Nonalcoholic fatty liver disease(NAFLD)is a global health concern associated with significant morbidity and mortality.NAFLD is a spectrum of diseases originating from simple steatosis,progressing through nonalcoholic ...Nonalcoholic fatty liver disease(NAFLD)is a global health concern associated with significant morbidity and mortality.NAFLD is a spectrum of diseases originating from simple steatosis,progressing through nonalcoholic steatohepatitis(NASH),fibrosis,and cirrhosis that may lead to hepatocellular carcinoma(HCC).The pathogenesis of NAFLD is mediated by the triglyceride accumulation followed by proinflam-matory cytokines expression leading to inflammation,oxidative stress,and mitochondrial dysfunction de-noted as“two-hit hypothesis”,advancing with a“third hit”of insufficient hepatocyte proliferation,lead-ing to the increase in hepatic progenitor cells contributing to fibrosis and HCC.Wnt/β-catenin signaling is responsible for normal liver development,regeneration,hepatic metabolic zonation,ammonia and drug detoxification,hepatobiliary development,etc.,maintaining the overall liver homeostasis.The key regula-tors of canonical Wnt signaling such as LRP6,Wnt1,Wnt3a,β-catenin,GSK-3β,and APC are abnormally regulated in NAFLD.Many experimental studies have shown the aberrated Wnt/β-catenin signaling dur-ing the NAFLD progression and NASH to hepatic fibrosis and HCC.Therefore,in this review,we have em-phasized the role of Wnt/β-catenin signaling and its modulators that can potentially aid in the inhibition of NAFLD.展开更多
[Objectives]To explore the protective effects and mechanism of Yinzhihuang combined with metformin on nonalcoholic fatty liver diseases(NAFLD)based on PPAR-αsignaling pathway.[Methods]54 male SD rats were randomly di...[Objectives]To explore the protective effects and mechanism of Yinzhihuang combined with metformin on nonalcoholic fatty liver diseases(NAFLD)based on PPAR-αsignaling pathway.[Methods]54 male SD rats were randomly divided into 2 groups,namely normal group(12 rats)and high-fat feed group(42 rats).After 8 weeks,2 rats were randomly selected from each group.After pathological examination confirmed the success of the NAFLD model,the high-fat feed group was divided into model group,Yinzhihuang(9000 mg/kg),metformin group(200 mg/kg),Yinzhihuang combined with metformin group(4500 mg/kg+100 mg/kg),10 rats in each group.Except the normal group and the model group,the other groups were given treatment drugs at the same time,one time a day,on the fifth weekend of the experiment,at the last time of administration,fasting but giving water for 16 h,then collected blood and liver tissue.Biochemical method was used to detect AST and ALT in serum and SOD,MDA,GSH-px biochemical indicators in liver tissue;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of TNF-α,IL-6 and TGF-βin liver tissue;Western blot was used to detect the expression of peroxisome proliferators-activated receptor-α(PPAR-α)protein in rat liver tissue.[Results]Compared with the model group,the serum levels of ALT,AST and MDA in liver tissue of model group rats were significantly increased;the levels of SOD and GSH-px in liver tissue were significantly increased;TNF-αand IL-6 and TGF-βcontents in liver tissue were significantly increased.[Conclusions]Both Yinzhihuang and metformin have a therapeutic effect on NAFLD rats,and the effect of combined application of the two is significantly better than the intervention effect of Yinzhihuang or metformin alone,the mechanism is possibly associated with the regulation of PPAR-αsignaling pathway.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(N...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with steatosis.Circulating microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains unknown.This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.AIM To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.METHODS This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study.Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD.Plasma samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform.We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key covariates.Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD.RESULTS We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with NAFLD.Moreover,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,respectively.Collectively,16 miRNAs were associated with two or more histological features of NAFLD.Among those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and positively associated with all histological features of NAFLD.Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression,while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B.CONCLUSION Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity.Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.展开更多
BACKGROUND Although the etiology of nonalcoholic fatty liver disease(NAFLD)has not been thoroughly understood,the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been hig...BACKGROUND Although the etiology of nonalcoholic fatty liver disease(NAFLD)has not been thoroughly understood,the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating evidence.AIM To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization(MR)design.METHODS The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators,including hip circumference(HC),waist circumference(WC),waist-to-hip ratio(WHR),body mass index(BMI),and body fat percentage(BF).Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen Consortium.Genome-wide significant single nucleotide polymorphisms were chosen as instrumental variables.Univariable MR(UVMR)and multivariable MR(MVMR)designs with analytical approaches,including inverse variance weighted(IVW),MR-Egger,weighted median(WM),and weighted mode methods,were used to assess the causal relationships between anthropometric indicators and NAFLD.RESULTS Causal relationships were revealed by UVMR,indicating that a higher risk of NAFLD was associated with a perunit increase in WC[IVW:odds ratio(OR)=2.67,95%CI:1.42-5.02,P=2.25×10^(−3)],and BF was causally associated with an increased risk of NAFLD(WM:OR=2.23,95%CI:1.07-4.66,P=0.033).The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and smoking.However,no causal association between BF and NAFLD was observed.In addition,other causal relationships of HC,WHR(BMI adjusted),and BMI with the risk of NAFLD were not retained after FDR correction.CONCLUSION This study establishes a causal relationship,indicating that an increase in WC is associated with a higher risk of NAFLD.This demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.展开更多
