Clinic-pathological features of metabolic associated fatty liver disease with hepatitis B virus infection

BACKGROUND Metabolic associated fatty liver disease(MAFLD)is a novel concept proposed in 2020.AIM To compare the characteristics of MAFLD and MAFLD with hepatitis B virus(HBV)infection.METHODS Patients with histopathologically proven MAFLD from a single medical center were included.Patients were divided into MAFLD group(without HBV infection)and HBV-MAFLD group(with HBV infection).Propensity score matching was utilized to balance the baseline characteristics between two groups.RESULTS A total of 417 cases with MAFLD were included,359(86.1%)of whom were infected with HBV.There were significantly more males in the HBV-MAFLD group than in the MAFLD group(P<0.05).After propensity score matching,58 pairs were successfully matched with no significant differences found in gender,age,body mass index,lipid levels,liver enzymes,and the other metabolic associated comorbidities between the two groups(P>0.05).The rank sum test results showed that the degree of liver steatosis in the MAFLD group was more severe than that in the HBV-MAFLD group,while the degree of inflammation and fibrosis in the liver was less severe(P<0.05).In multivariate analysis,HBV infection was associated with significantly lower grade of hepatic steatosis[odds ratio(OR)=0.088,95%confidence interval(CI):0.027-0.291]but higher inflammation level(OR=4.059,95%CI:1.403-11.742)and fibrosis level(OR=3.016,95%CI:1.087-8.370)after adjusting for age,gender,and other metabolic parameters.CONCLUSION HBV infection is associated with similar metabolic risks,lower steatosis grade,higher inflammation,and fibrosis grade in MAFLD patients.

Validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease

BACKGROUND Non-invasive fibrosis scores are not yet validated in the newly defined metabolic associated fatty liver disease(MAFLD).AIM To evaluate the diagnostic performance of four non-invasive scores including aspartate aminotransferase to platelet ratio index(APRI),fibrosis-4 index(FIB-4),body mass index,aspartate aminotransferase/alanine aminotransferase ratio,diabetes score(BARD),and nonalcoholic fatty liver disease fibrosis score(NFS)in patients with MAFLD.METHODS Consecutive patients with histologically confirmed MAFLD were included.The discrimination ability of different non-invasive scores was compared.RESULTS A total of 417 patients were included;156(37.4%)of them had advanced fibrosis(Metavir≥F3).The area under receiver operating characteristic curve of FIB-4,NFS,APRI,and BARD for predicting advanced fibrosis was 0.736,0.724,0.671,and 0.609,respectively.The area under receiver operating characteristic curve of FIB-4 and NFS was similar(P=0.523),while the difference between FIB-4 and APRI(P=0.001)and FIB-4 and BARD(P<0.001)was statistically significant.The best thresholds of FIB-4,NFS,APRI,and BARD for diagnosis of advanced fibrosis in MAFLD were 1.05,-2.1,0.42,and 2.A subgroup analysis showed that FIB-4,APRI,and NFS performed worse in the pure MAFLD group than in the hepatitis B virus-MAFLD group.CONCLUSION APRI and BARD scores do not perform well in MAFLD.The FIB-4 and NFS could be more useful,but a new threshold is needed.Novel non-invasive scoring systems for fibrosis are required for MAFLD.

Metabolic associated fatty liver disease:Addressing a new era in liver transplantation

Metabolic associated fatty liver disease(MAFLD),previously termed nonalcoholic fatty liver disease,is the leading global cause of liver disease and is fast becoming the most common indication for liver transplantation.The recent change in nomenclature to MAFLD refocuses the conceptualisation of this disease entity to its metabolic underpinnings and may help to spur a paradigm shift in the approach to its management,including in the setting of liver transplantation.Patients with MAFLD present significant challenges in the pre-,peri-and posttransplant settings,largely due to the presence of medical comorbidities that include obesity,metabolic syndrome and cardiovascular risk factors.As the community prevalence of MAFLD increases concurrently with the obesity epidemic,donor liver steatosis is also a current and future concern.This review outlines current epidemiology,nomenclature,management issues and outcomes of liver transplantation in patients with MAFLD.

