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Roles of hepatic immunity in metabolic dysfunction-associated steatotic liver disease:Cellular and molecular mechanisms and clinical trials 认领 引用
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作者 Ming Yang Olamide T Olaoba +5 位作者 Stephanie C Chinwo Hannah LeVasseur Beiyan Zhou Eric T Kimchi Kevin F Staveley-O’Carroll Guangfu Li 《World Journal of Gastroenterology》 SCIE CAS 2026年第14期1-17,共17页
Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common type of chronic liver disease,encompassing a broad spectrum of pathology ranging from hepatic steatosis to metabolic dysfunction-associ... Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common type of chronic liver disease,encompassing a broad spectrum of pathology ranging from hepatic steatosis to metabolic dysfunction-associated steatohepatitis(MASH).Characterized by hepatic inflammation,cell death,and different severities of fibrosis,MASLD can lead to liver cirrhosis and hepatocellular carcinoma(HCC).Although over 100 million people are affected in the United States,effective treatment remains limited,including the only United States Food and Drug Administration-approved resmetirom targeting thyroid hormone receptor-β,which failed to prevent MASLD progression to HCC based on clinic studies.It is necessary and urgent to develop new therapies by advancing the understanding of molecular mechanisms underlying MASLD.Hepatic innate immune cells play an essential role in maintaining liver physiologic homeostasis,as well as actively contributing to MASLD pathogenesis and progression by interacting with liver parenchymal cells and adaptive immune cells in the progression of MASLD and MASH.In this review,we summarize current knowledge about the function of various residential and infiltration innate immune cells in the pathogenesis of MASLD and discuss the molecular mechanisms by which they contribute to liver inflammation,metabolic dysregulation,and fibrogenesis.Additionally,we recapitulate current clinical trials focusing on targeted innate immune cell manipulation and metabolic modulation as therapeutic strategies for MASLD. 展开更多
关键词 Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis Innate immune cells Molecular mechanisms Clinical trials Drugs
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Modulation of the gut-liver axis by oxymatrine alleviates metabolic dysfunction-associated steatotic liver disease 认领 引用
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作者 Jing-Fang Xiong Ying He +6 位作者 Na Jiang Yi-Hui Liu Gao-Feng Chen Chang-Qing Zhao Shu-Yan Zhang Yi-Jun Wu Hong Xu 《World Journal of Gastroenterology》 SCIE CAS 2026年第16期124-145,共22页
BACKGROUND Oxymatrine(OMT)has the potential to regulate intestinal microbiota and hepatic metabolites.AIM To explore the underlying mechanisms by which OMT exerts its effects on metabolic dysfunction-associated steato... BACKGROUND Oxymatrine(OMT)has the potential to regulate intestinal microbiota and hepatic metabolites.AIM To explore the underlying mechanisms by which OMT exerts its effects on metabolic dysfunction-associated steatotic liver disease(MASLD).METHODS An MASLD rat model induced by a high-fat,high-sucrose diet was treated with OMT.Assessments included serum/Liver biochemical parameters,histopathology(hematoxylin eosin and oil red O staining),intestinal permeability,16S rRNA gut microbiota sequencing,and hepatic metabolomics.Correlation analysis linked changes in microbiota to metabolic shifts.To test the hypothesis that gut microbiota mediates the efficacy of OMT,we conducted fecal microbiota transplantation experiments.RESULTS OMT effectively alleviated MASLD in rats by improving serum lipid profiles(P<0.05),reducing hepatic steatosis(P<0.05)and inflammatory cytokine levels(P<0.05),and enhancing intestinal barrier function.It substantially restored gut microbiota diversity,increasing beneficial genera such as Lactobacillus,modulating hepatic metabolites such as luteolin(P<0.001),and lowering adrenic acid(P<0.001),which are linked to lipid and inflammatory pathways.Correlation analysis indicated a strong association between changes in specific microbiota and metabolic improvement.Fecal microbiota transplantation experiments indicated that transferring OMT-modulated microbiota recapitulated the therapeutic effects in recipients,suggesting that the gut microbiota contributed substantially to the efficacy of OMT.CONCLUSION This study indicated that OMT alleviated MASLD in rats by regulating intestinal microbiota and hepatic metabolites,highlighting its promise as a therapeutic agent. 展开更多
关键词 Metabolic dysfunction-associated steatotic liver disease Alcoholic liver disease Metabolic dysfunction-associated steatohepatitis Insulin resistance Oxidative stress
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Emerging treatment options for metabolic dysfunction-associated steatotic liver disease and its related liver diseases 认领 引用
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作者 Chun-Ye Zhang Ming Yang 《World Journal of Hepatology》 2026年第6期56-70,共15页
Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading and increasingly prevalent chronic liver disease,affecting approximately 1.2 billion people worldwide.It can be triggered by genetic suscepti... Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading and increasingly prevalent chronic liver disease,affecting approximately 1.2 billion people worldwide.It can be triggered by genetic susceptibility factors and dietary habits.MASLD is characterized by liver fat accumulation,inflammation,cell death,and varying degrees of liver fibrosis.Without appropriate treatment and management,the progressive form of MASLD,metabolic dysfunction-associated steatohepatitis(MASH),can lead to liver cirrhosis and hepatocellular carcinoma.Currently,there are two United States Food and Drug Administration approved drugs for the treatment of MASH with moderate to advanced liver fibrosis:resmetirom,an oral agonist of thyroid hormone receptor-β,and semaglutide,a glucagon-like peptide-1(GLP-1)receptor agonist.Ongoing clinical trials indicate that many emerging therapies show promising efficacy and potential applications for MASLD and MASH treatment,including dual glucagon receptor and GLP-1 receptor agonists,fibroblast growth factor analogues,and pan-peroxisome proliferator-activated receptor agonists.In this review,we summarize the pathogenesis of MASLD and MASH and examine current clinical trials for their treatment,with a focus on pharmaceutical therapies,dietary modifications,and natural products.Additionally,repurposing currently approved drugs for metabolic diseases,as well as combination therapies,may provide effective treatment strategies for MASLD and MASH. 展开更多
