Objective:To detect and compare serum lipid abnormalities in patients diagnosed with different grades of non-alcoholic fatly liver on ultrasonography.Methods:A total of 70 cases which included 30 males and 40 females,...Objective:To detect and compare serum lipid abnormalities in patients diagnosed with different grades of non-alcoholic fatly liver on ultrasonography.Methods:A total of 70 cases which included 30 males and 40 females,diagnosed as nonalcoholic fatty liver disease(NAFLD)on ultrasound were investigated with serum lipid profile.Then a comparison of lipid abnormalities between different grades of fatty liver diagnosed on ultrasound was done.P value was calculated by using analysis of variance lest(ANOVA)and P value<0.05 was considered as statistically significant.Results:Out of 70 cases which were diagnosed as NAFLD on ultrasonography,gradeⅠNAFLD cases were 47.15%,gradeⅡwere 42.85%and gradeⅢwere 10%.The mean age of the patients was49.14 years.Male to female ratio was 3:4.Serum triglycerides,total cholesterol,LDL and VLDL levels were raised in 67.14%,45.71%34.28%,25.71%of cases respectively.Low serum HDL levels were seen in 62.85%of patients.On statistical analysis we found increasing grades of NAFLD were significantly associated with increasing values of total cholesterol(P value-0.001),LDL(P value-0.000)and VLDL(P value-0.003)and decreasing HDL(P value-0.000).Conclusion:Most of the patients of NAFLD in India is asymptomatic,non-diabetic and non-hypertensive.Though liver biopsy is the gold standard melhod for diagnosis of NAFLD,Ultrasonography which is non-invasive,simple tool,can be used for the early detection of NAFLD in asymptomatic patients.展开更多
Non-alcoholic fatty liver disease(NAFLD),which has a global prevalence of 20%–33%,has become the main cause of chronic liver disease.Except for lifestyle medication,no definitive medical treatment has been establishe...Non-alcoholic fatty liver disease(NAFLD),which has a global prevalence of 20%–33%,has become the main cause of chronic liver disease.Except for lifestyle medication,no definitive medical treatment has been established so far,making it urgent to find effective strategies for the treatment of NAFLD.With the identification of the significant role played by the gut microbiota in the pathogenesis of NAFLD,studies on probiotics for the prevention and treatment of NAFLD are increasing in number.Bacteria from the Bifidobacterium and Lactobacillus genera constitute the most widely used traditional probiotics.More recently,emerging next-generation probiotics(NGPs)such as Akkermansia muciniphila and Faecalibacterium prausnitzii have also gained attention due to their potential as therapeutic options for the treatment of NAFLD.This review provides an overview of the effects of oral administration of traditional probiotics and NGPs on the development and progress of NAFLD.The mechanisms by which probiotics directly or indirectly affect the disease are illustrated,based on the most recent animal and clinical studies.Although numerous studies have been published on this topic,further research is required to comprehensively understand the specific underlying mechanisms among probiotics,gut microbiota,and NAFLD,and additional large-scale clinical trials are required to evaluate the therapeutic efficacy of probiotics for the treatment of NAFLD,as well as the safety of probiotics in the human body.展开更多
Soy glycinin derived octapeptide(SGP8)is a peptide obtained from degradation of the soy glycinin,whose amino acid sequence is IAVPGEVA.To determine the effect of SGP8 on non-alcoholic fatty liver disease(NAFLD),steato...Soy glycinin derived octapeptide(SGP8)is a peptide obtained from degradation of the soy glycinin,whose amino acid sequence is IAVPGEVA.To determine the effect of SGP8 on non-alcoholic fatty liver disease(NAFLD),steatosis Hep G2 cells were induced by 1 mmol/L free fatty acid(FFA)and C57 BL/6 J mice were fed with methionine-choline defi cient(MCD)diet for 3 weeks to establish NAFLD model.The results of oil red O staining and total cholesterol(TC)/triglyceride(TG)contents showed that SGP8 could signifi cantly reduce the lipid content of steatosis Hep G2 cells.In vivo,SGP8 lowered plasma alanine aminotransferase(ALT)and low density lipoprotein(LDL)content,normalized hepatic superoxide dismutase(SOD)and malondialdehyde(MDA)production,and reduced the severity of liver infl ammation.The results of Western blotting showed that SGP8 increased expression of Sirtuin-1(SIRT1)and phosphorylation level of AMP activated protein kinase(AMPK)in hepatocytes.Through activation of SIRT1/AMPK pathway,SGP8 downregulated the expression of sterol regulatory element binding protein 1 c(SREBP-1 c)and its target genes ACC and FAS expression levels,and increased the phosphorylation level of acetyl Co A carboxylase(ACC).Furthermore,SGP8 also upregulated the expression of transcription factor peroxisome proliferator activated receptorα(PPARα),which was regulated by SIRT1/AMPK pathway,and its target gene CPT1 level.In conclusion,SGP8 might improve NAFLD by activating the SIRT1/AMPK pathway.Our data suggest that SGP8 may act as a novel and potent therapeutic agent against NAFLD.展开更多
Non-alcoholic fatty liver disease(NAFLD)is a common chronic liver disease characterized by diffuse hepatic steatosis.With the improvement of people's living standard,the incidence rate of NAFLD has been increasing...Non-alcoholic fatty liver disease(NAFLD)is a common chronic liver disease characterized by diffuse hepatic steatosis.With the improvement of people's living standard,the incidence rate of NAFLD has been increasing,which has become one of the global health problems in 21st Century.However,there is no specific drug or standard treatment for NAFLD,which brings challenges to treatment.Acupuncture,moxibustion,massage and other external therapies based on the characteristics of traditional Chinese medicine have obvious curative effect in the clinical treatment of NAFLD,but the mechanism has not been systematically explained,which makes the clinical promotion evidence insufficient.This paper aims to summarize the researches on the treatment of NAFLD by external therapies of traditional Chinese medicine in recent years,and analyze its possible mechanism,so as to provide a scientific theoretical basis for future basic experiments and clinical research,and form a set of standardized clinical diagnosis and treatment scheme with the characteristics of traditional Chinese medicine.展开更多
Non-alcoholic fatty liver disease (NAFLD) is a common liver disease worldwide. There is no specific biomarker for the diagnosis of NAFLD. Trigly-ceride and glucose index (TyG) may predict the subsequent occurrence of ...Non-alcoholic fatty liver disease (NAFLD) is a common liver disease worldwide. There is no specific biomarker for the diagnosis of NAFLD. Trigly-ceride and glucose index (TyG) may predict the subsequent occurrence of NAFLD in later life. This cross sectional study was aimed to evaluate the effectiveness of triglyceride and glucose index (TyG) as a possible biomarker of NAFLD. The study was conducted at the Department of Laboratory Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from March 2019 to February 2020. A total of 124 subjects were taken as study population following selection criteria. Among them 62 were diagnosed patients of NAFLD and 62 were healthy subjects as control group. Fasting plasma glucose was measured by glucose oxidase method and serum triglyceride was measured by enzymatic-colorimetric method, while TyG index was calculated accordingly. The mean age was 39.5 ± 11.27 years in NAFLD patients and 37.10 ± 12.28 years in control subjects with male female ratio 1:1.7 and 1:1.8 respectively. Major portion of NAFLD patients (62.9%) were overweight (BMI ≥ 25). The mean fasting plasma glucose level was 5.73 ± 1.47 mmol/L in NAFLD patients and 5.27 ± 0.69 mmol/L in control group (p < 0.027). The mean serum triglyceride level was 237.19 ± 96.47 mg/dl in NAFLD patients and 117.32 ± 53.07 mg/dl in control group (p < 0.001). The triglyceride and glucose index (TyG) was 9.36 ± 0.47 in NAFLD group and 8.53 ± 0.42 in control group. TyG index was significantly higher in NAFLD patients in comparison to control group (p < 0.001). In ROC analysis, cut off value of TyG index was 8.85 with sensitivity 93.5% and specificity 79%. As a fast and effective method, TyG index can be used as a diagnostic tool to predict NAFLD.展开更多
