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.

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.

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.

Metabolic dysfunction-associated steatotic liver disease:A silent pandemic

The worldwide epidemiology of non-alcoholic fatty liver disease(NAFLD)is showing an upward trend,parallel to the rising trend of metabolic syndrome,owing to lifestyle changes.The pathogenesis of NAFLD has not been fully understood yet.Therefore,NAFLD has emerged as a public health concern in the field of hepatology and metabolisms worldwide.Recent changes in the nomenclature from NAFLD to metabolic dysfunction-associated steatotic liver disease have brought a positive outlook changes in the understanding of the disease process and doctor-patient communication.Lifestyle changes are the main treatment modality.Recently,clinical trial using drugs that target‘insulin resistance’which is the driving force behind NAFLD,have shown promising results.Further translational research is needed to better understand the underlying pathophysiological mechanism of NAFLD which may open newer avenues of therapeutic targets.The role of gut dysbiosis in etiopathogenesis and use of fecal microbiota modification in the treatment should be studied extensively.Prevention of this silent epidemic by spreading awareness and early intervention should be our priority.

Insulin resistance and adipose tissue interactions as the cornerstone of metabolic(dysfunction)-associated fatty liver disease pathogenesis

The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.

Implications of metabolic dysfunction associated fatty liver disease in COVID-19

Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the world population.In 2020,the coronavirus disease 2019(COVID-19)crisis was unprecedented,and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2.MAFLD patients are frequently obese with added metabolic menace like diabetes,hypertension,and dyslipidemia leading to greater jeopardy of COVID-19.MAFLD patients are 4 to 6-fold more prone towards infections.COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin.Hence,MAFLD in COVID-19 patients worsens the condition significantly.The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission.Direct hepatic injury,enhanced levels of inflammatory cytokines,declined hepatic mitochondrial activity,and compromised immunity are considered as some underlying mechanisms.The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients.The review systematically analyzes the effect of striking two worldwide pandemics(MAFLD and COVID-19)together in the present era.

Comparison between metabolic-associated fatty liver disease and nonalcoholic fatty liver disease:From nomenclature to clinical outcomes

As a result of the obesity epidemic,Nonalcoholic fatty liver disease(NAFLD)and its complications have increased among millions of people.Consequently,a group of experts recommended changing the term NAFLD to an inclusive terminology more reflective of the underlying pathogenesis;metabolic-associated fatty liver disease(MAFLD).This new term of MAFLD has its own disease epidemiology and clinical outcomes prompting efforts in studying its differences from NAFLD.This article discusses the rationale behind the nomenclature change,the main differences,and its clinical implications.

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.

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.

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.

Metabolic dysfunction is associated with steatosis but no other histologic features in nonalcoholic fatty liver disease

BACKGROUND Recently,nonalcoholic fatty liver disease(NAFLD)has been renamed metabolicassociated fatty liver disease(MAFLD).Based on the definition for MAFLD,a group of non-obese and metabolically healthy individuals with fatty liver are excluded from the newly proposed nomenclature.AIM To analyze the histologic features in the MAFLD and non-MAFLD subgroups of NAFLD.METHODS Eighty-three patients with biopsy-proven NAFLD were separated into MAFLD and non-MAFLD groups.The diagnosis of MAFLD was established as hepatic steatosis along with obesity/diabetes or evidence of metabolic dysfunction.The histologic features were compared according to different metabolic disorders and liver enzyme levels.RESULTS MAFLD individuals had a higher NAFLD activity score(P=0.002)and higher severity of hepatic steatosis(42.6%Grade 1,42.6%Grade 2,and 14.8%Grade 3 in MAFLD;81.8%Grade 1,13.6%Grade 2,and 4.5%Grade 3 in non-MAFLD;P=0.007)than the non-MAFLD group.Lobular and portal inflammation,hepatic ballooning,fibrosis grade,and the presence of nonalcoholic steatohepatitis(NASH)and significant fibrosis were comparable between the two groups.The higher the liver enzyme levels,the more severe the grades of hepatic steatosis(75.0%Grade 1 and 25.0%Grade 2 in normal liver function;56.6%Grade 1,39.6%Grade 2,and 3.8%Grade 3 in increased liver enzyme levels;27.8%Grade 1,27.8%Grade 2,and 44.4%Grade 3 in liver injury;P<0.001).Patients with liver injury(alanine aminotransferase>3×upper limit of normal)presented a higher severity of hepatocellular ballooning(P=0.021).Moreover,the grade of steatosis correlated significantly with hepatocellular ballooning degree(r=0.338,P=0.002)and the presence of NASH(r=0.466,P<0.001).CONCLUSION Metabolic dysfunction is associated with hepatic steatosis but no other histologic features in NAFLD.Further research is needed to assess the dynamic histologic characteristics in NAFLD based on the presence or absence of metabolic disorders.

