Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its glo...Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its global prevalence is rising,largely driven by urbanization,sedentary lifestyles,and dietary changes.These same factors are also associated with the increasing incidence of inflammatory bowel diseases(IBD),including Crohn’s disease and ulcerative colitis.Emerging evidence supports a potential biological link between chronic gastrointestinal inflammation and the later development of cardiometabolic disorders;a con-nection that is particularly relevant for patients with IBD.Comparative studies examining cardiometabolic risk associated with Crohn’s disease versus ulcerative colitis have reported inconsistent findings,likely due to confounding factors such as age,lifestyle,and comorbidities.This review summarizes current evidence linking IBD and cardiometabolic disorders,and highlights the need for clinicians to recognize cardiometabolic risk in patients with IBD.Future research should investigate whether treat-to-target strategies focused on controlling intestinal inflammation can simultaneously improve both long-term IBD and cardiometabolic outcomes.展开更多
This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use o...This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use of glucagon-like peptide 1 receptor agonists,especially when used in combination therapy.However,despite their notable efficacy,these drugs were not initially designed to target MASLD directly.In a groundbreaking development,the Food and Drug Administration has recently approved resmetirom,the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated steatohepatitis.Resmetirom,an orally administered,liver-directed thyroid hormone beta-selective agonist,acts directly on intrahepatic pathways,enhancing its therapeutic potential and marking the beginning of a new era in the treatment of MASLD.Furthermore,the integration of lifestyle modifications into liver disease management is an essential component that should be considered and reinforced.By incorporating dietary changes and regular physical exercise into treatment,patients may achieve improved outcomes,reducing the need for pharmacological interventions and/or improving treatment efficacy.As a complement to medical therapies,lifestyle factors should not be overlooked in the broader strategy for managing MASLD.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)has become a leading cause of liver-related morbidity worldwide.Despite broad consensus on the importance of diet in managing the disease,numerous myths a...Metabolic dysfunction-associated steatotic liver disease(MASLD)has become a leading cause of liver-related morbidity worldwide.Despite broad consensus on the importance of diet in managing the disease,numerous myths and miscon-ceptions persist among patients,healthcare professionals,and the general public.This article aims to critically review the main myths and facts surrounding the role of diet in MASLD,in light of the most current scientific evidence.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highli...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highlighting the need for non-invasive alternatives.AIM To investigate extracellular vesicles(EVs)as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning(ML)and explainable artificial intelligence(XAI).METHODS In this single-center observational study,798 patients with metabolic dysfunction were enrolled.Of these,194 met the eligibility criteria,and 76 successfully completed all study procedures.Transient elastography was used for steatosis and fibrosis staging,and circulating plasma EV characteristics were analyzed through nanoparticle tracking.Twenty ML models were developed:Six to differentiate non-steatosis(S0)from steatosis(S1-S3);and fourteen to identify severe steatosis(S3).Models utilized EV features(size and concentration),clinical(advanced fibrosis and presence of type 2 diabetes mellitus),and anthropomorphic(sex,age,height,weight,body mass index)data.Their performance was assessed using receiver operating characteristic(ROC)-area under the curve(AUC),specificity,and sensitivity,while correlation and XAI analysis were also conducted.RESULTS The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86(train/test)on average across ten random five-fold cross-validations,using EV features alone to distinguish S0 from S1-S3.The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00(train/test)on average across ten random three-fold cross-validations,using engineered features including EVs,clinical features like diabetes and advanced fibrosis,and anthropomorphic data like body mass index and weight for identifying severe steatosis(S3).Key predictors included EV mean size and concentration.Correlation,XAI,and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages.CONCLUSION The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis(S0)in patients with metabolic dysfunction,while the combination of EV,clinical,and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis.The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights.However,further large multicenter studies,comparisons,and validation with histopathology and advanced imaging methods are needed.展开更多
This research is to explore the relationship between Helicobacter pylori (H. pylori)infection and the development of metabolic dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD), based on...This research is to explore the relationship between Helicobacter pylori (H. pylori)infection and the development of metabolic dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD), based on research by Ye et al.Their investigation analyzed the association of H. pylori infection with obesity,glucose, lipids, blood pressure, and MASLD in Chinese adults, through a crosssectionalstudy of 28624 participants. Clinical data analysis demonstrated thatH. pylori-positive participants exhibited significantly higher ages, blood glucose,total cholesterol, low-density lipoprotein, body mass index, systolic and diastolicblood pressure levels, and greater MASLD detection rates compare to the H. pylori-negative participants. These differences achieved statistical significance (P <0.05). Multivariate analysis identified, elevated glucose, body mass index, anddiastolic pressure as independent risk factors for H. pylori infection, while highdensitylipoprotein demonstrated protective effects. These findings suggest thatH. pylori infection may contribute to metabolic disturbances and MASLD.