BACKGROUND The severity of nonalcoholic fatty liver disease(NAFLD)and lipid metabolism are related to the occurrence of colorectal polyps.Liver-controlled attenuation parameters(liver-CAPs)have been established to pre...BACKGROUND The severity of nonalcoholic fatty liver disease(NAFLD)and lipid metabolism are related to the occurrence of colorectal polyps.Liver-controlled attenuation parameters(liver-CAPs)have been established to predict the prognosis of hepatic steatosis patients.AIM To explore the risk factors associated with colorectal polyps in patients with NAFLD by analyzing liver-CAPs and establishing a diagnostic model.METHODS Patients who were diagnosed with colorectal polyps in the Department of Gastroenterology of our hospital between June 2021 and April 2022 composed the case group,and those with no important abnormalities composed the control group.The area under the receiver operating characteristic curve was used to predict the diagnostic efficiency.Differences were considered statistically significant when P<0.05.RESULTS The median triglyceride(TG)and liver-CAP in the case group were significantly greater than those in the control group(mmol/L,1.74 vs 1.05;dB/m,282 vs 254,P<0.05).TG and liver-CAP were found to be independent risk factors for colorectal polyps,with ORs of 2.338(95%CI:1.154–4.733)and 1.019(95%CI:1.006–1.033),respectively(P<0.05).And there was no difference in the diagnostic efficacy between liver-CAP and TG combined with liver-CAP(TG+CAP)(P>0.05).When the liver-CAP was greater than 291 dB/m,colorectal polyps were more likely to occur.CONCLUSION The levels of TG and liver-CAP in patients with colorectal polyps are significantly greater than those patients without polyps.Liver-CAP alone can be used to diagnose NAFLD with colorectal polyps.展开更多
Objective: To explore the therapeutic effect of Linggui Zhugan Decoction on nonalcoholic fatty liver disease through in vivo animal experiments, and to explore the mechanism of action of Linggui Zhugan Decoction in th...Objective: To explore the therapeutic effect of Linggui Zhugan Decoction on nonalcoholic fatty liver disease through in vivo animal experiments, and to explore the mechanism of action of Linggui Zhugan Decoction in the intervention of nonalcoholic fatty liver disease through network pharmacology and molecular docking technology. Methods: A rat model of non- alcoholic fatty liver disease was established after 20 weeks of high-fat feeding, and the rats were divided into six groups, normal group, model group, simvastatin group (4 mg/kg), low- dose group of Linggui Zhugan Decoction (2.1 g/kg), medium-dose group of Linggui Zhugan Decoction (4.2 g/kg), and high-dose group of Linggui Zhugan Decoction (8.4 g/kg), and the liver morphological changes of HE staining and oil red O staining after the intervention of Linggui Zhugan Decoction were observed, and the microplate reader detected aspartate aminotransferase, alanine aminotransferase, Four levels of blood lipids. Network pharmacology combined with molecular docking was used to screen the potential mechanism and target of Linggui Zhugan Decoction for the intervention of non-alcoholic fatty liver disease. Results: Linggui Zhugan Decoction significantly improved the levels of alanine aminotransferase and alanine aminotransferase in model rats (P<0.05). HE staining and oil red O staining showed that Linggui Zhugan Decoction significantly reduced liver lipid deposition in rats in the model group. Linggui Zhugan Decoction could significantly reduce the quadruplical levels of blood lipids in model rats (P<0.05). Network pharmacology screened out 10 key targets and 5 key signaling pathways;The molecular docking results showed that the first 20 active ingredients all had good binding ability to the top 10 targets. Conclusion: The results show that Linggui Zhugan Decoction has the effect of regulating blood lipids and improving liver tissue lesions in non-alcoholic fatty liver disease, and preliminarily verifies the regulatory effect of Linggui Zhugan Decoction on lipid metabolism-related genes.展开更多
Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH ...Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH may develop in earlier stages of NAFLD,suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis.The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning,leading to the compression of liver sinusoids.External compression and intraluminal obstacles cause mechanical forces such as strain,shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways,resulting in endothelial dysfunction and the development of fibrosis.The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD.Thus,current diagnostic methods such as hepatic venous pressure gradient(HVPG)measurement tend to underestimate portal pressure(PP)in NAFLD patients,who might decompensate below the HVPG threshold of 10 mmHg,which is traditionally considered the most relevant indicator of clinically significant portal hypertension(CSPH).This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients.In theory,the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component,but more investigations are needed to test its clinical utility for this indication.Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment.Lifestyle change remains the cornerstone of the treatment of PH in NAFLD,together with correcting the components of metabolic syndrome,using nonselective beta blockers,whereas emerging candidate drugs require more robust confirmation from clinical trials.展开更多
