6.10 and P=0.0002.For supplemental oxygen utilization,the OR was 2.04 with a 95%CI of 1.17-3.53 and P=0.01.CONCLUSION Our meta-analysis suggests that there are increased odds of hospitalization,longer hospital length of stay,and increased use of supplemental oxygen in NAFLD/MAFLD patients.展开更多
An international panel recently proposed an update to the terminology and diagnostic criteria for fatty liver disease.The experts proposed a change in the nomenclature from non-alcoholic fatty liver disease(NAFLD)to m...An international panel recently proposed an update to the terminology and diagnostic criteria for fatty liver disease.The experts proposed a change in the nomenclature from non-alcoholic fatty liver disease(NAFLD)to metabolic(dysfunction)-associated fatty liver disease(MAFLD).This single-letter change,we believe,heralds the dawn of a new era in clinical practice and in clinical and basic research as well.The new nomenclature with the easily applicable approach has stimulated the enthusiasm of the researchers worldwide,resulting in a large number of publications over the past two years.Several recent studies have provided tremendous evidence of the superiority of the MAFLD criteria over the NAFLD criteria.Many studies in different geographic areas of the world including the United States,Europe,and Asia on a large number of patients proved that the utility of MAFLD criteria was higher than that of the NAFLD criteria in different aspects of fatty liver diseases.Consequently,many societies,physician and nurse groups,health stakeholders,representatives of regulatory sciences,and others endorsed the new nomenclature.Here we highlight the endorsement of the new name by different societies and groups and the outcome of different studies on the new nomenclature in addition to a short discussion of the debate by some experts.展开更多
Metabolic-associated fatty liver disease(MAFLD)is one of the most common chronic liver diseases worldwide.In recent years,the occurrence rate of MAFLD has been on the rise,mainly due to lifestyle changes,high-calorie ...Metabolic-associated fatty liver disease(MAFLD)is one of the most common chronic liver diseases worldwide.In recent years,the occurrence rate of MAFLD has been on the rise,mainly due to lifestyle changes,high-calorie diets,and imbalanced dietary structures,thereby posing a threat to human health and creating heavy social and economic burdens.With the development of 16S sequencing and integrated multi-omics analysis,the role of the gut microbiota(GM)and its metabolites in MAFLD has been further recognized.The GM plays a role in digestion,energy metabolism,vitamin synthesis,the prevention of pathogenic bacteria colonisation,and immunoregulation.The gut-liver axis is one of the vital links between the GM and the liver.Toxic substances in the intestine can enter the liver through the portal vascular system when the intestinal barrier is severely damaged.The liver also influences the GM in various ways,such as bile acid circulation.The gut-liver axis is essential in maintaining the body’s normal physiological state and plays a role in the onset and prognosis of many diseases,including MAFLD.This article reviews the status of the GM and MAFLD and summarizes the GM characteristics in MAFLD.The relationship between the GM and MAFLD is discussed in terms of bile acid circulation,energy metabolism,micronutrients,and signalling pathways.Current MAFLD treat ments targeting the GM are also listed.展开更多
Objective:To classify the subtypes of metabolic-associated fatty liver disease(MAFLD)and provide new insights into the heterogeneity of MAFLD.Methods:Electronic medical records(EMR)of MAFLD diagnosed in accordance wit...Objective:To classify the subtypes of metabolic-associated fatty liver disease(MAFLD)and provide new insights into the heterogeneity of MAFLD.Methods:Electronic medical records(EMR)of MAFLD diagnosed in accordance with the diagnostic criteria of Hubei Provincial Hospital of Traditional Chinese Medicine from 2016-2020 were included in the study.for physical annotation,and the data on each clinical phenotype was normalized according to corresponding aspirational standards.The MAFLD heterogeneous medical record network(HEMnet)was constructed using sex,age,disease diagnosis,symptoms,and Western medicine prescriptions as nodes and the co-occurrence times between phenotypes as edges.K-means clustering was used for disease classification.Relative risk(RR)was used to assess the specificity of each phenotype.Statistical methods were used to compare differences in laboratory indicators among subtypes.Results:A total of patients(12,626)with a mean age of 55.02(±14.21)years were included in the study.MAFLD can be divided into five subtypes:digestive diseases(C0),mental disorders and gynecological diseases(C1),chronic liver diseases and decompensated complications(C2),diabetes mellitus and its complications(C3),and immune joint system diseases(C4).Conclusions:Patients with MAFLD experience various symptoms and complications.The classification of MAFLD based on the HEMnet method is highly reliable.展开更多
