BACKGROUND This review evaluated the diagnostic effectiveness of various ultrasound(US)methods compared to liver biopsy.AIM To determine the diagnostic accuracy of US techniques in assessing liver fibrosis and steatos...BACKGROUND This review evaluated the diagnostic effectiveness of various ultrasound(US)methods compared to liver biopsy.AIM To determine the diagnostic accuracy of US techniques in assessing liver fibrosis and steatosis in adults,using the area under the receiver operating characteristic curve(AUROC)as the standard measure.METHODS The review included original retrospective or prospective studies published in the last three years in peer-reviewed medical journals,that reported AUROC values.Studies were identified through PubMed searches on January 3 and April 30,2024.Quality was assessed using the QUADAS-2 tool.Results were tabulated according to the diagnostic method and the type of liver pathology.RESULTS The review included 52 studies.For liver fibrosis detection,2D-shear wave elastography(SWE)AUROCs ranged from 0.54 to 0.994,showing better accuracy for advanced stages.Modifications,including 2D-SWE with propagation map guidance and supersonic imagine achieved AUROCs of 0.84 to nearly 1.0.point SWE and classical SWE had AUROCs of 0.741-0.99,and 0.507-0.995,respectively.Transient elastography(TE),visual TE,vibration-controlled TE(VCTE),and FibroTouch reported AUROCs close to 1.0.For steatosis,VCTE with controlled attenuation parameter showed AUROCs up to 0.89(for≥S1),acoustic radiation force impulse ranged from 0.762 to 0.784,US attenuation parameter from 0.88 to 0.93,and normalized local variance measurement from 0.583 to 0.875.Most studies had a low risk of bias across all or most domains,but evidence was limited by variability in study quality and small sample sizes.Innovative SWE variants were evaluated in a single study.CONCLUSION Modern US techniques can serve as effective noninvasive diagnostic tools for liver fibrosis and steatosis,with the potential to reduce the reliance on biopsies.展开更多
BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is the most common cause of chronic liver disease and remains under-recognized within the health check-up population.Ultrasonography during physical examinatio...BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is the most common cause of chronic liver disease and remains under-recognized within the health check-up population.Ultrasonography during physical examination fail to accurately identify at-risk patients as they involve multiple metabolic aspects.AIM To rapidly identify hepatic steatosis patients from high-metabolic-risk populations and reduce medical costs.METHODS We analyzed all data from a prospective cohort study to identify potential predictors of MAFLD risk.The LASSO and recursive feature elimination were used to screen for feature selection.Four machine learning models were employed to construct the prediction model for hepatic steatosis.RESULTS We found that 86.2%of the 1011 individuals in the trial phase exhibited metabolic abnormalities,with 70.8%presenting with hepatic steatosis.After data cleaning,711 participants(207 non-MAFLD patients vs 504 MAFLD patients)were included,and the prediction models were validated.After overlapping and reducing the feature set based on feature importance ranking,we developed an interpretable final XGBoost model with 10 features,achieving an area under the curve of 0.82.CONCLUSION We have introduced a valuable noninvasive tool for efficiently identifying hepatic steatosis patients in highmetabolic-risk populations.This tool may improve screening effectiveness and reduce medical costs.展开更多
BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diag...BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diagnosed via imaging or biopsy with metabolic criteria and may progress to metabolic dysfunction–asso-ciated steatohepatitis,potentially leading to fibrosis,cirrhosis,or cancer.The coexistence of hepatic steatosis with chronic hepatitis B(CHB)is mainly related to metabolic factors and increases mortality and cancer risks.As a noninvasive method,attenuation imaging(ATI)shows promise in quantifying liver fat,demonstrating strong correlation with liver biopsy.AIM To investigate the disparity of ATI for assessing biopsy-based hepatic steatosis in CHB patients and MASLD patients.METHODS The study enrolled 249 patients who underwent both ATI and liver biopsy,including 78 with CHB and 171 with MASLD.Hepatic steatosis was classified into grades S0 to S3 according to the proportion of fat cells present.Liver fibrosis was staged from 0 to 4 according to the meta-analysis of histological data in viral hepatitis scoring system.The diagnostic performance of attenuation coefficient(AC)values across different groups was compared for each grade of steatosis.Factors associated with the AC values were determined through linear regression analysis.A multivariate logistic regression model was established to predict≥S2 within the MASLD group.RESULTS In both the CHB and the MASLD groups,AC values increased significantly with higher steatosis grade(P<0.001).In the CHB group,the areas under the curve(AUCs)of AC for predicting steatosis grades≥S1,≥S2 and S3 were 0.918,0.960 and 0.987,respectively.In contrast,the MASLD group showed AUCs of 0.836,0.774,and 0.688 for the same steatosis grades.The diagnostic performance of AC for detecting≥S2 and S3 indicated significant differences between the two groups(both P<0.001).Multivariate linear regression analysis identified body mass index,trigly-cerides,and steatosis grade as significant factors for AC.When the steatosis grade is≥S2,it can progress to more serious liver conditions.A clinical model integrating blood biochemical parameters and AC was developed in the MASLD group to enhance the prediction of≥S2,achieving an AUC of 0.848.CONCLUSION The AC could effectively discriminate the degree of steatosis in both the CHB and MASLD groups.In the MASLD group,when combined with blood biochemical parameters,AC exhibited better predictive ability for moderate to severe steatosis.展开更多
