Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,defined by several phases,ranging from benign fat accumulation to non-alcoholic steatohepatitis(NASH),which can lead to liver cancer and...Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,defined by several phases,ranging from benign fat accumulation to non-alcoholic steatohepatitis(NASH),which can lead to liver cancer and cirrhosis.Although NAFLD is a disease of disordered metabolism,it also involves several immune cell-mediated inflammatory processes,either promoting and/or suppressing hepatocyte inflammation through the secretion of pro-inflammatory and/or anti-inflammatory factors to influence the NAFLD process.However,the underlying disease mechanism and the role of immune cells in NAFLD are still under investigation,leaving many open-ended questions.In this review,we presented the recent concepts about the interplay of immune cells in the onset and pathogenesis of NAFLD.We also highlighted the specific non-immune cells exhibiting immunological properties of therapeutic significance in NAFLD.We hope that this review will help guide the development of future NAFLD therapeutics.展开更多
Objective:To analyze the independent risk factors for the occurrence of moderate-to-severe metabolic-associated fatty liver disease(MAFLD),to construct a prediction model for moderate-to-severe MAFLD,and to verify the...Objective:To analyze the independent risk factors for the occurrence of moderate-to-severe metabolic-associated fatty liver disease(MAFLD),to construct a prediction model for moderate-to-severe MAFLD,and to verify the validity of the model.Methods:In the first part,278 medical examiners who were diagnosed with MAFLD in Medical Examination Center at the Second Affiliated Hospital of Hainan University from January to May 2022 were taken as the study subjects(training set),and they were divided into mild MAFLD group(200)and moderate-severe MAFLD group(78)based on ultrasound results.Demographic data and laboratory indexes were collected,and risk factors were screened by univariate and multifactor analysis.In the second part,a dichotomous logistic regression equation was used to construct a prediction model for moderate-to-severe MAFLD,and the model was visualized in a line graph.In the third part,the MAFLD population(200 people in the external validation set)from our physical examination center from November to December 2022 was collected as the moderate-to-severe MAFLD prediction model,and the risk factors in both groups were compared.The receiver operating characteristic(ROC)curves,calibration curves,and clinical applicability of the model were plotted to represent model discrimination for internal and external validation.Results:The risk factors of moderate-to-severe MAFLD were fasting glucose(FPG),blood uric acid(UA),triglycerides(TG),triglyceride glucose index(TyG),total cholesterol(CHOL),and high-density lipoprotein(HDL-C).UA[OR=1.021,95%CI(1.015,1.027),P<0.001]and FPG[OR=1.575,95%CI(1.158,2.143),P=0.004]were independent risk factors for people with moderate to severe MAFLD.The visualized line graph model showed that UA was the factor contributing more to the risk of moderate to severe MAFLD in this model.The ROC curves showed AUC values of 0.8701,0.8686 and 0.7991 for the training set,internal validation set and external validation set,respectively.The curves almost coincided with the reference line after calibration of the model calibration degree with P>0.05 in Hosmer-Lemeshow test.The decision curve analysis(DCA)plotted by the clinical applicability of the model was higher than the two extreme curves,predicting that patients with moderate to severe MAFLD would benefit from the prediction model.Conclusion:The prediction model constructed by combining FPG with UA has higher accuracy and better clinical applicability,and can be used for clinical diagnosis.展开更多
Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 20...Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.展开更多
Background:To evaluate the associations between a new definition of metabolic dysfunction-associated fatty liver disease(MAFLD)and extrahepatic cancers and compare with nonalcoholic fatty liver disease(NAFLD).Methods:...Background:To evaluate the associations between a new definition of metabolic dysfunction-associated fatty liver disease(MAFLD)and extrahepatic cancers and compare with nonalcoholic fatty liver disease(NAFLD).Methods:We enrolled 151,391 Chinese participants in the Kailuan cohort.Hepatic steatosis was detected by abdominal ultrasound.Fine and Gray competing risk regression models were used to estimate hazard ratios(HRs)and 95%confidence interval(CI)between MAFLD and extrahepatic cancers.Results:MAFLD was associated with increased risk of prostate(HR=1.49,95%CI:1.07-2.08)and obesity-related cancers,including thyroid(HR=1.47,95%CI:1.01-2.12),kidney(HR=1.54,95%CI:1.18-2.00),colorectal(HR=1.15,95%CI:0.98-1.34)and breast cancer(HR=1.31,95%CI:1.04-1.66).The