Background: The objective of this study was to compare and analyze the variations in clinical indices before and after treatment of type 2 mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) that we...Background: The objective of this study was to compare and analyze the variations in clinical indices before and after treatment of type 2 mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) that were treated with glucagon-like peptide 1 receptor agonists (GLP-1RAs). Methods: The electronic medical record system was utilized to search for a total of 16 patients with type 2 diabetes complicated by NAFLD who were hospitalized at the First Affiliated Hospital of Yangtze University from October 2022 to April 2023 and treated with GLP-1RA for the first time. The clinical indices were compared before and after 12 weeks of treatment with GLP-1RA. Results: The liver-spleen CT ratio (L/S), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in all patients treated with GLP-1RA after 12 weeks were significantly different (P 0.05). The patients were categorized into two groups based on the types of GLP-1RAs. The changes in L/S, TC, TG, and LDL-C in the long-acting group after treatment were statistically significant (P Conclusions: GLP-1RAs can improve liver function, regulate lipid metabolism, and reduce the severity of fatty liver in patients with T2DM complicated by NAFLD, which demonstrates the importance of clinical applications.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)has become the leading cause of cirrhosis and other chronic liver diseases(COCLDs).AIM To conduct a comprehensive and comparable updated analysis of the global,regiona...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)has become the leading cause of cirrhosis and other chronic liver diseases(COCLDs).AIM To conduct a comprehensive and comparable updated analysis of the global,regional,and national burden of COCLDs due to NAFLD in 204 countries and territories from 1990 and 2019 by age,sex,and sociodemographic index.METHODS Data on COCLDs due to NAFLD were collected from the Global Burden of Diseases,Injuries,and Risk Factors Study 2019.Numbers and age-standardized prevalence,death,and disability-adjusted life years(DALYs)were estimated through a systematic analysis of modelled data from the Global Burden of Diseases,Injuries,and Risk Factors Study 2019.The estimated annual percentage change was used to determine the burden trend.RESULTS In 2019,the global age-standardized prevalence rate of COCLDs due to NAFLD was 15022.90 per 100000 population[95%uncertainty interval(UI):13493.19-16764.24],which increased by 24.51%(22.63%to 26.08%)from 1990,with an estimated annual percentage change of 0.78(95%confidence interval:0.74-0.82).In the same year,however,the age-standardized death rate and age-standardized DALYs per 100000 population were 1.66(95%UI:1.20-2.17)and 43.69(95%UI:31.28-58.38),respectively.North Africa and the Middle East had the highest prevalence rates of COCLDs due to NAFLD.The death rate increased with age up to the 95+age group for both sexes.Males had higher numbers of prevalence,death rate,and DALYs than females across all age groups before the 65-69 age group.The sociodemographic index was negatively correlated with the age-standardized DALYs.CONCLUSION Globally,the age-standardized prevalence rate has increased during the past three decades.However,the agestandardized death rate and age-standardized DALYs decreased.There is geographical variation in the burden of COCLDs due to NAFLD.It is strongly recommended to improve the data quality of COCLDs due to NAFLD across all countries and regions to facilitate better monitoring of the burden of COCLDs due to NAFLD.展开更多
Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver disease.However,the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies.Several studies...Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver disease.However,the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies.Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoe-tiology and suggest functional therapeutic and diagnostic options.Pyroptosis,ferroptosis,and necroptosis are the main subtypes of non-apoptotic regulated cell deaths(RCDs),each of which represents particular characteristics.Considering the complexity of the findings,the present study aimed to review these types of RCDs and their contribution to NAFLD progression,and subsequently discuss in detail the role of necroptosis in the pathoetiology,diagnosis,and treatment of the disease.The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer,hence it has potential in diagnostic and therapeutic approaches.Nevertheless,further studies are necessary.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is chronic,with its progression leading to liver fibrosis and end-stage cirrhosis.Although NAFLD is increasingly common,no treatment guideline has been established.Man...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is chronic,with its progression leading to liver fibrosis and end-stage cirrhosis.Although NAFLD is increasingly common,no treatment guideline has been established.Many mechanistic studies and drug trials have been conducted for new drug development to treat NAFLD.An up-to-date overview on the knowledge structure of NAFLD through bibliometrics,focusing on research hotspots,is necessary to reveal the rational and timely directions of development in this field.AIM To research the latest literature and determine the current trends in treatment for NAFLD.METHODS Publications related to treatment for NAFLD were searched on the Web of Science Core Collection database,from 2010 to 2023.VOSviewers,CiteSpace,and R package“bibliometrix”were used to conduct this bibliometric analysis.The key information was extracted,and the results of the cluster analysis were based on network data for generating and investigating maps for country,institution,journal,and author.Historiography analysis,bursts and cluster analysis,cooccurrence analysis,and trend topic revealed the knowledge structure and research hotspots in this field.GraphPad Prism 9.5.1.733 and Microsoft Office Excel 2019 were used for data analysis and visualization.RESULTS In total,10829 articles from 120 countries(led by China and the United States)and 8785 institutions were included.The number of publications related to treatment for NAFLD increased annually.While China produced the most publications,the United States was the most cited country,and the United Kingdom collaborated the most from an international standpoint.The University of California-San Diego,Shanghai Jiao Tong University,and Shanghai University of Traditional Chinese Medicine produced the most publications of all the research institutions.The International Journal of Molecular Sciences was the most frequent journal out of the 1523 total journals,and Hepatology was the most cited and co-cited journal.Sanyal AJ was the most cited author,the most co-cited author was Younossi ZM,and the most influential author was Loomba R.The most studied topics included the epidemiology and mechanism of NAFLD,the development of accurate diagnosis,the precise management of patients with NAFLD,and the associated metabolic comorbidities.The major cluster topics were“emerging drug,”“glucagon-like peptide-1 receptor agonist,”“metabolic dysfunction-associated fatty liver disease,”“gut microbiota,”and“glucose metabolism.”CONCLUSION The bibliometric study identified recent research frontiers and hot directions,which can provide a valuable reference for scholars researching treatments for NAFLD.展开更多