BACKGROUND The global prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)has continued to increase annually.Recent studies have indicated that inhibition of metabotropic glutamate receptor 5(...BACKGROUND The global prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)has continued to increase annually.Recent studies have indicated that inhibition of metabotropic glutamate receptor 5(mGluR5)may alleviate hepatic steatosis.However,the precise mechanism warrants further exploration.AIM To investigate the potential mechanism by which mGluR5 attenuates hepatocyte steatosis in vitro and in vivo.METHODS Free fatty acids(FFAs)-stimulated HepG2 cells were treated with the mGluR5 antagonist MPEP and the mGluR5 agonist CHPG.Oil Red O staining and a triglyceride assay kit were used to evaluate lipid content.Western blot analysis was conducted to detect the expression of the autophagy-associated proteins p62 and LC3-II,as well as the expression of the key signaling molecules AMPK and ULK1,in the treated cells.To further elucidate the contributions of autophagy and AMPK,we used chloroquine(CQ)to inhibit autophagy and compound C(CC)to inhibit AMPK activity.In parallel,wild-type mice and mGluR5 knockout(KO)mice fed a normal chow diet or a high-fat diet(HFD)were used to evaluate the effect of mGluR5 inhibition in vivo.RESULTS mGluR5 inhibition by MPEP attenuated hepatocellular steatosis and increased LC3-II and p62 protein expression.The autophagy inhibitor CQ reversed the effects of MPEP.In addition,MPEP promoted AMPK and ULK1 expression in HepG2 cells exposed to FFAs.MPEP treatment led to the nuclear translocation of transcription factor EB,which is known to promote p62 expression.This effect was negated by the AMPK inhibitor CC.mGluR5 KO mice presented reduced body weight,improved glucose tolerance and reduced hyperlipidemia when fed a HFD.Additionally,the livers of HFD-fed mGluR5 KO mice presented increases in LC3-II and p62.CONCLUSION Our results suggest that mGluR5 inhibition promoted autophagy and reduced hepatocyte steatosis through activation of the AMPK signaling pathway.These findings reveal a new functional mechanism of mGluR5 as a target in the treatment of MASLD.展开更多
Non-alcoholic fatty liver disease(NAFLD),a critical global health concern,continues to challenge medical researchers with limited treatment options.This letter examines on the study by Luo et al,demonstrating that vit...Non-alcoholic fatty liver disease(NAFLD),a critical global health concern,continues to challenge medical researchers with limited treatment options.This letter examines on the study by Luo et al,demonstrating that vitamin D 1,25-dihydroxyvitamin D3[1,25(OH)2D3]improves hepatic steatosis in NAFLD by inhibiting M1 macrophage polarization via the vitamin D receptor-peroxisome proliferator-activated receptor gamma signaling pathway.This letter critically appraises these findings,comparing them to similar studies,and discusses their potential implications for treating NAFLD.Furthermore,we highlight future directions,including dose optimization and mechanistic studies.展开更多
[Objectives]To explore the target and mechanism of Schaftoside on cholestasis and steatosis based on network pharmacology and molecular docking.[Methods]The targets of"cholestasis"and"steatosis"wer...[Objectives]To explore the target and mechanism of Schaftoside on cholestasis and steatosis based on network pharmacology and molecular docking.[Methods]The targets of"cholestasis"and"steatosis"were predicted using databases(OMIM and GeneCards),and the key targets were obtained after screening the retrieval data.The binding relationship between Schaftoside and key targets was analyzed by molecular docking.[Results]There were 3370 and 4433 targets for"cholestasis"and"steatosis",respectively,and 1767 overlapping genes were obtained.The results of molecular docking showed that Schaftoside had high binding energy with key targets.[Conclusions]Schaftoside can alleviate cholestasis and steatosis by regulating SREBP-1,CYP7,PPAR-gamma and other key targets to protect liver.展开更多
Introduction: Fibroscan is a recent, non-invasive and non-irradiating diagnostic method. It is based on the principle of ultrasound, which enables liver tissue elasticity to be quantified using a probe, and fibrosis t...Introduction: Fibroscan is a recent, non-invasive and non-irradiating diagnostic method. It is based on the principle of ultrasound, which enables liver tissue elasticity to be quantified using a probe, and fibrosis to be assessed. Fibroscan measures both elasticity correlated with hepatic fibrosis and CAP correlated with steatosis. The aim of this study was to evaluate hepatic fibrosis and steatosis using pulse elastometry (Fibroscan/CAP). Methods: This was a descriptive and analytical cross-sectional study in which 170 patients were included. It was conducted from October 1 2021 to December 31 2023, i.e. 27 months, in an outpatient clinic in the hepato-gastroenterology department of the Donka national hospital of the CHU Conakry. Results: Of the 170 patients identified, 87 were male (51%) and 83 female (49%), giving a M/F sex ratio of 1.04. The average age of our patients was 40. The 30 - 50 age group was the most affected, with a frequency of 58.23% (n = 99), followed by the 50 age group with a frequency of 29.41% (n = 50). Hepatomegaly, steatotic liver on ultrasonography, transaminase elevation and obesity were the main indications, respectively: (21.76%), (17.65%), (14.71%), and (13.53%). The examinations were requested by hepatogastroenterologists (47.06%), diabetologists (35.88%) and general practitioners (29%). Of the 170 patients, 100 patients (58.82%) had no significant fibrosis F0F1, 39 (22.94%) had moderate fibrosis F2, 20 patients (11.76%) had severe fibrosis F3 and 11 patients (6.47%) had fibrosis F4. Hepatic steatosis: 62 patients (36.47%) had no S0 steatosis;29.41% had S1 steatosis, 20% had S2 steatosis and 24 patients (14.11%) had S3 steatosis. Abdominal ultrasound revealed a normal liver in 67.05% of patients, hepatic steatosis in 29.41% and non-decompensated cirrhosis in 6 cases. Thus, 108 patients had the parameters required to calculate the Fatty Liver Index (FLI), steatosis was present in 20% of our patients, while 29.41% had an undetermined status and 24 14.11% had a normal FLI. Conclusion: Identifying subjects at risk of metabolic steatopathy, diagnosing and managing these patients is a public health issue and one of the future challenges of hepato-gastroenterology. Fibroscan is an increasingly popular screening tool for hepatic fibrosis and steatosis. The fight against obesity must be a priority.展开更多
Intestinal dysbiosis and disrupted bile acid(BA)homeostasis are associated with obesity,but the precise mechanisms remain insufficiently explored.Hepatic protein phosphatase 1 regulatory subunit 3G(PPP1R3G)plays a piv...Intestinal dysbiosis and disrupted bile acid(BA)homeostasis are associated with obesity,but the precise mechanisms remain insufficiently explored.Hepatic protein phosphatase 1 regulatory subunit 3G(PPP1R3G)plays a pivotal role in regulating glycolipid metabolism;nevertheless,its obesity-combatting potency remains unclear.In this study,a substantial reduction was observed in serum PPP1R3G levels in high-body mass index(BMI)and high-fat diet(HFD)-exposed mice,establishing a positive correlation between PPP1R3G and non-12a-hydroxylated(non-12-OH)BA content.Additionally,hepatocyte-specific overexpression of Ppp1r3g(PPP1R3G HOE)mitigated HFD-induced obesity as evidenced by reduced weight,fat mass,and an improved serum lipid profile;hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology.PPP1R3G HOE considerably impacted systemic BA homeostasis,which notably increased the non-12-OH BAs ratio,particularly lithocholic acid(LCA).16S ribosomal DNA(16S rDNA)sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population,and elevating the relative abundance of Blautia,which exhibited a positive correlation with serum LCA levels.A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiotadependent.Mechanistically,PPP1R3G HOE markedly suppressed hepatic cholesterol 7a-hydroxylase(CYP7A1)and sterol-12a-hydroxylase(CYP8B1),and concurrently upregulated oxysterol 7-a hydroxylase and Takeda G protein-coupled BA receptor 5(TGR5)expression under HFD conditions.Furthermore,LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels.These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis,which may serve as potential therapeutic targets for obesity-related disorders.展开更多
BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence ...BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.展开更多
Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed...Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed to systematically investigate the genetic regulatory mechanisms of hepatic steatosis in laying hens.Methods Ninety individuals with the most prominent characteristics were selected from 686 laying hens according to the accumulation of lipid droplets in the liver, and were graded into three groups, including the control, mild hepatic steatosis and severe hepatic steatosis groups. A combination of transcriptome, proteome, acetylome and lipidome analyses, along with bioinformatics analysis were used to screen the key biological processes, modifications and lipids associated with hepatic steatosis.Results The rationality of the hepatic steatosis grouping was verified through liver biochemical assays and RNA-seq. Hepatic steatosis was characterized by increased lipid deposition and multiple metabolic abnormalities. Integration of proteome and acetylome revealed that differentially expressed proteins(DEPs) interacted with differentially acetylated proteins(DAPs) and were involved in maintaining the metabolic balance in the liver. Acetylation alterations mainly occurred in the progression from mild to severe hepatic steatosis, i.e., the enzymes in the fatty acid oxidation and bile acid synthesis pathways were significantly less acetylated in severe hepatic steatosis group than that in mild group(P < 0.05). Lipidomics detected a variety of sphingolipids(SPs) and glycerophospholipids(GPs) were negatively correlated with hepatic steatosis(r ≤-0.5, P < 0.05). Furthermore, the severity of hepatic steatosis was associated with a decrease in cholesterol and bile acid synthesis and an increase in exogenous cholesterol transport.Conclusions In addition to acquiring a global and thorough picture of hepatic steatosis in laying hens, we were able to reveal the role of acetylation in hepatic steatosis and depict the changes in hepatic cholesterol metabolism. The findings provides a wealth of information to facilitate a deeper understanding of the pathophysiology of fatty liver and contributes to the development of therapeutic strategies.展开更多
In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic...In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic steatohepatitis(NASH).The authors found that MXS treatment mitigated hepatic steatosis and inflam-mation in the NASH model,as evidenced by the reduction in lipid droplets(LDs),fibrosis markers and lipogenic factors.Interestingly,these hepatoprotective effects were associated with androgen upregulation(based on metabolomics analysis of male steroid hormone metabolites),adenosine 5’-monophosphate-activated protein kinase(AMPK)activation,and restoration of phosphatase and tensin homolog(PTEN)expression.However,the authors did not clearly discuss the relationships between MXS-induced hepatic steatosis reduction in the NASH model,and androgen upregulation,AMPK activation,and restoration of PTEN expression.This editorial emphasizes the reported mechanisms and explains how they act or interact with each other to reduce hepatic steatosis and inflammation in the NASH model.As a perspective,we propose additional mechanisms(such as autophagy/lipophagy activation in hepatocytes)for the clearance of LDs and suppression of hepatic steatosis by MXS in the NASH model.A proper understanding of the mechanisms of MXS-induced reduction of hepatic steatosis might help in the treatment of NASH and related diseases.展开更多
Objective: Describe the etiological factors of hepatic steatosis in the Internal Medicine and Medical Emergencies department of the Sylvanus Olympio University Hospital of Lomé. Framework and Method: Cross-sectio...Objective: Describe the etiological factors of hepatic steatosis in the Internal Medicine and Medical Emergencies department of the Sylvanus Olympio University Hospital of Lomé. Framework and Method: Cross-sectional and retrospective study carried out over a period of 5 years from February 1, 2021 to February 28, 2024 (4 years). All patients aged over 18 years with a hyperechoic appearance of the hepatic parenchymal structure on abdominal ultrasound suggestive of focal or diffuse steatosis of the liver were included. Results: The prevalence of steatosis was 17.21%. The average age of our patients was 42.91 ± 11.71 years. We noted a sex ratio (M/F) of 1.21. Diffuse abdominal pain was the main reason for consultation (38.60%). Hepatomegaly was found on abdominal ultrasound in 28.16% of cases. Two main groups of etiological factors were noted. These included metabolic factors (alcoholism, obesity, type 2 diabetes and high blood pressure (hypertension)) and infectious factors (HIV, HBV, HCV). Conclusion: Hepatic steatosis is a chronic pathology associated with etiological factors. It can progress to steatohepatitis, cirrhosis or even liver cancer.展开更多
BACKGROUND:The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the po...BACKGROUND:The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the postoperative outcome after liver transplantation.METHODS:Ninety-four patients undergoing liver transplantation at the University Hospital Aachen were included in this study. The patient cohort was divided into three groups according to the grade of microvesicular steatosis(MiS):MiS <30%(n=27), MiS 30%-60%(n=41) and MiS >60%(n=26).The outcomes after liver transplantation were evaluated, including the 30-day and 1-year patient and graft survival rates and the incidences of early allograft dysfunction(EAD) and primary nonfunction(PNF). RESULTS:The incidences of EAD and PNF did not differ significantly between the groups. We observed 5 cases of PNF,one occurred in the MiS <30% group and 4 in the MiS 30%-60% group. The 30-day and 1-year graft survivals did not differ significantly between groups. The 30-day patient survival rates were 100% in all groups. The 1-year patient survival rates were 94.4% in the MiS <30% group, 87.9% in the MiS 30%-60% group and 90.9% in the MiS >60% group.CONCLUSION:Microvesicular steatosis of donor livers has no negative effect on the postoperative outcome after liver transplantation.展开更多