BACKGROUND Exosomes play an important role in metabolic-associated fatty liver disease(MAFLD),but the mechanism by which exosomes participate in MAFLD still remain unclear.AIM To figure out the function of lipotoxic e...BACKGROUND Exosomes play an important role in metabolic-associated fatty liver disease(MAFLD),but the mechanism by which exosomes participate in MAFLD still remain unclear.AIM To figure out the function of lipotoxic exosomal miR-1297 in MAFLD.METHODS MicroRNA sequencing was used to detect differentially expressed miRNAs(DEmiR)in lipotoxic exosomes derived from primary hepatocytes.Bioinformatic tools were applied to analyze the target genes and pathways regulated by the DE-miRs.Quantitative real-time PCR(qPCR)was conducted for the verification of DEmiRs.qPCR,western blot,immunofluorescence staining and ethynyl-20-deoxyuridine assay were used to evaluate the function of lipotoxic exosomal miR-1297 on hepatic stellate cells(LX2 cells).A luciferase reporter experiment was performed to confirm the relationship of miR-1297 and its target gene PTEN.RESULTS MicroRNA sequencing revealed that there were 61 exosomal DE-miRs(P<0.05)with a fold-change>2 from palmitic acid treated primary hepatocytes compared with the vehicle control group.miR-1297 was the most highly upregulated according to the microRNA sequencing.Bioinformatic tools showed a variety of target genes and pathways regulated by these DE-miRs were related to liver fibrosis.miR-1297 was overexpressed in exosomes derived from lipotoxic hepatocytes by qPCR.Fibrosis promoting genes(α-SMA,PCNA)were altered in LX2 cells after miR-1297 overexpression or miR-1297-rich lipotoxic exosome incubation via qPCR and western blot analysis.Immunofluorescence staining and ethynyl-20-deoxyuridine staining demonstrated that the activation and proliferation of LX2 cells were also promoted after the above treatment.PTEN was found to be the target gene of miR-1297 and knocking down PTEN contributed to the activation and proliferation of LX2 cells via modulating the PI3K/AKT signaling pathway.CONCLUSION miR-1297 was overexpressed in exosomes derived from lipotoxic hepatocytes.The lipotoxic hepatocyte-derived exosomal miR-1297 could promote the activation and proliferation of hepatic stellate cells through the PTEN/PI3K/AKT signaling pathway,accelerating the progression of MAFLD.展开更多
BACKGROUND Looking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring.There are still plenty of unresolved issues related to the actual role of hematological indices ...BACKGROUND Looking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring.There are still plenty of unresolved issues related to the actual role of hematological indices as potential markers of liver function.AIM To study red blood cell distribution width(RDW),RDW-to-platelet ratio(RPR)and RDW-to-lymphocyte ratio(RLR) in alcohol-related liver cirrhosis(ALC) and metabolic-associated fatty liver disease(MAFLD).METHODS The study group was composed of 302 people:142 patients with ALC and 92 with MAFLD;68 persons were included as controls.RDW,RPR and RLR were measured in each person.Indirect and direct parameters of liver fibrosis were also assessed [aspartate transaminase to alkaline transaminase ratio,aspartate transaminase to platelet ratio index(APRI),fibrosis-4(FIB-4),gamma-glutamyl transpeptidase to platelet ratio(GPR),procollagen I carboxyterminal propeptide,procollagen Ⅲ aminoterminal propeptide,transforming growth factor-α,plateletderived growth factor AB,laminin].MELD score in ALC patients and nonalcoholic fatty liver disease(NAFLD) fibrosis score together with BARD score were obtained in the MAFLD group.The achieved results were compared to controls.Then a correlation between assessed markers was done.Diagnostic value of each investigated parameter and its suggested cut-off in the research group RESULTS RDW,RPR and RLR values turned out to be significantly higher in ALC and MAFLD groups compared to controls(ALC:P<0.0001;NAFLD:P<0.05,P<0.0001 and P<0.0001,respectively).RPR correlated positively with MELD score(P<0.01) and indirect indices of liver fibrosis(FIB-4 and GPR;P<0.0001) in ALC patients;negative correlations were found between PDGF-AB and both:RDW and RPR(P<0.01 and P<0.0001,respectively).RPR correlated positively with NAFLD fibrosis score and APRI(P<0.0001) in the MAFLD group;a positive relationship was observed between RDW and FIB-4,too(P<0.05).AUC values and suggested cut-offs for RDW,RPR and RLR in ALC patients were:0.912(>14.2%),0.965(>0.075) and 0.914(>8.684),respectively.AUC values and suggested cut-offs for RDW,RPR and RLR in MAFLD patients were:0.606(>12.8%),0.724(>0.047) and 0.691(>6.25),respectively.CONCLUSION RDW with its derivatives appear to be valuable diagnostic markers in patients with ALC.They can also be associated with a deterioration of liver function in this group.展开更多
BACKGROUND Early identification of metabolic-associated fatty liver disease(MAFLD)is urgent.Atherogenic index of plasma(AIP)is a reference predictor of obesity-related diseases,but its predictive value for MAFLD remai...BACKGROUND Early identification of metabolic-associated fatty liver disease(MAFLD)is urgent.Atherogenic index of plasma(AIP)is a reference predictor of obesity-related diseases,but its predictive value for MAFLD remains unclear.No studies have reported whether its combination with waist circumference(WC)and body mass index(BMI)can improve the predictive performance for MAFLD.AIM To systematically explore the relationship between AIP and MAFLD and evaluate its predictive value for MAFLD and to pioneer a novel noninvasive predictive model combining AIP,WC,and BMI while validating its predictive performance for MAFLD.METHODS This cross-sectional study consecutively enrolled 864 participants.Multivariate logistic regression analysis and receiver operating characteristic curve were used to evaluate the relationship between AIP and MAFLD and its predictive power for MAFLD.The novel prediction model A-W-B combining AIP,WC,and BMI to predict MAFLD was established,and internal verification was completed by magnetic resonance imaging diagnosis.RESULTS Subjects with higher AIP exhibited a significantly increased risk of MAFLD,with an odds ratio of 12.420(6.008-25.675)for AIP after adjusting for various confounding factors.The area under receiver operating characteristic curve of the A-W-B model was 0.833(0.807-0.858),which was significantly higher than that of AIP,WC,and BMI(all P<0.05).Subgroup analysis illustrated that the A-W-B model had significantly higher area under receiver operating characteristic curves in female,young and nonobese subgroups(all P<0.05).The best cutoff values for the A-W-B model to predict MAFLD in males and females were 0.5932 and 0.4105,respectively.Additionally,in the validation set,the area under receiver operating characteristic curve of the A-W-B model to predict MAFLD was 0.862(0.791-0.916).The A-W-B level was strongly and positively associated with the liver proton density fat fraction(r=0.630,P<0.001)and significantly increased with the severity of MAFLD(P<0.05).CONCLUSION AIP was strongly and positively associated with the risk of MAFLD and can be a reference predictor for MAFLD.The novel prediction model A-W-B combining AIP,WC,and BMI can significantly improve the predictive ability of MAFLD and provide better services for clinical prediction and screening of MAFLD.展开更多
BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is the commonest cause of abnormal liver function tests(LFTs).Current upper normal of limit(UNL)of LFTs was derived from a“healthy”population,where undiagnos...BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is the commonest cause of abnormal liver function tests(LFTs).Current upper normal of limit(UNL)of LFTs was derived from a“healthy”population,where undiagnosed MAFLD and viral hepatitis might be suspected.AIM To evaluated potential implications of changes in UNL of alanine aminotransferase(ALT)in MAFLD.METHODS We retrospectively assessed consecutive first referrals with a diagnosis of MAFLD from 2010 to 2017.The conventional UNL of ALT was 45 IU/L for men and 34 IU/L for women,while a low UNL of ALT was 30 IU/L for men and 19 IU/L for women.The UNL of aspartate aminotransferase(AST)was 40 IU/L.RESULTS Total 436 patients were enrolled;of these,288 underwent liver biopsy.Setting a lower UNL reduced the percentage of those with significant disease despite normal ALT;specifically,patients with advanced fibrosis(F≥F3)or definite“metabolic-associated steato-hepatitis(MASH)”(NAS≥5)within normal ALT decreased from 10%to 1%and from 28%to 4%respectively.However,the proportion of those with elevated ALT and no evidence of advanced fibrosis or“definite MASH”increased from 39%to 47%and from 3%to 19%.Overall,LFTs performed poorly in distinguishing“definite MASH”from simple steatosis(receiver operating characteristic areas under the curves 0.59 for ALT and 0.55 for AST).CONCLUSION Liver function tests might both under-and overestimate MASH-related liver disease.Reducing the UNL might not be beneficial and imply an increase in healthcare burden.Risk stratification in MAFLD should rely on a combination of risk factors,not on LFTs alone.展开更多
Metabolisc-associated fatty liver disease(MAFLD)is a multi-system disease in which cardiovascular disease plays an important role and is considered the main cause of death.Notably,cardiovascular disease events in youn...Metabolisc-associated fatty liver disease(MAFLD)is a multi-system disease in which cardiovascular disease plays an important role and is considered the main cause of death.Notably,cardiovascular disease events in young patients with MAFLD have attracted extensive attention.This article reviews the research progress on the correlation between MAFLD and cardiovascular disease.展开更多
Metabolic-associated fatty liver disease(MAFLD)is a positive diagnostic criterion and metabolic dysfunction is listed as an important cause of hepatic liver disease.MAFLD is a liver manifestation of metabolic syndrome...Metabolic-associated fatty liver disease(MAFLD)is a positive diagnostic criterion and metabolic dysfunction is listed as an important cause of hepatic liver disease.MAFLD is a liver manifestation of metabolic syndrome and a key driver of metabolic syndrome.Glucose and lipid metabolism are disordered in MAFLD,which leads to extrahepatic complications through cytokines,genetic variation,visceral fat accumulation,dietary intake,and complex intestinal microbiome.Extensive clinical evidence suggests that MAFLD is independently associated with various metabolic diseases.With its renaming,the epidemiology,pathogenesis,and treatment of MAFLD and metabolic-related diseases need to be reassessed and studied to lay out a foundation for effective prevention and treatment strategies in the future.展开更多
Liver steatosis(i.e.,excessive triglyceride accumulation within the hepatocyte)is a very common finding in both the adult and pediatric populations.In the latter,epidemiologic data using validated diagnostic technique...Liver steatosis(i.e.,excessive triglyceride accumulation within the hepatocyte)is a very common finding in both the adult and pediatric populations.In the latter,epidemiologic data using validated diagnostic techniques(either liver biopsy or ultrasound-based technologies)have shown an alarmingly high prevalence,paralleling the ever-increasing rates of overweight and obesity.展开更多
The gut microbiome plays a key role in the health-disease balance in the human body.Although its composition is unique for each person and tends to remain stable throughout lifetime,it has been shown that certain bact...The gut microbiome plays a key role in the health-disease balance in the human body.Although its composition is unique for each person and tends to remain stable throughout lifetime,it has been shown that certain bacterial patterns may be determining factors in the onset of certain chronic metabolic diseases,such as type 2 diabetes mellitus(T2DM),obesity,metabolic-associated fatty liver disease(MAFLD),and metabolic syndrome.The gut-liver axis embodies the close relationship between the gut and the liver;disturbance of the normal gut microbiota,also known as dysbiosis,may lead to a cascade of mechanisms that modify the epithelial properties and facilitate bacterial translocation.Regulation of gut microbiota is fundamental to maintaining gut integrity,as well as the bile acids composition.In the present review,we summarize the current knowledge regarding the microbiota,bile acids composition and their association with MAFLD,obesity,T2DM and metabolic syndrome.展开更多