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is now the predominant global cause of chronic liver disease and represents a major indication for liver transplantation.Post-transplant MASLD manifests a...Metabolic dysfunction-associated steatotic liver disease(MASLD)is now the predominant global cause of chronic liver disease and represents a major indication for liver transplantation.Post-transplant MASLD manifests as recurrent disease in nearly all recipients by five years post-transplantation,while de novo MASLD shows variable incidence(18%-78%).Although histologically similar,recurrent MASLD follows a more aggressive trajectory,with accelerated fibrosis and cirrhosis.Metabolic disturbances,immunosuppression regimens,donorrelated factors,and chronic inflammation synergistically contribute to disease pathogenesis.The disorder not only compromises graft function but is also associated with elevated cardiovascular and overall morbidity,and malignancy risk.Despite advancements in noninvasive diagnostics,histopathology remains essential for definitive diagnosis and prognostic stratification.Management should prioritize metabolic optimization,lifestyle intervention,and tailored immunosuppressive regimens.Glucagon-like peptide-1 receptor agonists represent a promising therapeutic avenue.However,the absence of standardized,transplant-specific guidelines is a significant limitation.Further research is necessary to define diagnostic criteria,risk stratification,and targeted therapy to improve graft survival and patient outcomes.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is a progressive metabolic disorder that is pathologically characterized by abnormal lipid deposition in the liver and metabolic inflammation.The current ...Metabolic dysfunction-associated steatotic liver disease(MASLD)is a progressive metabolic disorder that is pathologically characterized by abnormal lipid deposition in the liver and metabolic inflammation.The current clinical mana-gement of MASLD largely involves generalized lifestyle modifications including diet and broad-spectrum metabolic interventions such as insulin sensitizers.These approaches often yield suboptimal outcomes because of poor long-term adhe-rence,heterogeneous patient responses,and limited efficacy in advanced disease stages.Crucially,they fail to address disease-specific molecular drivers,such as aging-associated pathways exemplified by vitamin D receptor dysregulation.Given the complexity and progressive nature of MASLD,it is crucial to further elucidate its mechanisms,develop precise therapeutic strategies,and raise awareness of the disease among the public and medical community.展开更多
Bariatric and metabolic surgeries have gained extensive popularity and trust due to their documented efficacy and safety in managing not only obesity but also associated comorbidities such as diabetes mellitus, hypert...Bariatric and metabolic surgeries have gained extensive popularity and trust due to their documented efficacy and safety in managing not only obesity but also associated comorbidities such as diabetes mellitus, hypertension, dyslipidemia, sleep apnea, and joint pain. Traditionally, bariatric surgeries have been categorized into hypoabsorptive, restrictive, or hybrid approaches. However, these classifications inadequately reflect the complex anatomical and physiological alterations associated with modern surgical methodologies. This paper explores the evolution of metabolic surgeries, emphasizing the integration of physiological concepts into classic procedures to provide more tailored and effective treatment options for obesity and its comorbidities. Finally, the proposal for a new classification based on current metabolic concepts will facilitate communication among patients, doctors, and healthcare professionals. Additionally, it will enable a more didactic and standardized approach to data collection for conducting studies and publications.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most widespread chronic liver disease signified by serious life-threatening conditions.The prevalence of MASLD increases along the growing prevalen...Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most widespread chronic liver disease signified by serious life-threatening conditions.The prevalence of MASLD increases along the growing prevalence in obesity and metabolic syndrome.To minimize costs and complications,non-invasive diagnostic tools,including transient elastography(TE),were introduced for assessment of MASLD.TE measures liver stiffness(LS),a clinical marker for the diagnosis of liver fibrosis and cirrhosis.LS measurements are based on ultrasound wave imaging and quantification.Vibration-controlled TE,including FibroScan®,is commonly used TE methods which can accurately identify the degree of liver fibrosis and cirrhosis progression.TE was reported to predict the progression towards hepatocellular carcinoma,portal hypertension,and varices.However,the accuracy of LS diagnostics alone in patients with MASLD remains controversial.TE measurements have several limitations,including inadequate precision due to focal liver lesions,cholestasis,inflammation,and other pathological and anatomical factors which can lead to the stiffness variability.Overestimations of TE readings were reported in obese patients with body mass index(BMI)over 30 kg/m2,and older patients with ascites,diabetes,or hypertension.Not all MASLD patients have high BMI.The prevalence of obesity among MASLD patients varies worldwide,indicating the urgent need for comprehensive diagnostic tools.In patients with MASLD,improved diagnostic accuracy has been demonstrated by combining LS measurements with other blood test-based scores and simple clinical parameters(agile scores based on age,sex,platelet count,aminotransferases,and diabetes).This study reviews the limitations of TE-based diagnostics and discusses the combined scoring algorithm.In conclusion,the sequence of LS measurements along assessment of other important clinical markers is an effective,low-cost,reliable tool to identify and monitor fibrosis progression in MASLD.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)is currently the leading cause of end-stage liver disease and liver cancer in the world because of the obesity pandemic.Insulin resistance resulting from abdo...Metabolic dysfunction-associated fatty liver disease(MAFLD)is currently the leading cause of end-stage liver disease and liver cancer in the world because of the obesity pandemic.Insulin resistance resulting from abdominal adiposity is the main cause of MAFLD and type 2 diabetes mellitus among these patients.Although very common,therapeutic options for MAFLD are currently limited.Metabolic and bariatric surgery is the best treatment option for weight loss that can also improve MAFLD in a very high proportion of patients.However,surgical interventions are expensive,technically challenging,and carry significant immediate and long-term postoperative risks.Duodenal mucosal ablation,a malabsorptive endoscopic bariatric intervention,has shown beneficial effects in the management of obesity with an improvement of insulin resistance.It alters the duodenal mucosal lining,which helps maintain cellular homeostasis and better intestinal endocrine function.This process helps reduce lipid deposition in the liver,maintain serum lipid levels,and promote weight loss,especially in patients with type 2 diabetes mellitus-related MAFLD.However,some of these effects were independent of weight loss and food intake.As a minimally invasive procedure,it is beneficial for patients who have not had success with drug therapy alone,though this approach needs to be tested and further developed in future clinical trials.A basic study by Yu et al in the recent issue of the World Journal of Gastroenterology on duodenal mucosal ablation using irreversible electroporation,when experimented on rats,has shown fewer complications compared to other metabolic surgeries.This editorial describes the minimally invasive endoscopic bariatric strategies for the management of obesity and MAFLD in light of this experimental study.展开更多