Redefining non-alcoholic fatty liver disease to metabolic associated fatty liver disease: Is this plausible?

Recently,a single letter change has taken the world by storm.A group of experts have developed a consensus to upgrade the term non-alcoholic fatty liver disease(NAFLD)to metabolic associated fatty liver disease(MAFLD),suggesting that MAFLD would more accurately reflect not only the disease pathogenesis but would also help in patient stratification for management with NAFLD.However,the difference of opinion exists,which has made the NAFLD vs MAFLD debate the current talk of the town.This review will focus on the plausibility and implications of redefining NAFLD as MAFLD.

Comments on validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease

To evaluate and predict liver fibrosis in patients with nonalcoholic fatty liver disease(NAFLD),several non-invasive scoring systems were built and widely used in the progress of diagnosis and treatment,which showed great diagnostic efficiency,such as aspartate aminotransferase to platelet ratio index,fibrosis-4 index,body mass index,aspartate aminotransferase to alanine aminotransferase ratio,diabetes score and NAFLD fibrosis score.Since the new concept of metabolic associated fatty liver disease(MAFLD)was proposed,the clinical application value of the non-invasive scoring systems mentioned above has not been assessed in MAFLD.The evaluation of the diagnostic performance of these non-invasive scoring systems will provide references for clinicians in the diagnosis of MAFLD.

Influence of Gut Microbiota and its Metabolites on Progression of Metabolic Associated Fatty Liver Disease

Metabolic associated fatty liver disease(MAFLD)has become a prevalent chronic liver disease worldwide because of lifestyle and dietary changes.Gut microbiota and its metabolites have been shown to play a critical role in the pathogenesis of MAFLD.Understanding of the function of gut microbiota and its metabolites in MAFLD may help to elucidate pathological mechanisms,identify diagnostic markers,and develop drugs or probiotics for the treatment of MAFLD.Here we review the pathogenesis of MAFLD by gut microbiota and its metabolites and discuss the feasibility of treating MAFLD from the perspective of gut microbes.

Construction and validation of a severity prediction model for metabolic associated fatty liver disease

Objective:To analyze the independent risk factors for the occurrence of moderate-to-severe metabolic-associated fatty liver disease(MAFLD),to construct a prediction model for moderate-to-severe MAFLD,and to verify the validity of the model.Methods:In the first part,278 medical examiners who were diagnosed with MAFLD in Medical Examination Center at the Second Affiliated Hospital of Hainan University from January to May 2022 were taken as the study subjects(training set),and they were divided into mild MAFLD group(200)and moderate-severe MAFLD group(78)based on ultrasound results.Demographic data and laboratory indexes were collected,and risk factors were screened by univariate and multifactor analysis.In the second part,a dichotomous logistic regression equation was used to construct a prediction model for moderate-to-severe MAFLD,and the model was visualized in a line graph.In the third part,the MAFLD population(200 people in the external validation set)from our physical examination center from November to December 2022 was collected as the moderate-to-severe MAFLD prediction model,and the risk factors in both groups were compared.The receiver operating characteristic(ROC)curves,calibration curves,and clinical applicability of the model were plotted to represent model discrimination for internal and external validation.Results:The risk factors of moderate-to-severe MAFLD were fasting glucose(FPG),blood uric acid(UA),triglycerides(TG),triglyceride glucose index(TyG),total cholesterol(CHOL),and high-density lipoprotein(HDL-C).UA[OR=1.021,95%CI(1.015,1.027),P<0.001]and FPG[OR=1.575,95%CI(1.158,2.143),P=0.004]were independent risk factors for people with moderate to severe MAFLD.The visualized line graph model showed that UA was the factor contributing more to the risk of moderate to severe MAFLD in this model.The ROC curves showed AUC values of 0.8701,0.8686 and 0.7991 for the training set,internal validation set and external validation set,respectively.The curves almost coincided with the reference line after calibration of the model calibration degree with P>0.05 in Hosmer-Lemeshow test.The decision curve analysis(DCA)plotted by the clinical applicability of the model was higher than the two extreme curves,predicting that patients with moderate to severe MAFLD would benefit from the prediction model.Conclusion:The prediction model constructed by combining FPG with UA has higher accuracy and better clinical applicability,and can be used for clinical diagnosis.