A growing body of evidence from multiple areas proposes that periodontal disease,accompanied by oral inflammation and pathological changes in the microbiome,induces gut dysbiosis and is involved in the pathogenesis of...A growing body of evidence from multiple areas proposes that periodontal disease,accompanied by oral inflammation and pathological changes in the microbiome,induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease(NAFLD).A subgroup of NAFLD patients have a severely progressive form,namely nonalcoholic steatohepatitis(NASH),which is characterized by histological findings that include inflammatory cell infiltration and fibrosis.NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma.The oral microbiota may serve as an endogenous reservoir for gut microbiota,and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis.Gut dysbiosis increases the production of potential hepatotoxins,including lipopolysaccharide,ethanol,and other volatile organic compounds such as acetone,phenol and cyclopentane.Moreover,gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall,leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation.In particular,many animal studies support that oral administration of Porphyromonas gingivalis,a typical periodontopathic bacterium,induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis.NAFLD,also known as the hepatic phenotype of metabolic syndrome,is strongly associated with metabolic complications,such as obesity and diabetes.Periodontal disease also has a bidirectional relationship with metabolic syndrome,and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively.In this review,we will describe the link between periodontal disease and NAFLD with a focus on basic,epidemiological,and clinical studies,and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome.In conclusion,it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease,gut microbiota,and metabolic syndrome.Thus,the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics,prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.展开更多
This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwid...This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.展开更多
The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver en...The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.展开更多
Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver diseas...Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.展开更多
The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A com...The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A community-based health check-up program was conducted in Qingdao,China.NAFLD was diagnosed by ultrasonography accompanied by epidemiological investigation.The dietary intakes of amino acids were investigated with 3-day,24-h dietary records and calculated by Nutrition Calculator software.Restricted cubic spline model was used to evaluate a nonlinear relationship between amino acid intake and NAFLD risk.Results:400 NAFLD subjects were identified,and 400 participants were randomly selected as controls and matched by gender and age(±3 years)Dose-response analysis showed that 1000 mg increment of aromatic amino acids(AAAs)was associated with reduced 16%risk of NAFLD.Dietary increments of 750 mg/d threonine,950 mg/d valine,or 1700 mg/d lysine were associated with a 20%reduction in the NAFLD risk(all P for linearity<0.05).Conclusion:The present study demonstrated that the dietary increases in milk,eggs and deep-sea fish,which are rich in the amino acids,might contribute to protecting against NAFLD in the elderly.展开更多
The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbio...The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.展开更多
Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were establi...Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.展开更多
The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease...The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and sarcopenia.Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies.Sarcopenia can be either part of the disease process that results in MAFLD(e.g.,obesity or adiposity)or a consequence of MAFLD,especially in the advanced stages such as fibrosis and cirrhosis.Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors.Therefore,it is crucial to thoroughly understand how we deal with these diseases,especially when they coexist.We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyl...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.展开更多
基金supported by a grant from the Extramural Re-search Project,Indian Council of Medical Research,New Delhi,In-dia(58/30/2020/PHA/BMS dtd 9.11.2021).
文摘Nonalcoholic fatty liver disease(NAFLD)is a global health concern associated with significant morbidity and mortality.NAFLD is a spectrum of diseases originating from simple steatosis,progressing through nonalcoholic steatohepatitis(NASH),fibrosis,and cirrhosis that may lead to hepatocellular carcinoma(HCC).The pathogenesis of NAFLD is mediated by the triglyceride accumulation followed by proinflam-matory cytokines expression leading to inflammation,oxidative stress,and mitochondrial dysfunction de-noted as“two-hit hypothesis”,advancing with a“third hit”of insufficient hepatocyte proliferation,lead-ing to the increase in hepatic progenitor cells contributing to fibrosis and HCC.Wnt/β-catenin signaling is responsible for normal liver development,regeneration,hepatic metabolic zonation,ammonia and drug detoxification,hepatobiliary development,etc.,maintaining the overall liver homeostasis.The key regula-tors of canonical Wnt signaling such as LRP6,Wnt1,Wnt3a,β-catenin,GSK-3β,and APC are abnormally regulated in NAFLD.Many experimental studies have shown the aberrated Wnt/β-catenin signaling dur-ing the NAFLD progression and NASH to hepatic fibrosis and HCC.Therefore,in this review,we have em-phasized the role of Wnt/β-catenin signaling and its modulators that can potentially aid in the inhibition of NAFLD.