This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellula...This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellular carcinoma(HCC).The study highlights the role of mitochondrial carnitine palmitoyltransferase Ⅱ(CPT Ⅱ)inactivity,which activates liver cancer stem cells marked by cluster of differentiation 44(CD44)and CD24 expression,promoting HCC development.Using dynamic mouse models and clinical samples,Wang et al identified CPT Ⅱ downregulation,mitochondrial membrane potential alterations,and reduced intrahepatic CD4^(+)T cell as key drivers of disease progression.The findings link these changes to steroid biosynthesis and p53 signaling,contributing to T-cell dysfunction and immunosuppression.This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT Ⅱ activity,mitochondrial function,and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.展开更多
In this article,we discuss the article recently published by Zhao et al.This study focused on the intersection of metabolic dysfunction-associated steatotic liver disease(MASLD)and drug-induced liver injury(DILI),two ...In this article,we discuss the article recently published by Zhao et al.This study focused on the intersection of metabolic dysfunction-associated steatotic liver disease(MASLD)and drug-induced liver injury(DILI),two major contributors to the global burden of liver disease.By analyzing clinical characteristics,metabolic parameters,immune profiles,and liver pathology,Zhao et al comprehensively explored how MASLD influences the presentation,severity,and prognosis of DILI.Additionally,this study underscores the importance of structured diagnostic tools,such as the Roussel Uclaf Causality Assessment Method,to accurately assess the causality of DILI within the MASLD population.Although this study provides valuable insights,limitations such as its retrospective design and cohort heterogeneity underscore the need for future prospective research to refine diagnostic approaches and therapeutic strategies.展开更多
The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health...The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.展开更多
BACKGROUND The global incidence of metabolic dysfunction-associated steatotic liver disease(MASLD)has increased in recent years.It has already been demonstrated that exercise and weight change are associated with the ...BACKGROUND The global incidence of metabolic dysfunction-associated steatotic liver disease(MASLD)has increased in recent years.It has already been demonstrated that exercise and weight change are associated with the occurrence of MASLD;however,the association between weight fluctuation caused by different exercise intensities and the risk of MASLD remains to be studied.AIM To investigate the impact of weight fluctuation and physical activity intensity on the risk of MASLD prevalence.METHODS Data from the National Health and Nutrition Examination Survey database including five cycles from 2009 to 2018 were analyzed.The model included variables such as age,sex,and poverty income ratio.Weighted multivariate logistic regression was used to examine the influence of different weight fluctuation patterns within the two time intervals on the prevalence of MASLD.Nonparametric restricted cubic spline curves were used to analyze the non-linear relationship between net weight change and MASLD prevalence.RESULTS Among 3183 MASLD cases,the risk of MASLD increased with age for individuals transitioning from non-obese to obese or maintaining obesity,with odds ratio(OR)changing from 8.91(95%CI:7.40-10.88)and 11.87(95%CI:9.65-14.60)at 10 years before baseline to 9.58(95%CI:8.08-11.37)and 12.51(95%CI:9.33-16.78)at 25 years.Stable obesity correlated with age-dependent MASLD prevalence escalation,whereas increased physical activity attenuated MASLD risk in this group,with an OR changing from 13.64(95%CI:10.59-17.57)to 6.42(95%CI:4.24-9.72).Further analysis of the net weight changes revealed a paradoxical risk elevation with intensified physical activity during different time periods.CONCLUSION The risk of MASLD increases in individuals transitioning from non-obese to obese or maintaining obesity.Highintensity physical activity is beneficial for MASLD among individuals with stable obesity.展开更多
BACKGROUND Metabolic dysfunction-associated fatty liver disease(MASLD)is a chronic liver disease characterized by hepatocellular steatosis,which is closely related to metabolic syndrome,with annually increasing morbid...BACKGROUND Metabolic dysfunction-associated fatty liver disease(MASLD)is a chronic liver disease characterized by hepatocellular steatosis,which is closely related to metabolic syndrome,with annually increasing morbidity in recent years.Gynecomastia(GYN),an abnormal proliferation of breast tissue in males,is common in males with sex hormone imbalance.Currently,there is insufficient research on the morbidity of GYN and its correlation among MASLD patients.AIM To investigate the prevalence of GYN and its associated clinical features in patients with MASLD and determine the prevalence of GYN in patients with MASLD and analyze the predictive effect of sex hormones on GYN using receiver operating characteristic(ROC)curves.METHODS A cross-sectional study was conducted in a tertiary care hospital.Among them,997 patients met the inclusion criteria and underwent breast ultrasonography to determine the presence of GYN.Anthropometric data,laboratory test data[estradiol(E2),androgens,liver function,glucose,lipids,low-density lipoprotein,high-density lipoprotein,creatinine,and uric acid,etc.],as well as information on medical history,severity of fatty liver(mild,moderate,and severe),and duration of the disease were collected.Package for the Social Sciences version 27 and R software(version 4.3.1)were used for data analysis.RESULTS The prevalence of GYN increased with the severity of fatty liver(27.6%for mild,33.5%for moderate,and 58%for severe,P<0.001);compared with non-GYN patients,GYN patients were older(54.11±9.71 years vs 47.89±9.92 years,P<0.001),with significantly higher E2 levels,higher estrogen to androgen ratio(P<0.001)and significantly lower androgen levels(P<0.001).In ROC curve analysis,the combined model of testosterone and E2 had a high diagnostic value in predicting GYN in MASLD patients,surpassing a single indicator.CONCLUSION The presence of GYN may suggest more severe metabolic abnormalities in patients with MASLD.Therefore,early recognition of GYN may be crucial for early intervention in metabolic syndrome and endocrine abnormalities in patients with MASLD.展开更多
