Metabolic dysfunction-associated steatotic liver disease(MASLD)significantly contributes to cardiovascular morbidity,with cardiovascular disease being the leading cause of mortality among affected individuals.Atrial f...Metabolic dysfunction-associated steatotic liver disease(MASLD)significantly contributes to cardiovascular morbidity,with cardiovascular disease being the leading cause of mortality among affected individuals.Atrial fibrillation(AF),the most common cardiac arrhythmia,is frequently observed in patients with MASLD.While shared metabolic risk factors such as obesity,diabetes,dyslipidemia,and hypertension are implicated,underlying pathophysiological mechanisms that include systemic inflammation,oxidative stress,insulin resistance,endothelial dysfunction,and activation of the renin-angiotensin-aldosterone system(RAAS)are proposed to play significant part in the increased risk of AF in MASLD.The aim is to review the pathogenesis linking MASLD and AF.A comprehensive literature review was conducted,focusing on studies that explore the epidemiology,pathogenesis,and clinical implications of MASLD and AF.Databases searched included PubMed,Scopus,and Web of Science,with keywords such as"metabolic associated steatotic liver disease","non fibrotic metabolic associated steatohepatitis","Nonalcoholic fatty liver disease","metabolic syndrome","atrial fibrillation","antifibrotic therapies","pathogenesis",and"cardiovascular risk".Chronic low-grade inflammation and oxidative stress in MASLD contribute to atrial structural and electrical remodeling,fostering an arrhythmogenic substrate.Insulin resistance,a hallmark of MASLD,exacerbates metabolic dysfunction and promotes atrial fibrosis.Dysregulated lipid metabolism and gut microbiota alterations further compound cardiovascular risk.Aldosterone dysregulation and systemic inflammation stemming from RAAS activation contributes to the shared pathophysiology.The severity of MASLD does not seem to directly influence the risk of AF,suggesting that even early stages of liver disease can increase susceptibility to this arrhythmia.Effective management of MASLD requires targeted risk-factor modification strategies,including weight management,glycemic control,and pharmacological interventions.A multidisciplinary approach is essential for comprehensive assessment and management of MASLD patients,with a focus on cardiovascular risk assessment and arrhythmia prevention.Future research should explore the impact of emerging MASLD therapeutic agents on the incidence and recurrence of cardiac arrhythmias.Early detection and comprehensive management of MASLD and AF are crucial to mitigate the dual burden of these conditions.展开更多
Metabolic-dysfunction associated steatotic liver disease(MASLD),formerly known as non-alcoholic fatty liver disease(NAFLD)(1),is characterized by the accumulation of fat in the liver cells,independent of excessive alc...Metabolic-dysfunction associated steatotic liver disease(MASLD),formerly known as non-alcoholic fatty liver disease(NAFLD)(1),is characterized by the accumulation of fat in the liver cells,independent of excessive alcohol consumption and has emerged as the most prevalent chronic liver condition in Western countries,underscoring a significant public health concern(2).The progression of MASLD to advanced fibrosis,marked by excessive extracellular matrix deposition and scar tissue formation,is a critical stage in MASLD natural history that significantly increases the risk of liver-related complications mortality(3).Non-invasive tests(NITs),such as liver stiffness measurement(LSM)with transient elastography(TE)and serum biomarkers,have gained prominence for assessing liver fibrosis in patients with suspected/confirmed NAFLD,offering a safer and less invasive alternative to liver biopsy(4).展开更多
Relevance of liver fibrosis amongst diabetic patients with metabolic-dysfunction associated steatotic liver disease(MASLD)and knowledge gaps Insulin resistance is paramount in the crosstalk between intrahepatic and ex...Relevance of liver fibrosis amongst diabetic patients with metabolic-dysfunction associated steatotic liver disease(MASLD)and knowledge gaps Insulin resistance is paramount in the crosstalk between intrahepatic and extrahepatic pathophysiological mechanisms leading to MASLD(1),hence gaining special relevance in patients diagnosed with type 2 diabetes(T2D).MASLD is the term that was recently endorsed by an international multidisciplinary consensus panel to replace non-alcoholic fatty liver disease[as non-alcoholic steatohepatitis(NASH)was replaced by metabolic dysfunction-associated steatohepatitis(MASH)](2).展开更多
The intestinal microbiome,often characterized as humanity’s“secondary genome,”possesses a genetic repertoire that dwarfs the coding capacity of the human genome by orders of magnitude.The essential architecture of ...The intestinal microbiome,often characterized as humanity’s“secondary genome,”possesses a genetic repertoire that dwarfs the coding capacity of the human genome by orders of magnitude.The essential architecture of this system is constituted by a vast phylogenetic tapestry of luminal microorganisms,whose dynamic symbiosis serves as a critical determinant of intestinal mucosal homeostasis and functional fidelity.The past decade has witnessed a paradigm shift in biomedical sciences,wherein technological breakthroughs in microbial single-cell genomics and spatial metatranscriptomics have unveiled the gut ecosystem’s pivotal role in host physiology.Emerging evidence from gut-liver interface research demonstrates how microbial-derived signals,facilitated by the portal circulatory nexus,mechanistically contribute to the initiation and perpetuation of chronic hepatopathies.This review elucidates the pathophysiological mechanisms through which intestinal dysbiosis propagates chronic hepatopathies,with the ultimate objective of informing novel diagnostic paradigms and therapeutic interventions.展开更多
