Regression of hepatic fibrosis after pharmacological therapy for nonalcoholic steatohepatitis

The global incidence of nonalcoholic fatty liver disease(NAFLD)is escalating considerably.NAFLD covers a range of liver conditions from simple steatosis to the more severe form known as nonalcoholic steatohepatitis,which involves chronic liver inflammation and the transformation of hepatic stellate cells into myofibroblasts that generate excess extracellular matrix,leading to fibrosis.Hepatocyte ballooning is a key catalyst for fibrosis progression,potentially advancing to cirrhosis and its decompensated state.Fibrosis is a critical prognostic factor for outcomes in patients with NAFLD;therefore,those with substantial fibrosis require timely intervention.Although liver biopsy is the most reliable method for fibrosis detection,it is associated with certain risks and limitations,particularly in routine screening.Consequently,various noninvasive diagnostic techniques have been introduced.This review examines the increasing prevalence of NAFLD,evaluates the noninvasive diagnostic techniques for fibrosis,and assesses their efficacy in staging the disease.In addition,it critically appraises current and emerging antifibrotic therapies,focusing on their mechanisms,efficacy,and potential in reversing fibrosis.This review underscores the urgent need for effective therapeutic strategies,given the dire consequences of advanced fibrosis.

Mapping global research trends: Nutrition associations with nonalcoholic fatty liver disease - a Scopus bibliometric analysis

BACKGROUND Several bibliometric analyses have been carried out to identify research hotspots and trends in nonalcoholic fatty liver disease(NAFLD)research.Nonetheless,there are still significant knowledge gaps that must be filled to advance our understanding of and ability to treat NAFLD.AIM To evaluate,through bibliometric and visual analysis,the current status of related research,related research frontiers,and the developmental trends in the field of diet and NAFLD.METHODS We retrieved publications about diet and NAFLD published between 1987 and 2022 from Scopus.Next,we used VOSviewer 1.6.20 to perform bibliometric analysis and visualization.RESULTS We found a total of 1905 studies,including 1637(85.93%)original articles and 195(10.24%)reviews,focused on the examination of NAFLD and its correlation with diet that were published between 1987 and 2022.Among the remaining five types of documents,38 were letters,notes,editorials,meeting minutes,or brief surveys,representing 1.99%of the total documents.The countries with the most publications on this topic were China(n=539;28.29%),followed by the United States(n=379;19.90%),Japan(n=133;6.98%),and South Korea(n=127;6.6%).According to the citation analysis,the retrieved papers were cited an average of 32.3 times and had an h-index of 106,with 61014 total citations.The two main clusters on the map included those related to:(1)Inflammation and oxidative stress;and(2)Dietary interventions for NAFLD.CONCLUSION This was the first study to use data taken from Scopus to visualize network mapping in a novel bibliometric analysis of studies focused on diet and NAFLD.After 2017,the two domains that received the most attention were“dietary interventions for NAFL”’and“‘inflammation and oxidative stress implicated in NAFLD and its correlation with diet.”We believe that this study provides important information for academics,dietitians,and doctors,and that additional research on dietary interventions and NAFLD is warranted.

Fanlian Huazhuo Formula alleviates high-fat diet-induced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway

BACKGROUND Fanlian Huazhuo Formula(FLHZF)has the functions of invigorating spleen and resolving phlegm,clearing heat and purging turbidity.It has been identified to have therapeutic effects on type 2 diabetes mellitus(T2DM)in clinical application.Non-alcoholic fatty liver disease(NAFLD)is frequently diagnosed in patients with T2DM.However,the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further investigation.AIM To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in vitro.METHODS HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell model.Subsequently,experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours.C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD,and then treated with the different concentrations of FLHZF for 10 weeks.RESULTS FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in vitro.Further experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress,regulating the AMPKα/SREBP-1C signaling pathway,activating autophagy,and inhibiting hepatocyte apoptosis.CONCLUSION FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species,autophagy,apoptosis,and lipid synthesis signaling pathways,indicating its potential for clinical application in NAFLD.

Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B:A meta-analysis

BACKGROUND Although hepatitis B virus infection is the leading cause of chronic liver injury globally,nonalcoholic fatty liver disease(NAFLD)is gradually gaining attention as another major chronic liver disease.The number of patients having chronic hepatitis B(CHB)with concomitant hepatic steatosis has increased.AIM To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB.METHODS Relevant English studies were systematically searched across PubMed,EMBASE,Web of Science,and Cochrane Library until October 2023.Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included.RESULTS Of the 2502 retrieved studies,11 articles were finally included.Biochemical response until 48 wk(OR=0.87,95%CI:0.50–1.53,P=0.000)and 96 wk(OR=0.35,95%CI:0.24–0.53,P=0.24)and virological response until 96 wk(OR=0.80,95%CI:0.43–1.49,P=0.097)were lower in patients with hepatic steatosis than in patients with CHB alone.CONCLUSION Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Transient elastography with controlled attenuation parameter for the diagnosis of colorectal polyps in patients with nonalcoholic fatty liver disease

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.

Impact of nonalcoholic fatty liver disease on the risk of gallbladder polyps in lean and non-obese individuals:A cohort study

Background:The association between non-obese or lean nonalcoholic fatty liver disease(NAFLD)and gallbladder polyps(GBPs)has not yet been evaluated.We aimed to determine whether NAFLD is an independent risk factor for the development of GBPs,even in non-obese and lean individuals.Methods:We analyzed a cohort of 331208 asymptomatic adults who underwent abdominal ultrasonography(US).The risk of GBP development was evaluated according to the obesity and NAFLD status.Results:The overall prevalence of NAFLD and GBPs≥5 mm was 28.5%and 2.9%,respectively.The prevalence of NAFLD among 160276 lean,77676 overweight and 93256 obese participants was 8.2%,31.2%,and 61.1%,respectively.Individuals with NAFLD had a significantly higher incidence of GBPs with a size of≥5 mm[adjusted odds ratio(OR)=1.18;95%confidence interval(CI):1.11–1.25].A higher body mass index and its categories were also significantly associated with an increased risk of GBPs≥5 mm.Moreover,risk of GBPs≥5 mm was significantly increased even in NAFLD individuals who are not obese(lean:adjusted OR=1.36,95%CI:1.19-1.54;overweight:adjusted OR=1.14,95%CI:1.03–1.26,respectively).Conclusions:Non-obese/lean NAFLD is an independent risk factor for GBP development,suggesting that NAFLD may play an important role in the pathogenesis of GBPs regardless of the obesity status.Therefore,a more thorough evaluation for GBPs may be necessary when hepatic steatosis is detected on abdominal US,even in non-obese or lean individuals.

Monocyte to High-density Lipoprotein Cholesterol Ratio as a Predictor of Nonalcoholic Fatty Liver Disease in Childhood Obesity

Objective Inflammation is involved in the development and progression of nonalcoholic fatty liver disease(NAFLD).The monocyte to high-density lipoprotein cholesterol ratio(MHR)has emerged as a marker for various inflammation-related diseases.The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity.Methods Based on hepatic ultrasound,a total of 504 children with obesity(357 with NAFLD and 147 without NAFLD)were included in the study.The correlation between the MHR and NAFLD risk factors was assessed by Pearson’s and Spearman’s analyses.Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD.Results The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD[0.52(0.44-0.67)versus 0.44(0.34-0.57),P<0.001].Multivariate stepwise logistic regression analysis demonstrated that the MHR[odds ratio(OR):1.033,95%confidence interval(CI):1.015-1.051;P<0.001]was an independent predictor of NAFLD in childhood obesity patients,as were age(OR:1.205,95%CI:1.059-1.371;P=0.005],waist circumference[OR:1.037,95%CI:1.008-1.067;P=0.012],and alanine transaminase[OR:1.067,95%CI:1.045-1.089;P<0.001].Additionally,MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors.Conclusion The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity.

A Novel Signature Combing Cuproptosis-and Ferroptosis Related Genes in Nonalcoholic Fatty Liver Disease