The growing global burden of metabolic dysfunction-associated steatohepatitis(MASH)demands a deeper understanding of its underlying mechanisms and risk factors.Recent studies,such as the large population-based case-co...The growing global burden of metabolic dysfunction-associated steatohepatitis(MASH)demands a deeper understanding of its underlying mechanisms and risk factors.Recent studies,such as the large population-based case-control analysis by Abdel-Razeq et al,suggest a significant association between Helicobacter pylori(H.pylori)infection and an increased risk of developing MASH.This study provides compelling data supporting this association,even after adjusting for confounders such as obesity,diabetes,and hyperlipidemia.However,the complexity of this relationship remains unresolved,requiring further investigation into the biological,genetic,and environmental pathways that connect these two conditions.This article critically reviews the study’s findings and identifies its limitations,offering innovative research directions for the future.Key areas of focus include integrating genomic and microbiome analyses,exploring the impact of H.pylori eradication on MASH progression,studying molecular mechanisms at the intersection of infection and liver disease,and developing personalized therapeutic strategies.展开更多
Gosnell and colleagues executed a large-scale cohort investigation delineating ethnic disparities in outcomes among individuals with metabolic dysfunction–as-sociated steatotic liver disease/steatohepatitis(MASLD/MAS...Gosnell and colleagues executed a large-scale cohort investigation delineating ethnic disparities in outcomes among individuals with metabolic dysfunction–as-sociated steatotic liver disease/steatohepatitis(MASLD/MASH).Uncovering such heterogeneity is pivotal to optimising management and prognostication,notably for hepatocellular carcinoma,fibrotic progression,and all-cause mortality.The authors furnish granular trajectories for Hispanic vs non-Hispanic popula-tions across the United States and southeastern Texas,alongside a comprehensive appraisal of MASLD/MASH-related event rates.These insights provide an indispensable framework for early risk stratification and the tailoring of thera-peutic algorithms and surveillance regimens.The study underscores the necessity for nuanced appreciation of MASLD/MASH outcome profiles and associated management strategies,while interrogating regional variation in disease burden,the benefits of integrated metabolic care,and the potential of lifestyle inter-ventions to attenuate complications and improve prognosis.展开更多
The dependence of energy metabolism on temperature is universally recognized as a critical physiological hallmark for evaluating the susceptibility of ectothermic organisms to global warming.However,the underlying phy...The dependence of energy metabolism on temperature is universally recognized as a critical physiological hallmark for evaluating the susceptibility of ectothermic organisms to global warming.However,the underlying physiological and biochemical bases of this temperature dependence remain largely unknown.In this study,we conducted a simulated climate warming experiment under seminatural enclosure conditions and compared the differences in resting metabolic rate (RMR) and key metabolic enzyme activities between the warming and control groups of Takydromus septentrionalis at various test temperatures.We found that the activities of hexokinase,lactate dehydrogenase,alanine aminotransferase and acetyl-CoA carboxylase of T.septentrionalis were not affected by climate warming,despite a decrease in RMR measured at high temperatures of 34°C and 38°C.Overall,these findings suggest that artificial warming simulating climate change can lead to a decline in RMR,but does not alter the activity of key metabolic enzymes.Our study provides insight into how climate warming influences the energy metabolism of lizards.展开更多
This article examines the study by Lin et al,which explores the effects of night sentry duties on cardiometabolic health in military personnel.The research identifies significant correlations between the frequency of ...This article examines the study by Lin et al,which explores the effects of night sentry duties on cardiometabolic health in military personnel.The research identifies significant correlations between the frequency of night shifts and nega-tive cardiometabolic outcomes,such as elevated resting pulse rates and lowered levels of high-density lipoprotein cholesterol.These outcomes underscore the health risks linked to partial sleep deprivation,a common challenge in military environments.The editorial highlights the clinical significance of these findings,advocating for the implementation of targeted health interventions to mitigate these risks.Strategies such as structured sleep recovery programs and lifestyle modifications are recommended to improve the health management of military personnel engaged in nocturnal duties.By addressing these issues,military health management can better safeguard the well-being and operational readiness of its personnel.展开更多
BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is the most common cause of chronic liver disease and remains under-recognized within the health check-up population.Ultrasonography during physical examinatio...BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is the most common cause of chronic liver disease and remains under-recognized within the health check-up population.Ultrasonography during physical examination fail to accurately identify at-risk patients as they involve multiple metabolic aspects.AIM To rapidly identify hepatic steatosis patients from high-metabolic-risk populations and reduce medical costs.METHODS We analyzed all data from a prospective cohort study to identify potential predictors of MAFLD risk.The LASSO and recursive feature elimination were used to screen for feature selection.Four machine learning models were employed to construct the prediction model for hepatic steatosis.RESULTS We found that 86.2%of the 1011 individuals in the trial phase exhibited metabolic abnormalities,with 70.8%presenting with hepatic steatosis.After data cleaning,711 participants(207 non-MAFLD patients vs 504 MAFLD patients)were included,and the prediction models were validated.After overlapping and reducing the feature set based on feature importance ranking,we developed an interpretable final XGBoost model with 10 features,achieving an area under the curve of 0.82.CONCLUSION We have introduced a valuable noninvasive tool for efficiently identifying hepatic steatosis patients in highmetabolic-risk populations.This tool may improve screening effectiveness and reduce medical costs.展开更多
文摘Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its global prevalence is rising,largely driven by urbanization,sedentary lifestyles,and dietary changes.These same factors are also associated with the increasing incidence of inflammatory bowel diseases(IBD),including Crohn’s disease and ulcerative colitis.Emerging evidence supports a potential biological link between chronic gastrointestinal inflammation and the later development of cardiometabolic disorders;a con-nection that is particularly relevant for patients with IBD.Comparative studies examining cardiometabolic risk associated with Crohn’s disease versus ulcerative colitis have reported inconsistent findings,likely due to confounding factors such as age,lifestyle,and comorbidities.This review summarizes current evidence linking IBD and cardiometabolic disorders,and highlights the need for clinicians to recognize cardiometabolic risk in patients with IBD.Future research should investigate whether treat-to-target strategies focused on controlling intestinal inflammation can simultaneously improve both long-term IBD and cardiometabolic outcomes.