Steatosis is a common feature of many liver diseases,namely non-alcoholic steatohepatitis(NASH) and hepatitis C virus(HCV) infection,but the pathogenic mechanisms differ.Insulin resistance(IR),a key feature of metabol...Steatosis is a common feature of many liver diseases,namely non-alcoholic steatohepatitis(NASH) and hepatitis C virus(HCV) infection,but the pathogenic mechanisms differ.Insulin resistance(IR),a key feature of metabolic syndrome,is crucial for NASH development,associated with many underlying genetically determined or acquired mitochondrial and metabolic defects and culminates to inflammation and progression to fibrosis.This may have potential implications for new drug therapy.In HCV-related disease,steatosis impacts both fibrosis progression and response to treatment.Steatosis in HCV-related disease relates to both viral factors(HCV genotype 3),and host factors(alcohol consumption,overweight,hyperlipidemia,diabetes).Among others,IR is a recognized factor.Hepatic steatosis is reported to be associated with disturbance in the signaling cascade of interferon and downregulation of its receptors.Thus,hepatic steatosis should not be considered a benign feature,but rather a silent killer.展开更多
AIM To investigate micro(mi)R-34 a-antagonizing circular(circ)RNA that underlies hepatocellular steatosis.METHODS The effect of circ RNA on mi R-34 a was recognized by the mi RNA response element(MRE), and validated b...AIM To investigate micro(mi)R-34 a-antagonizing circular(circ)RNA that underlies hepatocellular steatosis.METHODS The effect of circ RNA on mi R-34 a was recognized by the mi RNA response element(MRE), and validated by the dual-luciferase reporter assay. Its association with hepatocellular steatosis was investigated in Hep G2-based hepatocellular steatosis induced by free fatty acids(FFAs; 2:1 oleate:palmitate) stimulation. After normalization of the steatosis-related circRNA by expression vector, analysis of mi R-34 a activity,peroxisome proliferator-activated receptor(PPAR)α level, and expression of downstream genes were carried out so as to reveal its impact on the mi R-34 a/PPARα regulatory system. Both triglyceride(TG) assessment and cytopathological manifestations uncovered the role of circRNA in miR-34 a-dependent hepatosteatogenesis.RESULTS Bioinformatic and functional analysis verified circRNA_0046366 to antagonize the activity of mi R-34 a via MRE-based complementation. In contrast to its lowered level during FFA-induced hepatocellular steatosis, circ RNA_0046366 up-regulation abolished the mi R-34 a-dependent inhibition of PPARα that played a critical role in metabolic signaling pathways. PPARα restoration exerted transcriptional improvement to multiple genes responsible for lipid metabolism. TGspecific lipolytic genes [carnitine palmitoyltransferase 1 A(CPT1 A) and solute-carrier family 27 A(SLC27 A)] among these showed significant increase in their expression levels. The circ RNA_0046366-related rebalancing of lipid homeostasis led to dramatic reduction of TG content, and resulted in the ameliorated phenotype of hepatocellular steatosis.CONCLUSION Dysregulation of circ RNA_0046366/mi R-34 a/PPARα signaling may be a novel epigenetic mechanism underlying hepatocellular steatosis. circ RNA_0046366 serves as a potential target for the treatment of hepatic steatosis.展开更多
With the increasing incidence of obesity and metabolic syndrome worldwide,concomitant nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has become highly prevalent.The risk of dual etiolo...With the increasing incidence of obesity and metabolic syndrome worldwide,concomitant nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has become highly prevalent.The risk of dual etiologies,outcome,and mechanism of CHB with concomitant NAFLD have not been fully characterized.In this review,we assessed the overlapping prevalence of metabolic disorders and CHB,assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD,and discussed the remaining clinical issues to be addressed in the outcome of such patients.We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation.For CHB patients,it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses.The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.展开更多
Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty...Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.展开更多
AIM: To investigate whether serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) may differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis in patients with ...AIM: To investigate whether serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) may differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 83 patients with suspected NAFLD and 49 healthy volunteers were investigated. Patients with suspected NAFLD were classified according to their liver histology into four groups: definitive NASH (n = 45), borderline NASH (n = 24), simple fatty liver (n = 9), and normal tissue (n = 5). Serum levels of caspase-3 generated cytokeratin-18 fragments (M30-antigen) and total cytokeratin-18 (M65-antigen) were determined by ELISA. RESULTS: Levels of M30-antigen and M65-antigen were significantly higher in patients with definitive NASH compared to the other groups. An abnormal value (> 121.60 IU/L) of M30-antigen yielded a 60.0% sensitivity and a 97.4% specificity for the diagnosis of NASH. Sensitivity and specificity of an abnormal M65-antigen level (> 243.82 IU/L) for the diagnosis of NASH were 68.9% and 81.6%, respectively. Among patients with NAFLD, M30-antigen and M65-antigen levels distinguished between advanced fibrosis and early-stage fibrosis with a sensitivity of 64.7% and 70.6%, and a specificity of 77.3% and 71.2%, respectively. CONCLUSION: Serum levels of M30-antigen and M65-antigen may be of clinical usefulness to identify patients with NASH. Further studies are mandatory to better assess the role of these apoptonecrotic biomarkers in NAFLD pathophysiology.展开更多
AIM: Although an association between hepatic steatosis and vascular risk factors has been described, direct relationships between fatty liver and atherosclerosis have not yet been investigated. The aim of the present ...AIM: Although an association between hepatic steatosis and vascular risk factors has been described, direct relationships between fatty liver and atherosclerosis have not yet been investigated. The aim of the present study has been to investigate those relationships. METHODS: The Study of Health in Pomerania examined a random population sample aged between 20 and 79 years. A study population of 4 222 subjects without hepatitis B and C infections and without liver cirrhosis was available for the present analysis. Hepatic steatosis was defined sonographically and intima-media thickness (IMT) as well as plaque prevalence were estimated by carotid ultrasound. RESULTS: The prevalence rate of hepatic steatosis was 29.9%. Among subjects aged ≥45 years, an association between hepatic steatosis and IMT of the carotid arteries was found in bivariate analysis, but not after adjustment for atherosclerotic risk factors. Individuals with fatty liver had more often carotid plaques than persons without fatty liver (plaque prevalence rate 76.8% vs 66.6%; P<0.001). This association persisted after adjustment for confounding factors and was predominantly present in subjects with no to mild alcohol consumption. CONCLUSION: There is an independent association between hepatic steatosis and carotid atherosclerotic plaques. Metabolic changes due to nonalcoholic fatty liver disease may explain this relationship.展开更多
基金Supported by Wroclaw Medical University’s Grant,No.SUBZ.C270.24.078.