Objective To identify cuproptosis-and ferroptosis-related genes involved in nonalcoholic fatty liver disease and to determine the diagnostic value of hub genes.Methods The gene expression dataset GSE89632 was retrieved from the Gene Expression Omnibus database to identify differentially expressed genes(DEGs)between the non-alcoholic steatohepatitis(NASH)group and the healthy group using the'limma'package in R software and weighted gene co-expression network analysis.Gene ontology,kyoto encyclopedia of genes and genomes pathway,and single-sample gene set enrichment analyses were performed to identify functional enrichment of DEGs.Ferroptosis-and cuproptosis-related genes were obtained from the FerrDb V2 database and available literatures,respectively.A combined signature for cuproptosis-and ferroptosis-related genes,called CRF,was constructed using the STRING database.Hub genes were identified by overlapping DEGs,WGCNA-derived key genes,and combined signature CRF genes,and validated using the GSE109836 and GSE227714 datasets and real-time quantitative polymerase chain reaction.A nomogram of NASH diagnostic model was established utilizing the'rms'package in R software based on the hub genes,and the diagnostic value of hub genes was assessed using receiver operating characteristic curve analysis.In addition,immune cell infiltration in NASH versus healthy controls was examined using the CIBERSORT algorithm.The relationships among various infiltrated immune cells were explored with Spearman's correlation analysis.Results Analysis of GSE89632 identified 236 DEGs between the NASH group and the healthy group.WGCNA highlighted 8 significant modules and 11,095 pivotal genes,of which 330 genes constituted CRF.Intersection analysis identified IL6,IL1B,JUN,NR4A1,and PTGS2 as hub genes.The hub genes were all downregulated in the NASH group,and this result was further verified by the NASH validation dataset and real-time quantitative polymerase chain reaction.Receiver operating characteristic curve analysis confirmed the diagnostic efficacy of these hub genes with areas under the curve of 0.985,0.941,1.000,0.967,and 0.985,respectively.Immune infiltration assessment revealed that gamma delta T cells,M1 macrophages,M2 macrophages,and resting mast cells were predominantly implicated.Conclusion Our investigation underscores the significant association of cuproptosis-and ferroptosis-related genes,specifically IL6,IL1B,JUN,NR4A1,and PTGS2,with NASH.These findings offer novel insights into the pathogenesis of NASH,potentially guiding future diagnostic and therapeutic strategies.

Genetic Variations and Nonalcoholic Fatty Liver Disease:Field Synopsis,Systematic Meta-Analysis,and Epidemiological Evidence

Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD).Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically searched.Meta-analyses of the genetic variants were conducted using at least five data sources.The epidemiologic credibility of the significant associations was graded using the Venice criteria.Results Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing studies.We identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the meta-analysis.The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR).Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

Caveolin‑1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the liver.This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.Methods:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study.Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro.Moreover,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload model.Besides,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and ELISA.The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.Results:Significant disorder of lipid and iron metabolism occurred in NAFLD.The expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism disorder.Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver.Further,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in hepatocytes.Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis.It is a pivotal molecule for predicting and protecting against the development of NAFLD.

Impact of lifestyle interventions on pathogenesis of nonalcoholic fatty liver disease

This editorial builds on the article titled“Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease”by Zeng et al.We carried out a critical examination of nonalcoholic fatty liver disease(NAFLD)pathogenesis and how lifestyle interventions could facilitate disease resolution,particularly highlighting that non-alcoholic steatohepatitis(NASH)is a severe form of NAFLD.Our discussion details that weight loss is a pivotal factor in disease outcomes:A 3%-5%reduction is enough for resolution in 50%of non-obese individuals,while a 7%-10%reduction achieves similar benefits in obese individuals,as demonstrated by magnetic resonance spectroscopy.Additionally,the editorial underscores that such lifestyle changes are instrumental not only in resolving NAFLD but also in reversing hepatic steatosis and inflammation.These insights,derived from the research,emphasize the critical role of personalized lifestyle modifications in halting the progression of NAFLD to NASH and even reversing fibrosis,thus offering a template for effective patient management.

Potential of traditional Chinese medicine in the treatment of nonalcoholic fatty liver disease:A promising future

In this editorial,we provide insights into the publication by Niu et al featured in the latest edition of the World Journal of Gastroenterology.Specifically,our focus was on exploring the potential of traditional Chinese medicine(TCM)in treating nonalcoholic fatty liver disease(NAFLD)induced by a high-fat diet through various mechanisms.NAFLD is a common liver condition,affecting approximately 25%of the world's population.It is closely linked to metabolic syndrome,insulin resistance,excessive body weight,and irregular lipid processing,leading to fat accumulation in the liver,as well as oxidative stress and inflammation.While maintaining a healthy diet and active lifestyle are essential for managing NAFLD,treatment options are limited due to undefined pathogenesis and a lack of specific medications.TCM,rooted in traditional Chinese practices,presents a promising alternative through its"syndrome differentiation and treatment"principles,enhancing liver lipid metabolism,reducing inflammation,and addressing fibrosis.Certain herbs,such as Poria cocos,Puaria lobata,and Salvia miltiorrhiza,have shown significant efficacy in reducing fat deposition and improving liver function.Due to systematic research and analysis of mechanisms,TCM is anticipated to yield new approaches to prevent and treat NAFLD,increasing its clinical application.