文摘This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use of glucagon-like peptide 1 receptor agonists,especially when used in combination therapy.However,despite their notable efficacy,these drugs were not initially designed to target MASLD directly.In a groundbreaking development,the Food and Drug Administration has recently approved resmetirom,the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated steatohepatitis.Resmetirom,an orally administered,liver-directed thyroid hormone beta-selective agonist,acts directly on intrahepatic pathways,enhancing its therapeutic potential and marking the beginning of a new era in the treatment of MASLD.Furthermore,the integration of lifestyle modifications into liver disease management is an essential component that should be considered and reinforced.By incorporating dietary changes and regular physical exercise into treatment,patients may achieve improved outcomes,reducing the need for pharmacological interventions and/or improving treatment efficacy.As a complement to medical therapies,lifestyle factors should not be overlooked in the broader strategy for managing MASLD.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)has become a leading cause of liver-related morbidity worldwide.Despite broad consensus on the importance of diet in managing the disease,numerous myths and miscon-ceptions persist among patients,healthcare professionals,and the general public.This article aims to critically review the main myths and facts surrounding the role of diet in MASLD,in light of the most current scientific evidence.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highlighting the need for non-invasive alternatives.AIM To investigate extracellular vesicles(EVs)as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning(ML)and explainable artificial intelligence(XAI).METHODS In this single-center observational study,798 patients with metabolic dysfunction were enrolled.Of these,194 met the eligibility criteria,and 76 successfully completed all study procedures.Transient elastography was used for steatosis and fibrosis staging,and circulating plasma EV characteristics were analyzed through nanoparticle tracking.Twenty ML models were developed:Six to differentiate non-steatosis(S0)from steatosis(S1-S3);and fourteen to identify severe steatosis(S3).Models utilized EV features(size and concentration),clinical(advanced fibrosis and presence of type 2 diabetes mellitus),and anthropomorphic(sex,age,height,weight,body mass index)data.Their performance was assessed using receiver operating characteristic(ROC)-area under the curve(AUC),specificity,and sensitivity,while correlation and XAI analysis were also conducted.RESULTS The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86(train/test)on average across ten random five-fold cross-validations,using EV features alone to distinguish S0 from S1-S3.The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00(train/test)on average across ten random three-fold cross-validations,using engineered features including EVs,clinical features like diabetes and advanced fibrosis,and anthropomorphic data like body mass index and weight for identifying severe steatosis(S3).Key predictors included EV mean size and concentration.Correlation,XAI,and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages.CONCLUSION The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis(S0)in patients with metabolic dysfunction,while the combination of EV,clinical,and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis.The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights.However,further large multicenter studies,comparisons,and validation with histopathology and advanced imaging methods are needed.
基金Supported by National Natural Science Foundation of China,No.82270594.
文摘This research is to explore the relationship between Helicobacter pylori (H. pylori)infection and the development of metabolic dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD), based on research by Ye et al.Their investigation analyzed the association of H. pylori infection with obesity,glucose, lipids, blood pressure, and MASLD in Chinese adults, through a crosssectionalstudy of 28624 participants. Clinical data analysis demonstrated thatH. pylori-positive participants exhibited significantly higher ages, blood glucose,total cholesterol, low-density lipoprotein, body mass index, systolic and diastolicblood pressure levels, and greater MASLD detection rates compare to the H. pylori-negative participants. These differences achieved statistical significance (P <0.05). Multivariate analysis identified, elevated glucose, body mass index, anddiastolic pressure as independent risk factors for H. pylori infection, while highdensitylipoprotein demonstrated protective effects. These findings suggest thatH. pylori infection may contribute to metabolic disturbances and MASLD.