文摘BACKGROUND This review evaluated the diagnostic effectiveness of various ultrasound(US)methods compared to liver biopsy.AIM To determine the diagnostic accuracy of US techniques in assessing liver fibrosis and steatosis in adults,using the area under the receiver operating characteristic curve(AUROC)as the standard measure.METHODS The review included original retrospective or prospective studies published in the last three years in peer-reviewed medical journals,that reported AUROC values.Studies were identified through PubMed searches on January 3 and April 30,2024.Quality was assessed using the QUADAS-2 tool.Results were tabulated according to the diagnostic method and the type of liver pathology.RESULTS The review included 52 studies.For liver fibrosis detection,2D-shear wave elastography(SWE)AUROCs ranged from 0.54 to 0.994,showing better accuracy for advanced stages.Modifications,including 2D-SWE with propagation map guidance and supersonic imagine achieved AUROCs of 0.84 to nearly 1.0.point SWE and classical SWE had AUROCs of 0.741-0.99,and 0.507-0.995,respectively.Transient elastography(TE),visual TE,vibration-controlled TE(VCTE),and FibroTouch reported AUROCs close to 1.0.For steatosis,VCTE with controlled attenuation parameter showed AUROCs up to 0.89(for≥S1),acoustic radiation force impulse ranged from 0.762 to 0.784,US attenuation parameter from 0.88 to 0.93,and normalized local variance measurement from 0.583 to 0.875.Most studies had a low risk of bias across all or most domains,but evidence was limited by variability in study quality and small sample sizes.Innovative SWE variants were evaluated in a single study.CONCLUSION Modern US techniques can serve as effective noninvasive diagnostic tools for liver fibrosis and steatosis,with the potential to reduce the reliance on biopsies.
文摘BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is the most common cause of chronic liver disease and remains under-recognized within the health check-up population.Ultrasonography during physical examination fail to accurately identify at-risk patients as they involve multiple metabolic aspects.AIM To rapidly identify hepatic steatosis patients from high-metabolic-risk populations and reduce medical costs.METHODS We analyzed all data from a prospective cohort study to identify potential predictors of MAFLD risk.The LASSO and recursive feature elimination were used to screen for feature selection.Four machine learning models were employed to construct the prediction model for hepatic steatosis.RESULTS We found that 86.2%of the 1011 individuals in the trial phase exhibited metabolic abnormalities,with 70.8%presenting with hepatic steatosis.After data cleaning,711 participants(207 non-MAFLD patients vs 504 MAFLD patients)were included,and the prediction models were validated.After overlapping and reducing the feature set based on feature importance ranking,we developed an interpretable final XGBoost model with 10 features,achieving an area under the curve of 0.82.CONCLUSION We have introduced a valuable noninvasive tool for efficiently identifying hepatic steatosis patients in highmetabolic-risk populations.This tool may improve screening effectiveness and reduce medical costs.
基金Supported by the National Natural Science Foundation of China,No.82202185and Shanghai Science and Technology Development Foundation,No.22Y11911500.
文摘BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diagnosed via imaging or biopsy with metabolic criteria and may progress to metabolic dysfunction–asso-ciated steatohepatitis,potentially leading to fibrosis,cirrhosis,or cancer.The coexistence of hepatic steatosis with chronic hepatitis B(CHB)is mainly related to metabolic factors and increases mortality and cancer risks.As a noninvasive method,attenuation imaging(ATI)shows promise in quantifying liver fat,demonstrating strong correlation with liver biopsy.AIM To investigate the disparity of ATI for assessing biopsy-based hepatic steatosis in CHB patients and MASLD patients.METHODS The study enrolled 249 patients who underwent both ATI and liver biopsy,including 78 with CHB and 171 with MASLD.Hepatic steatosis was classified into grades S0 to S3 according to the proportion of fat cells present.Liver fibrosis was staged from 0 to 4 according to the meta-analysis of histological data in viral hepatitis scoring system.The diagnostic performance of attenuation coefficient(AC)values across different groups was compared for each grade of steatosis.Factors associated with the AC values were determined through linear regression analysis.A multivariate logistic regression model was established to predict≥S2 within the MASLD group.RESULTS In both the CHB and the MASLD groups,AC values increased significantly with higher steatosis grade(P<0.001).In the CHB group,the areas under the curve(AUCs)of AC for predicting steatosis grades≥S1,≥S2 and S3 were 0.918,0.960 and 0.987,respectively.In contrast,the MASLD group showed AUCs of 0.836,0.774,and 0.688 for the same steatosis grades.The diagnostic performance of AC for detecting≥S2 and S3 indicated significant differences between the two groups(both P<0.001).Multivariate linear regression analysis identified body mass index,trigly-cerides,and steatosis grade as significant factors for AC.When the steatosis grade is≥S2,it can progress to more serious liver conditions.A clinical model integrating blood biochemical parameters and AC was developed in the MASLD group to enhance the prediction of≥S2,achieving an AUC of 0.848.CONCLUSION The AC could effectively discriminate the degree of steatosis in both the CHB and MASLD groups.In the MASLD group,when combined with blood biochemical parameters,AC exhibited better predictive ability for moderate to severe steatosis.
基金Supported by National Natural Science Foundation of China,No.81800771 and No.81300702.
文摘BACKGROUND The global prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)has continued to increase annually.Recent studies have indicated that inhibition of metabotropic glutamate receptor 5(mGluR5)may alleviate hepatic steatosis.However,the precise mechanism warrants further exploration.AIM To investigate the potential mechanism by which mGluR5 attenuates hepatocyte steatosis in vitro and in vivo.METHODS Free fatty acids(FFAs)-stimulated HepG2 cells were treated with the mGluR5 antagonist MPEP and the mGluR5 agonist CHPG.Oil Red O staining and a triglyceride assay kit were used to evaluate lipid content.Western blot analysis was conducted to detect the expression of the autophagy-associated proteins p62 and LC3-II,as well as the expression of the key signaling molecules AMPK and ULK1,in the treated cells.To further elucidate the contributions of autophagy and AMPK,we used chloroquine(CQ)to inhibit autophagy and compound C(CC)to inhibit AMPK activity.In parallel,wild-type mice and mGluR5 knockout(KO)mice fed a normal chow diet or a high-fat diet(HFD)were used to evaluate the effect of mGluR5 inhibition in vivo.RESULTS mGluR5 inhibition by MPEP attenuated hepatocellular steatosis and increased LC3-II and p62 protein expression.The autophagy inhibitor CQ reversed the effects of MPEP.In addition,MPEP promoted AMPK and ULK1 expression in HepG2 cells exposed to FFAs.MPEP treatment led to the nuclear translocation of transcription factor EB,which is known to promote p62 expression.This effect was negated by the AMPK inhibitor CC.mGluR5 KO mice presented reduced body weight,improved glucose tolerance and reduced hyperlipidemia when fed a HFD.Additionally,the livers of HFD-fed mGluR5 KO mice presented increases in LC3-II and p62.CONCLUSION Our results suggest that mGluR5 inhibition promoted autophagy and reduced hepatocyte steatosis through activation of the AMPK signaling pathway.These findings reveal a new functional mechanism of mGluR5 as a target in the treatment of MASLD.