关键词 Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis Clinical trials Molecular mechanisms Treatments Therapeutic strategies
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Role of hepatic sonic hedgehog protein expression in the diagnosis of metabolic dysfunction-associated steatohepatitis 认领 引用 被引量：1
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作者 Xu Han Miao-Yang Chen +4 位作者 Qing-Fang Xiong Yan-Dan Zhong Du-Xian Liu Jia Li Yong-Feng Yang 《World Journal of Gastroenterology》 SCIE CAS 2026年第12期51-61,共11页
BACKGROUND Ballooned hepatocytes are a histological hallmark in the diagnosis of metabolic dysfunction-associated steatohepatitis(MASH).Identifying ballooned hepatocytes on routine stains is challenging.Cytokeratin 8/... BACKGROUND Ballooned hepatocytes are a histological hallmark in the diagnosis of metabolic dysfunction-associated steatohepatitis(MASH).Identifying ballooned hepatocytes on routine stains is challenging.Cytokeratin 8/18 protein is diffusely expressed in normal hepatocytes but absent in ballooned hepatocytes.Conversely,sonic hedgehog(SHH)protein is absent in normal hepatocytes but present in ballooned hepatocytes.AIM To investigate the utility of immunostaining for positive SHH protein expression in ballooned hepatocytes in MASH.METHODS Clinicopathological data from hospitalized patients with metabolic dysfunctionassociated steatotic liver(MASL)disease at the Second Hospital of Nanjing from January 2020 to November 2022 were analyzed.The Nonalcoholic Steatohepatitis Clinical Research Network scoring system was used.Post-staining,digitized images were acquired,and area quantification algorithms were used to quantify SHH expression.RESULTS A total of 190 MASL disease patients who underwent liver biopsy were enrolled in this study;58.9%(112/190)had definite MASH,and 41.1%(78/190)had MASL.There were significant differences in body mass index(P<0.001),diabetes(P<0.01),metabolic syndrome(P<0.02),and circulating M65 and M30(P<0.001),as well as aspartate aminotransferase(AST),alanine aminotransferase,glucose,uric acid,controlled attenuation parameter(CAP),liver stiffness measurement,and nonalcoholic fatty liver disease fibrosis score(P<0.05).Serum M30 and M65 levels were almost three times greater in MASH than in MASL patients.Hepatic SHH expression correlated with circulating M65(r=0.346,P=0.002)and circulating M30(r=0.471,P<0.001),as did alanine aminotransferase(r=0.490,P<0.001),AST and CAP(r=0.554,P<0.001 and r=0.432,P<0.001,respectively).Hepatic SHH expression correlated with histological steatosis grade(r=0.502,P<0.001),ballooning hepatocytes(r=0.496,P<0.001),lobular inflammation(r=0.450,P<0.001),and fibrosis stage(r=0.303,P=0.006).Logistic modeling revealed diabetes,AST,CAP and hepatic SHH expression as independent predictors of MASH[defined as nonalcoholic fatty liver disease activity score≥5:Odds ratio(OR)=20.95,P=0.043,OR=1.044,P=0.023,OR=1.034,P=0.008,and OR=7.151,P=0.017,respectively]and histological ballooning hepatocytes and circulating M30 as independent predictors of advanced fibrosis(defined as portal and pericellular fibrosis≥2:OR=6.440,P=0.023,and OR=1.012,P=0.005,respectively).The Fleiss’kappa increased interobserver agreement of assessment of ballooning using SHH immunostaining,from 0.65 to 0.85.CONCLUSION Hepatic SHH protein expression assisted in the diagnosis of MASH.SHH immunostaining may be useful for classifying and quantifying ballooned hepatocytes by artificial intelligence algorithms. 展开更多
关键词 Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis Ballooned hepatocytes Cytokeratin 8/18 Sonic hedgehog
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Effect of cholecystectomy on liver fat and fibrosis in metabolic dysfunction-associated steatotic liver disease patients 认领 引用
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作者 Khellaf Amalou Nassila Belal +5 位作者 Abdelghani Tibouk Yasmine Ghedada Rym Rekab Sabrina Fadel Nabil Debzi Abderezak Bousloub 《World Journal of Gastrointestinal Pharmacology and Therapeutics》 2026年第2期125-141,共17页
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is highly prevalent worldwide.Experimental studies have shown that cholecystectomy(Chx)increases metabolic dysfunction-associated steatotic liv... BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is highly prevalent worldwide.Experimental studies have shown that cholecystectomy(Chx)increases metabolic dysfunction-associated steatotic liver(MASL)and is associated with MASLD in large retrospective cohort studies.AIM To prospectively evaluate the effect of Chx on MASL and fibrosis,assess the prevalence of MASLD,and identify its risk factors in this population.METHODS There were 213 MASLD patients enrolled,with 103 being Chx and 110 being non-Chx patients.The patients were followed up for 36 months.RESULTS Body mass index increased in the Chx group(30.15±4.08 to 31.58±4.64)vs(31.90±4.07 to 30.03±4.16)in the control group(P<0.001).Median controlled attenuation parameter increased from 300.77±47.42 to 314.17±44.7(Chx)and decreased from 325.06±41.74 to 296.36±56.51(control)(P<0.01).MASL/magnetic resonance imaging(MRI)moved from 14.22±8.64 and 18.55±8.57 at baseline to 15.98±7.93 and 13.88±8.12 at the end of the study(P<0.001).The biological scores of MASL(fatty liver index,hepatic steatosis index,and lipid accumulation product)all progressed in the Chx group and regressed in the control group(P<0.001).The prevalence of hepatic steatosis was 42.38%(Chx).Risk factors associated with significant hepatic steatosis were metabolic syndrome,Chx,MASL/MRI,and fatty liver index scores.Risk factors associated with advanced fibrosis are body mass index,aspartate aminotransferase/alanine aminotransferase ratio,diabetes mellitus score,stiffness,and Chx.Stiffness,obesity,Chx,gamma-glutamyl transferase,and MASL/MRI are associated with metabolic dysfunction-associated steatohepatitis(MASH)lesions.CONCLUSION Chx increases MASL and fibrosis.MASLD prevalence in the Chx group is higher than in the overall population. 展开更多