Background and Aims:Metabolic-associated fatty liver disease(MAFLD)is a newly proposed terminology from 2020;yet,the applicability of conventional noninvasive fi-brosis models is still unknown for it.We aimed to evalu...Background and Aims:Metabolic-associated fatty liver disease(MAFLD)is a newly proposed terminology from 2020;yet,the applicability of conventional noninvasive fi-brosis models is still unknown for it.We aimed to evaluate the performance of conventional noninvasive fibrosis scores in MAFLD.Methods:The NHANES 2017-2018 datasets were used to compare the performances of different non-invasive fibrosis scores in MAFLD,including the aspartate aminotransferase(AST)to platelet ratio index(APRI),body mass index(BMI)-AST/alanine aminotransferase(ALT)ratio and diabetes score(BARD),fibrosis-4 index(FIB-4),and NAFLD fibrosis score(NFS).Moreover,Asian patients with biopsy-proven MAFLD were enrolled to further validate the findings.Results:A total of 2,622 participants in the Na-tional Health and Nutrition Examination Survey(NHANES)cohort and 293 patients with MAFLD in the Asian cohort were included.Patients in the Asian cohort had a lower BMI and higher liver enzymes(p<0.001).The area under the receiver operating characteristic curve(AUROC)of NFS was the largest in the NHANES cohort and Asian cohorts(0.679 and 0.699,respectively).The AUROC of NFS was followed by APRI,FIB-4,and BARD in the NHANES cohort(0.616,0.601,and 0.589,respectively).In the Asian cohort,the AUROC of APRI,FIB-4,and BARD for predicting advanced fibrosis were 0.625,0.683,and 0.615,respectively.The performance of FIB-4 was better in the Asian cohort than that in the NHANES cohort.Conclusions:NFS is better for predicting advanced fibrosis in MAFLD.FIB-4 can be an al-ternative choice for MAFLD with high liver enzymes when NFS is unavailable.Novel efficient noninvasive fibrosis scor-ing systems are highly required for patients with MAFLD.展开更多
文摘The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and sarcopenia.Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies.Sarcopenia can be either part of the disease process that results in MAFLD(e.g.,obesity or adiposity)or a consequence of MAFLD,especially in the advanced stages such as fibrosis and cirrhosis.Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors.Therefore,it is crucial to thoroughly understand how we deal with these diseases,especially when they coexist.We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.
文摘Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment options and improve patient outcomes.This article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease(ALD),as reported by Koizumi et al in the World Journal of Gastroenterology.We summarize the impact and mechanisms of Elafibranor on ALD,metabolic-associated fatty liver disease,and cholestatic liver disease based on current research.We also explore its potential as a dual agonist of PPARα/δ,which is undergoing Phase III clinical trials for metabolic-associated steatohepatitis.Our goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application.
文摘Non-alcoholic fatty liver disease(NAFLD)was the term first used to describe hepatic steatosis in patients with the metabolic syndrome who did not consume excess amounts of alcohol.Alcoholic liver disease(ALD)has many similarities to NAFLD in both pathogenesis and histology.This entity is now the most prevalent chronic liver disease worldwide as a consequence of the epidemic of obesity.Attempts to incorporate the importance of the metabolic syndrome in the development of steatosis resulted in the renaming of NAFLD as metabolic-associated fatty liver disease.This new term,however,has the disadvantage of the use of terms that may be perceived as derogatory.The terms fatty and non-alcoholic have negative connotations in many cultures.In addition,non-alcoholic is not usually a term applicable to pediatric cases of hepatic steatosis.Recently,an international collaborative effort,with participants from 56 countries,after a global consultation process,recommended to change the nomenclature to steatotic liver disease-including metabolic dysfunction-associated steatotic liver disease,metabolic-associated steatohepatitis and metabolic dysfunction-associated ALD.The new terminology is consistent with most of the previously published epidemiological studies and will have a major impact on research into diagnosis,prognosis and treatment.
基金Supported by Shanghai Natural Science Foundation,No.22ZR1455900Shanghai Putuo District Health System Science and Technology Innovation Project Key Project,No.ptkwws202201Shanghai Putuo District Xinglin Excellent Youth Talent Training Program,No.ptxlyq2201.
文摘BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious charac-teristics.Approximately 50%of the patients have a normal weight or are not obese.They are said to have lean-type MAFLD,and few studies of such patients are available.Because MAFLD is associated with abnormal lipid metabolism,lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis.MAFLD and analyze metabolic pathways.UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid(PA),oleic acid(OA),linoleic acid(LA),and arachidonic acid(AA)levels in lean-type MAFLD patients.RESULTS Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals(P<0.05).Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy indi-viduals(P<0.01).The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals(P<0.05)and the expression of triglycerides and fasting blood glucose were increased(P<0.01).A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P<0.05 and variable importance in projection>1.The levels of PA,OA,LA,and AA were significantly increased compared with healthy individuals.CONCLUSION The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly,yielding 65 identified biomarkers.PA,OA,LA,and AA exhibited the most significant changes,offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.