<b>Background: </b>Non-alcoholic fatty liver disease (NAFLD) has emerged a major challenge and become the leading indication for liver transplantation. We aimed to assess the applicability and performance ...<b>Background: </b>Non-alcoholic fatty liver disease (NAFLD) has emerged a major challenge and become the leading indication for liver transplantation. We aimed to assess the applicability and performance of real-time elastography (RTE) in diagnosis of liver fibrosis in patients with NAFLD compared with NAFLD fibrosis score (NFS) and FIB-4 index. <b>Patients and Methods:</b> A prospective case-control study was conducted on 260 subjects attended Hepatology, Gastroenterology and Infectious diseases and Internal Medicine departments in Benha University Hospital from Marsh 20, 2018, to September 1, 2019 and divided into group I included 200 cases with NAFLD and group II included 60 healthy control subjects. <b>Results</b>:<b> </b>There was statistically significant increase in FIB-4 scores between two groups (1.39 ± 1.02 and -0.75 ± 0.32 respectively with p < 0.001), also there was statistically significant increase in NAFLD fibrosis score mean ± SD between two groups (-1.74 ± 1.17 and -2.75 ± 0.91 respectively with p < 0.001). Fibrosis stages in NAFLD patients significantly higher than in control group diagnosed by RTE (P = 0.001). There was an agreement between RTE and FIB-4 index (93%) and NAFLD fibrosis score (86%). Diagnostic performance of RTE in advanced liver fibrosis ≥ F3 was assessed in comparing with FIB-4 index show sensitivity 90%, specificity 93.3%, PPV 60%, NPV 98.8% and accuracy 93% with AUC0.917 (p = 0.001) and in comparing with NAFLD fibrosis score sensitivity 52.6%, specificity 93.8%, PPV 66.7%, NPV 98.4% and accuracy 86% with AUC 0.732 (p = 0.002). <b>Conclusion: </b>Real time elastography could be valuable in diagnosis of fibrosis in NAFLD especially in cases more than F3 score.展开更多
[Objectives]To study the effect and mechanism of Gynura divaricate(L.)DC(GD)on non-alcoholic fatty liver disease(NAFLD).[Methods]Male mice were randomly divided into 2 groups:normal group and model group.The mice were...[Objectives]To study the effect and mechanism of Gynura divaricate(L.)DC(GD)on non-alcoholic fatty liver disease(NAFLD).[Methods]Male mice were randomly divided into 2 groups:normal group and model group.The mice were fed with high-fat diet(HFD)for 4 weeks to induce NAFLD in the model group.The successfully modeled mice were divided into model group,positive drug group,GD high dose group,and GD low dose group.After 4 weeks of administration,the liver index,serum AST,ALT and blood lipid levels,liver tissue pathological changes,antioxidant enzymes,non-enzymatic antioxidants and inflammatory factors levels were measured in each group,and the expression of NF-κB,Nrf-2 and HO-1 in liver tissues were compared.[Results]GD significantly reduced the serum AST,ALT and blood lipid levels,increased enzyme antioxidant and non-enzymatic antioxidant content,reduced the steatosis and inflammatory infiltration of liver cells,down-regulated the level of inflammatory factors,and inhibited the expression of NF-κB,Nrf-2 and HO-1 in liver tissue.[Conclusions]GD has a protective effect on NAFLD in mice and its mechanism may be related to the regulation of NF-κB and Nrf-2/HO-1 pathways.展开更多
Background:We examined the comparative associations between non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated steatotic liver disease(MASLD)definitions with risk of developing chronic kidney...Background:We examined the comparative associations between non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated steatotic liver disease(MASLD)definitions with risk of developing chronic kidney disease(CKD)and abnormal albuminuria.Methods:We conducted a cohort study of 214,145 Korean adults with normal kidney function at baseline who underwent liver ultrasonography.Participants were further subdivided into no steatotic liver disease(no-SLD),NAFLD-only,MASLD-only,both NAFLD and MASLD,and SLD not categorized as NAFLD or MASLD groups.Cox proportional hazards models were used to analyze the risk of incident CKD and albuminuria.Results:Compared with either the no-NAFLD or no-MASLD groups,the NAFLD and MASLD groups were associated with a higher risk of incident CKD(NAFLD:adjusted hazard ratio(HR),1.18[95%CI,1.01-1.38];MASLD:adjusted HR,1.21[95%CI,1.04-1.39]).Among the five subgroups,both NAFLD and MASLD group had the strongest association with risk of incident CKD(adjusted HR,1.21[95%CI,1.04-1.42]).The MASLD-only group had the strongest association with incident abnormal albuminuria,with an adjusted HR comparable to that of the both NAFLD and MASLD group(adjusted HR 1.96[95%CI,1.44-2.67]for the MASLD-only,and adjusted HR 1.98[95%CI,1.58-2.49]for the both NAFLD and MASLD group versus the no-SLD group).The NAFLD-only group was not independently associated with risk of CKD or abnormal albuminuria.Conclusions:These findings suggest that MASLD definition identifies individuals at high risk of developing incident CKD or abnormal albuminuria better than NAFLD definition.展开更多
Non-alcoholic fatty liver disease(NAFLD)and non-alcoholic steatohepatitis(NASH)are national and global epidemics.The disease is characterized by a spectrum of liver steatosis(fat deposition),inflammation(in NASH)and f...Non-alcoholic fatty liver disease(NAFLD)and non-alcoholic steatohepatitis(NASH)are national and global epidemics.The disease is characterized by a spectrum of liver steatosis(fat deposition),inflammation(in NASH)and fibrosis.NAFLD and specifically NASH can lead to cirrhosis,which carry risks of progression to portal hypertension and hepatocellular carcinoma(HCC).NASH is also associated with higher mortality from cardiovascular causes.Most of the data for NAFLD has been obtained from the perspective of developed nations,although the disease is increasing and threatening to reach epidemic proportions across the world.Emerging data is notable for high prevalence of NAFLD in South Asian populations,presumably resulting from a combination of underlying genetic polymorphisms and changes in socio-economic status.It is also notable that an‘Asian Paradox'has been defined for NAFLD based upon the observation of lower than predefined body mass index(BMI),otherwise termed as"lean NAFLD",among this population.Yet,data remains limited in regards to the characteristics of NAFLD/NASH in this population.In this article,we present a review of the literature and discuss the prevalence,associated risk factors and burden of HCC in South Asians with NAFLD.展开更多