基金Student's Platform for Innovation and Entrepreneurship Training Program of Guangxi Zhuang Autonomous Region,China(201810601070)。
文摘[Objectives]To explore the protective effects and mechanism of Yinzhihuang combined with metformin on nonalcoholic fatty liver diseases(NAFLD)based on PPAR-αsignaling pathway.[Methods]54 male SD rats were randomly divided into 2 groups,namely normal group(12 rats)and high-fat feed group(42 rats).After 8 weeks,2 rats were randomly selected from each group.After pathological examination confirmed the success of the NAFLD model,the high-fat feed group was divided into model group,Yinzhihuang(9000 mg/kg),metformin group(200 mg/kg),Yinzhihuang combined with metformin group(4500 mg/kg+100 mg/kg),10 rats in each group.Except the normal group and the model group,the other groups were given treatment drugs at the same time,one time a day,on the fifth weekend of the experiment,at the last time of administration,fasting but giving water for 16 h,then collected blood and liver tissue.Biochemical method was used to detect AST and ALT in serum and SOD,MDA,GSH-px biochemical indicators in liver tissue;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of TNF-α,IL-6 and TGF-βin liver tissue;Western blot was used to detect the expression of peroxisome proliferators-activated receptor-α(PPAR-α)protein in rat liver tissue.[Results]Compared with the model group,the serum levels of ALT,AST and MDA in liver tissue of model group rats were significantly increased;the levels of SOD and GSH-px in liver tissue were significantly increased;TNF-αand IL-6 and TGF-βcontents in liver tissue were significantly increased.[Conclusions]Both Yinzhihuang and metformin have a therapeutic effect on NAFLD rats,and the effect of combined application of the two is significantly better than the intervention effect of Yinzhihuang or metformin alone,the mechanism is possibly associated with the regulation of PPAR-αsignaling pathway.
基金Supported by National Institute of Environmental Health,No.R01ES030691No.R01ES030364,No.R01ES029944,No.U01HG013288,No.T32-ES013678,No.P30ES007048,No.U2CES030859,No.R01ES032831,No.R01ES033688,No.P30ES023515,and No.P2CES033433+8 种基金National Human Genome Research Institute and National Institute of Environmental Health,No.U01HG013288California Environmental Protection Agency,No.20-E0017National Cancer Institute and National Institute of Environmental Health,No.P01CA196569Ministry of Science and Innovation and State Research Agency,No.CEX2018-000806-SEuropean Union(“NextGenerationEU/PRTR”),No.IJC2020-043630-IEuropean Union’s Horizon Europe Research And Innovation Programme Under the Marie Skłodowska-Curie Actions Postdoctoral Fellowships,No.101059245United States Department of Agriculture,No.6250-51000-053National Institutes of Health,No.R01DK128117-01A1The Teen-LABS Consortium:National Institute of Diabetes and Digestive and Kidney Diseases,No.UM1DK072493 and No.UM1DK095710.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with steatosis.Circulating microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains unknown.This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.AIM To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.METHODS This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study.Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD.Plasma samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform.We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key covariates.Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD.RESULTS We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with NAFLD.Moreover,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,respectively.Collectively,16 miRNAs were associated with two or more histological features of NAFLD.Among those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and positively associated with all histological features of NAFLD.Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression,while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B.CONCLUSION Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity.Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.
基金Supported by Science and Technology Research Project of Sichuan Administration of Traditional Chinese Medicine,No.2023MS419.
文摘BACKGROUND Although the etiology of nonalcoholic fatty liver disease(NAFLD)has not been thoroughly understood,the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating evidence.AIM To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization(MR)design.METHODS The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators,including hip circumference(HC),waist circumference(WC),waist-to-hip ratio(WHR),body mass index(BMI),and body fat percentage(BF).Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen Consortium.Genome-wide significant single nucleotide polymorphisms were chosen as instrumental variables.Univariable MR(UVMR)and multivariable MR(MVMR)designs with analytical approaches,including inverse variance weighted(IVW),MR-Egger,weighted median(WM),and weighted mode methods,were used to assess the causal relationships between anthropometric indicators and NAFLD.RESULTS Causal relationships were revealed by UVMR,indicating that a higher risk of NAFLD was associated with a perunit increase in WC[IVW:odds ratio(OR)=2.67,95%CI:1.42-5.02,P=2.25×10^(−3)],and BF was causally associated with an increased risk of NAFLD(WM:OR=2.23,95%CI:1.07-4.66,P=0.033).The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and smoking.However,no causal association between BF and NAFLD was observed.In addition,other causal relationships of HC,WHR(BMI adjusted),and BMI with the risk of NAFLD were not retained after FDR correction.CONCLUSION This study establishes a causal relationship,indicating that an increase in WC is associated with a higher risk of NAFLD.This demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.
