Protective Effects of Yinzhihuang Combined with Metformin on Nonalcoholic Fatty Liver Diseases Based on PPAR-αSignaling Pathway

[Objectives]To explore the protective effects and mechanism of Yinzhihuang combined with metformin on nonalcoholic fatty liver diseases(NAFLD)based on PPAR-αsignaling pathway.[Methods]54 male SD rats were randomly divided into 2 groups,namely normal group(12 rats)and high-fat feed group(42 rats).After 8 weeks,2 rats were randomly selected from each group.After pathological examination confirmed the success of the NAFLD model,the high-fat feed group was divided into model group,Yinzhihuang(9000 mg/kg),metformin group(200 mg/kg),Yinzhihuang combined with metformin group(4500 mg/kg+100 mg/kg),10 rats in each group.Except the normal group and the model group,the other groups were given treatment drugs at the same time,one time a day,on the fifth weekend of the experiment,at the last time of administration,fasting but giving water for 16 h,then collected blood and liver tissue.Biochemical method was used to detect AST and ALT in serum and SOD,MDA,GSH-px biochemical indicators in liver tissue;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of TNF-α,IL-6 and TGF-βin liver tissue;Western blot was used to detect the expression of peroxisome proliferators-activated receptor-α(PPAR-α)protein in rat liver tissue.[Results]Compared with the model group,the serum levels of ALT,AST and MDA in liver tissue of model group rats were significantly increased;the levels of SOD and GSH-px in liver tissue were significantly increased;TNF-αand IL-6 and TGF-βcontents in liver tissue were significantly increased.[Conclusions]Both Yinzhihuang and metformin have a therapeutic effect on NAFLD rats,and the effect of combined application of the two is significantly better than the intervention effect of Yinzhihuang or metformin alone,the mechanism is possibly associated with the regulation of PPAR-αsignaling pathway.

Significance of gut microbiota in alcoholic and non-alcoholic fatty liver diseases

Liver-gut communication is vital in fatty liver diseases,and gut microbes are the key regulators in maintaining liver homeostasis.Chronic alcohol abuse and persistent overnutrition create dysbiosis in gut ecology,which can contribute to fatty liver disease.In this review,we discuss the gut microbial compositional changes that occur in alcoholic and nonalcoholic fatty liver diseases and how this gut microbial dysbiosis and its metabolic products are involved in fatty liver disease pathophysiology.We also summarize the new approaches related to gut microbes that might help in the diagnosis and treatment of fatty liver disease.

Mechanism and therapeutic strategy of hepatic TM6SF2-deficient non-alcoholic fatty liver diseases via in vivo and in vitro experiments

BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclear,resulting in a lack of therapeutic strategies for TM6SF2-deficient patients.AIM To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency.METHODS Liver samples collected from both NAFLD mouse models and human participants(80 cases)were used to evaluate the expression of TM6SF2 by using western blotting,immunohistochemistry,and quantitative polymerase chain reaction.RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2.Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD.MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency.RESULTS Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models.TM6SF2 overexpression can reduce hepatic lipid accumulation,suggesting a protective role for TM6SF2 in a high-fat diet(HFD).Downregulation of TM6SF2,simulating the TM6SF2 E167K mutation condition,increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis,accompanied by impaired fatty acid oxidation.Owing to the potential effect of TM6SF2 deficiency on lipid metabolism,the application of an acetyl-CoA carboxylase inhibitor(MK-4074)could reverse the NAFLD phenotypes caused by TM6SF2 deficiency.CONCLUSION TM6SF2 plays a protective role in the HFD condition;its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism,and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.

Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.

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.

Transient elastography with controlled attenuation parameter for the diagnosis of colorectal polyps in patients with nonalcoholic fatty liver disease

BACKGROUND The severity of nonalcoholic fatty liver disease(NAFLD)and lipid metabolism are related to the occurrence of colorectal polyps.Liver-controlled attenuation parameters(liver-CAPs)have been established to predict the prognosis of hepatic steatosis patients.AIM To explore the risk factors associated with colorectal polyps in patients with NAFLD by analyzing liver-CAPs and establishing a diagnostic model.METHODS Patients who were diagnosed with colorectal polyps in the Department of Gastroenterology of our hospital between June 2021 and April 2022 composed the case group,and those with no important abnormalities composed the control group.The area under the receiver operating characteristic curve was used to predict the diagnostic efficiency.Differences were considered statistically significant when P<0.05.RESULTS The median triglyceride(TG)and liver-CAP in the case group were significantly greater than those in the control group(mmol/L,1.74 vs 1.05;dB/m,282 vs 254,P<0.05).TG and liver-CAP were found to be independent risk factors for colorectal polyps,with ORs of 2.338(95%CI:1.154–4.733)and 1.019(95%CI:1.006–1.033),respectively(P<0.05).And there was no difference in the diagnostic efficacy between liver-CAP and TG combined with liver-CAP(TG+CAP)(P>0.05).When the liver-CAP was greater than 291 dB/m,colorectal polyps were more likely to occur.CONCLUSION The levels of TG and liver-CAP in patients with colorectal polyps are significantly greater than those patients without polyps.Liver-CAP alone can be used to diagnose NAFLD with colorectal polyps.

Genetically predicted fatty liver disease and risk of psychiatric disorders: A mendelian randomization study

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.