Importance:Non-alcoholic fatty liver disease(NAFLD)is a rapidly growing cause of chronic liver disease and is becoming a leading cause of hepatocellular carcinoma(HCC)in many developed countries.This presents major ch...Importance:Non-alcoholic fatty liver disease(NAFLD)is a rapidly growing cause of chronic liver disease and is becoming a leading cause of hepatocellular carcinoma(HCC)in many developed countries.This presents major challenges for the surveillance,diagnosis and treatment of HCC.Objective:To discuss the clinical challenges faced by clinicians in managing the rising number of NAFLD-HCC cases.Evidence Review:MEDLINE,PubMed and Embase databases were searched using the keywords;NAFLD,HCC,surveillance,hepatectomy,liver transplantation,percutaneous ablation,transarterial chemoembolization(TACE),selective internal radiotherapy treatment(SIRT)and sorafenib.Relevant clinical studies were included.Findings:Current HCC surveillance programmes are inadequate because they only screen for HCC in patients with cirrhosis,whereas in NAFLD a significant proportion of HCC develops in the absence of cirrhosis.Consequently NAFLD patients often present with a more advanced stage of HCC,with a poorer prognosis.NAFLD-HCC patients also tend to be older and to have more co-morbidities compared to HCC of other etiologies.This limits the use of curative treatments such as liver resection and orthotopic liver transplantation(OLT).Evidence suggests that although NAFLD-HCC patients who undergo liver resection or OLT have worse perioperative and short-term outcomes,overall long-term survival is comparable to HCC of other etiologies.This highlights the importance of careful patient selection,pre-habilitation and perioperative planning for NAFLD-HCC patients being considered for surgical treatment.Careful consideration is also important for non-surgical treatments,although the evidence supporting treatment selection is frequently lacking,as these patients tend to be poorly represented in clinical trials.Locoregional therapies such as percutaneous ablation and TACE may be less well tolerated and less effective in NAFLD patients with obesity or diabetes.The tyrosine kinase inhibitor sorafenib may also be less effective.Conclusions and Relevance:This review highlights how international guidelines,for which NAFLD traditionally has made up a small part of the evidence base,may not be appropriate for all NAFLD-HCC patients.Future guidelines need to reflect the changing landscape of HCC,by making specific recommendations for the management of NAFLD-HCC.展开更多
The incidence of non-alcoholic fatty liver disease(NAFLD)is rising rapidly across the globe.NAFLD pathogenesis is largely driven by an imbalance in hepatic energy metabolism,and at present,there is no approved drug fo...The incidence of non-alcoholic fatty liver disease(NAFLD)is rising rapidly across the globe.NAFLD pathogenesis is largely driven by an imbalance in hepatic energy metabolism,and at present,there is no approved drug for its treatment.The liver plays a crucial role in micronutrient metabolism,and deregulation of this micronutrient metabolism may contribute to the pathogenesis of NAFLD.Vitamins regulate several enzymatic processes in the liver,and derangement in vitamin metabolism is believed to play a critical role in NAFLD progression.The anti-oxidant activities of vitamins C and E have been attributed to mitigate hepatocyte injury,and alterations in the serum levels of vitamin D,vitamin B12 and folate have shown a strong correlation with NAFLD severity.This review aims to highlight the role of these vitamins,which represent promising therapeutic targets for the management of NAFLD.展开更多
Autophagy is an evolutionarily conserved intracellular degradative function that is important for liver homeostasis.Accumulating evidence suggests that autophagy is deregulated during the progression and development o...Autophagy is an evolutionarily conserved intracellular degradative function that is important for liver homeostasis.Accumulating evidence suggests that autophagy is deregulated during the progression and development of alcoholic and non-alcoholic liver diseases.Impaired autophagy prevents the clearance of excessive lipid droplets(LDs),damaged mitochondria,and toxic protein aggregates,which can be generated during the progression of various liver diseases,thus contributing to the development of steatosis,injury,steatohepatitis,fibrosis,and tumors.In this review,we look at the status of hepatic autophagy during the pathogenesis of alcoholic and non-alcoholic liver diseases.We also examine the mechanisms of defects in autophagy,and the hepato-protective roles of autophagy in non-alcoholic fatty liver disease(NAFLD)and alcoholic liver disease(ALD),focusing mainly on steatosis and liver injury.Finally,we discuss the therapeutic potential of autophagy modulating agents for the treatment of these two common liver diseases.展开更多
Bile acids are a family of atypical steroids generated at the interface of liver-intestinal microbiota acting on a ubiquitously expressed family of membrane and nuclear receptors known as bile acid activated receptors...Bile acids are a family of atypical steroids generated at the interface of liver-intestinal microbiota acting on a ubiquitously expressed family of membrane and nuclear receptors known as bile acid activated receptors.The two best characterized receptors of this family are the nuclear receptor,farnesoid X re-ceptor(FXR)and the G protein-coupled receptor,G protein-coupled bile acid receptor 1(GPBAR1).FXR and GPBAR1 regulate major aspects of lipid and glucose metabolism,energy balance,autophagy and immunity and have emerged as potential pharmaceutical targets for the treatment of metabolic and inflammatory disorders.Clinical trials in non-alcoholic fatty liver disease(NAFLD),however,have shown that selective FXR agonists cause side effects while their efficacy is partial.Because FXR and GPBAR1 exert additive effects,dual FXR/GPBAR1 ligands have been developed for the treatment of metabolic disorders and are currently advanced to clinical trials.Here,we will review the role of FXR and GPBAR1 agonism in NAFLD and how the two receptors could be exploited to target multiple components of the disease.展开更多
Non-alcoholic fatty liver disease(NAFLD)is a chronic progressive liver disorder that begins with simple hepatic steatosis and progresses to non-alcoholic steatohepatitis,fibrosis,cirrhosis,and even liver cancer.As the...Non-alcoholic fatty liver disease(NAFLD)is a chronic progressive liver disorder that begins with simple hepatic steatosis and progresses to non-alcoholic steatohepatitis,fibrosis,cirrhosis,and even liver cancer.As the global prevalence of NAFLD rises,it is increasingly important that we understand its pathogenesis and develop effective therapies for this chronic disease.Forkhead box O(FOXO)transcription factors are key downstream regulators in the insulin/insulin-like growth factor 1(IGF1)signaling pathway,and have been implicated in a range of cellular functions including the regulation of glucose,triglyceride,and cholesterol homeostasis.The role of FOXOs in the modulation of immune response and inflammation is complex,with reports of both pro-and anti-inflammatory effects.FOXOs are reported to protect against hepatic fibrosis by inhibiting proliferation and transdifferentiation of hepatic stellate cells.Mice that are deficient in hepatic FOXOs are more susceptible to non-alcoholic steatohepatitis than wild-type controls.In summary,FOXOs play a critical role in maintaining metabolic and cellular homeostasis in the liver,and dysregulation of FOXOs may be involved in the NAFLD development.展开更多