基金National Natural Science Foundation of China,No.82170406 and No.81970238.
文摘Non-alcoholic fatty liver disease(NAFLD),a critical global health concern,continues to challenge medical researchers with limited treatment options.This letter examines on the study by Luo et al,demonstrating that vitamin D 1,25-dihydroxyvitamin D3[1,25(OH)2D3]improves hepatic steatosis in NAFLD by inhibiting M1 macrophage polarization via the vitamin D receptor-peroxisome proliferator-activated receptor gamma signaling pathway.This letter critically appraises these findings,comparing them to similar studies,and discusses their potential implications for treating NAFLD.Furthermore,we highlight future directions,including dose optimization and mechanistic studies.
基金Supported by Qingmiao Talent Funding Research Project of Guangxi ProvinceNational College Student Innovation and Entrepreneurship Training Program(202310601031).
文摘[Objectives]To explore the target and mechanism of Schaftoside on cholestasis and steatosis based on network pharmacology and molecular docking.[Methods]The targets of"cholestasis"and"steatosis"were predicted using databases(OMIM and GeneCards),and the key targets were obtained after screening the retrieval data.The binding relationship between Schaftoside and key targets was analyzed by molecular docking.[Results]There were 3370 and 4433 targets for"cholestasis"and"steatosis",respectively,and 1767 overlapping genes were obtained.The results of molecular docking showed that Schaftoside had high binding energy with key targets.[Conclusions]Schaftoside can alleviate cholestasis and steatosis by regulating SREBP-1,CYP7,PPAR-gamma and other key targets to protect liver.
文摘Introduction: Fibroscan is a recent, non-invasive and non-irradiating diagnostic method. It is based on the principle of ultrasound, which enables liver tissue elasticity to be quantified using a probe, and fibrosis to be assessed. Fibroscan measures both elasticity correlated with hepatic fibrosis and CAP correlated with steatosis. The aim of this study was to evaluate hepatic fibrosis and steatosis using pulse elastometry (Fibroscan/CAP). Methods: This was a descriptive and analytical cross-sectional study in which 170 patients were included. It was conducted from October 1 2021 to December 31 2023, i.e. 27 months, in an outpatient clinic in the hepato-gastroenterology department of the Donka national hospital of the CHU Conakry. Results: Of the 170 patients identified, 87 were male (51%) and 83 female (49%), giving a M/F sex ratio of 1.04. The average age of our patients was 40. The 30 - 50 age group was the most affected, with a frequency of 58.23% (n = 99), followed by the 50 age group with a frequency of 29.41% (n = 50). Hepatomegaly, steatotic liver on ultrasonography, transaminase elevation and obesity were the main indications, respectively: (21.76%), (17.65%), (14.71%), and (13.53%). The examinations were requested by hepatogastroenterologists (47.06%), diabetologists (35.88%) and general practitioners (29%). Of the 170 patients, 100 patients (58.82%) had no significant fibrosis F0F1, 39 (22.94%) had moderate fibrosis F2, 20 patients (11.76%) had severe fibrosis F3 and 11 patients (6.47%) had fibrosis F4. Hepatic steatosis: 62 patients (36.47%) had no S0 steatosis;29.41% had S1 steatosis, 20% had S2 steatosis and 24 patients (14.11%) had S3 steatosis. Abdominal ultrasound revealed a normal liver in 67.05% of patients, hepatic steatosis in 29.41% and non-decompensated cirrhosis in 6 cases. Thus, 108 patients had the parameters required to calculate the Fatty Liver Index (FLI), steatosis was present in 20% of our patients, while 29.41% had an undetermined status and 24 14.11% had a normal FLI. Conclusion: Identifying subjects at risk of metabolic steatopathy, diagnosing and managing these patients is a public health issue and one of the future challenges of hepato-gastroenterology. Fibroscan is an increasingly popular screening tool for hepatic fibrosis and steatosis. The fight against obesity must be a priority.
基金supported by the Natural Science Foundation for Young Scientists of China(Grant No.:82201545)the Natural Science Foundation of Jiangsu Province,China(Grant No.:BK20221221)+4 种基金the Practice Innovation Program of Jiangsu Province,China(Grant No.:KYCX21_2641)the Medical Science Foundation of Jiangsu Province,China(Grant No.:H2019007)the Key Medical Talents Training Project of Xuzhou,China(Grant No.:XWRCHT20220060)the Xuzhou“Pengcheng Talent”Youth Medical Reserve Talent Project,China(Grant No.:XWRCHT20220014)the Science and Technology Projects of Xuzhou,China(Grant No.:KC21061).
文摘Intestinal dysbiosis and disrupted bile acid(BA)homeostasis are associated with obesity,but the precise mechanisms remain insufficiently explored.Hepatic protein phosphatase 1 regulatory subunit 3G(PPP1R3G)plays a pivotal role in regulating glycolipid metabolism;nevertheless,its obesity-combatting potency remains unclear.In this study,a substantial reduction was observed in serum PPP1R3G levels in high-body mass index(BMI)and high-fat diet(HFD)-exposed mice,establishing a positive correlation between PPP1R3G and non-12a-hydroxylated(non-12-OH)BA content.Additionally,hepatocyte-specific overexpression of Ppp1r3g(PPP1R3G HOE)mitigated HFD-induced obesity as evidenced by reduced weight,fat mass,and an improved serum lipid profile;hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology.PPP1R3G HOE considerably impacted systemic BA homeostasis,which notably increased the non-12-OH BAs ratio,particularly lithocholic acid(LCA).16S ribosomal DNA(16S rDNA)sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population,and elevating the relative abundance of Blautia,which exhibited a positive correlation with serum LCA levels.A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiotadependent.Mechanistically,PPP1R3G HOE markedly suppressed hepatic cholesterol 7a-hydroxylase(CYP7A1)and sterol-12a-hydroxylase(CYP8B1),and concurrently upregulated oxysterol 7-a hydroxylase and Takeda G protein-coupled BA receptor 5(TGR5)expression under HFD conditions.Furthermore,LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels.These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis,which may serve as potential therapeutic targets for obesity-related disorders.