关键词 Metabolic dysfunction-associated steatotic liver disease Cholecystectomy Hepatic fibrosis Metabolic dysfunction-associated steatotic liver Metabolic dysfunction-associated steatohepatitis
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Metabolic dysfunction-associated steatotic liver disease and type 2 diabetes:Pathophysiology,diagnosis,and emerging therapeutic strategies 认领 引用 被引量：2
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作者 Mithil Gowda Suresh Safia Mohamed +9 位作者 Harinivaas S Geetha Sushmita Prabhu Nitin Trivedi Zhu C Ng Priyal D Mehta Ajit S Brar Aalam Sohal Manjeet K Goyal Juniali Hatwal Akash Batta 《World Journal of Diabetes》 SCIE 2026年第2期40-59,共20页
Metabolic dysfunction-associated steatotic liver disease(MASLD),the updated terminology for fatty liver disease linked to metabolic dysfunction,is highly prevalent among individuals with type 2 diabetes mellitus(T2DM)... Metabolic dysfunction-associated steatotic liver disease(MASLD),the updated terminology for fatty liver disease linked to metabolic dysfunction,is highly prevalent among individuals with type 2 diabetes mellitus(T2DM).MASLD affects a majority of patients with T2DM and markedly increases the risk of fibrosis,cirrhosis,hepatocellular carcinoma,and cardiovascular mortality.The pathogenesis in diabetic populations reflects a convergence of insulin resistance,dyslipidemia,mitochondrial dysfunction,chronic inflammation,and genetic predisposition.Advances in non-invasive diagnostics,including elastography and serum biomarkers,enable earlier identification and staging of disease,though limitations remain in diabetic cohorts.Lifestyle modification is the cornerstone of therapy,yet emerging pharmacotherapies are reshaping the therapeutic landscape.Antidiabetic agents such as glucagon-like peptide-1 receptor agonists,sodium-glucose cotransporter-2 inhibitors,and pioglitazone show hepatic benefits beyond glycemic control,while novel agents and combination regimens are under active evaluation.This narrative review synthesizes current evidence on epidemiology,mechanisms,diagnostics,and therapeutics of MASLD in T2DM,and highlights future directions in precision medicine.Integration of multidisciplinary care is essential to address this converging epidemic. 展开更多
关键词 Metabolic dysfunction-associated steatotic liver disease Type 2 diabetes mellitus Insulin resistance Hepatic fibrosis Non-invasive diagnostics Glucagon-like peptide-1 receptor agonists Sodium-glucose cotransporter-2 inhibitors Personalized medicine Fatty liver Metabolic associated steatohepatitis
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Impact of metabolic dysfunction-associated steatotic liver disease on liver metastasis and survival in pancreatic cancer 认领 引用 被引量：1
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作者 Hye Yeon Chon Hyungjin Rhee +8 位作者 Jeehoon Kim Galam Leem Jung Hyun Jo Moon Jae Chung Jeong Youp Park Seungmin Bang Seung Woo Park Seung Up Kim Hee Seung Lee 《World Journal of Gastroenterology》 SCIE CAS 2026年第11期22-31,共10页
BACKGROUND Pancreatic cancer frequently metastasizes to the liver,and thereby confers high mortality risk.AIM To investigated the effect of metabolic dysfunction-associated steatotic liver disease(MASLD)on liver metas... BACKGROUND Pancreatic cancer frequently metastasizes to the liver,and thereby confers high mortality risk.AIM To investigated the effect of metabolic dysfunction-associated steatotic liver disease(MASLD)on liver metastasis and survival outcomes in patients with pancreatic cancer,as the increasing incidence of MASLD.METHODS We retrospectively analyzed data from 2123 patients who were diagnosed with pancreatic cancer between 2006 and 2021.MASLD was diagnosed based on a hepatic steatosis index(HSI)>30.RESULTS In the study population,which predominantly comprised males,the median age was 66 years(n=1118,52.6%).Patients with liver metastasis at baseline(n=540,25.4%)had larger tumors(median,41 mm vs 35 mm)and higher carbohydrate antigen(CA)19-9 levels(median 975.0 U/mL vs 206.2 U/mL;all P0.05).In contrast,younger age[hazard ratio(HR)=0.985,95%confidence interval(CI):0.974-0.997],increased tumor size(HR=1.008,95%CI:1.001-1.016),and elevated CA19-9 levels(HR=1.662,95%CI:1.279-2.160)were significantly associated with new liver metastases during the follow-up(all P0.05).CONCLUSION Thus,HSI-defined MASLD does not directly influence liver metastasis or survival in patients with pancreatic cancer. 展开更多
关键词 Hepatic steatosis Pancreatic cancer Liver metastases Hepatic steatosis index Metabolic dysfunction-associated steatotic liver disease
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Qiweizhigan granule ameliorates metabolic dysfunction-associated steatohepatitis by modulating the galectin 3/tumor necrosis factor receptor-associated factor 6-mediated ferroptosis 认领 引用 被引量：1
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作者 Yu-Nuo Yang Yun-Hong Sun +9 位作者 Ming-Zhe Zhu Yi-Rong Wang Meng Li Kai Wang Jing Ma Li Zhang Dan Hu Wen-Jun Zhou Guang Ji Yan-Qi Dang 《World Journal of Gastroenterology》 SCIE CAS 2026年第17期116-134,共19页