基金supported by grants from the National Natural Science Foundation of China(No.82172983).
文摘Objective Ferritin,initially acting as an iron-storage protein,was found to be associated with metabolic diseases.Our study was designed to investigate the association between serum ferritin and metabolic-associated fatty liver disease(MAFLD)using data from the National Health and Nutrition Examination Survey(NHANES)of the United State of America.Methods A cross-sectional study was conducted,enrolling a total of 2145 participants from the NHANES in the 2017–2018 cycles.Hepatic steatosis and liver fibrosis were assessed by ultrasound images and several non-invasive indexes.Multiple regression analysis was conducted to determine the associations between serum ferritin concentration and MAFLD and liver fibrosis.Results The analysis revealed that participants with higher serum ferritin levels(Q3 and Q4 groups)had a higher prevalence of MAFLD than those with the lowest serum ferritin levels[Q3 vs.Q1:OR=2.17(1.33,3.53),P<0.05 in fatty liver index(FLI);Q4 vs.Q1:OR=3.13(1.91,5.13),P<0.05 in FLI].Additionally,participants with the highest serum ferritin levels(Q4 group)displayed a higher prevalence of liver fibrosis[Q4 vs.Q1:OR=2.59(1.19,5.62),P<0.05 in liver stiffness measurement;OR=5.06(1.12,22.94),P<0.05 in fibrosis-4 index],with significantly increased risk observed in participants with concomitant diabetes[OR=7.45(1.55,35.72),P=0.012].Conclusion Our study revealed that elevated serum ferritin levels are associated with a higher prevalence of MAFLD and advanced liver fibrosis in patients.Elevated serum ferritin levels combined with diabetes are important risk factors for liver fibrosis.
基金Supported by the Faculty of Medicine,Ramathibodi Hospital,Mahidol University。
文摘BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.
文摘The metabolic syndrome as a consequence of the obesity pandemic resulted in a substantial increase in the prevalence of metabolic-associated fatty live disease(MAFLD)and type 2 diabetes mellitus(T2DM).Because of the similarity in pathobiology shared between T2DM and MAFLD,both disorders coexist in many patients and may potentiate the disease-related outcomes with rapid progression and increased complications of the individual diseases.In fact,awareness about this coexistence and the risk of complications are often overlooked by both hepatologists and diabetologists.Management of these individual disorders in a patient should be addressed wholistically using an appropriate multidisciplinary team approach involving both the specialists and,when necessary,liaising with dieticians and surgeons.This comprehensive review is to compile the current evidence from a diabetologist's perspective on MAFLD and T2DM and to suggest optimal management strategies.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD)are on the rise like any other liver disease,and tend to affect 25%of the United States population.The impact of NAFLD and MAFLD on patients with coronavirus disease 2019(COVID-19)remains unclear.AIM To identify the association of NAFLD and MAFLD with mortality,hospitalization,hospital length of stay,and supplemental oxygen utilization in COVID-19 patients.METHODS A systematic review of literature on Cochrane,Embase,PubMed,ScienceDirect,and Web of Science databases was conducted from January 2019 to July 2022.Studies that evaluated NAFLD/MAFLD using laboratory methods,noninvasive imaging,or liver biopsy were included.The study protocol was registered in PROSPERO(ID CRD42022313259)and PRISMA guidelines were followed.The National Institutes of Health quality assessment tool was used to assess the quality of the studies.Pooled analysis was conducted using software Rev Man version 5.3.The stability of the results was assessed using sensitivity analysis.RESULTS Thirty-two studies with 43388 patients were included in the meta-analysis of whom 8538(20%)patients were observed to have NAFLD.There were 42254 patients from 28 studies included in the mortality analysis.A total of 2008 patients died from COVID-19;837(10.52%)in the NAFLD group and 1171(3.41%)in the non-NAFLD group.The odds ratio(OR)was 1.38 for mortality with a 95%confidence interval(95%CI)=0.97-1.95 and P=0.07.A total of 5043 patients from eight studies were included in the hospital length of stay analysis.There were 1318 patients in the NAFLD group and 3725 patients in the non-NAFLD group.A qualitative synthesis showed that the mean difference in hospital length of stay was about 2 d between the NAFLD and non-NAFLD groups with a 95%CI=0.71-3.27 and P=0.002.For hospitalization rates,the OR was 3.25 with a 95%CI of 1.73-6.10 and P=0.0002.For supplemental oxygen utilization,the OR was 2.04 with a 95%CI of 1.17-3.53 and P=0.01.CONCLUSION Our meta-analysis suggests that there are increased odds of hospitalization,longer hospital length of stay,and increased use of supplemental oxygen in NAFLD/MAFLD patients.
文摘An international panel recently proposed an update to the terminology and diagnostic criteria for fatty liver disease.The experts proposed a change in the nomenclature from non-alcoholic fatty liver disease(NAFLD)to metabolic(dysfunction)-associated fatty liver disease(MAFLD).This single-letter change,we believe,heralds the dawn of a new era in clinical practice and in clinical and basic research as well.The new nomenclature with the easily applicable approach has stimulated the enthusiasm of the researchers worldwide,resulting in a large number of publications over the past two years.Several recent studies have provided tremendous evidence of the superiority of the MAFLD criteria over the NAFLD criteria.Many studies in different geographic areas of the world including the United States,Europe,and Asia on a large number of patients proved that the utility of MAFLD criteria was higher than that of the NAFLD criteria in different aspects of fatty liver diseases.Consequently,many societies,physician and nurse groups,health stakeholders,representatives of regulatory sciences,and others endorsed the new nomenclature.Here we highlight the endorsement of the new name by different societies and groups and the outcome of different studies on the new nomenclature in addition to a short discussion of the debate by some experts.