results were consistent in NAFLD vs.non-NAFLD and MAFLD-NAFLD vs.neither FLD.Compared with the neither FLD group,the NAFLD-only group had a higher risk of extrahepatic cancers(HR=1.57,95%CI:1.18-2.09),esophageal(HR=5.11,95%CI:2.25-11.62),and bladder cancer(HR=3.36,95%CI:1.23-9.17).The additional risk of extrahepatic cancers(HR=1.42,95%CI:1.17-1.73),esophageal(HR=4.37,95%CI:2.55-7.49),and breast cancer(HR=1.99,95%CI:1.01-3.92)was observed in MAFLD with metabolic dysregulation,and kidney(HR=1.83,95%CI:1.38-2.43),prostate(HR=1.46,95%CI:1.00-2.14)and breast cancer(HR=1.33,95%CI:1.02-1.74)was observed in MAFLD with overweight and metabolic dysregulation,as well as colorectal(HR=1.45,95%CI:1.07-1.96)and prostate cancer(HR=2.44,95%CI:1.42-4.21)in MAFLD with three risk factors.Additionally,MAFLD with excessive alcohol consumption would increase extrahepatic cancers(HR=1.14,95%CI:1.01-1.29)and breast cancer(HR=7.27,95%CI:2.33-22.69)risk.Conclusions:MAFLD and NAFLD shared similar excessive risks of obesity-related cancers,suggesting a driving role of FLD in these cancers.Metabolic dysregulation beyond obesity may play additional kidney,colorectal,and prostate cancer risks in MAFLD patients.It may be helpful in the clinic to relieve symptoms by treating metabolic disorders and preventing adverse outcomes of extrahepatic cancers.展开更多
Non-alcoholic fatty liver disease(NAFLD),defined as the presence of fat accumulation in imaging or histology in more than 5%of hepatocytes and exclusion of other causes for secondary hepatic fat accumulation,is one of...Non-alcoholic fatty liver disease(NAFLD),defined as the presence of fat accumulation in imaging or histology in more than 5%of hepatocytes and exclusion of other causes for secondary hepatic fat accumulation,is one of the major causes of chronic liver disease worldwide.Metabolic syndrome is associated with an increased risk of progression from NAFLD to non-alcoholic steatohepatitis(NASH),fibrosis,and forthcoming liver failure.Also,genetic predisposition contributes to the risk of NAFLD development.This review explores the role of diets and nutraceuticals in delaying the development and the evolution of NAFLD to chronic liver disease.The Mediterranean diet,high-protein diet,lowcarbohydrate/high-fat diet,high-carbohydrate/low-fat diet,and intermittent fasting are the dietary approaches investigated given the presence of relevant literature data.Moreover,this review focused on nutraceuticals with proven efficacy in ameliorating NAFLD and grouped them into four different categories:plant-based nutraceuticals(Ascophyllum nodosum and Fucus vesiculosus,Silymarin,Berberine,Curcumin,Resveratrol,Nigella sativa,Quercetin),vitamin-like substances(vitamin E,vitamin D,vitamin C,coenzyme Q10,inositol),fatty acids(omega-3),and microbiota-management tools(probiotics).展开更多
Liver steatosis(i.e.,excessive triglyceride accumulation within the hepatocyte)is a very common finding in both the adult and pediatric populations.In the latter,epidemiologic data using validated diagnostic technique...Liver steatosis(i.e.,excessive triglyceride accumulation within the hepatocyte)is a very common finding in both the adult and pediatric populations.In the latter,epidemiologic data using validated diagnostic techniques(either liver biopsy or ultrasound-based technologies)have shown an alarmingly high prevalence,paralleling the ever-increasing rates of overweight and obesity.展开更多
Accumulating evidence in recent years has reinforced the notion that non-alcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease/metabolic dysfunction steatotic liver disease(NAFLD/MAFLD/MAS...Accumulating evidence in recent years has reinforced the notion that non-alcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease/metabolic dysfunction steatotic liver disease(NAFLD/MAFLD/MASLD)is a multisystem disease that increases the risk of all-cause and disease-specific mortality(1,2).展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD),previously termed non-alcoholic fatty liver disease,is one of the most common causes of chronic liver disease,affecting around 30%of the world’s adults(1).M...Metabolic dysfunction-associated fatty liver disease(MAFLD),previously termed non-alcoholic fatty liver disease,is one of the most common causes of chronic liver disease,affecting around 30%of the world’s adults(1).MAFLD encompasses a spectrum of liver conditions,ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis(MASH),which can progress to cirrhosis and hepatocellular carcinoma(HCC)(2,3).展开更多
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