BACKGROUND Qiweizhigan granule(QWZG)is employed in clinical settings for the treatment of metabolic dysfunctionassociated steatohepatitis(MASH).However,the precise biological mechanisms underlying its therapeutic effe... BACKGROUND Qiweizhigan granule(QWZG)is employed in clinical settings for the treatment of metabolic dysfunctionassociated steatohepatitis(MASH).However,the precise biological mechanisms underlying its therapeutic effects are not yet fully elucidated.AIM To assess the efficacy and the mechanism of QWZG against MASH.METHODS Animal models were established,including normal group,a choline-deficient,L-amino acid-defined high-fat diet(CDAHFD)group,and low/medium/high-dose QWZG groups,as well as a rosiglitazone group.Through comprehensive biochemical,histopathological,RNA sequencing,and bioinformatics analyses,galectin 3(LGALS3)was identified as a critical target of QWZG in the treatment of MASH.The level of LGALS3 was quantitatively assessed and validated using Western blotting,real-time quantitative PCR,and immunofluorescence.The role and function of LGALS3 in inflammation and MASH progression were further investigated through gene knockdown,overexpression,iron assay,and transmission electron microscopy.RESULTS QWZG significantly ameliorated liver pathology by reducing steatosis,inflammation,and fibrosis.RNA sequencing analysis identified 1507 co-expressed differentially expressed genes among the CDAHFD,normal,and QWZG groups.Among these,LGALS3 was identified as one of the most significantly altered differentially expressed genes.Both mRNA and protein levels of LGALS3 were elevated in the CDAHFD group compared to the normal group,whereas treatment with QWZG reduced their levels.Analysis of Human Protein Atlas database indicated that LGALS3 was predominantly expressed in Kupffer cells,and was validated by real-time quantitative PCR and immunofluorescence.Furthermore,the level of LGALS3 was significantly increased in lipopolysaccharide-induced RAW264.7 cells,where its overexpression and recombinant LGALS3 protein both significantly enhanced the expression of interleukin-6,interleukin-1β,and tumor necrosis factor-α.LGALS3 overexpression significantly inhibited glutathione peroxidase 4(GPX4)expression,and exacerbated mitochondrial damage,whereas LGALS3 knockdown markedly increased GPX4 level,and significantly reduced the levels of both total iron and ferrous iron.QWZG treatment significantly reduced the levels of malondialdehyde and ferrous iron,increased the levels of superoxide dismutase and glutathione.In addition,QWZG treatment also significantly enhanced GPX4 expression.Mechanistically,LGALS3 knockdown was associated with reduced expression of tumor necrosis factor receptor-associated factor 6(TRAF6)and NOD-like receptor family pyrin domain containing 3,while its overexpression led to increased levels of these proteins.The TRAF6 inhibitor C25-140 effectively reversed the LGALS3-induced alterations in GPX4 expression and iron accumulation.Furthermore,QWZG treatment significantly decreased the levels of TRAF6 and NOD-like receptor family pyrin domain containing 3.CONCLUSION QWZG ameliorated the progression of MASH by modulating ferroptosis through the LGALS3/TRAF6/GPX4 axis. 展开更多
关键词 Qiweizhigan granule Metabolic dysfunction-associated steatohepatitis Galectin 3 Tumor necrosis factor receptorassociated factor 6 Ferroptosis
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Interplay of childhood metabolic dysfunction-associated steatotic liver disease and obesity in the development of youth-onset type 2 diabetes 认领 引用 被引量：2
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作者 Razieh Parizad Juniali Hatwal +4 位作者 Ajit Singh Brar Leila Alizadeh Manjeet Kumar Goyal Akash Batta Bishav Mohan 《World Journal of Clinical Pediatrics》 2026年第1期232-251,共20页
BACKGROUND The global increase in childhood and adolescent obesity has significantly contributed to the rising prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)–a condition now recognized ... BACKGROUND The global increase in childhood and adolescent obesity has significantly contributed to the rising prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)–a condition now recognized as a key metabolic complication in youth.MASLD significantly increases the risk of youth-onset type 2 diabetes(T2D),particularly among obese individuals.Its asymptomatic progression presents considerable challenges for timely diagnosis and intervention.AIM To review epidemiology,pathophysiological mechanisms,and management strategies related to pediatric MASLD,exploring its interaction with obesity and youth-onset T2D.METHODS A comprehensive literature search was conducted using PubMed,Scopus,and Google Scholar to identify peerreviewed studies published between 2015 and 2025.Keywords included“pediatric MASLD”,“childhood obesity”,“youth-onset type 2 diabetes”,“hepatic insulin resistance”,and“noninvasive biomarkers”.Articles were selected based on relevance,methodological quality,and focus on human pediatric populations.RESULTS MASLD affects approximately 13%of children globally and up to 47%of those with obesity,with the highest prevalence reported in urban areas of the United States,China,and India.In children and adolescents,excess adiposity is the leading contributor to hepatic steatosis and metabolic dysfunction,particularly when body mass exceeds standard growth benchmarks for age and sex.MASLD increases the risk of adolescent T2D by approximately 2.7-fold.Key pathophysiological mechanisms include hepatic insulin resistance,mitochondrial dysfunction,and chronic inflammation,driven by lipotoxic metabolites such as ceramides and pro-inflammatory cytokines.Lifestyle modifications–particularly low free-sugar diets and structured physical activity–have demonstrated moderate efficacy in reducing hepatic fat and improving metabolic outcomes.Pharmacologic interventions,including glucagon-like peptide-1 receptor agonists such as liraglutide and semaglutide,show potential for weight reduction and glycemic control,though their effects on hepatic histology remain under investigation.CONCLUSION MASLD represents a critical metabolic threat in pediatric populations,strongly influenced by obesity and closely associated with increased risk of youth-onset T2D.Effective management requires early detection,multidisciplinary interventions,and equitable access to care.Future research should prioritize the validation of noninvasive diagnostic tools,development of targeted therapies,and reduction of socioeconomic and ethnic disparities in disease burden and treatment outcomes. 展开更多
关键词 Pediatric Metabolic dysfunction-associated steatotic liver disease Childhood obesity Type 2 diabetes mellitus Metabolic syndrome Non-alcoholic fatty liver disease Insulin resistance
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Diagnosis and management of metabolic dysfunction-associated steatohepatitis in patients with chronic hepatitis B infection 认领 引用
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作者 Talal K Bhatti Joseph K Lim 《World Journal of Gastroenterology》 SCIE CAS 2026年第9期41-50,共10页