基金Guangzhou Planned Project of Science and Technology,No.2023A04J0612。
文摘Metabolic-associated fatty liver disease(MAFLD)is one of the most common chronic liver diseases worldwide.In recent years,the occurrence rate of MAFLD has been on the rise,mainly due to lifestyle changes,high-calorie diets,and imbalanced dietary structures,thereby posing a threat to human health and creating heavy social and economic burdens.With the development of 16S sequencing and integrated multi-omics analysis,the role of the gut microbiota(GM)and its metabolites in MAFLD has been further recognized.The GM plays a role in digestion,energy metabolism,vitamin synthesis,the prevention of pathogenic bacteria colonisation,and immunoregulation.The gut-liver axis is one of the vital links between the GM and the liver.Toxic substances in the intestine can enter the liver through the portal vascular system when the intestinal barrier is severely damaged.The liver also influences the GM in various ways,such as bile acid circulation.The gut-liver axis is essential in maintaining the body’s normal physiological state and plays a role in the onset and prognosis of many diseases,including MAFLD.This article reviews the status of the GM and MAFLD and summarizes the GM characteristics in MAFLD.The relationship between the GM and MAFLD is discussed in terms of bile acid circulation,energy metabolism,micronutrients,and signalling pathways.Current MAFLD treat ments targeting the GM are also listed.
基金supported by grants from the Key project Natural Science Foundation of Hubei Province(No.2020CFA023)Project of the State Administration of Traditional Chinese Medicine(No Z155080000004):Key Laboratory of Liver and Kidney Treatment of Chronic Liver Diseases.
文摘Objective:To classify the subtypes of metabolic-associated fatty liver disease(MAFLD)and provide new insights into the heterogeneity of MAFLD.Methods:Electronic medical records(EMR)of MAFLD diagnosed in accordance with the diagnostic criteria of Hubei Provincial Hospital of Traditional Chinese Medicine from 2016-2020 were included in the study.for physical annotation,and the data on each clinical phenotype was normalized according to corresponding aspirational standards.The MAFLD heterogeneous medical record network(HEMnet)was constructed using sex,age,disease diagnosis,symptoms,and Western medicine prescriptions as nodes and the co-occurrence times between phenotypes as edges.K-means clustering was used for disease classification.Relative risk(RR)was used to assess the specificity of each phenotype.Statistical methods were used to compare differences in laboratory indicators among subtypes.Results:A total of patients(12,626)with a mean age of 55.02(±14.21)years were included in the study.MAFLD can be divided into five subtypes:digestive diseases(C0),mental disorders and gynecological diseases(C1),chronic liver diseases and decompensated complications(C2),diabetes mellitus and its complications(C3),and immune joint system diseases(C4).Conclusions:Patients with MAFLD experience various symptoms and complications.The classification of MAFLD based on the HEMnet method is highly reliable.
基金The National Natural Science Foundation of China(General Program),No.81770597the Development Program of China during the 13th Five-year Plan Period,No.2017ZX10203202003005.
文摘BACKGROUND Exosomes play an important role in metabolic-associated fatty liver disease(MAFLD),but the mechanism by which exosomes participate in MAFLD still remain unclear.AIM To figure out the function of lipotoxic exosomal miR-1297 in MAFLD.METHODS MicroRNA sequencing was used to detect differentially expressed miRNAs(DEmiR)in lipotoxic exosomes derived from primary hepatocytes.Bioinformatic tools were applied to analyze the target genes and pathways regulated by the DE-miRs.Quantitative real-time PCR(qPCR)was conducted for the verification of DEmiRs.qPCR,western blot,immunofluorescence staining and ethynyl-20-deoxyuridine assay were used to evaluate the function of lipotoxic exosomal miR-1297 on hepatic stellate cells(LX2 cells).A luciferase reporter experiment was performed to confirm the relationship of miR-1297 and its target gene PTEN.RESULTS MicroRNA sequencing revealed that there were 61 exosomal DE-miRs(P<0.05)with a fold-change>2 from palmitic acid treated primary hepatocytes compared with the vehicle control group.miR-1297 was the most highly upregulated according to the microRNA sequencing.Bioinformatic tools showed a variety of target genes and pathways regulated by these DE-miRs were related to liver fibrosis.miR-1297 was overexpressed in exosomes derived from lipotoxic hepatocytes by qPCR.Fibrosis promoting genes(α-SMA,PCNA)were altered in LX2 cells after miR-1297 overexpression or miR-1297-rich lipotoxic exosome incubation via qPCR and western blot analysis.Immunofluorescence staining and ethynyl-20-deoxyuridine staining demonstrated that the activation and proliferation of LX2 cells were also promoted after the above treatment.PTEN was found to be the target gene of miR-1297 and knocking down PTEN contributed to the activation and proliferation of LX2 cells via modulating the PI3K/AKT signaling pathway.CONCLUSION miR-1297 was overexpressed in exosomes derived from lipotoxic hepatocytes.The lipotoxic hepatocyte-derived exosomal miR-1297 could promote the activation and proliferation of hepatic stellate cells through the PTEN/PI3K/AKT signaling pathway,accelerating the progression of MAFLD.