Macrophages in metabolic associated fatty liver disease

Metabolic associated fatty liver disease(MAFLD),formerly named non-alcoholic fatty liver disease is the most common liver disorder in many countries.The inflammatory subtype termed steatohepatitis is a driver of disease progression to cirrhosis,hepatocellular carcinoma,liver transplantation,and death,but also to extrahepatic complications including cardiovascular disease,diabetes and chronic kidney disease.The plasticity of macrophages in response to various environmental cues and the fact that they can orchestrate cross talk between different cellular players during disease development and progression render them an ideal target for drug development.This report reviews recent advances in our understanding of macrophage biology during the entire spectrum of MAFLD including steatosis,inflammation,fibrosis,and hepatocellular carcinoma,as well as for the extra-hepatic manifestations of MAFLD.We discuss the underlying molecular mechanisms of macrophage activation and polarization as well as cross talk with other cell types such as hepatocytes,hepatic stellate cells,and adipose tissue.We conclude with a discussion on the potential translational implications and challenges for macrophage based therapeutics for MAFLD.

Impact renaming non-alcoholic fatty liver disease to metabolic associated fatty liver disease in prevalence,characteristics and risk factors

BACKGROUND Recently,a group of hepatologists proposed to rename non-alcoholic fatty liver disease(NAFLD)as metabolic associated fatty liver disease(MAFLD)with modified diagnostic criteria.It is important to note,however,that there are some differences between the diagnostic criteria used for NAFLD and MAFLD.Since the research on MAFLD is just beginning,however,evidence on its incidence and prevalence in the general population and in speci
c subpopulations remains limited.AIM To assess epidemiology of fatty liver in new definition and compare MAFLD with NAFLD.Exploring risk factors of MAFLD individuals.METHODS This was a retrospective,cross-sectional study.A total of 85242 adults were selected from the Chinese health management database in 2017–2022.The data of general information,laboratory indicators,lifestyle management and psychological status were obtained.MAFLD was diagnosed as ultrasound diagnosis of fatty liver and at least one between these three conditions:Overweight/obesity,type 2 diabetes mellitus(T2DM)or metabolic dysregulation.Metabolic factors were not considered in NAFLD diagnosis standard.The clinical characteristics of MAFLD and NAFLD were analysed using descriptive statistics.Continuous variables normally distributed were expressed as means±SD.Categorical variables were expressed as frequencies and proportions.Binary logistic regression was used to determine risk factors of the MAFLD.RESULTS The prevalence of MAFLD and NAFLD was 40.5%and 31.0%,respectively.The MAFLD or NAFLD population is more likely to be older(M:47.19±10.82 vs 43.43±11.96;N:47.72±11.17 vs 43.71±11.66),male(M:77.21%vs 44.43%;N:67.90%vs 53.12%)and high body mass index(M:26.79±2.69 vs 22.44±2.48;N:26.29±2.84 vs 23.29±3.12)than the non-MAFLD or non-MAFLD population.In multivariate analysis,general information(e.g.,≥2 metabolic abnormalities OR=3.38,(95%CI:2.99-3.81),P<0.001;diastolic blood pressure OR=1.01,(95%CI:1.00–1.01),P=0.002),laboratory results[e.g.,total bilirubin(TBIL)OR=0.98,(95%CI:0.98-0.99),P<0.001;serum uric acid(SUA)OR=1.01,(95%CI:1.01-1.01),P<0.001],and lifestyle factors[e.g.,drink beverage OR=0.32,(95%CI:0.17-0.63),P=0.001]were influence factors for MAFLD.Our study results offer new insight into potential risk factors associated with fatty liver disease,including SUA,TBIL and creatinine,all of which are related to chronic renal disease(CKD).CONCLUSION MAFLD is more prevalent than NAFLD,with two-fifths of individuals meeting the diagnosis criteria.MAFLD and NAFLD populations have different clinical characteristics.CKD may be related with MAFLD.

Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

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.

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease

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.

Effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease:Clinical implications

In this editorial,we comment on the article by Chen et al recently published in 2024.We focus the debate on whether reducing the upper limit of normal of alanine aminotransferase(ALT)would effectively identify cases of fibrosis in metabolic-dysfunction associated fatty liver disease(MAFLD).This is important given the increasing prevalence of MAFLD and obesity globally.Currently,a suitable screening test to identify patients in the general population does not exist and most patients are screened after the finding of an abnormal ALT.The authors of this paper challenge the idea of what a normal ALT is and whether that threshold should be lowered,particularly as their study found that 83.12%of their study population with a diagnosis of MAFLD had a normal ALT.The main advantages of screening would be to identify patients and provide intervention early,the mainstay of this being changing modifiable risk factors and monitoring for liver fibrosis.However,there is not enough suitable therapeutic options available as of yet although this is likely to change in the coming years with more targets for therapy being discovered.Semaglutide is one example of this which has demonstrated benefit with an acceptable side effect profile for those patients with MAFLD and obesity,although studies have not yet shown a significant improvement in fibrosis regression.It would also require a huge amount of resource if a reduced ALT level alone was used as criteria;it is more likely that current scoring systems such as fibrosis-4 may be amended to represent this additional risk.Currently,there is not a good argument to recommend wide-spread screening with a reduced ALT level as this is unlikely to be cost-effective.This is compounded by the fact that there is a significant heterogeneity in what is considered a normal ALT between laboratories.Although studies previously have suggested a more pragmatic approach in screening those over the age of 60,this is likely to change with the increasing incidence of obesity within the younger age groups.The main message from this study is that those who have hypercholesterolemia and high body metabolic index should have these risk factors modified to maintain a lower level of ALT to reduce the risk of progression to fibrosis and cirrhosis.

Exploring non-invasive diagnostics for metabolic dysfunctionassociated fatty liver disease

The population with metabolic dysfunction-associated fatty liver disease(MAFLD)is increasingly common worldwide.Identification of people at risk of progression to advanced stages is necessary to timely offer interventions and appropriate care.Liver biopsy is currently considered the gold standard for the diagnosis and staging of MAFLD,but it has associated risks and limitations.This has spurred the exploration of non-invasive diagnostics for MAFLD,especially for steatohepatitis and fibrosis.These non-invasive approaches mostly include biomarkers and algorithms derived from anthropometric measurements,serum tests,imaging or stool metagenome profiling.However,they still need rigorous and widespread clinical validation for the diagnostic performance.

Screening for metabolic dysfunction-associated fatty liver disease:Time to discard the emperor’s clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

Metabolic dysfunction-associated fatty liver disease and low muscle strength: A comment

The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.

Interplay between metabolic dysfunction-associated fatty liver disease and renal function: An intriguing pediatric perspective

Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.

Alanine aminotransferase as a risk marker for new-onset metabolic dysfunction-associated fatty liver disease

In this editorial,we comment on the article by Chen et al.Metabolic dysfunction-associated fatty liver disease(MAFLD)is a global public health burden whose incidence has risen concurrently with overweight and obesity.Given its detri-mental health impact,early identification of at-risk individuals is crucial.MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy,imaging,or blood biomarkers,and one of the following conditions:Overweight/obesity,type 2 diabetes mellitus,or metabolic dysregulation.However,in large-scale epidemiological studies,liver biopsies are not feasible.The application of techniques such as ultrasonography,computed tomography,magnetic resonance imaging,and magnetic resonance spectroscopy is restricted by their limited sensitivity,low effectiveness,high costs,and need for specialized software.Blood biomarkers offer several advantages,particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical.Analysis of cumulative effects of excess high-normal blood alanine aminotrans-ferase(ALT)levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods.Accordingly,investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring,enabling timely inter-vention and management and improving patient outcomes.