Chronic hepatitis B(CHB)infection is a global public health burden,affecting over 250 million persons globally,and is associated with substantial morbidity and mortality due to cirrhosis,hepatic decompensation,and hep... Chronic hepatitis B(CHB)infection is a global public health burden,affecting over 250 million persons globally,and is associated with substantial morbidity and mortality due to cirrhosis,hepatic decompensation,and hepatocellular carcinoma.Metabolic syndrome and metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly common co-morbidity among patients with CHB,affecting an estimated 25%-40%of individuals.The physiologic and clinical impact of co-existing CHB and metabolic syndrome and/or MASLD[met-hepatitis B virus(HBV)]is poorly understood,although recent data suggest important associations with poorer antiviral response and clinical outcomes.This review summarizes current and emerging evidence addressing this relationship,and outline recommendations for the diagnosis,risk stratification,staging,and management of Met-HBV. 展开更多
关键词 Hepatitis B virus Hepatic steatosis Metabolic syndrome Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis Liver fibrosis Clinical outcomes
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Evaluation of hepatic sonic hedgehog protein expression in the diagnosis of metabolic dysfunction-associated steatohepatitis 认领 引用
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作者 Tian-Tian Chen Hao-Xian Gou Zhu-Lin Luo 《World Journal of Hepatology》 2026年第6期8-16,共9页
Metabolic dysfunction-associated steatohepatitis(MASH)is an advanced form of metabolic dysfunction-associated fatty liver disease,with diagnosis relying on liver biopsy.The identification of ballooned hepatocytes in r... Metabolic dysfunction-associated steatohepatitis(MASH)is an advanced form of metabolic dysfunction-associated fatty liver disease,with diagnosis relying on liver biopsy.The identification of ballooned hepatocytes in routine hematoxylineosin staining is subjective and exhibits significant interobserver variability.Sonic hedgehog homolog(SHH)is specifically expressed in ballooned hepatocytes and holds potential as a positive immunohistochemical marker.This review evaluates the diagnostic value of SHH expression in MASH based on available evidence.Studies demonstrate that SHH staining improves the consistency of interpretation of ballooned hepatocytes and correlates with disease severity,serum biomarkers,and fibrosis staging.However,most evidence comes from single-center retrospective studies with a limited number of observers.The independent predictive value of SHH requires validation through prospective multicenter cohort studies.In summary,SHH immunohistochemistry is a promising adjunctive diagnostic tool for MASH,though its clinical application remains in the preliminary stages. 展开更多
关键词 Sonic hedgehog Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis Ballooned hepatocytes Liver fibrosis
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Exercise-responsive skeletal muscle genes mechanistically linked to metabolic dysfunction-associated steatotic liver disease 认领 引用
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作者 Jia-Hui Zhang Kang Chen +6 位作者 Xiao-Min Zhu Huan Zhou Jia-Mi Jiang Yu-Qing Zou Ke-Rong Liu Le Zhang Yun Li 《World Journal of Gastroenterology》 SCIE CAS 2026年第13期78-96,共19页
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a common chronic liver disease that progresses from simple steatosis to inflammation,fibrosis,and cirrhosis.Currently,no effective targeted ... BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a common chronic liver disease that progresses from simple steatosis to inflammation,fibrosis,and cirrhosis.Currently,no effective targeted therapy is available.Exercise is a well-recognized non-pharmacological intervention with clear benefits.However,the biological mechanisms by which skeletal muscle responds to regular exercise and contributes to MASLD improvement remain poorly understood.AIM To identify exercise-responsive biomarkers in skeletal muscle associated with MASLD and explore their diagnostic and therapeutic potential.METHODS We analyzed skeletal muscle transcriptomic datasets from the gene expression omnibus.Differentially expressed genes(DEGs)were detected and then analyzed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment methods.To identify key genes,we employed weighted gene co-expression network analysis(WGCNA)and least absolute shrinkage and selection operator(LASSO)regression.Correlation with diagnostic efficacy was performed utilizing a validation group and receiver operating characteristic(ROC)analysis.Finally,an obese mouse model was established and subjected to endurance aerobic training.Gastrocnemius muscle tissue was validated at the messenger RNA,protein,and secretion levels to confirm the identified biomarkers.RESULTS Transcriptomic analysis identified 61 DEGs between pre-exercise and post-exercise samples,with 40 upregulated and 21 downregulated genes.GO enrichment analysis showed that extracellular matrix(ECM)organization and collagen fibril formation were significantly enriched.KEGG pathway analysis further highlighted cytoskeleton dynamics in muscle cells and ECM-receptor interactions.Integrated DEGs,WGCNA and LASSO analysis identified 12 hub genes.Validation cohort and ROC analysis demonstrated strong diagnostic performance for nine hub genes(COL3A1,COL1A2,BGN,LAMB1,PECAM1,LAMA4,THBS4,PXDN and THY1).In the mouse model,three hub genes(Lama4,Pecam1 and Pxdn)were significantly upregulated,while Thbs4 was downregulated after exercise in skeletal muscle tissue.CONCLUSION This study identified four exercise-responsive skeletal muscle-expressed genes(LAMA4,PECAM1,PXDN and THBS4).These genes are mechanistically associated with MASLD and may serve as myokine-like candidates.Our research offers new perspectives on the pathophysiology of MASLD and suggest possible strategies for precision diagnosis and therapy. 展开更多
关键词 Metabolic dysfunction-associated steatotic liver disease Myokines Weighted gene co-expression network analysis LAMA4 PECAM1 PXDN THBS4