Metabolic-associated fatty liver disease and sarcopenia:A double whammy

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.

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.

Caveolin‑1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the liver.This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.Methods:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study.Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro.Moreover,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload model.Besides,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and ELISA.The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.Results:Significant disorder of lipid and iron metabolism occurred in NAFLD.The expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism disorder.Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver.Further,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in hepatocytes.Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis.It is a pivotal molecule for predicting and protecting against the development of NAFLD.

Muscle strength and non-alcoholic fatty liver disease/metabolicassociated fatty liver disease

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.

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.

Reorganization of 3D genome architecture provides insights into pathogenesis of early fatty liver disease in laying hens

Background Fatty liver disease causes huge economic losses in the poultry industry due to its high occurrence and lethality rate.Three-dimensional(3D)chromatin architecture takes part in disease processing by regulating tran-scriptional reprogramming.The study is carried out to investigate the alterations of hepatic 3D genome and H3K27ac profiling in early fatty liver(FLS)and reveal their effect on hepatic transcriptional reprogramming in laying hens.Results Results show that FLS model is constructed with obvious phenotypes including hepatic visible lipid deposi-tion as well as higher total triglyceride and cholesterol in serum.A/B compartment switching,topologically associat-ing domain(TAD)and chromatin loop changes are identified by high-throughput/resolution chromosome conforma-tion capture(HiC)technology.Targeted genes of these alternations in hepatic 3D genome organization significantly enrich pathways related to lipid metabolism and hepatic damage.H3K27ac differential peaks and differential expres-sion genes(DEGs)identified through RNA-seq analysis are also enriched in these pathways.Notably,certain DEGs are found to correspond with changes in 3D chromatin structure and H3K27ac binding in their promoters.DNA motif analysis reveals that candidate transcription factors are implicated in regulating transcriptional reprogram-ming.Furthermore,disturbed folate metabolism is observed,as evidenced by lower folate levels and altered enzyme expression.Conclusion Our findings establish a link between transcriptional reprogramming changes and 3D chromatin struc-ture variations during early FLS formation,which provides candidate transcription factors and folate as targets for FLS prevention or treatment.

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions

Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver disease.However,the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies.Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoe-tiology and suggest functional therapeutic and diagnostic options.Pyroptosis,ferroptosis,and necroptosis are the main subtypes of non-apoptotic regulated cell deaths(RCDs),each of which represents particular characteristics.Considering the complexity of the findings,the present study aimed to review these types of RCDs and their contribution to NAFLD progression,and subsequently discuss in detail the role of necroptosis in the pathoetiology,diagnosis,and treatment of the disease.The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer,hence it has potential in diagnostic and therapeutic approaches.Nevertheless,further studies are necessary.

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with steatosis.Circulating microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains unknown.This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.AIM To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.METHODS This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study.Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD.Plasma samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform.We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key covariates.Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD.RESULTS We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with NAFLD.Moreover,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,respectively.Collectively,16 miRNAs were associated with two or more histological features of NAFLD.Among those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and positively associated with all histological features of NAFLD.Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression,while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B.CONCLUSION Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity.Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

Management of non-alcoholic fatty liver disease:Lifestyle changes

In this editorial,we commented on a recently released manuscript by Zeng et al in the World Journal of Gastroenterology.We focused specifically on lifestyle changes in patients with non-alcoholic fatty liver disease(NAFLD).NAFLD is a hepatic manifestation of the metabolic syndrome,which ultimately leads to advanced hepatic fibrosis,cirrhosis,and hepatocellular carcinoma and affects more than 25%of the population globally.Existing therapeutic strategies against NAFLD such as pharmacologic therapies focus on liver protection,anti-inflammation,and regulating disease-related metabolic disorder symptoms.Although several drugs are in late-stage development,potent drugs against the diseases are lacking.Additionally,existing surgical approaches such as bariatric surgery are not routinely used to treat NAFLD.Intervening in patients’unhealthy lifestyles,such as weight loss through dietary changes and exercises to ameliorate patientassociated metabolic disorders and metabolic syndrome,is the first-line treatment for patients with NAFLD.With sufficient intrinsic motivation and adherence,the management of unhealthy lifestyles can reduce the severity of the disease,improve the quality of life,and increase the survival expectancy of patients with NAFLD.

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.

Impact of lifestyle interventions on pathogenesis of nonalcoholic fatty liver disease

This editorial builds on the article titled“Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease”by Zeng et al.We carried out a critical examination of nonalcoholic fatty liver disease(NAFLD)pathogenesis and how lifestyle interventions could facilitate disease resolution,particularly highlighting that non-alcoholic steatohepatitis(NASH)is a severe form of NAFLD.Our discussion details that weight loss is a pivotal factor in disease outcomes:A 3%-5%reduction is enough for resolution in 50%of non-obese individuals,while a 7%-10%reduction achieves similar benefits in obese individuals,as demonstrated by magnetic resonance spectroscopy.Additionally,the editorial underscores that such lifestyle changes are instrumental not only in resolving NAFLD but also in reversing hepatic steatosis and inflammation.These insights,derived from the research,emphasize the critical role of personalized lifestyle modifications in halting the progression of NAFLD to NASH and even reversing fibrosis,thus offering a template for effective patient management.

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.