Metabolic(dysfunction)-associated fatty liver disease(MAFLD)affects a third of the population and is a leading cause of liver-related death.Since no effective treatments exist,novel approaches to drug development are ...Metabolic(dysfunction)-associated fatty liver disease(MAFLD)affects a third of the population and is a leading cause of liver-related death.Since no effective treatments exist,novel approaches to drug development are required.Unfortunately,outdated terminology and definitions of the disease are hampering efforts to develop new drugs and treatments.An international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease(NAFLD)to MAFLD,includ-ing a proposal for how the disease should be diagnosed.As allies with the many stakeholders in MAFLD care―including patients,patients’advocates,clinicians,researchers,nurse and allied health groups,regional societies,and others―we are aware of the negative consequences of the NAFLD term and definition.We share the sense of urgency for change and will act in new ways to achieve our goals.Although there is much work to be done to overcome clinical inertia and reverse worrisome recent trends,the MAFLD initiative provides a firm foundation to build on.It provides a roadmap for moving for-ward toward more efficient care and affordable,sustainable drug and device innovation in MAFLD care.We hope it will bring promising new opportunities for a brighter future for MAFLD care and improve care and outcomes for patients of one of the globe’s largest and costliest public health burdens.From this viewpoint,we have revisited this initiative through the perspectives of drug development and regulatory science.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
Background and Aims:In Europeans,variants in the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene impact liver histology in metabolic-associated fatty liver disease(MAFLD).The impact of these variants in ethnic C...Background and Aims:In Europeans,variants in the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene impact liver histology in metabolic-associated fatty liver disease(MAFLD).The impact of these variants in ethnic Chinese is unknown.The aim of this study was to investigate the potential associations in Chinese patients.Methods:In total,427 Han Chinese with biopsy-confirmed MAFLD were enrolled.Two single nucleotide polymorphisms in HSD17B13 were genotyped:rs72613567 and rs6531975.Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology.Results:In our cohort,the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis[odds ratio(OR):2.93(1.20–7.17),p=0.019 for the additive model;OR:3.32(1.39–7.91),p=0.007 for the recessive model],representing an inverse association as compared to the results from European cohorts.In contrast,we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant[OR:0.48(0.24–0.98),p=0.043 for the additive model;OR:0.62(0.40–0.94),p=0.025 for the dominant model].HSD17B13 variants were only associated with fibrosis but no other histological features.Furthermore,HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis.Conclusions:HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans.These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.展开更多
Non-alcoholic fatty liver disease(NAFLD)has become a global epidemic nowadays.Although the pathogenesis of NAFLD remains to be uncovered,it is highly correlated with the changing of environment as other metabolic dise...Non-alcoholic fatty liver disease(NAFLD)has become a global epidemic nowadays.Although the pathogenesis of NAFLD remains to be uncovered,it is highly correlated with the changing of environment as other metabolic diseases.Epigenetics is the study on the differences of gene expression not caused by the changes in DNA sequencing.The epigenetics is considered to link the environment factors and the onset and development of NAFLD.As an increasing number of researches on epigenetics have emerged in recent years,our understanding of how epigenetic factors take part in the pathogenesis of NAFLD has been improved.This article reviews the recent studies on important epigenetic factors contributing to the progression of NAFLD including the DNA methylation,modification of histones and non-coding RNAs.It may give us a hint to discover novel diagnosis methods and drug targets for NAFLD.展开更多
文摘Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,defined by several phases,ranging from benign fat accumulation to non-alcoholic steatohepatitis(NASH),which can lead to liver cancer and cirrhosis.Although NAFLD is a disease of disordered metabolism,it also involves several immune cell-mediated inflammatory processes,either promoting and/or suppressing hepatocyte inflammation through the secretion of pro-inflammatory and/or anti-inflammatory factors to influence the NAFLD process.However,the underlying disease mechanism and the role of immune cells in NAFLD are still under investigation,leaving many open-ended questions.In this review,we presented the recent concepts about the interplay of immune cells in the onset and pathogenesis of NAFLD.We also highlighted the specific non-immune cells exhibiting immunological properties of therapeutic significance in NAFLD.We hope that this review will help guide the development of future NAFLD therapeutics.