In this editorial,we comment on the article by Chen et al recently published in 2024.We focus the debate on whether reducing the upper limit of normal of alanine aminotransferase(ALT)would effectively identify cases o...In this editorial,we comment on the article by Chen et al recently published in 2024.We focus the debate on whether reducing the upper limit of normal of alanine aminotransferase(ALT)would effectively identify cases of fibrosis in metabolic-dysfunction associated fatty liver disease(MAFLD).This is important given the increasing prevalence of MAFLD and obesity globally.Currently,a suitable screening test to identify patients in the general population does not exist and most patients are screened after the finding of an abnormal ALT.The authors of this paper challenge the idea of what a normal ALT is and whether that threshold should be lowered,particularly as their study found that 83.12%of their study population with a diagnosis of MAFLD had a normal ALT.The main advantages of screening would be to identify patients and provide intervention early,the mainstay of this being changing modifiable risk factors and monitoring for liver fibrosis.However,there is not enough suitable therapeutic options available as of yet although this is likely to change in the coming years with more targets for therapy being discovered.Semaglutide is one example of this which has demonstrated benefit with an acceptable side effect profile for those patients with MAFLD and obesity,although studies have not yet shown a significant improvement in fibrosis regression.It would also require a huge amount of resource if a reduced ALT level alone was used as criteria;it is more likely that current scoring systems such as fibrosis-4 may be amended to represent this additional risk.Currently,there is not a good argument to recommend wide-spread screening with a reduced ALT level as this is unlikely to be cost-effective.This is compounded by the fact that there is a significant heterogeneity in what is considered a normal ALT between laboratories.Although studies previously have suggested a more pragmatic approach in screening those over the age of 60,this is likely to change with the increasing incidence of obesity within the younger age groups.The main message from this study is that those who have hypercholesterolemia and high body metabolic index should have these risk factors modified to maintain a lower level of ALT to reduce the risk of progression to fibrosis and cirrhosis.展开更多
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)significantly contributes to cardiovascular morbidity,with cardiovascular disease being the leading cause of mortality among affected individuals.Atrial fibrillation(AF),the most common cardiac arrhythmia,is frequently observed in patients with MASLD.While shared metabolic risk factors such as obesity,diabetes,dyslipidemia,and hypertension are implicated,underlying pathophysiological mechanisms that include systemic inflammation,oxidative stress,insulin resistance,endothelial dysfunction,and activation of the renin-angiotensin-aldosterone system(RAAS)are proposed to play significant part in the increased risk of AF in MASLD.The aim is to review the pathogenesis linking MASLD and AF.A comprehensive literature review was conducted,focusing on studies that explore the epidemiology,pathogenesis,and clinical implications of MASLD and AF.Databases searched included PubMed,Scopus,and Web of Science,with keywords such as"metabolic associated steatotic liver disease","non fibrotic metabolic associated steatohepatitis","Nonalcoholic fatty liver disease","metabolic syndrome","atrial fibrillation","antifibrotic therapies","pathogenesis",and"cardiovascular risk".Chronic low-grade inflammation and oxidative stress in MASLD contribute to atrial structural and electrical remodeling,fostering an arrhythmogenic substrate.Insulin resistance,a hallmark of MASLD,exacerbates metabolic dysfunction and promotes atrial fibrosis.Dysregulated lipid metabolism and gut microbiota alterations further compound cardiovascular risk.Aldosterone dysregulation and systemic inflammation stemming from RAAS activation contributes to the shared pathophysiology.The severity of MASLD does not seem to directly influence the risk of AF,suggesting that even early stages of liver disease can increase susceptibility to this arrhythmia.Effective management of MASLD requires targeted risk-factor modification strategies,including weight management,glycemic control,and pharmacological interventions.A multidisciplinary approach is essential for comprehensive assessment and management of MASLD patients,with a focus on cardiovascular risk assessment and arrhythmia prevention.Future research should explore the impact of emerging MASLD therapeutic agents on the incidence and recurrence of cardiac arrhythmias.Early detection and comprehensive management of MASLD and AF are crucial to mitigate the dual burden of these conditions.