基金The survey was accepted by the local ethics committee of the Medical University of Lublin(No.KE-0254/86/2016).
文摘BACKGROUND Looking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring.There are still plenty of unresolved issues related to the actual role of hematological indices as potential markers of liver function.AIM To study red blood cell distribution width(RDW),RDW-to-platelet ratio(RPR)and RDW-to-lymphocyte ratio(RLR) in alcohol-related liver cirrhosis(ALC) and metabolic-associated fatty liver disease(MAFLD).METHODS The study group was composed of 302 people:142 patients with ALC and 92 with MAFLD;68 persons were included as controls.RDW,RPR and RLR were measured in each person.Indirect and direct parameters of liver fibrosis were also assessed [aspartate transaminase to alkaline transaminase ratio,aspartate transaminase to platelet ratio index(APRI),fibrosis-4(FIB-4),gamma-glutamyl transpeptidase to platelet ratio(GPR),procollagen I carboxyterminal propeptide,procollagen Ⅲ aminoterminal propeptide,transforming growth factor-α,plateletderived growth factor AB,laminin].MELD score in ALC patients and nonalcoholic fatty liver disease(NAFLD) fibrosis score together with BARD score were obtained in the MAFLD group.The achieved results were compared to controls.Then a correlation between assessed markers was done.Diagnostic value of each investigated parameter and its suggested cut-off in the research group RESULTS RDW,RPR and RLR values turned out to be significantly higher in ALC and MAFLD groups compared to controls(ALC:P<0.0001;NAFLD:P<0.05,P<0.0001 and P<0.0001,respectively).RPR correlated positively with MELD score(P<0.01) and indirect indices of liver fibrosis(FIB-4 and GPR;P<0.0001) in ALC patients;negative correlations were found between PDGF-AB and both:RDW and RPR(P<0.01 and P<0.0001,respectively).RPR correlated positively with NAFLD fibrosis score and APRI(P<0.0001) in the MAFLD group;a positive relationship was observed between RDW and FIB-4,too(P<0.05).AUC values and suggested cut-offs for RDW,RPR and RLR in ALC patients were:0.912(>14.2%),0.965(>0.075) and 0.914(>8.684),respectively.AUC values and suggested cut-offs for RDW,RPR and RLR in MAFLD patients were:0.606(>12.8%),0.724(>0.047) and 0.691(>6.25),respectively.CONCLUSION RDW with its derivatives appear to be valuable diagnostic markers in patients with ALC.They can also be associated with a deterioration of liver function in this group.
基金This study was approved by the Clinical Research Ethics Committee of China-Japan Friendship Hospital(2018-110-K79-1).
文摘BACKGROUND Early identification of metabolic-associated fatty liver disease(MAFLD)is urgent.Atherogenic index of plasma(AIP)is a reference predictor of obesity-related diseases,but its predictive value for MAFLD remains unclear.No studies have reported whether its combination with waist circumference(WC)and body mass index(BMI)can improve the predictive performance for MAFLD.AIM To systematically explore the relationship between AIP and MAFLD and evaluate its predictive value for MAFLD and to pioneer a novel noninvasive predictive model combining AIP,WC,and BMI while validating its predictive performance for MAFLD.METHODS This cross-sectional study consecutively enrolled 864 participants.Multivariate logistic regression analysis and receiver operating characteristic curve were used to evaluate the relationship between AIP and MAFLD and its predictive power for MAFLD.The novel prediction model A-W-B combining AIP,WC,and BMI to predict MAFLD was established,and internal verification was completed by magnetic resonance imaging diagnosis.RESULTS Subjects with higher AIP exhibited a significantly increased risk of MAFLD,with an odds ratio of 12.420(6.008-25.675)for AIP after adjusting for various confounding factors.The area under receiver operating characteristic curve of the A-W-B model was 0.833(0.807-0.858),which was significantly higher than that of AIP,WC,and BMI(all P<0.05).Subgroup analysis illustrated that the A-W-B model had significantly higher area under receiver operating characteristic curves in female,young and nonobese subgroups(all P<0.05).The best cutoff values for the A-W-B model to predict MAFLD in males and females were 0.5932 and 0.4105,respectively.Additionally,in the validation set,the area under receiver operating characteristic curve of the A-W-B model to predict MAFLD was 0.862(0.791-0.916).The A-W-B level was strongly and positively associated with the liver proton density fat fraction(r=0.630,P<0.001)and significantly increased with the severity of MAFLD(P<0.05).CONCLUSION AIP was strongly and positively associated with the risk of MAFLD and can be a reference predictor for MAFLD.The novel prediction model A-W-B combining AIP,WC,and BMI can significantly improve the predictive ability of MAFLD and provide better services for clinical prediction and screening of MAFLD.
