The prevalence of metabolic-dysfunction-associated steatotic liver disease(MASLD)is alarmingly high;it is estimated to affect up to a quarter of the global population,making it the most common liver disorder worldwide...The prevalence of metabolic-dysfunction-associated steatotic liver disease(MASLD)is alarmingly high;it is estimated to affect up to a quarter of the global population,making it the most common liver disorder worldwide.MASLD is characterized by excessive hepatic fat accumulation and is commonly associated with comorbidities such as obesity,dyslipidemia,and insulin resistance;however,it can also manifest in lean individuals.Therefore,it is crucial to develop effective therapies for this complex condition.Currently,there are no approved medications for MASLD treatment,so there is a pressing need to investigate alternative approaches.Extensive research has characterized MASLD as a multifaceted disease,frequently linked to metabolic disorders that stem from dietary habits.Evidence suggests that changes in the gut microbiome play a fundamental role in the development and progression of MASLD from simple steatosis to steatohepatitis and even hepatocellular carcinoma(HCC).In this review,we critically examine the literature on the emerging field of gut-microbiota-based therapies for MASLD and metabolicdysfunction-associated steatohepatitis(MASH),including interventions such as fecal microbiota transplantation(FMT),probiotics,prebiotics,short-chain fatty acids,antibiotics,metabolic pathway targeting,and immune checkpoint kinase blockade.展开更多
As a non-communicable disease,cardiovascular disorders have become the lea-ding cause of death for men and women.Of additional concern is that cardio-vascular disease is linked to chronic comorbidity disorders that in...As a non-communicable disease,cardiovascular disorders have become the lea-ding cause of death for men and women.Of additional concern is that cardio-vascular disease is linked to chronic comorbidity disorders that include nonal-coholic fatty liver disease(NAFLD).NAFLD,also termed metabolic-dysfunction-associated steatotic liver disease,is the greatest cause of liver disease throughout the world,increasing in prevalence concurrently with diabetes mellitus(DM),and can progress to nonalcoholic steatohepatitis that leads to cirrhosis and liver fi-brosis.Individuals with metabolic disorders,such as DM,are more than two times likely to experience cardiac disease,stroke,and liver disease that includes NAFLD when compared individuals without metabolic disorders.Interestingly,cardiovascular disorders and NAFLD share a common underlying cellular me-chanism for disease pathology,namely the silent mating type information regu-lation 2 homolog 1(SIRT1;Saccharomyces cerevisiae).SIRT1,a histone deacetylase,is linked to metabolic pathways through nicotinamide adenine dinucleotide and can offer cellular protection though multiple avenues,including trophic factors such as erythropoietin,stem cells,and AMP-activated protein kinase.Translating SIRT1 pathways into clinical care for cardiovascular and hepatic disease can offer significant hope for patients,but further insights into the complexity of SIRT1 pathways are necessary for effective treatment regimens.展开更多
Background:The recently introduced set of terminologies defining categories of steatotic liver disease(SLD)includes metabolic dysfunction-associated SLD(MASLD),alcohol-associated liver disease(ALD),and metabolic dysfu...Background:The recently introduced set of terminologies defining categories of steatotic liver disease(SLD)includes metabolic dysfunction-associated SLD(MASLD),alcohol-associated liver disease(ALD),and metabolic dysfunction associated steatotic liver disease and increased alcohol intake(MetALD).The present retrospective cohort study examines clinical characteristics,prevalence,and mortality risk across alcoholic intake spectrum in SLD individuals.Methods:Data between 1999 to 2018 were extracted from National Health and Nutrition Examination Survey registries and analysed.Population baseline characteristics were evaluated across classifications of SLD.SLD was confirmed using either fatty liver index(FLI)or United States FLI(US-FLI).Multivariate analyses were used to study mortality-related outcomes.Results:The 20,510 individuals with SLD included were classified into MASLD predominant(69.00%),MetALD(18.77%),and ALD