基金Supported by The LTx Unit at Hospital Israelita Albert Einstein is financed by the Programa de Apoio ao Desenvolvimento Insitucional do SUS(PROADI-SUS)a partnership with the Brazilian Ministry of Health,No.25000.171086/2023-80.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is now the predominant global cause of chronic liver disease and represents a major indication for liver transplantation.Post-transplant MASLD manifests as recurrent disease in nearly all recipients by five years post-transplantation,while de novo MASLD shows variable incidence(18%-78%).Although histologically similar,recurrent MASLD follows a more aggressive trajectory,with accelerated fibrosis and cirrhosis.Metabolic disturbances,immunosuppression regimens,donorrelated factors,and chronic inflammation synergistically contribute to disease pathogenesis.The disorder not only compromises graft function but is also associated with elevated cardiovascular and overall morbidity,and malignancy risk.Despite advancements in noninvasive diagnostics,histopathology remains essential for definitive diagnosis and prognostic stratification.Management should prioritize metabolic optimization,lifestyle intervention,and tailored immunosuppressive regimens.Glucagon-like peptide-1 receptor agonists represent a promising therapeutic avenue.However,the absence of standardized,transplant-specific guidelines is a significant limitation.Further research is necessary to define diagnostic criteria,risk stratification,and targeted therapy to improve graft survival and patient outcomes.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is a progressive metabolic disorder that is pathologically characterized by abnormal lipid deposition in the liver and metabolic inflammation.The current clinical mana-gement of MASLD largely involves generalized lifestyle modifications including diet and broad-spectrum metabolic interventions such as insulin sensitizers.These approaches often yield suboptimal outcomes because of poor long-term adhe-rence,heterogeneous patient responses,and limited efficacy in advanced disease stages.Crucially,they fail to address disease-specific molecular drivers,such as aging-associated pathways exemplified by vitamin D receptor dysregulation.Given the complexity and progressive nature of MASLD,it is crucial to further elucidate its mechanisms,develop precise therapeutic strategies,and raise awareness of the disease among the public and medical community.
文摘Bariatric and metabolic surgeries have gained extensive popularity and trust due to their documented efficacy and safety in managing not only obesity but also associated comorbidities such as diabetes mellitus, hypertension, dyslipidemia, sleep apnea, and joint pain. Traditionally, bariatric surgeries have been categorized into hypoabsorptive, restrictive, or hybrid approaches. However, these classifications inadequately reflect the complex anatomical and physiological alterations associated with modern surgical methodologies. This paper explores the evolution of metabolic surgeries, emphasizing the integration of physiological concepts into classic procedures to provide more tailored and effective treatment options for obesity and its comorbidities. Finally, the proposal for a new classification based on current metabolic concepts will facilitate communication among patients, doctors, and healthcare professionals. Additionally, it will enable a more didactic and standardized approach to data collection for conducting studies and publications.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most widespread chronic liver disease signified by serious life-threatening conditions.The prevalence of MASLD increases along the growing prevalence in obesity and metabolic syndrome.To minimize costs and complications,non-invasive diagnostic tools,including transient elastography(TE),were introduced for assessment of MASLD.TE measures liver stiffness(LS),a clinical marker for the diagnosis of liver fibrosis and cirrhosis.LS measurements are based on ultrasound wave imaging and quantification.Vibration-controlled TE,including FibroScan®,is commonly used TE methods which can accurately identify the degree of liver fibrosis and cirrhosis progression.TE was reported to predict the progression towards hepatocellular carcinoma,portal hypertension,and varices.However,the accuracy of LS diagnostics alone in patients with MASLD remains controversial.TE measurements have several limitations,including inadequate precision due to focal liver lesions,cholestasis,inflammation,and other pathological and anatomical factors which can lead to the stiffness variability.Overestimations of TE readings were reported in obese patients with body mass index(BMI)over 30 kg/m2,and older patients with ascites,diabetes,or hypertension.Not all MASLD patients have high BMI.The prevalence of obesity among MASLD patients varies worldwide,indicating the urgent need for comprehensive diagnostic tools.In patients with MASLD,improved diagnostic accuracy has been demonstrated by combining LS measurements with other blood test-based scores and simple clinical parameters(agile scores based on age,sex,platelet count,aminotransferases,and diabetes).This study reviews the limitations of TE-based diagnostics and discusses the combined scoring algorithm.In conclusion,the sequence of LS measurements along assessment of other important clinical markers is an effective,low-cost,reliable tool to identify and monitor fibrosis progression in MASLD.
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)is currently the leading cause of end-stage liver disease and liver cancer in the world because of the obesity pandemic.Insulin resistance resulting from abdominal adiposity is the main cause of MAFLD and type 2 diabetes mellitus among these patients.Although very common,therapeutic options for MAFLD are currently limited.Metabolic and bariatric surgery is the best treatment option for weight loss that can also improve MAFLD in a very high proportion of patients.However,surgical interventions are expensive,technically challenging,and carry significant immediate and long-term postoperative risks.Duodenal mucosal ablation,a malabsorptive endoscopic bariatric intervention,has shown beneficial effects in the management of obesity with an improvement of insulin resistance.It alters the duodenal mucosal lining,which helps maintain cellular homeostasis and better intestinal endocrine function.This process helps reduce lipid deposition in the liver,maintain serum lipid levels,and promote weight loss,especially in patients with type 2 diabetes mellitus-related MAFLD.However,some of these effects were independent of weight loss and food intake.As a minimally invasive procedure,it is beneficial for patients who have not had success with drug therapy alone,though this approach needs to be tested and further developed in future clinical trials.A basic study by Yu et al in the recent issue of the World Journal of Gastroenterology on duodenal mucosal ablation using irreversible electroporation,when experimented on rats,has shown fewer complications compared to other metabolic surgeries.This editorial describes the minimally invasive endoscopic bariatric strategies for the management of obesity and MAFLD in light of this experimental study.