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.

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.

Intestinal microbiota in the treatment of metabolically associated fatty liver disease

Metabolically associated fatty liver disease (MAFLD) is a common cause ofchronic liver disease, the hepatic manifestation of metabolic syndrome. Despitethe increasing incidence of MAFLD, no effective treatment is available. Recentresearch indicates a link between the intestinal microbiota and liver diseases suchas MAFLD. The composition and characteristics of the intestinal microbiota andtherapeutic perspectives of MAFLD are reviewed in the current study. Animbalance in the intestinal microbiota increases intestinal permeability andexposure of the liver to adipokines. Furthermore, we focused on reviewing thelatest "gut-liver axis" targeted therapy.

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.

Metabolic-associated fatty liver disease from childhood to adulthood:State of art and future directions

In 2020,an international group of experts proposed to replace the term of nonalcoholic fatty liver disease with metabolic-associated fatty liver disease(MAFLD).This recent proposal reflects the close association of fatty liver with metabolic derangements,as demonstrated by previous robust data.Several factors[including genetics,inflammation,metabolic abnormalities,insulin resistance(IR),obesity,prenatal determinants,and gut–liver axis]have been found to be involved in MAFLD pathophysiology,but this tangled puzzle remains to be clearly understood.In particular,IR has been recognized as a key player in metabolic impairments development in children with fatty liver.On this ground,MAFLD definition focuses on the pathophysiological basis of the disease,by emphasizing the crucial role of metabolic impairments in this condition.Although primarily developed for adults,MAFLD diagnostic criteria have been recently updated with an age-appropriate definition for sex and age percentiles,because of the increasing attention to cardiometabolic risk in childhood.To date,accumulating evidence is available on the feasibility of MAFLD definition in clinical practice,but some data are still conflicting in highly selected populations.Considering the growing prevalence worldwide of fatty liver and its close relationship with metabolic dysfunction both in children and adults with subsequent increased cardiovascular risk,early strategies for MAFLD identification,treatment and prevention are needed.Novel therapeutic insights for MAFLD based on promising innovative biological techniques are also emerging.We aimed to summarize the most recent evidence in this intriguing research area both in children and adults.

Semaglutide might be a key for breaking the vicious cycle of metabolically associated fatty liver disease spectrum?

Metabolically associated fatty liver disease(MAFLD)is a liver manifestation of metabolic syndrome potentially related to unfavorable hepatic and extrahepatic outcomes and progression to cirrhosis.Up to date,there are no approved pharmacotherapies for the treatment of MAFLD,so management focused on lifestyle interventions to encourage weight loss,and treatment of coexisting conditions is the only available option.Unfortunately,the aforementioned is often not potent enough to offer reversal or slow down hepatic inflammation and fibrosis.Glucagon-like peptide-1 receptor agonists have a favorable effect on glycemic management and weight loss of patients with type 2 diabetes mellitus and recently published data suggest their potential in MAFLD treatment.In addition,some of the agents have proven cardiovascular and renal benefits in dedicated cardiovascular outcome trials,making them an interesting therapeutic option.In this opinion review,we discuss the role of semaglutide in MAFLD.