predominant(12.23%)groups.Temporal analysis revealed significant decreases in MASLD prevalence in the SLD population from 1999-2018 in general[average annual percentage change(AAPC)−4.802%,P=0.001],as well as in females,Mexican Americans,and Non-Hispanic Blacks.MetALD prevalence in the SLD population increased from 1999-2018 in general(AAPC+1.635%,P<0.001),and in males,females,Mexican Americans,Non-Hispanic Blacks and other ethnicities.No significant change in ALD prevalence was found.Compared to MASLD predominant individuals,ALD predominant individuals had higher risks of all-cause[hazard ratio(HR):1.189,95%confidence interval(CI):1.026 to 1.378,P=0.02]and cancer-related mortality(subdistribution HR:1.277,95%CI:1.032 to 1.579,P=0.02).No significant difference was observed for all-cause,cancer-related,or cardiovascular disease(CVD)-related mortality in MetALD and CVD-related mortality in ALD predominant individuals,relative to MASLD predominant individuals.Conclusions:ALD predominant patients have higher all-cause and cancer-related mortality risks than MASLD predominant patients but not CVD-related mortality.SLD is highly heterogeneous in clinical characteristics,prevalence,and mortality risks which healthcare professionals must account for to avert adverse health outcomes.展开更多
Metabolic-dysfunction-associated fatty liver disease(MAFLD)is a group of highly heterogeneous multi-system diseases,which is closely related to metabolic dysfunction and is one of the most important public health prob...Metabolic-dysfunction-associated fatty liver disease(MAFLD)is a group of highly heterogeneous multi-system diseases,which is closely related to metabolic dysfunction and is one of the most important public health problems in the world.Studies have shown that paracrine fibroblast growth factors(FGFs)play an important role in the occurrence and development of MAFLD by regulating glucose and lipid metabolism,inflammation,and fibrosis.This article reviews the latest progress in understanding of the distribution,function,and metabolic regulation of paracrine FGFs,which paves the way for future FGF-based therapies targeting MAFLD.展开更多
基金Federal Ministry of Education and Research(Q-HCC,01KD2214)the Sino-German Center for Research Promotion(GZ-1546 and C-0012)+5 种基金the State Ministry of Baden-Wuerttemberg for Sciences,Research and Arts supporting the Clinical Cooperation Unit Healthy Metabolism at the Center for Preventive Medicine and Digital Health(CCU Healthy Metabolism)the Baden-Wuerttemberg Center for Digital Early Disease Detection and Prevention(BW-ZDFP)the Foundation for Biomedical Alcohol Research,Schriesheim,Germanyfunded by the Federal Ministry of Education and Research(BMBF)the Ministry of Culture and Science of the German State of North Rhine-Westphalia(MKW)(NRW Rueckkehrprogramm)under the Excellence Strategy of the Federal Government and the Länderthe German Research Foundation(DFG,403224013-SFB1382,gut-liver axis).
文摘The prevalence of metabolic-dysfunction-associated steatotic liver disease(MASLD)is alarmingly high;it is estimated to affect up to a quarter of the global population,making it the most common liver disorder worldwide.MASLD is characterized by excessive hepatic fat accumulation and is commonly associated with comorbidities such as obesity,dyslipidemia,and insulin resistance;however,it can also manifest in lean individuals.Therefore,it is crucial to develop effective therapies for this complex condition.Currently,there are no approved medications for MASLD treatment,so there is a pressing need to investigate alternative approaches.Extensive research has characterized MASLD as a multifaceted disease,frequently linked to metabolic disorders that stem from dietary habits.Evidence suggests that changes in the gut microbiome play a fundamental role in the development and progression of MASLD from simple steatosis to steatohepatitis and even hepatocellular carcinoma(HCC).In this review,we critically examine the literature on the emerging field of gut-microbiota-based therapies for MASLD and metabolicdysfunction-associated steatohepatitis(MASH),including interventions such as fecal microbiota transplantation(FMT),probiotics,prebiotics,short-chain fatty acids,antibiotics,metabolic pathway targeting,and immune checkpoint kinase blockade.
基金Supported by American Diabetes AssociationAmerican Heart Association+4 种基金NIH NIEHSNIH NIANIH NINDSNS053956NIH ARRA.