Current remarks and future directions on the interactions between metabolic dysfunction-associated fatty liver disease and COVID-19

During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Several studies highlighted the fact that individuals with MAFLD had higher probability of severe acute respiratory syndrome coronavirus 2 infection and more severe adverse clinical outcomes.One of the proposed mechanisms is the inflammatory response pathway,especially the one involving cytokines,such as interleukin 6,which appeared particularly elevated in those patients and was deemed responsible for additional insult to the already damaged liver.This should increase our vigilance in terms of early detection,close follow up and early treatment for individuals with MAFLD and COVID-19 infection.In the direction of early diagnosis,biomarkers such as cytokeratin-18 and scoring systems such as Fibrosis-4 index score are proposed.COVID-19 is a newly described entity,expected to be of concern for the years to come,and MAFLD is a condition with an ever-increasing impact.Delineating the interaction between these two entities should be brought into the focus of research.Reducing morbidity and mortality of patients with COVID-19 and MAFLD should be the ultimate objective,and the optimal way to achieve this is by designing evidence-based prevention and treatment policies.

Novel insights into autophagy in gastrointestinal pathologies,mechanisms in metabolic dysfunction-associated fatty liver disease and acute liver failure

In this editorial,we comment on three articles published in a recent issue of World Journal of Gastroenterology.There is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains incomplete.Moreover,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further elucidation.Similarly,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly understood.Innovative studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.

Metabolic puzzle: Exploring liver fibrosis differences in Asian metabolic-associated fatty liver disease subtypes

BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is a liver condition marked by excessive fat buildup in the absence of heavy alcohol use.It is primarily linked with metabolic issues like insulin resistance,obesity,and abnormal lipid levels,and is often observed with other conditions such as type 2 diabetes and cardiovascular disease.However,whether the subtypes of MAFLD based on the metabolic disorder differentially impact liver fibrosis is not well explicated,especially in the Asian population.AIM To compare the severity of liver fibrosis among different MAFLD subtypes.METHODS A total of 322 adult patients of either gender with fatty liver on ultrasound were enrolled between January to December 2021.MAFLD was defined as per the Asian Pacific Association for the Study of the Liver guidelines.Fibrosis-4 index(Fib-4)and nonalcoholic fatty liver disease fibrosis score(NFS)were employed to evaluate liver fibrosis.RESULTS The mean age was 44.84±11 years.Seventy-two percent of the patients were female.Two hundred and seventy-three patients were classified as having MAFLD,of which 110(40.3%)carried a single,129(47.3%)had two,and 34(12.5%)had all three metabolic conditions.The cumulative number of metabolic conditions was related to elevated body mass index,triglyceride(TG)levels,and glycated hemoglobin,lower high-density lipoprotein(HDL)levels,higher liver inflammation(by aspartate aminotransferase andγ-glutamyl transferase),and higher likelihood of fibrosis(by NFS and Fib-4 scores)(P<0.05 for all).The proportion of advanced fibrosis also increased with an increase in the number of metabolic conditions(4.1%,25.5%,35.6%,and 44.1%by NFS and 6.1%,10.9%,17%,and 26.5%by Fib-4 for no MAFLD and MAFLD with 1,2,and 3 conditions,respectively).Among MAFLD patients,those with diabetes alone were the eldest and had the highest mean value of NFS score and Fib-4 score(P<0.05),while MAFLD patients diagnosed with lean metabolic dysfunction exhibited the highest levels of TG and alanine aminotransferase but the lowest HDL levels(P<0.05).CONCLUSION The study suggests that the severity of liver fibrosis in MAFLD patients is influenced by the number and type of metabolic conditions present.Early identification and management of MAFLD,particularly in patients with multiple metabolic conditions,are crucial to prevent liver-related complications.