Non-alcoholic fatty liver disease(NAFLD),characterized by the accumulation of excessive intrahepatic fat,is a leading metabolic disorder also considered as the hepatic manifestation of metabolic syndrome(MS).Though mo...Non-alcoholic fatty liver disease(NAFLD),characterized by the accumulation of excessive intrahepatic fat,is a leading metabolic disorder also considered as the hepatic manifestation of metabolic syndrome(MS).Though more commonly observed in obese individuals and those with metabolic risk factors,it also develops in a considerable number of non-obese individuals as well as participants without having any component of MS.The basic mechanism involved in the development of fatty liver is the imbalance between lipid uptake,synthesis,and metabolism in the liver,normally controlled by several mechanisms to maintain lipid homeostasis.As a complex progressive liver disorder,the NAFLD pathogenesis is multifactorial,and several new pathogenic phenomena were discovered over time.The available literature suggests the role of both genetic and environmental factors and associated metabolic factors;however,the mechanism of progression is not completely understood.In this review,we discuss different pathogenic mechanisms and their interplay to provide an elaborate idea regarding NAFLD development and progression.Better understanding of pathogenic mechanisms will be useful in finding new treatment for patients with NAFLD.展开更多
Non-alcoholic fatty liver disease(NAFLD)has become the most common cause of chronic liver disease worldwide,and is closely associated with the increased risk of the prevalence of obesity and diabetes.NAFLD begins with...Non-alcoholic fatty liver disease(NAFLD)has become the most common cause of chronic liver disease worldwide,and is closely associated with the increased risk of the prevalence of obesity and diabetes.NAFLD begins with the presence of>5%excessive lipid accumulation in the liver,and potentially de-velops into non-alcoholic steatohepatitis,fibrosis,cirrhosis and hepatocellular carcinoma.Therefore,insight into the pathogenesis of NAFLD is of key importance to its effective treatment.Iron is an essential element in the life of all mammalian organisms.However,the free iron deposition is positively associated with histological severity in NAFLD patients due to the production of reactive oxygen species via the Fenton reaction.Recently,several iron metabolism-targeted therapies,such as phlebotomy,iron chela-tors,nanotherapeutics.and ferroptosis,have shown their potential as a therapeutic option in the treatment of NAFLD and as a clinical strategy to intervene in the progression of NAFLD.Herein,we review the recent overall evidence on iron metabolism and provide the mechanism of hepatic iron overload-induced liver pathologies and the recent advances in iron metabolism-targeted therapeutics in the treatment of NAFLD.展开更多
Background and Objective:Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients who undergo liver transplantation(LT).Whereas there is huge data on NAFLD,little is known about NAFLD in LT.In this revi...Background and Objective:Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients who undergo liver transplantation(LT).Whereas there is huge data on NAFLD,little is known about NAFLD in LT.In this review,we aim to explore extrahepatic organs and their potential mechanisms in the development of NAFLD in LT patients and discuss current limitations in preclinical and clinical scenarios with suggestions for future study.Methods:The following keywords,such as NAFLD,NASH,liver transplant,therapy,pathogenesis and biomarkers,were set for literature retrieval.The articles which were published articles in English till 25th June 2020 in PubMed database were included,and there is no limit for the study design type.Key Content and Findings:Following LT,there are significant shifts in the microbiota and farnesoid X receptor may be a potential therapeutic target for NAFLD in LT settings.The roles of probiotics and diet on NALFD remain inconclusive in LT background.Nevertheless,the adipokines and cytokines disorder and local insulin resistance of adipose tissue may contribute to NAFLD process.Bariatric surgeries are promising in controlling de novo and recurrent NAFLD with significant reduction in abdominal adipose tissue,despite the optimal timing is inconclusive in LT cases.Furthermore,circumstantial evidence indicates that miRNA-33a may function as a mediator bridging sarcopenia and NAFLD of post-LT.β-Hydroxy-β-Methyl-Butyrate treatment could improve muscle status in graft recipients and shows protective potential for NAFLD in LT settings.Conclusions:Gut,adipose tissue and muscle are intricately intertwined in promoting NAFLD in LT cases.Further animal studies are needed to deepen our understanding of mechanisms in multi-organ crosstalk.High quality clinical trials are warrant for making guidelines and developing management strategies on NAFLD after LT.展开更多
Background:We aimed to evaluate the medium-term efficacy of sleeve gastrectomy(SG)vs.Roux-en-Y gastric bypass(RYGB)on remission of non-alcoholic fatty liver disease(NAFLD)in patients with type 2 diabetes mellitus(T2DM...Background:We aimed to evaluate the medium-term efficacy of sleeve gastrectomy(SG)vs.Roux-en-Y gastric bypass(RYGB)on remission of non-alcoholic fatty liver disease(NAFLD)in patients with type 2 diabetes mellitus(T2DM).Methods:We identified severely obese patients[body mass index(BMI)>35 kg/m^(2)]with NAFLD(as defined by the Longitudinal Assessment of Bariatric Surgery Study)and T2DM(as defined by the American Association of Clinical Endocrinologists and the American College of Endocrinology)who underwent SG or RYGB in a single university surgical centre.The cohorts were match-paired and data were analysed after at least 3 years of follow up.The key outcomes measured were:(I)the improvement of liver function tests and NAFLD markers;(II)glycemic control and insulin resistance.Results:Ninety-six patients were investigated;44(45.8%)were women.The mean pre-operative BMI was 45.2 kg/m2 in the SG and 42.0 kg/m^(2) in the RYGB group.SG and RYGB both significantly reduced serum liver enzyme concentrations.NAFLD markers resolved 2 years after SG in all patients.In contrast,only 78%and 80%of patients achieved remission of NAFLD 2 and 3 years after RYBG respectively.Both procedures resulted in comparable rates of remission of T2DM.Conclusions:Bariatric surgery with SG may be preferable to RYGB for obese patients with NAFLD and T2DM based on the rates of remission of markers of these co-morbidities.However,our results need to be confirmed in prospective trials.Understanding the metabolic effects of specific bariatric surgical procedures may facilitate the development of a personalised approach to weight-loss surgery.展开更多
Macroautophagy(hereafter autophagy)is a catabolic process by which autophagosomes arising from an isolation membrane fuse with lysosomes to degrade components in the cytoplasm.Autophagosomelysosome fusion step is one ...Macroautophagy(hereafter autophagy)is a catabolic process by which autophagosomes arising from an isolation membrane fuse with lysosomes to degrade components in the cytoplasm.Autophagosomelysosome fusion step is one of the key steps during the process of macroautophagy.The step is extremely complicated and its detailed mechanisms remain unclear.It consists of two phases:first phase is autophagosome migration phase and second phase is fusion of autophagosomes and lysosomes phase.Recently,various molecules have been reported to be involved in each phase.In the first phase,microtubules and actin remodeling mechanism are involved.In the second phase,soluble N-ethylmaleimide-sensitive factor attachment protein receptor(SNARE)proteins,Rab family proteins,phosphoinositide 3-kinase(PI3K)complex and Rubicon are involved.In the present review,we introduce recent findings related to autophagosome-lysosome fusion step and discuss liver diseases possibly associated with autophagosome-lysosome fusion dysfunction.展开更多
Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease characterized by hepatic steatosis in the absence of other causes,such as chronic alcohol consumption,that cause secondary hepatic fat accumulation.NA...Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease characterized by hepatic steatosis in the absence of other causes,such as chronic alcohol consumption,that cause secondary hepatic fat accumulation.NAFLD has become the most common liver disease worldwide over the past two decades,and the prevalence of NAFLD is 20e30%in Western countries.However,the mechanism of NAFLD re-mains unclear.The gut microbiota plays an important role in the metabolism of the host;in fact,it has been implicated in inflammatory diseases,metabolic syndrome and cardiovascular disease.Accumu-lating evidence has indicated that gut microbiota component changes are linked to human obesity,in-sulin resistance(IR),type 2 diabetes and NAFLD.Here,we provide insight into the role of gut microbiota,especially bile salt hydrolase(BSH)in modulating the bile acid pool and farnesoid X receptor(FXR),which promotes the synthesis of ceramide and contributes to the development of NAFLD.展开更多
基金Funded by the department of radiodiagnosis with approval by institutional ethics committce of G.R.Medical College,Gwalior,Madhya pradesh,Indiawith Grant no.-GRM/01/15/2009
文摘Objective:To detect and compare serum lipid abnormalities in patients diagnosed with different grades of non-alcoholic fatly liver on ultrasonography.Methods:A total of 70 cases which included 30 males and 40 females,diagnosed as nonalcoholic fatty liver disease(NAFLD)on ultrasound were investigated with serum lipid profile.Then a comparison of lipid abnormalities between different grades of fatty liver diagnosed on ultrasound was done.P value was calculated by using analysis of variance lest(ANOVA)and P value<0.05 was considered as statistically significant.Results:Out of 70 cases which were diagnosed as NAFLD on ultrasonography,gradeⅠNAFLD cases were 47.15%,gradeⅡwere 42.85%and gradeⅢwere 10%.The mean age of the patients was49.14 years.Male to female ratio was 3:4.Serum triglycerides,total cholesterol,LDL and VLDL levels were raised in 67.14%,45.71%34.28%,25.71%of cases respectively.Low serum HDL levels were seen in 62.85%of patients.On statistical analysis we found increasing grades of NAFLD were significantly associated with increasing values of total cholesterol(P value-0.001),LDL(P value-0.000)and VLDL(P value-0.003)and decreasing HDL(P value-0.000).Conclusion:Most of the patients of NAFLD in India is asymptomatic,non-diabetic and non-hypertensive.Though liver biopsy is the gold standard melhod for diagnosis of NAFLD,Ultrasonography which is non-invasive,simple tool,can be used for the early detection of NAFLD in asymptomatic patients.
基金This study was supported by grants from the National Key Research and Development Program of China(2018YFC2000500)the National Natural Science Foundation of China(81790631 and 81330011).
文摘Non-alcoholic fatty liver disease(NAFLD),which has a global prevalence of 20%–33%,has become the main cause of chronic liver disease.Except for lifestyle medication,no definitive medical treatment has been established so far,making it urgent to find effective strategies for the treatment of NAFLD.With the identification of the significant role played by the gut microbiota in the pathogenesis of NAFLD,studies on probiotics for the prevention and treatment of NAFLD are increasing in number.Bacteria from the Bifidobacterium and Lactobacillus genera constitute the most widely used traditional probiotics.More recently,emerging next-generation probiotics(NGPs)such as Akkermansia muciniphila and Faecalibacterium prausnitzii have also gained attention due to their potential as therapeutic options for the treatment of NAFLD.This review provides an overview of the effects of oral administration of traditional probiotics and NGPs on the development and progress of NAFLD.The mechanisms by which probiotics directly or indirectly affect the disease are illustrated,based on the most recent animal and clinical studies.Although numerous studies have been published on this topic,further research is required to comprehensively understand the specific underlying mechanisms among probiotics,gut microbiota,and NAFLD,and additional large-scale clinical trials are required to evaluate the therapeutic efficacy of probiotics for the treatment of NAFLD,as well as the safety of probiotics in the human body.
基金funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘Soy glycinin derived octapeptide(SGP8)is a peptide obtained from degradation of the soy glycinin,whose amino acid sequence is IAVPGEVA.To determine the effect of SGP8 on non-alcoholic fatty liver disease(NAFLD),steatosis Hep G2 cells were induced by 1 mmol/L free fatty acid(FFA)and C57 BL/6 J mice were fed with methionine-choline defi cient(MCD)diet for 3 weeks to establish NAFLD model.The results of oil red O staining and total cholesterol(TC)/triglyceride(TG)contents showed that SGP8 could signifi cantly reduce the lipid content of steatosis Hep G2 cells.In vivo,SGP8 lowered plasma alanine aminotransferase(ALT)and low density lipoprotein(LDL)content,normalized hepatic superoxide dismutase(SOD)and malondialdehyde(MDA)production,and reduced the severity of liver infl ammation.The results of Western blotting showed that SGP8 increased expression of Sirtuin-1(SIRT1)and phosphorylation level of AMP activated protein kinase(AMPK)in hepatocytes.Through activation of SIRT1/AMPK pathway,SGP8 downregulated the expression of sterol regulatory element binding protein 1 c(SREBP-1 c)and its target genes ACC and FAS expression levels,and increased the phosphorylation level of acetyl Co A carboxylase(ACC).Furthermore,SGP8 also upregulated the expression of transcription factor peroxisome proliferator activated receptorα(PPARα),which was regulated by SIRT1/AMPK pathway,and its target gene CPT1 level.In conclusion,SGP8 might improve NAFLD by activating the SIRT1/AMPK pathway.Our data suggest that SGP8 may act as a novel and potent therapeutic agent against NAFLD.
基金Qihuang scholar of the"hundred and ten million"talent project of Inheritance and innovation of traditional Chinese Medicine(2018)National key project on modernization of traditional Chinese medicine(No.2018YFC1707800)The three-year Action Plan for Further Speed Up the Development of Chinese Medicine in Shanghai[No.ZY(2018-2020)-CCCX-2004-02]。
文摘Non-alcoholic fatty liver disease(NAFLD)is a common chronic liver disease characterized by diffuse hepatic steatosis.With the improvement of people's living standard,the incidence rate of NAFLD has been increasing,which has become one of the global health problems in 21st Century.However,there is no specific drug or standard treatment for NAFLD,which brings challenges to treatment.Acupuncture,moxibustion,massage and other external therapies based on the characteristics of traditional Chinese medicine have obvious curative effect in the clinical treatment of NAFLD,but the mechanism has not been systematically explained,which makes the clinical promotion evidence insufficient.This paper aims to summarize the researches on the treatment of NAFLD by external therapies of traditional Chinese medicine in recent years,and analyze its possible mechanism,so as to provide a scientific theoretical basis for future basic experiments and clinical research,and form a set of standardized clinical diagnosis and treatment scheme with the characteristics of traditional Chinese medicine.