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Exposure to Endocrine-disrupting Chemicals,Iron Metabolism,and Risk of Metabolic Dysfunction-associated Steatotic Liver Disease:A Nationwide Cross-sectional Study in China 认领 引用
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作者 Zongyao Li Yongbin Zhao +7 位作者 Zhenyu Wu Huijun Wang Yanzhen Hu Xiaofan Zhang Xi Kang Chang Su Tao Zhang Aidong Liu 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2026年第6期677-689,共13页
Objective This study aimed to investigate the association between exposure to mixtures of environmental endocrine-disrupting chemicals(EDCs)and metabolic dysfunction-associated steatotic liver disease(MASLD)and to ass... Objective This study aimed to investigate the association between exposure to mixtures of environmental endocrine-disrupting chemicals(EDCs)and metabolic dysfunction-associated steatotic liver disease(MASLD)and to assess the potential mediating role of iron metabolism.Methods A total of 6,989 adults from the China Health and Nutrition Survey(2015 cycle)were included.The serum concentrations of 22 EDCs were measured.Logistic regression,weighted quantile sum(WQS)regression,and Bayesian kernel machine regression(BKMR)models were used to evaluate the association between EDC exposure and risk of MASLD.Mediation analyses were performed to assess the mediating role of serum ferritin(SF).Results Eight EDCs were positively associated with MASLD.The WQS regression model identified six major contributors,including β-hexachlorocyclohexane,p,p'-DDT,monoethyl phthalate,acenaphthene,perfluorooctanoic acid,and perfluoro-n-pentanoic acid,in mixture effects.The BKMR model demonstrated that higher levels of EDC mixture were associated with an increased risk of MASLD.Subgroup analyses suggested stronger correlations in males and in individuals aged<65 years.SF was estimated to mediate 11.2%-32.1%of the association between key EDCs and MASLD.Conclusion Exposure to EDC mixtures was associated with an increased risk of MASLD,with iron metabolism playing a notable mediating role.Reducing the exposure to key EDCs may help alleviate the burden of MASLD. 展开更多
关键词 Endocrine-disrupting chemicals Metabolic dysfunction-associated steatotic liver disease Ferritins Complex mixtures Mediation analysis
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Do biomarkers matter?Cardiovascular risk stratification in Asian patients with metabolic dysfunction-associated steatotic liver disease in the era of fibrosis-centric assessment 认领 引用
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作者 Manjeet Kumar Goyal Juniali Hatwal +2 位作者 Rupak Desai Tanisha Sehgal Akash Batta 《World Journal of Gastroenterology》 SCIE CAS 2026年第28期10-18,共9页
Metabolic dysfunction-associated steatotic liver disease(MASLD)is increasingly recognized as a multisystem disorder with significant cardiovascular implications,particularly in Asian populations characterized by a hig... Metabolic dysfunction-associated steatotic liver disease(MASLD)is increasingly recognized as a multisystem disorder with significant cardiovascular implications,particularly in Asian populations characterized by a high prevalence of lean phenotypes and early metabolic dysregulation.Identifying reliable biomarkers for cardiovascular risk stratification in this group remains a clinical priority.This review critically appraises the current evidence on metabolic,inflammatory,cardiac,and fibrosis-related biomarkers in Asian patients with MASLD.Metabolic indices such as the uric acid-to-high-density lipoprotein ratio and triglycerideglucose index capture underlying insulin resistance and oxidative stress and show consistent associations with steatotic liver disease.However,direct validation for cardiovascular outcomes remains limited.Inflammatory markers,including highsensitivity C-reactive protein and homeostasis model assessment of insulin resistance,are mechanistically important but are confounded by their inclusion within MASLD diagnostic criteria,limiting their incremental predictive value.Cardiac biomarkers such as high-sensitivity troponins and natriuretic peptides demonstrate strong associations with adverse outcomes but lack sufficient validation in Asian MASLD cohorts for routine screening.In contrast,fibrosis-based indices,particularly the fibrosis-4 score,consistently associate with cardiovascular events,coronary artery calcification,and mortality across multiple Asian studies.These markers likely reflect cumulative metabolic and inflammatory injury linking hepatic and vascular pathology.An integrated,multivariable approach incorporating fibrosis markers alongside metabolic and cardiac indices may provide the most clinically meaningful framework for cardiovascular risk assessment in Asian patients with MASLD. 展开更多
关键词 Cardiovascular diseases Metabolic dysfunction-associated steatotic liver disease Obesity Uric acid Endothelial dysfunction High-density lipoprotein cholesterol Framingham risk score
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Association between overt,subclinical hypothyroidism and metabolic dysfunction-associated steatotic liver disease using magnetic resonance imaging 认领 引用
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作者 Amany Sholkamy Ahmed El-Meligui +4 位作者 Eman H Saad Samar Amin Mirette Makram Noha Elmansy Shrook Mousa 《World Journal of Hepatology》 2026年第5期201-214,共14页