文摘This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellular carcinoma(HCC).The study highlights the role of mitochondrial carnitine palmitoyltransferase Ⅱ(CPT Ⅱ)inactivity,which activates liver cancer stem cells marked by cluster of differentiation 44(CD44)and CD24 expression,promoting HCC development.Using dynamic mouse models and clinical samples,Wang et al identified CPT Ⅱ downregulation,mitochondrial membrane potential alterations,and reduced intrahepatic CD4^(+)T cell as key drivers of disease progression.The findings link these changes to steroid biosynthesis and p53 signaling,contributing to T-cell dysfunction and immunosuppression.This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT Ⅱ activity,mitochondrial function,and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.
文摘In this article,we discuss the article recently published by Zhao et al.This study focused on the intersection of metabolic dysfunction-associated steatotic liver disease(MASLD)and drug-induced liver injury(DILI),two major contributors to the global burden of liver disease.By analyzing clinical characteristics,metabolic parameters,immune profiles,and liver pathology,Zhao et al comprehensively explored how MASLD influences the presentation,severity,and prognosis of DILI.Additionally,this study underscores the importance of structured diagnostic tools,such as the Roussel Uclaf Causality Assessment Method,to accurately assess the causality of DILI within the MASLD population.Although this study provides valuable insights,limitations such as its retrospective design and cohort heterogeneity underscore the need for future prospective research to refine diagnostic approaches and therapeutic strategies.
基金American Heart Association Award,No.24IVPHA1288417and FCT Fellowships,No.2022.13253.BDANA.
文摘The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.
基金Supported by National Natural Science Foundation of China,No.82474378Shanghai Natural Science Foundation,No.22ZR1455900+4 种基金Shanghai Municipal Health Planning Commission Clinical Research Specialized Face Project,No.201940449Key Project of Science and Technology Innovation Program of Shanghai Putuo District Health and Health System,No.ptkwws202201Reserve Excellent Chinese Medicine Talent Program of Shanghai University of Traditional Chinese Medicine,No.20D-RC-02Apricot Grove,Shanghai Putuo District Excellent Young Talent Training Program,No.ptxlyq2201Shanghai Putuo District Health and Health System Characteristic Specialty Disease Construction Project,No.2023tszb01.
文摘BACKGROUND The global incidence of metabolic dysfunction-associated steatotic liver disease(MASLD)has increased in recent years.It has already been demonstrated that exercise and weight change are associated with the occurrence of MASLD;however,the association between weight fluctuation caused by different exercise intensities and the risk of MASLD remains to be studied.AIM To investigate the impact of weight fluctuation and physical activity intensity on the risk of MASLD prevalence.METHODS Data from the National Health and Nutrition Examination Survey database including five cycles from 2009 to 2018 were analyzed.The model included variables such as age,sex,and poverty income ratio.Weighted multivariate logistic regression was used to examine the influence of different weight fluctuation patterns within the two time intervals on the prevalence of MASLD.Nonparametric restricted cubic spline curves were used to analyze the non-linear relationship between net weight change and MASLD prevalence.RESULTS Among 3183 MASLD cases,the risk of MASLD increased with age for individuals transitioning from non-obese to obese or maintaining obesity,with odds ratio(OR)changing from 8.91(95%CI:7.40-10.88)and 11.87(95%CI:9.65-14.60)at 10 years before baseline to 9.58(95%CI:8.08-11.37)and 12.51(95%CI:9.33-16.78)at 25 years.Stable obesity correlated with age-dependent MASLD prevalence escalation,whereas increased physical activity attenuated MASLD risk in this group,with an OR changing from 13.64(95%CI:10.59-17.57)to 6.42(95%CI:4.24-9.72).Further analysis of the net weight changes revealed a paradoxical risk elevation with intensified physical activity during different time periods.CONCLUSION The risk of MASLD increases in individuals transitioning from non-obese to obese or maintaining obesity.Highintensity physical activity is beneficial for MASLD among individuals with stable obesity.
文摘BACKGROUND Metabolic dysfunction-associated fatty liver disease(MASLD)is a chronic liver disease characterized by hepatocellular steatosis,which is closely related to metabolic syndrome,with annually increasing morbidity in recent years.Gynecomastia(GYN),an abnormal proliferation of breast tissue in males,is common in males with sex hormone imbalance.Currently,there is insufficient research on the morbidity of GYN and its correlation among MASLD patients.AIM To investigate the prevalence of GYN and its associated clinical features in patients with MASLD and determine the prevalence of GYN in patients with MASLD and analyze the predictive effect of sex hormones on GYN using receiver operating characteristic(ROC)curves.METHODS A cross-sectional study was conducted in a tertiary care hospital.Among them,997 patients met the inclusion criteria and underwent breast ultrasonography to determine the presence of GYN.Anthropometric data,laboratory test data[estradiol(E2),androgens,liver function,glucose,lipids,low-density lipoprotein,high-density lipoprotein,creatinine,and uric acid,etc.],as well as information on medical history,severity of fatty liver(mild,moderate,and severe),and duration of the disease were collected.Package for the Social Sciences version 27 and R software(version 4.3.1)were used for data analysis.RESULTS The prevalence of GYN increased with the severity of fatty liver(27.6%for mild,33.5%for moderate,and 58%for severe,P<0.001);compared with non-GYN patients,GYN patients were older(54.11±9.71 years vs 47.89±9.92 years,P<0.001),with significantly higher E2 levels,higher estrogen to androgen ratio(P<0.001)and significantly lower androgen levels(P<0.001).In ROC curve analysis,the combined model of testosterone and E2 had a high diagnostic value in predicting GYN in MASLD patients,surpassing a single indicator.CONCLUSION The presence of GYN may suggest more severe metabolic abnormalities in patients with MASLD.Therefore,early recognition of GYN may be crucial for early intervention in metabolic syndrome and endocrine abnormalities in patients with MASLD.