文摘As a non-communicable disease,cardiovascular disorders have become the lea-ding cause of death for men and women.Of additional concern is that cardio-vascular disease is linked to chronic comorbidity disorders that include nonal-coholic fatty liver disease(NAFLD).NAFLD,also termed metabolic-dysfunction-associated steatotic liver disease,is the greatest cause of liver disease throughout the world,increasing in prevalence concurrently with diabetes mellitus(DM),and can progress to nonalcoholic steatohepatitis that leads to cirrhosis and liver fi-brosis.Individuals with metabolic disorders,such as DM,are more than two times likely to experience cardiac disease,stroke,and liver disease that includes NAFLD when compared individuals without metabolic disorders.Interestingly,cardiovascular disorders and NAFLD share a common underlying cellular me-chanism for disease pathology,namely the silent mating type information regu-lation 2 homolog 1(SIRT1;Saccharomyces cerevisiae).SIRT1,a histone deacetylase,is linked to metabolic pathways through nicotinamide adenine dinucleotide and can offer cellular protection though multiple avenues,including trophic factors such as erythropoietin,stem cells,and AMP-activated protein kinase.Translating SIRT1 pathways into clinical care for cardiovascular and hepatic disease can offer significant hope for patients,but further insights into the complexity of SIRT1 pathways are necessary for effective treatment regimens.
文摘Background:The recently introduced set of terminologies defining categories of steatotic liver disease(SLD)includes metabolic dysfunction-associated SLD(MASLD),alcohol-associated liver disease(ALD),and metabolic dysfunction associated steatotic liver disease and increased alcohol intake(MetALD).The present retrospective cohort study examines clinical characteristics,prevalence,and mortality risk across alcoholic intake spectrum in SLD individuals.Methods:Data between 1999 to 2018 were extracted from National Health and Nutrition Examination Survey registries and analysed.Population baseline characteristics were evaluated across classifications of SLD.SLD was confirmed using either fatty liver index(FLI)or United States FLI(US-FLI).Multivariate analyses were used to study mortality-related outcomes.Results:The 20,510 individuals with SLD included were classified into MASLD predominant(69.00%),MetALD(18.77%),and ALD predominant(12.23%)groups.Temporal analysis revealed significant decreases in MASLD prevalence in the SLD population from 1999-2018 in general[average annual percentage change(AAPC)−4.802%,P=0.001],as well as in females,Mexican Americans,and Non-Hispanic Blacks.MetALD prevalence in the SLD population increased from 1999-2018 in general(AAPC+1.635%,P<0.001),and in males,females,Mexican Americans,Non-Hispanic Blacks and other ethnicities.No significant change in ALD prevalence was found.Compared to MASLD predominant individuals,ALD predominant individuals had higher risks of all-cause[hazard ratio(HR):1.189,95%confidence interval(CI):1.026 to 1.378,P=0.02]and cancer-related mortality(subdistribution HR:1.277,95%CI:1.032 to 1.579,P=0.02).No significant difference was observed for all-cause,cancer-related,or cardiovascular disease(CVD)-related mortality in MetALD and CVD-related mortality in ALD predominant individuals,relative to MASLD predominant individuals.Conclusions:ALD predominant patients have higher all-cause and cancer-related mortality risks than MASLD predominant patients but not CVD-related mortality.SLD is highly heterogeneous in clinical characteristics,prevalence,and mortality risks which healthcare professionals must account for to avert adverse health outcomes.
基金This work was supported by the National Natural Science Foundation of China(Grant number 82070593)。
文摘Metabolic-dysfunction-associated fatty liver disease(MAFLD)is a group of highly heterogeneous multi-system diseases,which is closely related to metabolic dysfunction and is one of the most important public health problems in the world.Studies have shown that paracrine fibroblast growth factors(FGFs)play an important role in the occurrence and development of MAFLD by regulating glucose and lipid metabolism,inflammation,and fibrosis.This article reviews the latest progress in understanding of the distribution,function,and metabolic regulation of paracrine FGFs,which paves the way for future FGF-based therapies targeting MAFLD.