BACKGROUND In addition to an elevated risk of cirrhosis and hepatocellular carcinoma,along with metabolic dysfunction-associated steatotic liver disease(MASLD)represents the primary contributor to chronic liver diseas... BACKGROUND In addition to an elevated risk of cirrhosis and hepatocellular carcinoma,along with metabolic dysfunction-associated steatotic liver disease(MASLD)represents the primary contributor to chronic liver disease,affecting 30%of the global population.Hypothyroidism is a common disorder that may influence MASLD development.Limited data have addressed the association between the whole spectrum of hypothyroidism(overt,subclinical)and MASLD.AIM To determine the association between the whole spectrum of hypothyroidism(overt,subclinical)and MASLD and its severity determinants.METHODS This observational investigation encompassed 144 adult participants from Egypt,consisting of 48 subjects diagnosed with obvious hypothyroidism,48 with subclinical hypothyroidism and 48 healthy control subjects,subsequent to the removal of those with a history of alcohol intake,diabetes mellitus,prediabetes,or any etiologies of chronic liver disease,such as chronic viral hepatitis B and C.All participants underwent evaluation for MASLD employing ultrasound imaging,with diagnosis thereafter corroborated through magnetic resonance imaging,and hepatic fat percentage(HF%)was determined to gauge MASLD severity at Kasralainy Hospitals,Cairo University,Egypt.RESULTS The 34 of the 48 overt hypothyroid,27 of the 48 subclinical hypothyroid and 3 of the control group were diagnosed to have MASLD.Mild steatosis was 38.2%and 63%whereas moderate steatosis was 61.8%and 37%among the overt and subclinical groups respectively.The statistically significant predictor for the risk of MASLD development was the thyroid-stimulating hormone(TSH)level(22.9±26.4,P value6.1 mIU/L or higher is associated with an increased risk of developing MASLD.CONCLUSION Overt and subclinical hypothyroidism are directly related to MASLD development.TSH exhibits an increased association with HF%and is an independent risk variable associated with the onset and severeness of MASLD. 展开更多
关键词 Metabolic dysfunction-associated steatotic liver disease Hypothyroidism Overt Subclinical Predictors Fibrosis Severity Ultrasonography Magnetic resonance imaging
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Letter to the Editor:How serum uric acid-to-high-density lipoprotein cholesterol ratio predicts cardiovascular risk in metabolic dysfunction-associated steatotic liver disease:Addressing challenges 认领 引用
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作者 Jing-Juan Xu Jing Ma +2 位作者 Shang Wei Dan Hu Yan-Qi Dang 《World Journal of Gastroenterology》 SCIE CAS 2026年第26期155-158,共4页
Chronic diseases frequently interact,forming complex comorbidity networks.Recent research published in the World Journal of Gastroenterology by Wang et al has identified that the ratio of serum uric acid to high-densi... Chronic diseases frequently interact,forming complex comorbidity networks.Recent research published in the World Journal of Gastroenterology by Wang et al has identified that the ratio of serum uric acid to high-density lipoprotein cholesterol(UHR)independently predicts the 10-year risk of cardiovascular disease(CVD),particularly in younger individuals,males,and those with central obesity.Individuals with metabolic dysfunction-associated steatotic liver disease represent at high-risk cohort for CVD.In these patients,the risk associated with cardiovascular events significantly surpasses that of liver disease,rendering CVD the primary cause of disability and mortality.The UHR is an emerging composite biomarker that effectively synthesizes indices of inflammation and metabolism,facilitating an assessment of a person’s metabolic and inflammatory status.This biomarker exhibits considerable clinical potential. 展开更多
关键词 Metabolic dysfunction-associated steatotic liver disease Cardiovascular risk Serum uric acid-to-high-density lipoprotein cholesterol ratio Emerging composite biomarker Asian patients
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Metabolic dysfunction-associated steatotic liver disease mediates the relationship between Helicobacter pylori infection and colorectal adenoma risk 认领 引用
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作者 Zhao-Bei Cai Bin-Bin Su +3 位作者 Pan-Yang Shi Sheng-Shu Wang Hui Shi Qian-Qian Chen 《World Journal of Hepatology》 2026年第4期103-112,共10页
BACKGROUND There is a potential connection between Helicobacter pylori(H.pylori)infection,metabolic dysfunction-associated steatotic liver disease(MASLD)and colorectal adenoma.AIM To determine whether H.pylori infecti... BACKGROUND There is a potential connection between Helicobacter pylori(H.pylori)infection,metabolic dysfunction-associated steatotic liver disease(MASLD)and colorectal adenoma.AIM To determine whether H.pylori infection and MASLD increase the probability of developing colorectal adenomas,and to analyze whether there is an interaction or mediation effect between these two risk factors.METHODS The study followed a retrospective cross-sectional design.Patients attending the Second Medical Center of Chinese PLA General Hospital for check-up between 2017 and 2021 were consecutively enrolled.We collected patients'basic information,laboratory test results,colonoscopy findings,H.pylori test results,and ultrasound data.Multivariate logistic regression analysis,interaction,and mediation effect tests were employed to assess the relationship between H.pylori infection,MASLD,and the risk of colorectal adenomas.RESULTS Of the 10066 participants,29.40%had colorectal adenomas,36.78%had H.pylori infection and 53.55%had MASLD.Adjusted multivariate analysis showed that both H.pylori[adjust odds ratio(aOR)=1.3,95%CI:1.2-1.4,P<0.001]and MASLD(aOR=1.3,95%CI:1.2-1.5,P<0.001)independently raised adenoma risk,with no interaction(P=0.1836).MASLD might act as a mediator of the increased colorectal adenoma risk associated with H.pylori infection(mediation effect=0.0009,95%CI:0.0002-0.0027,P=0.0180).CONCLUSION H.pylori infection and MASLD independently elevate the risk of colorectal adenomas,with MASLD potentially mediating the relationship between H.pylori infection and the increased adenoma risk. 展开更多
关键词 Colorectal adenomas Helicobacter pylori infection Metabolic dysfunction-associated steatotic liver disease Interaction Mediation
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Is metabolic dysfunction-associated steatotic liver disease truly irrelevant?Unmasking the heterogeneity and confounders in pancreatic cancer outcomes 认领 引用
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作者 Zhe-Kun Xiong Yu-Zi Jiang +3 位作者 Yan-Hua Lin Jian-Dong Cao Tao-Ying Deng Yi-Yuan Zheng 《World Journal of Gastroenterology》 SCIE CAS 2026年第27期7-14,共8页