基金Supported by Chongqing Fundamental Research Funds,No.jbky20210001Key Programs of Technological Innovation and Application Development of Chongqing,China,No.cstc2021jscx-dxwtBX0016+2 种基金Natural Science Foundation of Chongqing,No.cstc2021jcyjmsxmX0793Science and Technology Project in Social Livelihood of Bishan District,Chongqing,China,No.BSKJ0078 and No.BSKJ0075Performance Incentive-oriented Project of Chongqing,No.jxjl20220007。
文摘BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.
基金funded in part by grants from the National Natural Science Foundation of China (No.31930105)National Key Research and Development Program of China (2022YFF1000204)China Agriculture Research Systems (CARS-40)。
文摘Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed to systematically investigate the genetic regulatory mechanisms of hepatic steatosis in laying hens.Methods Ninety individuals with the most prominent characteristics were selected from 686 laying hens according to the accumulation of lipid droplets in the liver, and were graded into three groups, including the control, mild hepatic steatosis and severe hepatic steatosis groups. A combination of transcriptome, proteome, acetylome and lipidome analyses, along with bioinformatics analysis were used to screen the key biological processes, modifications and lipids associated with hepatic steatosis.Results The rationality of the hepatic steatosis grouping was verified through liver biochemical assays and RNA-seq. Hepatic steatosis was characterized by increased lipid deposition and multiple metabolic abnormalities. Integration of proteome and acetylome revealed that differentially expressed proteins(DEPs) interacted with differentially acetylated proteins(DAPs) and were involved in maintaining the metabolic balance in the liver. Acetylation alterations mainly occurred in the progression from mild to severe hepatic steatosis, i.e., the enzymes in the fatty acid oxidation and bile acid synthesis pathways were significantly less acetylated in severe hepatic steatosis group than that in mild group(P < 0.05). Lipidomics detected a variety of sphingolipids(SPs) and glycerophospholipids(GPs) were negatively correlated with hepatic steatosis(r ≤-0.5, P < 0.05). Furthermore, the severity of hepatic steatosis was associated with a decrease in cholesterol and bile acid synthesis and an increase in exogenous cholesterol transport.Conclusions In addition to acquiring a global and thorough picture of hepatic steatosis in laying hens, we were able to reveal the role of acetylation in hepatic steatosis and depict the changes in hepatic cholesterol metabolism. The findings provides a wealth of information to facilitate a deeper understanding of the pathophysiology of fatty liver and contributes to the development of therapeutic strategies.
文摘In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic steatohepatitis(NASH).The authors found that MXS treatment mitigated hepatic steatosis and inflam-mation in the NASH model,as evidenced by the reduction in lipid droplets(LDs),fibrosis markers and lipogenic factors.Interestingly,these hepatoprotective effects were associated with androgen upregulation(based on metabolomics analysis of male steroid hormone metabolites),adenosine 5’-monophosphate-activated protein kinase(AMPK)activation,and restoration of phosphatase and tensin homolog(PTEN)expression.However,the authors did not clearly discuss the relationships between MXS-induced hepatic steatosis reduction in the NASH model,and androgen upregulation,AMPK activation,and restoration of PTEN expression.This editorial emphasizes the reported mechanisms and explains how they act or interact with each other to reduce hepatic steatosis and inflammation in the NASH model.As a perspective,we propose additional mechanisms(such as autophagy/lipophagy activation in hepatocytes)for the clearance of LDs and suppression of hepatic steatosis by MXS in the NASH model.A proper understanding of the mechanisms of MXS-induced reduction of hepatic steatosis might help in the treatment of NASH and related diseases.
文摘Objective: Describe the etiological factors of hepatic steatosis in the Internal Medicine and Medical Emergencies department of the Sylvanus Olympio University Hospital of Lomé. Framework and Method: Cross-sectional and retrospective study carried out over a period of 5 years from February 1, 2021 to February 28, 2024 (4 years). All patients aged over 18 years with a hyperechoic appearance of the hepatic parenchymal structure on abdominal ultrasound suggestive of focal or diffuse steatosis of the liver were included. Results: The prevalence of steatosis was 17.21%. The average age of our patients was 42.91 ± 11.71 years. We noted a sex ratio (M/F) of 1.21. Diffuse abdominal pain was the main reason for consultation (38.60%). Hepatomegaly was found on abdominal ultrasound in 28.16% of cases. Two main groups of etiological factors were noted. These included metabolic factors (alcoholism, obesity, type 2 diabetes and high blood pressure (hypertension)) and infectious factors (HIV, HBV, HCV). Conclusion: Hepatic steatosis is a chronic pathology associated with etiological factors. It can progress to steatohepatitis, cirrhosis or even liver cancer.
文摘BACKGROUND:The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the postoperative outcome after liver transplantation.METHODS:Ninety-four patients undergoing liver transplantation at the University Hospital Aachen were included in this study. The patient cohort was divided into three groups according to the grade of microvesicular steatosis(MiS):MiS <30%(n=27), MiS 30%-60%(n=41) and MiS >60%(n=26).The outcomes after liver transplantation were evaluated, including the 30-day and 1-year patient and graft survival rates and the incidences of early allograft dysfunction(EAD) and primary nonfunction(PNF). RESULTS:The incidences of EAD and PNF did not differ significantly between the groups. We observed 5 cases of PNF,one occurred in the MiS <30% group and 4 in the MiS 30%-60% group. The 30-day and 1-year graft survivals did not differ significantly between groups. The 30-day patient survival rates were 100% in all groups. The 1-year patient survival rates were 94.4% in the MiS <30% group, 87.9% in the MiS 30%-60% group and 90.9% in the MiS >60% group.CONCLUSION:Microvesicular steatosis of donor livers has no negative effect on the postoperative outcome after liver transplantation.