文摘Non-alcoholic fatty liver disease (NAFLD) is a common liver disease worldwide. There is no specific biomarker for the diagnosis of NAFLD. Trigly-ceride and glucose index (TyG) may predict the subsequent occurrence of NAFLD in later life. This cross sectional study was aimed to evaluate the effectiveness of triglyceride and glucose index (TyG) as a possible biomarker of NAFLD. The study was conducted at the Department of Laboratory Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from March 2019 to February 2020. A total of 124 subjects were taken as study population following selection criteria. Among them 62 were diagnosed patients of NAFLD and 62 were healthy subjects as control group. Fasting plasma glucose was measured by glucose oxidase method and serum triglyceride was measured by enzymatic-colorimetric method, while TyG index was calculated accordingly. The mean age was 39.5 ± 11.27 years in NAFLD patients and 37.10 ± 12.28 years in control subjects with male female ratio 1:1.7 and 1:1.8 respectively. Major portion of NAFLD patients (62.9%) were overweight (BMI ≥ 25). The mean fasting plasma glucose level was 5.73 ± 1.47 mmol/L in NAFLD patients and 5.27 ± 0.69 mmol/L in control group (p < 0.027). The mean serum triglyceride level was 237.19 ± 96.47 mg/dl in NAFLD patients and 117.32 ± 53.07 mg/dl in control group (p < 0.001). The triglyceride and glucose index (TyG) was 9.36 ± 0.47 in NAFLD group and 8.53 ± 0.42 in control group. TyG index was significantly higher in NAFLD patients in comparison to control group (p < 0.001). In ROC analysis, cut off value of TyG index was 8.85 with sensitivity 93.5% and specificity 79%. As a fast and effective method, TyG index can be used as a diagnostic tool to predict NAFLD.
文摘<b>Background: </b>Non-alcoholic fatty liver disease (NAFLD) has emerged a major challenge and become the leading indication for liver transplantation. We aimed to assess the applicability and performance of real-time elastography (RTE) in diagnosis of liver fibrosis in patients with NAFLD compared with NAFLD fibrosis score (NFS) and FIB-4 index. <b>Patients and Methods:</b> A prospective case-control study was conducted on 260 subjects attended Hepatology, Gastroenterology and Infectious diseases and Internal Medicine departments in Benha University Hospital from Marsh 20, 2018, to September 1, 2019 and divided into group I included 200 cases with NAFLD and group II included 60 healthy control subjects. <b>Results</b>:<b> </b>There was statistically significant increase in FIB-4 scores between two groups (1.39 ± 1.02 and -0.75 ± 0.32 respectively with p < 0.001), also there was statistically significant increase in NAFLD fibrosis score mean ± SD between two groups (-1.74 ± 1.17 and -2.75 ± 0.91 respectively with p < 0.001). Fibrosis stages in NAFLD patients significantly higher than in control group diagnosed by RTE (P = 0.001). There was an agreement between RTE and FIB-4 index (93%) and NAFLD fibrosis score (86%). Diagnostic performance of RTE in advanced liver fibrosis ≥ F3 was assessed in comparing with FIB-4 index show sensitivity 90%, specificity 93.3%, PPV 60%, NPV 98.8% and accuracy 93% with AUC0.917 (p = 0.001) and in comparing with NAFLD fibrosis score sensitivity 52.6%, specificity 93.8%, PPV 66.7%, NPV 98.4% and accuracy 86% with AUC 0.732 (p = 0.002). <b>Conclusion: </b>Real time elastography could be valuable in diagnosis of fibrosis in NAFLD especially in cases more than F3 score.
文摘[Objectives]To study the effect and mechanism of Gynura divaricate(L.)DC(GD)on non-alcoholic fatty liver disease(NAFLD).[Methods]Male mice were randomly divided into 2 groups:normal group and model group.The mice were fed with high-fat diet(HFD)for 4 weeks to induce NAFLD in the model group.The successfully modeled mice were divided into model group,positive drug group,GD high dose group,and GD low dose group.After 4 weeks of administration,the liver index,serum AST,ALT and blood lipid levels,liver tissue pathological changes,antioxidant enzymes,non-enzymatic antioxidants and inflammatory factors levels were measured in each group,and the expression of NF-κB,Nrf-2 and HO-1 in liver tissues were compared.[Results]GD significantly reduced the serum AST,ALT and blood lipid levels,increased enzyme antioxidant and non-enzymatic antioxidant content,reduced the steatosis and inflammatory infiltration of liver cells,down-regulated the level of inflammatory factors,and inhibited the expression of NF-κB,Nrf-2 and HO-1 in liver tissue.[Conclusions]GD has a protective effect on NAFLD in mice and its mechanism may be related to the regulation of NF-κB and Nrf-2/HO-1 pathways.
文摘Background:We examined the comparative associations between non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated steatotic liver disease(MASLD)definitions with risk of developing chronic kidney disease(CKD)and abnormal albuminuria.Methods:We conducted a cohort study of 214,145 Korean adults with normal kidney function at baseline who underwent liver ultrasonography.Participants were further subdivided into no steatotic liver disease(no-SLD),NAFLD-only,MASLD-only,both NAFLD and MASLD,and SLD not categorized as NAFLD or MASLD groups.Cox proportional hazards models were used to analyze the risk of incident CKD and albuminuria.Results:Compared with either the no-NAFLD or no-MASLD groups,the NAFLD and MASLD groups were associated with a higher risk of incident CKD(NAFLD:adjusted hazard ratio(HR),1.18[95%CI,1.01-1.38];MASLD:adjusted HR,1.21[95%CI,1.04-1.39]).Among the five subgroups,both NAFLD and MASLD group had the strongest association with risk of incident CKD(adjusted HR,1.21[95%CI,1.04-1.42]).The MASLD-only group had the strongest association with incident abnormal albuminuria,with an adjusted HR comparable to that of the both NAFLD and MASLD group(adjusted HR 1.96[95%CI,1.44-2.67]for the MASLD-only,and adjusted HR 1.98[95%CI,1.58-2.49]for the both NAFLD and MASLD group versus the no-SLD group).The NAFLD-only group was not independently associated with risk of CKD or abnormal albuminuria.Conclusions:These findings suggest that MASLD definition identifies individuals at high risk of developing incident CKD or abnormal albuminuria better than NAFLD definition.
文摘Non-alcoholic fatty liver disease(NAFLD)and non-alcoholic steatohepatitis(NASH)are national and global epidemics.The disease is characterized by a spectrum of liver steatosis(fat deposition),inflammation(in NASH)and fibrosis.NAFLD and specifically NASH can lead to cirrhosis,which carry risks of progression to portal hypertension and hepatocellular carcinoma(HCC).NASH is also associated with higher mortality from cardiovascular causes.Most of the data for NAFLD has been obtained from the perspective of developed nations,although the disease is increasing and threatening to reach epidemic proportions across the world.Emerging data is notable for high prevalence of NAFLD in South Asian populations,presumably resulting from a combination of underlying genetic polymorphisms and changes in socio-economic status.It is also notable that an‘Asian Paradox'has been defined for NAFLD based upon the observation of lower than predefined body mass index(BMI),otherwise termed as"lean NAFLD",among this population.Yet,data remains limited in regards to the characteristics of NAFLD/NASH in this population.In this article,we present a review of the literature and discuss the prevalence,associated risk factors and burden of HCC in South Asians with NAFLD.