文摘Metabolic-dysfunction associated steatotic liver disease(MASLD),formerly known as non-alcoholic fatty liver disease(NAFLD)(1),is characterized by the accumulation of fat in the liver cells,independent of excessive alcohol consumption and has emerged as the most prevalent chronic liver condition in Western countries,underscoring a significant public health concern(2).The progression of MASLD to advanced fibrosis,marked by excessive extracellular matrix deposition and scar tissue formation,is a critical stage in MASLD natural history that significantly increases the risk of liver-related complications mortality(3).Non-invasive tests(NITs),such as liver stiffness measurement(LSM)with transient elastography(TE)and serum biomarkers,have gained prominence for assessing liver fibrosis in patients with suspected/confirmed NAFLD,offering a safer and less invasive alternative to liver biopsy(4).
文摘Relevance of liver fibrosis amongst diabetic patients with metabolic-dysfunction associated steatotic liver disease(MASLD)and knowledge gaps Insulin resistance is paramount in the crosstalk between intrahepatic and extrahepatic pathophysiological mechanisms leading to MASLD(1),hence gaining special relevance in patients diagnosed with type 2 diabetes(T2D).MASLD is the term that was recently endorsed by an international multidisciplinary consensus panel to replace non-alcoholic fatty liver disease[as non-alcoholic steatohepatitis(NASH)was replaced by metabolic dysfunction-associated steatohepatitis(MASH)](2).
文摘The intestinal microbiome,often characterized as humanity’s“secondary genome,”possesses a genetic repertoire that dwarfs the coding capacity of the human genome by orders of magnitude.The essential architecture of this system is constituted by a vast phylogenetic tapestry of luminal microorganisms,whose dynamic symbiosis serves as a critical determinant of intestinal mucosal homeostasis and functional fidelity.The past decade has witnessed a paradigm shift in biomedical sciences,wherein technological breakthroughs in microbial single-cell genomics and spatial metatranscriptomics have unveiled the gut ecosystem’s pivotal role in host physiology.Emerging evidence from gut-liver interface research demonstrates how microbial-derived signals,facilitated by the portal circulatory nexus,mechanistically contribute to the initiation and perpetuation of chronic hepatopathies.This review elucidates the pathophysiological mechanisms through which intestinal dysbiosis propagates chronic hepatopathies,with the ultimate objective of informing novel diagnostic paradigms and therapeutic interventions.
文摘In this editorial,we comment on the article by Chen et al recently published in 2024.We focus the debate on whether reducing the upper limit of normal of alanine aminotransferase(ALT)would effectively identify cases of fibrosis in metabolic-dysfunction associated fatty liver disease(MAFLD).This is important given the increasing prevalence of MAFLD and obesity globally.Currently,a suitable screening test to identify patients in the general population does not exist and most patients are screened after the finding of an abnormal ALT.The authors of this paper challenge the idea of what a normal ALT is and whether that threshold should be lowered,particularly as their study found that 83.12%of their study population with a diagnosis of MAFLD had a normal ALT.The main advantages of screening would be to identify patients and provide intervention early,the mainstay of this being changing modifiable risk factors and monitoring for liver fibrosis.However,there is not enough suitable therapeutic options available as of yet although this is likely to change in the coming years with more targets for therapy being discovered.Semaglutide is one example of this which has demonstrated benefit with an acceptable side effect profile for those patients with MAFLD and obesity,although studies have not yet shown a significant improvement in fibrosis regression.It would also require a huge amount of resource if a reduced ALT level alone was used as criteria;it is more likely that current scoring systems such as fibrosis-4 may be amended to represent this additional risk.Currently,there is not a good argument to recommend wide-spread screening with a reduced ALT level as this is unlikely to be cost-effective.This is compounded by the fact that there is a significant heterogeneity in what is considered a normal ALT between laboratories.Although studies previously have suggested a more pragmatic approach in screening those over the age of 60,this is likely to change with the increasing incidence of obesity within the younger age groups.The main message from this study is that those who have hypercholesterolemia and high body metabolic index should have these risk factors modified to maintain a lower level of ALT to reduce the risk of progression to fibrosis and cirrhosis.