基金Supported by the Special Research Project of the Capital’s Health Development,No.2024-3-7037and the Beijing Clinical Key Specialty Project.
文摘BACKGROUND The severity of nonalcoholic fatty liver disease(NAFLD)and lipid metabolism are related to the occurrence of colorectal polyps.Liver-controlled attenuation parameters(liver-CAPs)have been established to predict the prognosis of hepatic steatosis patients.AIM To explore the risk factors associated with colorectal polyps in patients with NAFLD by analyzing liver-CAPs and establishing a diagnostic model.METHODS Patients who were diagnosed with colorectal polyps in the Department of Gastroenterology of our hospital between June 2021 and April 2022 composed the case group,and those with no important abnormalities composed the control group.The area under the receiver operating characteristic curve was used to predict the diagnostic efficiency.Differences were considered statistically significant when P<0.05.RESULTS The median triglyceride(TG)and liver-CAP in the case group were significantly greater than those in the control group(mmol/L,1.74 vs 1.05;dB/m,282 vs 254,P<0.05).TG and liver-CAP were found to be independent risk factors for colorectal polyps,with ORs of 2.338(95%CI:1.154–4.733)and 1.019(95%CI:1.006–1.033),respectively(P<0.05).And there was no difference in the diagnostic efficacy between liver-CAP and TG combined with liver-CAP(TG+CAP)(P>0.05).When the liver-CAP was greater than 291 dB/m,colorectal polyps were more likely to occur.CONCLUSION The levels of TG and liver-CAP in patients with colorectal polyps are significantly greater than those patients without polyps.Liver-CAP alone can be used to diagnose NAFLD with colorectal polyps.
基金Anhui Natural Science Foundat ion General Project(No.2208085MH277)。
文摘Objective: To explore the therapeutic effect of Linggui Zhugan Decoction on nonalcoholic fatty liver disease through in vivo animal experiments, and to explore the mechanism of action of Linggui Zhugan Decoction in the intervention of nonalcoholic fatty liver disease through network pharmacology and molecular docking technology. Methods: A rat model of non- alcoholic fatty liver disease was established after 20 weeks of high-fat feeding, and the rats were divided into six groups, normal group, model group, simvastatin group (4 mg/kg), low- dose group of Linggui Zhugan Decoction (2.1 g/kg), medium-dose group of Linggui Zhugan Decoction (4.2 g/kg), and high-dose group of Linggui Zhugan Decoction (8.4 g/kg), and the liver morphological changes of HE staining and oil red O staining after the intervention of Linggui Zhugan Decoction were observed, and the microplate reader detected aspartate aminotransferase, alanine aminotransferase, Four levels of blood lipids. Network pharmacology combined with molecular docking was used to screen the potential mechanism and target of Linggui Zhugan Decoction for the intervention of non-alcoholic fatty liver disease. Results: Linggui Zhugan Decoction significantly improved the levels of alanine aminotransferase and alanine aminotransferase in model rats (P<0.05). HE staining and oil red O staining showed that Linggui Zhugan Decoction significantly reduced liver lipid deposition in rats in the model group. Linggui Zhugan Decoction could significantly reduce the quadruplical levels of blood lipids in model rats (P<0.05). Network pharmacology screened out 10 key targets and 5 key signaling pathways;The molecular docking results showed that the first 20 active ingredients all had good binding ability to the top 10 targets. Conclusion: The results show that Linggui Zhugan Decoction has the effect of regulating blood lipids and improving liver tissue lesions in non-alcoholic fatty liver disease, and preliminarily verifies the regulatory effect of Linggui Zhugan Decoction on lipid metabolism-related genes.
文摘Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH may develop in earlier stages of NAFLD,suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis.The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning,leading to the compression of liver sinusoids.External compression and intraluminal obstacles cause mechanical forces such as strain,shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways,resulting in endothelial dysfunction and the development of fibrosis.The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD.Thus,current diagnostic methods such as hepatic venous pressure gradient(HVPG)measurement tend to underestimate portal pressure(PP)in NAFLD patients,who might decompensate below the HVPG threshold of 10 mmHg,which is traditionally considered the most relevant indicator of clinically significant portal hypertension(CSPH).This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients.In theory,the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component,but more investigations are needed to test its clinical utility for this indication.Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment.Lifestyle change remains the cornerstone of the treatment of PH in NAFLD,together with correcting the components of metabolic syndrome,using nonselective beta blockers,whereas emerging candidate drugs require more robust confirmation from clinical trials.