文摘Importance:Non-alcoholic fatty liver disease(NAFLD)is a rapidly growing cause of chronic liver disease and is becoming a leading cause of hepatocellular carcinoma(HCC)in many developed countries.This presents major challenges for the surveillance,diagnosis and treatment of HCC.Objective:To discuss the clinical challenges faced by clinicians in managing the rising number of NAFLD-HCC cases.Evidence Review:MEDLINE,PubMed and Embase databases were searched using the keywords;NAFLD,HCC,surveillance,hepatectomy,liver transplantation,percutaneous ablation,transarterial chemoembolization(TACE),selective internal radiotherapy treatment(SIRT)and sorafenib.Relevant clinical studies were included.Findings:Current HCC surveillance programmes are inadequate because they only screen for HCC in patients with cirrhosis,whereas in NAFLD a significant proportion of HCC develops in the absence of cirrhosis.Consequently NAFLD patients often present with a more advanced stage of HCC,with a poorer prognosis.NAFLD-HCC patients also tend to be older and to have more co-morbidities compared to HCC of other etiologies.This limits the use of curative treatments such as liver resection and orthotopic liver transplantation(OLT).Evidence suggests that although NAFLD-HCC patients who undergo liver resection or OLT have worse perioperative and short-term outcomes,overall long-term survival is comparable to HCC of other etiologies.This highlights the importance of careful patient selection,pre-habilitation and perioperative planning for NAFLD-HCC patients being considered for surgical treatment.Careful consideration is also important for non-surgical treatments,although the evidence supporting treatment selection is frequently lacking,as these patients tend to be poorly represented in clinical trials.Locoregional therapies such as percutaneous ablation and TACE may be less well tolerated and less effective in NAFLD patients with obesity or diabetes.The tyrosine kinase inhibitor sorafenib may also be less effective.Conclusions and Relevance:This review highlights how international guidelines,for which NAFLD traditionally has made up a small part of the evidence base,may not be appropriate for all NAFLD-HCC patients.Future guidelines need to reflect the changing landscape of HCC,by making specific recommendations for the management of NAFLD-HCC.
基金This work was supported by the Indian Council of Medical Research(ICMR)(59/05/2019/ONLINE/BMS/TRM),SERB(SRG/2019/000398)Wellcome Trust/DBT India Alliance Fellowship(IA/I/16/2/502691)awarded to R.A.Sinha.
文摘The incidence of non-alcoholic fatty liver disease(NAFLD)is rising rapidly across the globe.NAFLD pathogenesis is largely driven by an imbalance in hepatic energy metabolism,and at present,there is no approved drug for its treatment.The liver plays a crucial role in micronutrient metabolism,and deregulation of this micronutrient metabolism may contribute to the pathogenesis of NAFLD.Vitamins regulate several enzymatic processes in the liver,and derangement in vitamin metabolism is believed to play a critical role in NAFLD progression.The anti-oxidant activities of vitamins C and E have been attributed to mitigate hepatocyte injury,and alterations in the serum levels of vitamin D,vitamin B12 and folate have shown a strong correlation with NAFLD severity.This review aims to highlight the role of these vitamins,which represent promising therapeutic targets for the management of NAFLD.
基金This work was supported in part by the USA National Institutes of Health(NIH)grants R01AA021751 and R21AA021450(to X.-M.Yin).
文摘Autophagy is an evolutionarily conserved intracellular degradative function that is important for liver homeostasis.Accumulating evidence suggests that autophagy is deregulated during the progression and development of alcoholic and non-alcoholic liver diseases.Impaired autophagy prevents the clearance of excessive lipid droplets(LDs),damaged mitochondria,and toxic protein aggregates,which can be generated during the progression of various liver diseases,thus contributing to the development of steatosis,injury,steatohepatitis,fibrosis,and tumors.In this review,we look at the status of hepatic autophagy during the pathogenesis of alcoholic and non-alcoholic liver diseases.We also examine the mechanisms of defects in autophagy,and the hepato-protective roles of autophagy in non-alcoholic fatty liver disease(NAFLD)and alcoholic liver disease(ALD),focusing mainly on steatosis and liver injury.Finally,we discuss the therapeutic potential of autophagy modulating agents for the treatment of these two common liver diseases.
文摘Bile acids are a family of atypical steroids generated at the interface of liver-intestinal microbiota acting on a ubiquitously expressed family of membrane and nuclear receptors known as bile acid activated receptors.The two best characterized receptors of this family are the nuclear receptor,farnesoid X re-ceptor(FXR)and the G protein-coupled receptor,G protein-coupled bile acid receptor 1(GPBAR1).FXR and GPBAR1 regulate major aspects of lipid and glucose metabolism,energy balance,autophagy and immunity and have emerged as potential pharmaceutical targets for the treatment of metabolic and inflammatory disorders.Clinical trials in non-alcoholic fatty liver disease(NAFLD),however,have shown that selective FXR agonists cause side effects while their efficacy is partial.Because FXR and GPBAR1 exert additive effects,dual FXR/GPBAR1 ligands have been developed for the treatment of metabolic disorders and are currently advanced to clinical trials.Here,we will review the role of FXR and GPBAR1 agonism in NAFLD and how the two receptors could be exploited to target multiple components of the disease.
基金This work was supported in part by the USA National Institutes of Health(NIH)grants including DK091592 and DK107682 from the National Institute of Diabetes and Digestive and Kidney Diseases and AA024550 from the National Institute on Alcohol Abuse and Alcoholism,by the Showalter Scholar award from Indiana University School of Medicine and Showalter Trust,and by Indiana Clinical and Translational Sciences Institute grant ULITR001108 from the NIH National Center for Advancing Translational Sciences,Clinical and Translational Sciences Award.
文摘Non-alcoholic fatty liver disease(NAFLD)is a chronic progressive liver disorder that begins with simple hepatic steatosis and progresses to non-alcoholic steatohepatitis,fibrosis,cirrhosis,and even liver cancer.As the global prevalence of NAFLD rises,it is increasingly important that we understand its pathogenesis and develop effective therapies for this chronic disease.Forkhead box O(FOXO)transcription factors are key downstream regulators in the insulin/insulin-like growth factor 1(IGF1)signaling pathway,and have been implicated in a range of cellular functions including the regulation of glucose,triglyceride,and cholesterol homeostasis.The role of FOXOs in the modulation of immune response and inflammation is complex,with reports of both pro-and anti-inflammatory effects.FOXOs are reported to protect against hepatic fibrosis by inhibiting proliferation and transdifferentiation of hepatic stellate cells.Mice that are deficient in hepatic FOXOs are more susceptible to non-alcoholic steatohepatitis than wild-type controls.In summary,FOXOs play a critical role in maintaining metabolic and cellular homeostasis in the liver,and dysregulation of FOXOs may be involved in the NAFLD development.
文摘Non-alcoholic fatty liver disease(NAFLD),characterized by the accumulation of excessive intrahepatic fat,is a leading metabolic disorder also considered as the hepatic manifestation of metabolic syndrome(MS).Though more commonly observed in obese individuals and those with metabolic risk factors,it also develops in a considerable number of non-obese individuals as well as participants without having any component of MS.The basic mechanism involved in the development of fatty liver is the imbalance between lipid uptake,synthesis,and metabolism in the liver,normally controlled by several mechanisms to maintain lipid homeostasis.As a complex progressive liver disorder,the NAFLD pathogenesis is multifactorial,and several new pathogenic phenomena were discovered over time.The available literature suggests the role of both genetic and environmental factors and associated metabolic factors;however,the mechanism of progression is not completely understood.In this review,we discuss different pathogenic mechanisms and their interplay to provide an elaborate idea regarding NAFLD development and progression.Better understanding of pathogenic mechanisms will be useful in finding new treatment for patients with NAFLD.