基金Clinical Medical Center Construction Project of Hainan Province(No.2021818)Construction of Innovation Center of Academician Team of Hainan Province(No.2022136)+2 种基金Academician Innovation Platform of Hainan Province(No.00817378)Health Industry Research Project of Hainan Province(No.22A200078)Innovative Research Project of Hainan Graduate Students(No.Qhyb2022‑133)。
文摘Objective:To analyze the independent risk factors for the occurrence of moderate-to-severe metabolic-associated fatty liver disease(MAFLD),to construct a prediction model for moderate-to-severe MAFLD,and to verify the validity of the model.Methods:In the first part,278 medical examiners who were diagnosed with MAFLD in Medical Examination Center at the Second Affiliated Hospital of Hainan University from January to May 2022 were taken as the study subjects(training set),and they were divided into mild MAFLD group(200)and moderate-severe MAFLD group(78)based on ultrasound results.Demographic data and laboratory indexes were collected,and risk factors were screened by univariate and multifactor analysis.In the second part,a dichotomous logistic regression equation was used to construct a prediction model for moderate-to-severe MAFLD,and the model was visualized in a line graph.In the third part,the MAFLD population(200 people in the external validation set)from our physical examination center from November to December 2022 was collected as the moderate-to-severe MAFLD prediction model,and the risk factors in both groups were compared.The receiver operating characteristic(ROC)curves,calibration curves,and clinical applicability of the model were plotted to represent model discrimination for internal and external validation.Results:The risk factors of moderate-to-severe MAFLD were fasting glucose(FPG),blood uric acid(UA),triglycerides(TG),triglyceride glucose index(TyG),total cholesterol(CHOL),and high-density lipoprotein(HDL-C).UA[OR=1.021,95%CI(1.015,1.027),P<0.001]and FPG[OR=1.575,95%CI(1.158,2.143),P=0.004]were independent risk factors for people with moderate to severe MAFLD.The visualized line graph model showed that UA was the factor contributing more to the risk of moderate to severe MAFLD in this model.The ROC curves showed AUC values of 0.8701,0.8686 and 0.7991 for the training set,internal validation set and external validation set,respectively.The curves almost coincided with the reference line after calibration of the model calibration degree with P>0.05 in Hosmer-Lemeshow test.The decision curve analysis(DCA)plotted by the clinical applicability of the model was higher than the two extreme curves,predicting that patients with moderate to severe MAFLD would benefit from the prediction model.Conclusion:The prediction model constructed by combining FPG with UA has higher accuracy and better clinical applicability,and can be used for clinical diagnosis.
文摘Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.
基金supported by CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2016-I2M-3-001).