文摘Background: The objective of this study was to compare and analyze the variations in clinical indices before and after treatment of type 2 mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) that were treated with glucagon-like peptide 1 receptor agonists (GLP-1RAs). Methods: The electronic medical record system was utilized to search for a total of 16 patients with type 2 diabetes complicated by NAFLD who were hospitalized at the First Affiliated Hospital of Yangtze University from October 2022 to April 2023 and treated with GLP-1RA for the first time. The clinical indices were compared before and after 12 weeks of treatment with GLP-1RA. Results: The liver-spleen CT ratio (L/S), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in all patients treated with GLP-1RA after 12 weeks were significantly different (P 0.05). The patients were categorized into two groups based on the types of GLP-1RAs. The changes in L/S, TC, TG, and LDL-C in the long-acting group after treatment were statistically significant (P Conclusions: GLP-1RAs can improve liver function, regulate lipid metabolism, and reduce the severity of fatty liver in patients with T2DM complicated by NAFLD, which demonstrates the importance of clinical applications.
基金National Key research and Development Program,No.2022YFE0131600National Natural Science Foundation of China,No.82160500+3 种基金Special Project of Central Government Guiding Local Science and Technology Development,No.ZY20198011Guangxi Science and Technology Base and Talent Project,No.GuikeAA21220002Natural Science Foundation of Guangxi,No.2022GXNSFAA035642The Liuzhou Science and Technology Plan Project,No.2021CB0101.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)has become the leading cause of cirrhosis and other chronic liver diseases(COCLDs).AIM To conduct a comprehensive and comparable updated analysis of the global,regional,and national burden of COCLDs due to NAFLD in 204 countries and territories from 1990 and 2019 by age,sex,and sociodemographic index.METHODS Data on COCLDs due to NAFLD were collected from the Global Burden of Diseases,Injuries,and Risk Factors Study 2019.Numbers and age-standardized prevalence,death,and disability-adjusted life years(DALYs)were estimated through a systematic analysis of modelled data from the Global Burden of Diseases,Injuries,and Risk Factors Study 2019.The estimated annual percentage change was used to determine the burden trend.RESULTS In 2019,the global age-standardized prevalence rate of COCLDs due to NAFLD was 15022.90 per 100000 population[95%uncertainty interval(UI):13493.19-16764.24],which increased by 24.51%(22.63%to 26.08%)from 1990,with an estimated annual percentage change of 0.78(95%confidence interval:0.74-0.82).In the same year,however,the age-standardized death rate and age-standardized DALYs per 100000 population were 1.66(95%UI:1.20-2.17)and 43.69(95%UI:31.28-58.38),respectively.North Africa and the Middle East had the highest prevalence rates of COCLDs due to NAFLD.The death rate increased with age up to the 95+age group for both sexes.Males had higher numbers of prevalence,death rate,and DALYs than females across all age groups before the 65-69 age group.The sociodemographic index was negatively correlated with the age-standardized DALYs.CONCLUSION Globally,the age-standardized prevalence rate has increased during the past three decades.However,the agestandardized death rate and age-standardized DALYs decreased.There is geographical variation in the burden of COCLDs due to NAFLD.It is strongly recommended to improve the data quality of COCLDs due to NAFLD across all countries and regions to facilitate better monitoring of the burden of COCLDs due to NAFLD.
文摘Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver disease.However,the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies.Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoe-tiology and suggest functional therapeutic and diagnostic options.Pyroptosis,ferroptosis,and necroptosis are the main subtypes of non-apoptotic regulated cell deaths(RCDs),each of which represents particular characteristics.Considering the complexity of the findings,the present study aimed to review these types of RCDs and their contribution to NAFLD progression,and subsequently discuss in detail the role of necroptosis in the pathoetiology,diagnosis,and treatment of the disease.The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer,hence it has potential in diagnostic and therapeutic approaches.Nevertheless,further studies are necessary.
基金National Science Foundation of China,No.81273142Anhui Provincial Natural Science Foundation,No.2108085MH298+3 种基金University Scientific Research Project of Anhui Provincial Education Department,No.KJ2021A0323Fund of Anhui Medical University,No.2021xkj196Clinical Medicine project of Anhui Medical University,No.2021LCXK027The Second Hospital of Anhui Medical University Natural Science Foundation,No.2019GMFY02。
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is chronic,with its progression leading to liver fibrosis and end-stage cirrhosis.Although NAFLD is increasingly common,no treatment guideline has been established.Many mechanistic studies and drug trials have been conducted for new drug development to treat NAFLD.An up-to-date overview on the knowledge structure of NAFLD through bibliometrics,focusing on research hotspots,is necessary to reveal the rational and timely directions of development in this field.AIM To research the latest literature and determine the current trends in treatment for NAFLD.METHODS Publications related to treatment for NAFLD were searched on the Web of Science Core Collection database,from 2010 to 2023.VOSviewers,CiteSpace,and R package“bibliometrix”were used to conduct this bibliometric analysis.The key information was extracted,and the results of the cluster analysis were based on network data for generating and investigating maps for country,institution,journal,and author.Historiography analysis,bursts and cluster analysis,cooccurrence analysis,and trend topic revealed the knowledge structure and research hotspots in this field.GraphPad Prism 9.5.1.733 and Microsoft Office Excel 2019 were used for data analysis and visualization.RESULTS In total,10829 articles from 120 countries(led by China and the United States)and 8785 institutions were included.The number of publications related to treatment for NAFLD increased annually.While China produced the most publications,the United States was the most cited country,and the United Kingdom collaborated the most from an international standpoint.The University of California-San Diego,Shanghai Jiao Tong University,and Shanghai University of Traditional Chinese Medicine produced the most publications of all the research institutions.The International Journal of Molecular Sciences was the most frequent journal out of the 1523 total journals,and Hepatology was the most cited and co-cited journal.Sanyal AJ was the most cited author,the most co-cited author was Younossi ZM,and the most influential author was Loomba R.The most studied topics included the epidemiology and mechanism of NAFLD,the development of accurate diagnosis,the precise management of patients with NAFLD,and the associated metabolic comorbidities.The major cluster topics were“emerging drug,”“glucagon-like peptide-1 receptor agonist,”“metabolic dysfunction-associated fatty liver disease,”“gut microbiota,”and“glucose metabolism.”CONCLUSION The bibliometric study identified recent research frontiers and hot directions,which can provide a valuable reference for scholars researching treatments for NAFLD.