Prevalence of nonalcoholic fatty liver disease in patients with hepatitis B:A meta-analysis

BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has increased in recent clinical practice;however,the relationship between CHB and hepatic steatosis(HS)remains controversial.AIM To shed light on the potential association between NAFLD and hepatitis B virus(HBV)infection.METHODS We conducted a systematic literature search using multiple databases,including PubMed,the Cochrane Library,Web of Science,and EMBASE,to identify relevant studies.Predefined inclusion criteria were used to determine the eligibility of the studies for further analysis.RESULTS Comprehensive meta-analysis software was used for statistical analysis,which covered 20 studies.The results indicated a lower NAFLD susceptibility in HBVinfected individuals(pooled OR=0.87;95%CI=0.69-1.08;I2=91.1%),with diabetes(P=0.015),body mass index(BMI;P=0.010),and possibly age(P=0.061)as heterogeneity sources.Of note,in four studies(6197 HBV patients),HBV-infected individuals had a reduced NAFLD risk(OR=0.68,95%CI=0.51-0.89,P=0.006).A positive link between hyperlipidemia and metabolic syndrome emerged in hepatitis B patients,along with specific biochemical indicators,including BMI,creatinine,uric acid,fasting blood glucose,and homeostasis model assessment of insulin resistance.CONCLUSION HBV infection may provide protection against HS;however,the occurrence of HS in patients with HBV infection is associated with metabolic syndrome and specific biochemical parameters.

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity

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.

External validation of EncephalApp Stroop test to screen minimal hepatic encephalopathy patients with nonalcoholic cirrhosis

BACKGROUND Neurocognitive impairment,including minimal hepatic encephalopathy(MHE)and overt hepatic encephalopathy,is one of the most common complications of all types of primary liver diseases,such as hepatitis B,biliary cholangitis,and autoi-mmune hepatitis.The EncephalApp Stroop test is a smartphone application-based test that is time-saving for MHE screening.However,neurocognitive impairment is different between alcoholic cirrhosis patients and nonalcoholic cirrhosis pa-tients,so the cutoff value for MHE diagnosis might be inflated.AIM To validate the Stroop test in nonalcoholic cirrhosis patients.METHODS This external validation was performed at the National Center for Infectious Diseases(Beijing).Liver cirrhosis patients aged between 18 and 65 years who voluntarily enrolled in the study and provided signed informed consent were included.The Psychometric Hepatic Encephalopathy Score(PHES)test was used as the standard diagnostic criterion for MHE.The EncephalApp Stroop test was then performed on the iPad,including two sessions of tests(“off”and“on”)to measure patients’ability to differentiate between numbers and letters.We assessed the performance of the EncephalApp Stroop test in terms of the area under the curve(AUC),sensitivity,specificity,positive predictive value,and negative predictive value,with the PHES as the standard criterion.RESULTS A total of 160 nonalcoholic cirrhosis patients were included in this validation study,including 87(54.4%)patients without MHE and 73(45.6%)patients with MHE.Taking the PHES as the gold standard,the EncephalApp Stroop test performed well for nonalcoholic liver cirrhosis patients in terms of“off”time[AUC:0.85,95%confidence interval(CI):0.79-0.91]and“on+off”time(AUC:0.85,95%CI:0.80-0.91);however,total runs of“off”session(AUC:0.61,95%CI:0.52-0.69),total runs of“on”session(AUC:0.57,95%CI:0.48-0.65),and“on–off”time(AUC:0.54,95%CI:0.44-0.63)were comparatively low.The optimal cutoff points were“off”time>101.93 seconds and“on+off”time>205.86 seconds,with sensitivities of 0.84 and 0.90,specificities of 0.77 and 0.71,positive predictive values of 0.75 and 0.72,and false-positive values of 0.85 and 0.89,respectively.CONCLUSION Our results suggest that different cutoffs should be used for the EncephalApp Stroop tool for MHE screening between alcoholic and nonalcoholic living patients,which is a critical check before generalization to screen for neurocognitive impairment among the whole population of chronic liver diseases.