文摘Background:To evaluate the associations between a new definition of metabolic dysfunction-associated fatty liver disease(MAFLD)and extrahepatic cancers and compare with nonalcoholic fatty liver disease(NAFLD).Methods:We enrolled 151,391 Chinese participants in the Kailuan cohort.Hepatic steatosis was detected by abdominal ultrasound.Fine and Gray competing risk regression models were used to estimate hazard ratios(HRs)and 95%confidence interval(CI)between MAFLD and extrahepatic cancers.Results:MAFLD was associated with increased risk of prostate(HR=1.49,95%CI:1.07-2.08)and obesity-related cancers,including thyroid(HR=1.47,95%CI:1.01-2.12),kidney(HR=1.54,95%CI:1.18-2.00),colorectal(HR=1.15,95%CI:0.98-1.34)and breast cancer(HR=1.31,95%CI:1.04-1.66).The results were consistent in NAFLD vs.non-NAFLD and MAFLD-NAFLD vs.neither FLD.Compared with the neither FLD group,the NAFLD-only group had a higher risk of extrahepatic cancers(HR=1.57,95%CI:1.18-2.09),esophageal(HR=5.11,95%CI:2.25-11.62),and bladder cancer(HR=3.36,95%CI:1.23-9.17).The additional risk of extrahepatic cancers(HR=1.42,95%CI:1.17-1.73),esophageal(HR=4.37,95%CI:2.55-7.49),and breast cancer(HR=1.99,95%CI:1.01-3.92)was observed in MAFLD with metabolic dysregulation,and kidney(HR=1.83,95%CI:1.38-2.43),prostate(HR=1.46,95%CI:1.00-2.14)and breast cancer(HR=1.33,95%CI:1.02-1.74)was observed in MAFLD with overweight and metabolic dysregulation,as well as colorectal(HR=1.45,95%CI:1.07-1.96)and prostate cancer(HR=2.44,95%CI:1.42-4.21)in MAFLD with three risk factors.Additionally,MAFLD with excessive alcohol consumption would increase extrahepatic cancers(HR=1.14,95%CI:1.01-1.29)and breast cancer(HR=7.27,95%CI:2.33-22.69)risk.Conclusions:MAFLD and NAFLD shared similar excessive risks of obesity-related cancers,suggesting a driving role of FLD in these cancers.Metabolic dysregulation beyond obesity may play additional kidney,colorectal,and prostate cancer risks in MAFLD patients.It may be helpful in the clinic to relieve symptoms by treating metabolic disorders and preventing adverse outcomes of extrahepatic cancers.
文摘Non-alcoholic fatty liver disease(NAFLD),defined as the presence of fat accumulation in imaging or histology in more than 5%of hepatocytes and exclusion of other causes for secondary hepatic fat accumulation,is one of the major causes of chronic liver disease worldwide.Metabolic syndrome is associated with an increased risk of progression from NAFLD to non-alcoholic steatohepatitis(NASH),fibrosis,and forthcoming liver failure.Also,genetic predisposition contributes to the risk of NAFLD development.This review explores the role of diets and nutraceuticals in delaying the development and the evolution of NAFLD to chronic liver disease.The Mediterranean diet,high-protein diet,lowcarbohydrate/high-fat diet,high-carbohydrate/low-fat diet,and intermittent fasting are the dietary approaches investigated given the presence of relevant literature data.Moreover,this review focused on nutraceuticals with proven efficacy in ameliorating NAFLD and grouped them into four different categories:plant-based nutraceuticals(Ascophyllum nodosum and Fucus vesiculosus,Silymarin,Berberine,Curcumin,Resveratrol,Nigella sativa,Quercetin),vitamin-like substances(vitamin E,vitamin D,vitamin C,coenzyme Q10,inositol),fatty acids(omega-3),and microbiota-management tools(probiotics).
文摘Liver steatosis(i.e.,excessive triglyceride accumulation within the hepatocyte)is a very common finding in both the adult and pediatric populations.In the latter,epidemiologic data using validated diagnostic techniques(either liver biopsy or ultrasound-based technologies)have shown an alarmingly high prevalence,paralleling the ever-increasing rates of overweight and obesity.
基金supported in part by the Southampton NIHR Biomedical Research Centre,UK (NIHR 203319).
文摘Accumulating evidence in recent years has reinforced the notion that non-alcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease/metabolic dysfunction steatotic liver disease(NAFLD/MAFLD/MASLD)is a multisystem disease that increases the risk of all-cause and disease-specific mortality(1,2).
基金supported by grants from the National Natural Science Foundation of China (No.82070588,No.82370577)supported in part by grants from the School of Medicine,University of Verona,Verona,Italysupported in part by the Southampton NIHR Biomedical Research Centre,UK (NIHR203319).
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD),previously termed non-alcoholic fatty liver disease,is one of the most common causes of chronic liver disease,affecting around 30%of the world’s adults(1).MAFLD encompasses a spectrum of liver conditions,ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis(MASH),which can progress to cirrhosis and hepatocellular carcinoma(HCC)(2,3).
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.