基金This study was supported by the National Natural Science Foundation of China (Grant Nos.32171370 and 11505193),the Natural Science Foundation of Guangdong Province (Grant No.2022A1515010415)the Research Foundation of Guangzhou First People's Hospital (Grant No.KY09040029).
文摘Non-alcoholic fatty liver disease(NAFLD)has become the most common cause of chronic liver disease worldwide,and is closely associated with the increased risk of the prevalence of obesity and diabetes.NAFLD begins with the presence of>5%excessive lipid accumulation in the liver,and potentially de-velops into non-alcoholic steatohepatitis,fibrosis,cirrhosis and hepatocellular carcinoma.Therefore,insight into the pathogenesis of NAFLD is of key importance to its effective treatment.Iron is an essential element in the life of all mammalian organisms.However,the free iron deposition is positively associated with histological severity in NAFLD patients due to the production of reactive oxygen species via the Fenton reaction.Recently,several iron metabolism-targeted therapies,such as phlebotomy,iron chela-tors,nanotherapeutics.and ferroptosis,have shown their potential as a therapeutic option in the treatment of NAFLD and as a clinical strategy to intervene in the progression of NAFLD.Herein,we review the recent overall evidence on iron metabolism and provide the mechanism of hepatic iron overload-induced liver pathologies and the recent advances in iron metabolism-targeted therapeutics in the treatment of NAFLD.
基金National Natural Science Funds for Distinguished Young Scholar of China/International(grant No.81625003)National Science and Technology Major Project of China(grant No.2017ZX10203205)+1 种基金Science Funds for Young Scholar of China(grant No.81702858)Youth Program of Natural Science Foundation of Zhejiang Province(grant No.LQ17H160006).
文摘Background and Objective:Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients who undergo liver transplantation(LT).Whereas there is huge data on NAFLD,little is known about NAFLD in LT.In this review,we aim to explore extrahepatic organs and their potential mechanisms in the development of NAFLD in LT patients and discuss current limitations in preclinical and clinical scenarios with suggestions for future study.Methods:The following keywords,such as NAFLD,NASH,liver transplant,therapy,pathogenesis and biomarkers,were set for literature retrieval.The articles which were published articles in English till 25th June 2020 in PubMed database were included,and there is no limit for the study design type.Key Content and Findings:Following LT,there are significant shifts in the microbiota and farnesoid X receptor may be a potential therapeutic target for NAFLD in LT settings.The roles of probiotics and diet on NALFD remain inconclusive in LT background.Nevertheless,the adipokines and cytokines disorder and local insulin resistance of adipose tissue may contribute to NAFLD process.Bariatric surgeries are promising in controlling de novo and recurrent NAFLD with significant reduction in abdominal adipose tissue,despite the optimal timing is inconclusive in LT cases.Furthermore,circumstantial evidence indicates that miRNA-33a may function as a mediator bridging sarcopenia and NAFLD of post-LT.β-Hydroxy-β-Methyl-Butyrate treatment could improve muscle status in graft recipients and shows protective potential for NAFLD in LT settings.Conclusions:Gut,adipose tissue and muscle are intricately intertwined in promoting NAFLD in LT cases.Further animal studies are needed to deepen our understanding of mechanisms in multi-organ crosstalk.High quality clinical trials are warrant for making guidelines and developing management strategies on NAFLD after LT.
文摘Background:We aimed to evaluate the medium-term efficacy of sleeve gastrectomy(SG)vs.Roux-en-Y gastric bypass(RYGB)on remission of non-alcoholic fatty liver disease(NAFLD)in patients with type 2 diabetes mellitus(T2DM).Methods:We identified severely obese patients[body mass index(BMI)>35 kg/m^(2)]with NAFLD(as defined by the Longitudinal Assessment of Bariatric Surgery Study)and T2DM(as defined by the American Association of Clinical Endocrinologists and the American College of Endocrinology)who underwent SG or RYGB in a single university surgical centre.The cohorts were match-paired and data were analysed after at least 3 years of follow up.The key outcomes measured were:(I)the improvement of liver function tests and NAFLD markers;(II)glycemic control and insulin resistance.Results:Ninety-six patients were investigated;44(45.8%)were women.The mean pre-operative BMI was 45.2 kg/m2 in the SG and 42.0 kg/m^(2) in the RYGB group.SG and RYGB both significantly reduced serum liver enzyme concentrations.NAFLD markers resolved 2 years after SG in all patients.In contrast,only 78%and 80%of patients achieved remission of NAFLD 2 and 3 years after RYBG respectively.Both procedures resulted in comparable rates of remission of T2DM.Conclusions:Bariatric surgery with SG may be preferable to RYGB for obese patients with NAFLD and T2DM based on the rates of remission of markers of these co-morbidities.However,our results need to be confirmed in prospective trials.Understanding the metabolic effects of specific bariatric surgical procedures may facilitate the development of a personalised approach to weight-loss surgery.
基金This study is partially supported by Japan MEXT KAKENHI to T.Takehara(18H02795)and by The Japanese Society of Gastroenterology to H.Hikita.
文摘Macroautophagy(hereafter autophagy)is a catabolic process by which autophagosomes arising from an isolation membrane fuse with lysosomes to degrade components in the cytoplasm.Autophagosomelysosome fusion step is one of the key steps during the process of macroautophagy.The step is extremely complicated and its detailed mechanisms remain unclear.It consists of two phases:first phase is autophagosome migration phase and second phase is fusion of autophagosomes and lysosomes phase.Recently,various molecules have been reported to be involved in each phase.In the first phase,microtubules and actin remodeling mechanism are involved.In the second phase,soluble N-ethylmaleimide-sensitive factor attachment protein receptor(SNARE)proteins,Rab family proteins,phosphoinositide 3-kinase(PI3K)complex and Rubicon are involved.In the present review,we introduce recent findings related to autophagosome-lysosome fusion step and discuss liver diseases possibly associated with autophagosome-lysosome fusion dysfunction.
基金This work was supported by the National Key Research and Development Program of China(2016YFC0903100,2016YFC0903102)the National Natural Science Foundation of China(81522007,81470554,31401011)the Fundamental Research Funds for the Central Universities:Clinical Medicine Plus X-Young Scholars Project of Peking University(PKU2018LCXQ013).
文摘Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease characterized by hepatic steatosis in the absence of other causes,such as chronic alcohol consumption,that cause secondary hepatic fat accumulation.NAFLD has become the most common liver disease worldwide over the past two decades,and the prevalence of NAFLD is 20e30%in Western countries.However,the mechanism of NAFLD re-mains unclear.The gut microbiota plays an important role in the metabolism of the host;in fact,it has been implicated in inflammatory diseases,metabolic syndrome and cardiovascular disease.Accumu-lating evidence has indicated that gut microbiota component changes are linked to human obesity,in-sulin resistance(IR),type 2 diabetes and NAFLD.Here,we provide insight into the role of gut microbiota,especially bile salt hydrolase(BSH)in modulating the bile acid pool and farnesoid X receptor(FXR),which promotes the synthesis of ceramide and contributes to the development of NAFLD.