文摘Steatosis is a common feature of many liver diseases,namely non-alcoholic steatohepatitis(NASH) and hepatitis C virus(HCV) infection,but the pathogenic mechanisms differ.Insulin resistance(IR),a key feature of metabolic syndrome,is crucial for NASH development,associated with many underlying genetically determined or acquired mitochondrial and metabolic defects and culminates to inflammation and progression to fibrosis.This may have potential implications for new drug therapy.In HCV-related disease,steatosis impacts both fibrosis progression and response to treatment.Steatosis in HCV-related disease relates to both viral factors(HCV genotype 3),and host factors(alcohol consumption,overweight,hyperlipidemia,diabetes).Among others,IR is a recognized factor.Hepatic steatosis is reported to be associated with disturbance in the signaling cascade of interferon and downregulation of its receptors.Thus,hepatic steatosis should not be considered a benign feature,but rather a silent killer.
基金National Key Research and Development Plan‘Precision Medicine Research’,No.2017YFSF090203National Natural Science Foundation of China,No.81070346,No.81270492,No.81470859,No.81270491 and No.81470840+2 种基金State Key Development Program for Basic Research of China,No.2012CB517501100 Talents Program,No.XBR2011007hProgram of the Committee of Science and Technology,No.09140903500
文摘AIM To investigate micro(mi)R-34 a-antagonizing circular(circ)RNA that underlies hepatocellular steatosis.METHODS The effect of circ RNA on mi R-34 a was recognized by the mi RNA response element(MRE), and validated by the dual-luciferase reporter assay. Its association with hepatocellular steatosis was investigated in Hep G2-based hepatocellular steatosis induced by free fatty acids(FFAs; 2:1 oleate:palmitate) stimulation. After normalization of the steatosis-related circRNA by expression vector, analysis of mi R-34 a activity,peroxisome proliferator-activated receptor(PPAR)α level, and expression of downstream genes were carried out so as to reveal its impact on the mi R-34 a/PPARα regulatory system. Both triglyceride(TG) assessment and cytopathological manifestations uncovered the role of circRNA in miR-34 a-dependent hepatosteatogenesis.RESULTS Bioinformatic and functional analysis verified circRNA_0046366 to antagonize the activity of mi R-34 a via MRE-based complementation. In contrast to its lowered level during FFA-induced hepatocellular steatosis, circ RNA_0046366 up-regulation abolished the mi R-34 a-dependent inhibition of PPARα that played a critical role in metabolic signaling pathways. PPARα restoration exerted transcriptional improvement to multiple genes responsible for lipid metabolism. TGspecific lipolytic genes [carnitine palmitoyltransferase 1 A(CPT1 A) and solute-carrier family 27 A(SLC27 A)] among these showed significant increase in their expression levels. The circ RNA_0046366-related rebalancing of lipid homeostasis led to dramatic reduction of TG content, and resulted in the ameliorated phenotype of hepatocellular steatosis.CONCLUSION Dysregulation of circ RNA_0046366/mi R-34 a/PPARα signaling may be a novel epigenetic mechanism underlying hepatocellular steatosis. circ RNA_0046366 serves as a potential target for the treatment of hepatic steatosis.
基金Supported by National Key Research and Development Program of China,No.2017YFC0908903National Natural Science Foundation of China,No.81873565 and No.81900507.
文摘With the increasing incidence of obesity and metabolic syndrome worldwide,concomitant nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has become highly prevalent.The risk of dual etiologies,outcome,and mechanism of CHB with concomitant NAFLD have not been fully characterized.In this review,we assessed the overlapping prevalence of metabolic disorders and CHB,assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD,and discussed the remaining clinical issues to be addressed in the outcome of such patients.We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation.For CHB patients,it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses.The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.
文摘Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.
文摘AIM: To investigate whether serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) may differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 83 patients with suspected NAFLD and 49 healthy volunteers were investigated. Patients with suspected NAFLD were classified according to their liver histology into four groups: definitive NASH (n = 45), borderline NASH (n = 24), simple fatty liver (n = 9), and normal tissue (n = 5). Serum levels of caspase-3 generated cytokeratin-18 fragments (M30-antigen) and total cytokeratin-18 (M65-antigen) were determined by ELISA. RESULTS: Levels of M30-antigen and M65-antigen were significantly higher in patients with definitive NASH compared to the other groups. An abnormal value (> 121.60 IU/L) of M30-antigen yielded a 60.0% sensitivity and a 97.4% specificity for the diagnosis of NASH. Sensitivity and specificity of an abnormal M65-antigen level (> 243.82 IU/L) for the diagnosis of NASH were 68.9% and 81.6%, respectively. Among patients with NAFLD, M30-antigen and M65-antigen levels distinguished between advanced fibrosis and early-stage fibrosis with a sensitivity of 64.7% and 70.6%, and a specificity of 77.3% and 71.2%, respectively. CONCLUSION: Serum levels of M30-antigen and M65-antigen may be of clinical usefulness to identify patients with NASH. Further studies are mandatory to better assess the role of these apoptonecrotic biomarkers in NAFLD pathophysiology.
基金Supported by Community Medicine Research net (CMR) of the University of Greifswald, which is funded by the Federal Ministry of Education and Research and the Federal State of Mecklenburg-West Pomerania
文摘AIM: Although an association between hepatic steatosis and vascular risk factors has been described, direct relationships between fatty liver and atherosclerosis have not yet been investigated. The aim of the present study has been to investigate those relationships. METHODS: The Study of Health in Pomerania examined a random population sample aged between 20 and 79 years. A study population of 4 222 subjects without hepatitis B and C infections and without liver cirrhosis was available for the present analysis. Hepatic steatosis was defined sonographically and intima-media thickness (IMT) as well as plaque prevalence were estimated by carotid ultrasound. RESULTS: The prevalence rate of hepatic steatosis was 29.9%. Among subjects aged ≥45 years, an association between hepatic steatosis and IMT of the carotid arteries was found in bivariate analysis, but not after adjustment for atherosclerotic risk factors. Individuals with fatty liver had more often carotid plaques than persons without fatty liver (plaque prevalence rate 76.8% vs 66.6%; P<0.001). This association persisted after adjustment for confounding factors and was predominantly present in subjects with no to mild alcohol consumption. CONCLUSION: There is an independent association between hepatic steatosis and carotid atherosclerotic plaques. Metabolic changes due to nonalcoholic fatty liver disease may explain this relationship.