文摘Metabolic(dysfunction)-associated fatty liver disease(MAFLD)affects a third of the population and is a leading cause of liver-related death.Since no effective treatments exist,novel approaches to drug development are required.Unfortunately,outdated terminology and definitions of the disease are hampering efforts to develop new drugs and treatments.An international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease(NAFLD)to MAFLD,includ-ing a proposal for how the disease should be diagnosed.As allies with the many stakeholders in MAFLD care―including patients,patients’advocates,clinicians,researchers,nurse and allied health groups,regional societies,and others―we are aware of the negative consequences of the NAFLD term and definition.We share the sense of urgency for change and will act in new ways to achieve our goals.Although there is much work to be done to overcome clinical inertia and reverse worrisome recent trends,the MAFLD initiative provides a firm foundation to build on.It provides a roadmap for moving for-ward toward more efficient care and affordable,sustainable drug and device innovation in MAFLD care.We hope it will bring promising new opportunities for a brighter future for MAFLD care and improve care and outcomes for patients of one of the globe’s largest and costliest public health burdens.From this viewpoint,we have revisited this initiative through the perspectives of drug development and regulatory science.
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.
基金This work was supported by grants from the National Natural Science Foundation of China(82070588)High Level Creative Talents from Department of Public Health in Zhejiang Province(S2032102600032)+3 种基金Project of New Century 551 Talent Nurturing in Wenzhou.GT was supported in part by grants from the University School of Medicine of Verona(Verona,Italy)CDB was supported in part by the Southampton NIHR Biomedical Research Centre(ISBRC-20004)UK.ME and JG were supported by the Robert W.Storr Bequest to the Sydney Medical Foundation,University of Sydney(Sydney,Australia)and the National Health and Medical Research Council of Australia(NHMRC)Program(APP1053206,APP1149976)Project(APP1107178 and APP1108422)grants.
文摘Background and Aims:In Europeans,variants in the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene impact liver histology in metabolic-associated fatty liver disease(MAFLD).The impact of these variants in ethnic Chinese is unknown.The aim of this study was to investigate the potential associations in Chinese patients.Methods:In total,427 Han Chinese with biopsy-confirmed MAFLD were enrolled.Two single nucleotide polymorphisms in HSD17B13 were genotyped:rs72613567 and rs6531975.Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology.Results:In our cohort,the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis[odds ratio(OR):2.93(1.20–7.17),p=0.019 for the additive model;OR:3.32(1.39–7.91),p=0.007 for the recessive model],representing an inverse association as compared to the results from European cohorts.In contrast,we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant[OR:0.48(0.24–0.98),p=0.043 for the additive model;OR:0.62(0.40–0.94),p=0.025 for the dominant model].HSD17B13 variants were only associated with fibrosis but no other histological features.Furthermore,HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis.Conclusions:HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans.These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.
基金This study was funded by the National Natural Science Foundation of China Grant(81670782 and 81970741 to F.Xu)the Local Innovative and Research Teams Projects of Guangdong Pearl River Talents Program of China(2017BT01S131 to F.Xu)+1 种基金the Guangdong High-Level Talents Special Support Program of China(2016TQ03R590 to F.Xu)the Pearl River S&T Nova Program of Guangzhou,China(201610010175 to F.Xu).
文摘Non-alcoholic fatty liver disease(NAFLD)has become a global epidemic nowadays.Although the pathogenesis of NAFLD remains to be uncovered,it is highly correlated with the changing of environment as other metabolic diseases.Epigenetics is the study on the differences of gene expression not caused by the changes in DNA sequencing.The epigenetics is considered to link the environment factors and the onset and development of NAFLD.As an increasing number of researches on epigenetics have emerged in recent years,our understanding of how epigenetic factors take part in the pathogenesis of NAFLD has been improved.This article reviews the recent studies on important epigenetic factors contributing to the progression of NAFLD including the DNA methylation,modification of histones and non-coding RNAs.It may give us a hint to discover novel diagnosis methods and drug targets for NAFLD.
基金Natural Science Foundation of Hunan Province(2021JJ80055)Natural Science Foundation of Guangxi Province(2020JJA140044)Funding Project for the Employment and Entrepreneurship of Overseas Students in Hunan Province[2022]。