基金Supported by National Institute of Health Research(NIHR)Biomedical Research Centre based at Imperial College Healthcare
文摘BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is the commonest cause of abnormal liver function tests(LFTs).Current upper normal of limit(UNL)of LFTs was derived from a“healthy”population,where undiagnosed MAFLD and viral hepatitis might be suspected.AIM To evaluated potential implications of changes in UNL of alanine aminotransferase(ALT)in MAFLD.METHODS We retrospectively assessed consecutive first referrals with a diagnosis of MAFLD from 2010 to 2017.The conventional UNL of ALT was 45 IU/L for men and 34 IU/L for women,while a low UNL of ALT was 30 IU/L for men and 19 IU/L for women.The UNL of aspartate aminotransferase(AST)was 40 IU/L.RESULTS Total 436 patients were enrolled;of these,288 underwent liver biopsy.Setting a lower UNL reduced the percentage of those with significant disease despite normal ALT;specifically,patients with advanced fibrosis(F≥F3)or definite“metabolic-associated steato-hepatitis(MASH)”(NAS≥5)within normal ALT decreased from 10%to 1%and from 28%to 4%respectively.However,the proportion of those with elevated ALT and no evidence of advanced fibrosis or“definite MASH”increased from 39%to 47%and from 3%to 19%.Overall,LFTs performed poorly in distinguishing“definite MASH”from simple steatosis(receiver operating characteristic areas under the curves 0.59 for ALT and 0.55 for AST).CONCLUSION Liver function tests might both under-and overestimate MASH-related liver disease.Reducing the UNL might not be beneficial and imply an increase in healthcare burden.Risk stratification in MAFLD should rely on a combination of risk factors,not on LFTs alone.
文摘Metabolisc-associated fatty liver disease(MAFLD)is a multi-system disease in which cardiovascular disease plays an important role and is considered the main cause of death.Notably,cardiovascular disease events in young patients with MAFLD have attracted extensive attention.This article reviews the research progress on the correlation between MAFLD and cardiovascular disease.
文摘Metabolic-associated fatty liver disease(MAFLD)is a positive diagnostic criterion and metabolic dysfunction is listed as an important cause of hepatic liver disease.MAFLD is a liver manifestation of metabolic syndrome and a key driver of metabolic syndrome.Glucose and lipid metabolism are disordered in MAFLD,which leads to extrahepatic complications through cytokines,genetic variation,visceral fat accumulation,dietary intake,and complex intestinal microbiome.Extensive clinical evidence suggests that MAFLD is independently associated with various metabolic diseases.With its renaming,the epidemiology,pathogenesis,and treatment of MAFLD and metabolic-related diseases need to be reassessed and studied to lay out a foundation for effective prevention and treatment strategies in the future.
文摘Liver steatosis(i.e.,excessive triglyceride accumulation within the hepatocyte)is a very common finding in both the adult and pediatric populations.In the latter,epidemiologic data using validated diagnostic techniques(either liver biopsy or ultrasound-based technologies)have shown an alarmingly high prevalence,paralleling the ever-increasing rates of overweight and obesity.
文摘The gut microbiome plays a key role in the health-disease balance in the human body.Although its composition is unique for each person and tends to remain stable throughout lifetime,it has been shown that certain bacterial patterns may be determining factors in the onset of certain chronic metabolic diseases,such as type 2 diabetes mellitus(T2DM),obesity,metabolic-associated fatty liver disease(MAFLD),and metabolic syndrome.The gut-liver axis embodies the close relationship between the gut and the liver;disturbance of the normal gut microbiota,also known as dysbiosis,may lead to a cascade of mechanisms that modify the epithelial properties and facilitate bacterial translocation.Regulation of gut microbiota is fundamental to maintaining gut integrity,as well as the bile acids composition.In the present review,we summarize the current knowledge regarding the microbiota,bile acids composition and their association with MAFLD,obesity,T2DM and metabolic syndrome.
基金This work was supported by the Fujian Province Health Education Joint Project(No.2019-WJ-16)the Fujian Province Health Technology Project(No.2020CXA040).
文摘Background and Aims:Metabolic-associated fatty liver disease(MAFLD)is a newly proposed terminology from 2020;yet,the applicability of conventional noninvasive fi-brosis models is still unknown for it.We aimed to evaluate the performance of conventional noninvasive fibrosis scores in MAFLD.Methods:The NHANES 2017-2018 datasets were used to compare the performances of different non-invasive fibrosis scores in MAFLD,including the aspartate aminotransferase(AST)to platelet ratio index(APRI),body mass index(BMI)-AST/alanine aminotransferase(ALT)ratio and diabetes score(BARD),fibrosis-4 index(FIB-4),and NAFLD fibrosis score(NFS).Moreover,Asian patients with biopsy-proven MAFLD were enrolled to further validate the findings.Results:A total of 2,622 participants in the Na-tional Health and Nutrition Examination Survey(NHANES)cohort and 293 patients with MAFLD in the Asian cohort were included.Patients in the Asian cohort had a lower BMI and higher liver enzymes(p<0.001).The area under the receiver operating characteristic curve(AUROC)of NFS was the largest in the NHANES cohort and Asian cohorts(0.679 and 0.699,respectively).The AUROC of NFS was followed by APRI,FIB-4,and BARD in the NHANES cohort(0.616,0.601,and 0.589,respectively).In the Asian cohort,the AUROC of APRI,FIB-4,and BARD for predicting advanced fibrosis were 0.625,0.683,and 0.615,respectively.The performance of FIB-4 was better in the Asian cohort than that in the NHANES cohort.Conclusions:NFS is better for predicting advanced fibrosis in MAFLD.FIB-4 can be an al-ternative choice for MAFLD with high liver enzymes when NFS is unavailable.Novel efficient noninvasive fibrosis scor-ing systems are highly required for patients with MAFLD.