文摘A growing body of evidence from multiple areas proposes that periodontal disease,accompanied by oral inflammation and pathological changes in the microbiome,induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease(NAFLD).A subgroup of NAFLD patients have a severely progressive form,namely nonalcoholic steatohepatitis(NASH),which is characterized by histological findings that include inflammatory cell infiltration and fibrosis.NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma.The oral microbiota may serve as an endogenous reservoir for gut microbiota,and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis.Gut dysbiosis increases the production of potential hepatotoxins,including lipopolysaccharide,ethanol,and other volatile organic compounds such as acetone,phenol and cyclopentane.Moreover,gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall,leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation.In particular,many animal studies support that oral administration of Porphyromonas gingivalis,a typical periodontopathic bacterium,induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis.NAFLD,also known as the hepatic phenotype of metabolic syndrome,is strongly associated with metabolic complications,such as obesity and diabetes.Periodontal disease also has a bidirectional relationship with metabolic syndrome,and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively.In this review,we will describe the link between periodontal disease and NAFLD with a focus on basic,epidemiological,and clinical studies,and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome.In conclusion,it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease,gut microbiota,and metabolic syndrome.Thus,the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics,prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.
基金Supported by National Natural Science Foundation of China,No.82000625the Doctoral Scientific Research Foundation of Liaoning Province,No.2020-BS-109.
文摘This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.
文摘The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.
文摘Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.
基金supported by National Natural Science Foundation of China(NSFC:82073538 and 81773433)by the 2018 Chinese Nutrition Society(CNS)Nutrition Research Foundation-DSM Research Fund(CNS-DSM2018A30)。
文摘The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A community-based health check-up program was conducted in Qingdao,China.NAFLD was diagnosed by ultrasonography accompanied by epidemiological investigation.The dietary intakes of amino acids were investigated with 3-day,24-h dietary records and calculated by Nutrition Calculator software.Restricted cubic spline model was used to evaluate a nonlinear relationship between amino acid intake and NAFLD risk.Results:400 NAFLD subjects were identified,and 400 participants were randomly selected as controls and matched by gender and age(±3 years)Dose-response analysis showed that 1000 mg increment of aromatic amino acids(AAAs)was associated with reduced 16%risk of NAFLD.Dietary increments of 750 mg/d threonine,950 mg/d valine,or 1700 mg/d lysine were associated with a 20%reduction in the NAFLD risk(all P for linearity<0.05).Conclusion:The present study demonstrated that the dietary increases in milk,eggs and deep-sea fish,which are rich in the amino acids,might contribute to protecting against NAFLD in the elderly.
基金the National Natural Science Foundation of China,No.82104525the Natural Science Foundation of the Jiangsu Higher Education Institutions of China,No.21KJB360009Health Commission of Zhejiang Province Scientific Research Foundation,No.2024KY247.
文摘The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.
基金supported by the National Natural Science Foundation of China(81971875,82300661)Natural Science Foundation of Anhui province(2308085QH246)+3 种基金Natural Science Foundation of the Anhui Higher Education Institutions(KJ2021A0205)Basic and Clinical Cooperative Research Program of Anhui Medical University(2019xkjT002,2019xkjT022,2022xkjT013)Talent Training Program,School of Basic Medical Sciences,Anhui Medical University(2022YPJH102)National College Students Innovation and Entrepreneurship Training Program of China(202210366024)。
文摘Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.
文摘The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and sarcopenia.Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies.Sarcopenia can be either part of the disease process that results in MAFLD(e.g.,obesity or adiposity)or a consequence of MAFLD,especially in the advanced stages such as fibrosis and cirrhosis.Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors.Therefore,it is crucial to thoroughly understand how we deal with these diseases,especially when they coexist.We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.