基金Supported by Scientific Research Project of Putian University,No.2022059.
文摘The growing global burden of metabolic dysfunction-associated steatohepatitis(MASH)demands a deeper understanding of its underlying mechanisms and risk factors.Recent studies,such as the large population-based case-control analysis by Abdel-Razeq et al,suggest a significant association between Helicobacter pylori(H.pylori)infection and an increased risk of developing MASH.This study provides compelling data supporting this association,even after adjusting for confounders such as obesity,diabetes,and hyperlipidemia.However,the complexity of this relationship remains unresolved,requiring further investigation into the biological,genetic,and environmental pathways that connect these two conditions.This article critically reviews the study’s findings and identifies its limitations,offering innovative research directions for the future.Key areas of focus include integrating genomic and microbiome analyses,exploring the impact of H.pylori eradication on MASH progression,studying molecular mechanisms at the intersection of infection and liver disease,and developing personalized therapeutic strategies.
文摘Gosnell and colleagues executed a large-scale cohort investigation delineating ethnic disparities in outcomes among individuals with metabolic dysfunction–as-sociated steatotic liver disease/steatohepatitis(MASLD/MASH).Uncovering such heterogeneity is pivotal to optimising management and prognostication,notably for hepatocellular carcinoma,fibrotic progression,and all-cause mortality.The authors furnish granular trajectories for Hispanic vs non-Hispanic popula-tions across the United States and southeastern Texas,alongside a comprehensive appraisal of MASLD/MASH-related event rates.These insights provide an indispensable framework for early risk stratification and the tailoring of thera-peutic algorithms and surveillance regimens.The study underscores the necessity for nuanced appreciation of MASLD/MASH outcome profiles and associated management strategies,while interrogating regional variation in disease burden,the benefits of integrated metabolic care,and the potential of lifestyle inter-ventions to attenuate complications and improve prognosis.
基金supported by the National Natural Science Foundation of China (Grant Nos.32330067,31971419,32311530110,and 32171486)。
文摘The dependence of energy metabolism on temperature is universally recognized as a critical physiological hallmark for evaluating the susceptibility of ectothermic organisms to global warming.However,the underlying physiological and biochemical bases of this temperature dependence remain largely unknown.In this study,we conducted a simulated climate warming experiment under seminatural enclosure conditions and compared the differences in resting metabolic rate (RMR) and key metabolic enzyme activities between the warming and control groups of Takydromus septentrionalis at various test temperatures.We found that the activities of hexokinase,lactate dehydrogenase,alanine aminotransferase and acetyl-CoA carboxylase of T.septentrionalis were not affected by climate warming,despite a decrease in RMR measured at high temperatures of 34°C and 38°C.Overall,these findings suggest that artificial warming simulating climate change can lead to a decline in RMR,but does not alter the activity of key metabolic enzymes.Our study provides insight into how climate warming influences the energy metabolism of lizards.
基金Supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education,No.NRF-RS-2023-00237287.
文摘This article examines the study by Lin et al,which explores the effects of night sentry duties on cardiometabolic health in military personnel.The research identifies significant correlations between the frequency of night shifts and nega-tive cardiometabolic outcomes,such as elevated resting pulse rates and lowered levels of high-density lipoprotein cholesterol.These outcomes underscore the health risks linked to partial sleep deprivation,a common challenge in military environments.The editorial highlights the clinical significance of these findings,advocating for the implementation of targeted health interventions to mitigate these risks.Strategies such as structured sleep recovery programs and lifestyle modifications are recommended to improve the health management of military personnel engaged in nocturnal duties.By addressing these issues,military health management can better safeguard the well-being and operational readiness of its personnel.
文摘BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is the most common cause of chronic liver disease and remains under-recognized within the health check-up population.Ultrasonography during physical examination fail to accurately identify at-risk patients as they involve multiple metabolic aspects.AIM To rapidly identify hepatic steatosis patients from high-metabolic-risk populations and reduce medical costs.METHODS We analyzed all data from a prospective cohort study to identify potential predictors of MAFLD risk.The LASSO and recursive feature elimination were used to screen for feature selection.Four machine learning models were employed to construct the prediction model for hepatic steatosis.RESULTS We found that 86.2%of the 1011 individuals in the trial phase exhibited metabolic abnormalities,with 70.8%presenting with hepatic steatosis.After data cleaning,711 participants(207 non-MAFLD patients vs 504 MAFLD patients)were included,and the prediction models were validated.After overlapping and reducing the feature set based on feature importance ranking,we developed an interpretable final XGBoost model with 10 features,achieving an area under the curve of 0.82.CONCLUSION We have introduced a valuable noninvasive tool for efficiently identifying hepatic steatosis patients in highmetabolic-risk populations.This tool may improve screening effectiveness and reduce medical costs.