Validation of adherence prediction system for lifestyle interventions in nonalcoholic fatty liver disease

This editorial delves into the research article by Zeng et al published in the latest issue of World Journal of Gastroenterology.The manuscript contributes significantly to addressing the global health issue of nonalcoholic fatty liver disease(NAFLD)by introducing and validating the Exercise and Diet Adherence Scale(EDAS).The article effectively conveys the importance of the study,highlighting the prevalence of NAFLD,the lack of approved drugs for its treatment,and the crucial role of lifestyle correction.The use of the Delphi method for scale development and the subsequent evaluation of its reliability add scientific rigor to the methodology.The results demonstrate that the scale is correlated with key lifestyle indicators,which makes it a promising tool for assessing patient adherence to interventions.The identification of specific score thresholds for predicting adherence to daily calorie intake and exercise adds practical value to the scale.The differentiation among scores indicative of good,average,and poor adherence enhances its clinical applicability.In conclusion,the manuscript introduces EDAS,a valuable instrument that can contribute substantially to the field of NAFLD research and clinical practice.

A Retrospective Analysis of Glucagon-Like Peptide 1 Receptor Agonists in Treating Type 2 Diabetes Mellitus Complicated by Nonalcoholic Fatty Liver Disease

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.

Mapping the global research landscape on nonalcoholic fatty liver disease and insulin resistance:A visualization and bibliometric study

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a liver condition that is prevalent worldwide and associated with significant health risks and economic burdens.As it has been linked to insulin resistance(IR),this study aimed to perform a bibliometric analysis and visually represent the scientific literature on IR and NAFLD.AIM To map the research landscape to underscore critical areas of focus,influential studies,and future directions of NAFLD and IR.METHODS This study conducted a bibliometric analysis of the literature on IR and NAFLD indexed in the SciVerse Scopus database from 1999 to 2022.The search strategy used terms from the literature and medical subject headings,focusing on terms related to IR and NAFLD.VOSviewer software was used to visualize research trends,collaborations,and key thematic areas.The analysis examined publication type,annual research output,contributing countries and institutions,funding agencies,journal impact factors,citation patterns,and highly cited references.RESULTS This analysis identified 23124 documents on NAFLD,revealing a significant increase in the number of publications between 1999 and 2022.The search retrieved 715 papers on IR and NAFLD,including 573(80.14%)articles and 88(12.31%)reviews.The most productive countries were China(n=134;18.74%),the United States(n=122;17.06%),Italy(n=97;13.57%),and Japan(n=41;5.73%).The leading institutions included the Universitàdegli Studi di Torino,Italy(n=29;4.06%),and the Consiglio Nazionale delle Ricerche,Italy(n=19;2.66%).The top funding agencies were the National Institute of Diabetes and Digestive and Kidney Diseases in the United States(n=48;6.71%),and the National Natural Science Foundation of China(n=37;5.17%).The most active journals in this field were Hepatology(27 publications),the Journal of Hepatology(17 publications),and the Journal of Clinical Endocrinology and Metabolism(13 publications).The main research hotspots were“therapeutic approaches for IR and NAFLD”and“inflammatory and high-fat diet impacts on NAFLD”.CONCLUSION This is the first bibliometric analysis to examine the relationship between IR and NAFLD.In response to the escalating global health challenge of NAFLD,this research highlights an urgent need for a better understanding of this condition and for the development of intervention strategies.Policymakers need to prioritize and address the increasing prevalence of NAFLD.

Evaluation of autoimmune phenomena in patients with nonalcoholic fatty liver disease on the basis of liver pathology

BACKGROUND Autoimmune phenomena can be used in some patients with nonalcoholic fatty liver disease(NAFLD)in the clinic,but these patients are not autoimmune hepatitis patients.AIM To determine whether autoimmunity is present in patients with NAFLD,this study was performed.METHODS A total of 104 patients with NAFLD diagnosed by liver biopsy at Tianjin Second People’s Hospital between 2019 and 2023 were enrolled.The patients were divided into three groups according to their biopsy results:The NAFL(n=36),nonalcoholic steatohepatitis(n=51),and liver cirrhosis groups(n=17).RESULTS The differences in IgA,an immune marker,among the three groups of patients were statistically significant(P=0.025).In all NAFLD patients,antinuclear antibody and anti-smooth muscle antibody were the most common autoantibodies.The antinuclear antibody detection rate was the highest at 48.1%.The cirrhosis group had the highest autoantibody positivity rate(64.7%).Portal enlargement is also common in NAFLD patients.The rates of positivity for portal lymphoplasmacytic infiltration,small bile duct hyperplasia and interfacial hepatitis were highest in the cirrhosis group;the differences between the cirrhosis group and the other two groups were significant(P<0.05).Hepatocellular rosettes were identified only in the cirrhosis group(11.8%).CONCLUSION Autoimmune phenomena occur in NAFLD patients,especially in patients with NAFLD-related cirrhosis,in whom this phenomenon may be more pronounced.