Metabolic dysfunction-associated steatotic liver disease(MASLD)has no significant impact on liver-metastatic patterns or survival outcomes in patients with pancreatic cancer.While the negative findings are clinically ... Metabolic dysfunction-associated steatotic liver disease(MASLD)has no significant impact on liver-metastatic patterns or survival outcomes in patients with pancreatic cancer.While the negative findings are clinically appealing,several issues may limit a definitive biological interpretation.First,the use of steatosisweighted,noninvasive surrogates may be prone to misclassification in pancreatic cancer,where cachexia,sarcopenia,and systemic inflammation can distort these components,thereby attenuating true associations toward the null.Second,accumulating evidence has suggested that MASLD is highly heterogeneous,in which adverse oncologic outcomes are more consistently linked to metabolic inflammation and fibrosis rather than steatosis alone and pooling these phenotypes may dilute signals from high-risk subgroups.Third,in pancreatic cancer with short survival,death is a major competing event,conventional time-to-event analyses without competing-risk frameworks may thereby underestimate the metastasisrelated effect.Additionally,mechanistic research supports the concept of a premetastatic hepatic niche that is driven by inflammation and metabolic reprogramming in pancreatic cancer.Therefore,we conclude that the statistical absence of correlation should not be conflated with the absence of biological causation.Instead,future studies incorporating fibrosis-focused phenotyping,treatment-aware modeling,and competing-risk analyses are warranted to clarify which MASLD subtypes may meaningfully influence metastasis and survival. 展开更多
关键词 Metabolic dysfunction-associated liver disease Pancreatic cancer Metastasis Statistical biases Phenotypic heterogeneity Biological plausibility
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Bile acid receptor signaling in metabolic dysfunction-associated steatotic liver disease:Mechanistic insights and emerging therapeutic strategies 认领 引用
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作者 Sanjay Bandyopadhyay Shambo Samrat Samajdar +1 位作者 Shatavisa Mukherjee Shashank R Joshi 《World Journal of Hepatology》 2026年第6期71-83,共13页
Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most prevalent chronic liver disease worldwide,spanning a spectrum from simple steatosis to metabolic dysfunction-associated steatohepatitis,fibros... Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most prevalent chronic liver disease worldwide,spanning a spectrum from simple steatosis to metabolic dysfunction-associated steatohepatitis,fibrosis,cirrhosis,and hepatocellular carcinoma.In addition to liver-related morbidity,MASLD is closely associated with systemic metabolic dysfunction and increased cardiovascular risk,emphasizing the need for mechanism-based therapies.Bile acids are now recognized as key metabolic and immunological signaling molecules acting through receptors such as the farnesoid X receptor(FXR)and the G proteincoupled bile acid receptor Takeda G-protein-coupled receptor 5.This narrative review summarizes current evidence on bile acid receptor signaling in MASLD,focusing on receptor biology,molecular mechanisms,and emerging therapeutic strategies.We discuss how changes in bile acid composition,receptor responsiveness,and downstream signaling contribute to metabolic dysregulation,inflammation,and fibrogenesis,while acknowledging inter-individual heterogeneity and limited stage-specific human data.Particular attention is given to FXR and Takeda G-protein-coupled receptor 5 signaling,their interaction with metabolic and inflammatory pathways,and modulation by gut microbiota-derived bile acid transformations.We also review clinical and translational data on bile acid-targeted therapies,including FXR agonists and norursodeoxycholic acid,highlighting therapeutic promise alongside challenges related to lipid effects,long-term safety,and variable efficacy.Overall,bile acid signaling represents a promising yet complex therapeutic axis in MASLD. 展开更多
关键词 Metabolic dysfunction-associated steatotic liver disease Bile acid receptors Farnesoid X receptor Takeda Gprotein-coupled receptor 5 Norursodeoxycholic acid
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Fighting the epidemic of pediatric metabolic dysfunction-associated steatotic liver disease:Role of non-invasive diagnostics and early pharmacological intervention 认领 引用
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作者 Nicholas Beng-Hui Ng Andrew Anjian Sng James Guoxian Huang 《World Journal of Hepatology》 2026年第1期47-59,共13页
The global rise in childhood obesity has made metabolic dysfunction-associated steatotic liver disease(MASLD)the leading cause of pediatric liver disease.Studies have consistently reported alarmingly high rates of adv... The global rise in childhood obesity has made metabolic dysfunction-associated steatotic liver disease(MASLD)the leading cause of pediatric liver disease.Studies have consistently reported alarmingly high rates of advanced fibrosis in up to 20%of adolescents with MASLD.There is evidence that pediatric MASLD may run a more severe clinical course compared to adults,as well as pose an independent risk factor for mortality than pediatric obesity or type 2 diabetes mellitus alone.This underscores the necessity for timely recognition,accurate diagnosis and early institution of therapeutic interventions for pediatric MASLD.In this minireview,we discuss the various non-invasive diagnostic modalities used for the evaluation of MASLD,and propose an updated diagnostic and monitoring algorithm incorporating recent multi-societal statements.The advent of noninvasive diagnostics such as vibration-controlled transient elastography in children allows for earlier recognition of liver fibrosis,and may prioritize the need for early pharmacological therapy.We also discuss the importance of early pharmacological intervention in pediatric MASLD,in particular the use of glucagonlike peptide 1 receptor agonists which may have potential to halt MASLD progression if instituted early,and the potential role for novel anti-fibrotic therapy in this population. 展开更多
关键词 Pediatric metabolic dysfunction-associated steatotic liver disease Glucagonlike peptide 1 receptor agonists Vibration-controlled transient elastography Resmetirom Pediatric obesity
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