As a result of the obesity epidemic,Nonalcoholic fatty liver disease(NAFLD)and its complications have increased among millions of people.Consequently,a group of experts recommended changing the term NAFLD to an inclus...As a result of the obesity epidemic,Nonalcoholic fatty liver disease(NAFLD)and its complications have increased among millions of people.Consequently,a group of experts recommended changing the term NAFLD to an inclusive terminology more reflective of the underlying pathogenesis;metabolic-associated fatty liver disease(MAFLD).This new term of MAFLD has its own disease epidemiology and clinical outcomes prompting efforts in studying its differences from NAFLD.This article discusses the rationale behind the nomenclature change,the main differences,and its clinical implications.展开更多
AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review.METHODS: The authors conducted both systematic and spec...AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review.METHODS: The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur.RESULTS: We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148M variant, TM6SF2, particularly the p. E167K variant, and on variants in FTO, LIPA, IFNλ4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine.CONCLUSION: Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management.展开更多
AIM: To study the prevalence and clinical biochemical, blood cell and metabolic features of lean-non-alcoholic fatty liver disease (lean-NAFLD) and its association with other diseases.
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), as conventionally recognized, is a metabolic disorder largely confined to residents of affluent industrialized Western countries. However, obesity and insulin res...BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), as conventionally recognized, is a metabolic disorder largely confined to residents of affluent industrialized Western countries. However, obesity and insulin resistance are not restricted to the West, as witnessed by their increasingly universal distribution. In particular, there has been an upsurge in metabolic syndrome in the Asia-Pacific region, although there are critical differences in the extent of adiposity between Eastern and Western populations. DATA SOURCES: An English-language literature search using PubMed (1999-2007) on obesity, metabolic syndrome and NAFLD, focusing on Asian definitions and Asian studies. RESULTS: NAFLD appears to be of long-standing insulin resistance and likely represents the hepatic manifestation of the metabolic syndrome. With insulin resistance as a common factor, the disease is associated with atherosclerosis and cardiovascular risk. All features of the metabolic syndrome and related events are assessed for practical management of NAFLD, although the criteria for the diagnosis of obesity and central obesity differ across racial groups. CONCLUSIONS: The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension and ultimately metabolic syndrome, puts a very large population at risk of developing NAFLD in the coming decades. The simultaneous identification and appropriate treatment of the components of metabolic syndrome are crucial to reduce hepatic as well as cardiovascular morbidity and mortality.展开更多
Background: Oxidative stress has been implicated in the progression of severe forms of non-alcoholic fatty liver disease(NAFLD). NADPH oxidase produces reactive oxygen species. In the present study, we investigated fo...Background: Oxidative stress has been implicated in the progression of severe forms of non-alcoholic fatty liver disease(NAFLD). NADPH oxidase produces reactive oxygen species. In the present study, we investigated for the first time two single nucleotide polymorphisms(SNPs) in the regulatory region of genes encoding NADPH oxidase 4(NOX4) and p22 phox(CYBA) in NAFLD.Methods: A total of 207 biopsy-proven NAFLD patients [simple steatosis(n = 27); nonalcoholic steatohepatitis(NASH)(n = 180)] were evaluated. Genomic DNA was extracted from peripheral blood cells, and polymorphisms in CYBA(unregistered) and NOX4(rs3017887) were determined by direct sequencing of PCR.Results: Associations of CYBA-675 T/A with high-density lipoprotein(HDL)(TT vs TA vs AA; P < 0.01) and triglycerides(TGL)(TT vs XA; P < 0.01) were observed only in NASH patients. For polymorphisms in the NOX4 gene, NOX4(rs3017887) CA + AA genotypes was significant associated with alanine aminotransferase(ALT)(CA + AA vs CC; P = 0.02). However, there was no association of SNPs in the CYBA and NOX4 genes encoding the NADPH oxidase system proteins and the presence of NASH. Regarding the clinical results, it was observed that the most advanced degrees of fibrosis occurred in patients diagnosed with type 2 diabetes mellitus(66.9% vs 37.5%, P < 0.01) and those who were more obese(32.2 vs 29.0 kg/m2,P < 0.01). In addition, serum glucose and insulin levels increased significantly in the presence of NASH.Conclusions: There were associations between the presence of the allele A in the NOX4 SNP and a higher concentration of ALT in the NAFLD population; between the presence of the AA genotype in the polymorphism of the CYBA-675 T/A CYBA gene and a higher level of TGL and lower HDL in NASH patients. The presence of metabolic syndrome was associated with advanced degrees of fibrosis in NAFLD patients.展开更多
Non-alcoholic fatty liver disease (NAFLD) is currently not a component of the diagnostic criteria for metabolic syndrome (MetS); however, the development of NAFLD has some common mechanisms with the development of Met...Non-alcoholic fatty liver disease (NAFLD) is currently not a component of the diagnostic criteria for metabolic syndrome (MetS); however, the development of NAFLD has some common mechanisms with the development of MetS, as they share the pathophysiologic basis of insulin resistance. It is also recognized that NAFLD is the hepatic manifestation of MetS. To define MetS, the presence of at least three of the proposed criteria is required, and sometimes it is sufficient to have only one laboratory value, modified by diet or drugs, for the classification of MetS. Ultrasonographically-detected NAFLD (US-NAFLD) is more stable, only changing during the middleto long-term. Although controversies over MetS continue, and considering that abdominal ultrasonography for diagnosing NAFLD has high specificity and guidelines to modify the natural course of NAFLD by diet composition or lifestyle have not yet been established, why should we not introduce US-NAFLD as a new criterion to define MetS?展开更多
AIM: To assess the relationship between non-alcoholic fatty liver disease(NAFLD) with metabolic risk factors and brachial ankle pulse wave velocity(ba PWV). METHODS: A total of 8603 subjects(6662 males and 1941 female...AIM: To assess the relationship between non-alcoholic fatty liver disease(NAFLD) with metabolic risk factors and brachial ankle pulse wave velocity(ba PWV). METHODS: A total of 8603 subjects(6662 males and 1941 females) were enrolled during an annual health check-up. Fatty liver was examined using a Philips HD 11 XE multi-function color Doppler diagnostic instrument, and ba PWV was determined using a novel arteriosclerosis detection device. Blood pressure(BP), fasting plasma glucose(FPG), waist circumference( W C), p l a s m a t r i g l y c e r i d e s( TG), h i g h- d e n s i t y lipoprotein(HDL), total cholesterol(TC), low-density lipoprotein(LDL) and uric acid(UA) were measured using standard methods. The relationship between fatty liver with metabolic risk factors and ba PWV was analyzed using regression analysis and the χ2 test. RESULTS: The values and abnormal rates of ba PWV were significantly different between NAFLD patients and non-NAFLD subjects(P < 0.001). In addition, the values of ba PWV were different by gender between NAFLD patients and non-NAFLD subjects. The OR values in females, males, and the entire population were 3.33, 1.67, and 2.13, respectively(P < 0.001). The incidence of high ba PWV increased with increasing degree of NAFLD(levels 0, 1, 2, and 3)(P < 0.001), which was 45.9%, 54.5%, 60.2%, and 71.4% in malesand 27.0%, 49.1%, 55.60%, and 60.0% in females(P < 0.001), respectively. Logistic regression analysis showed that the OR value for ba PWV in the nonmetabolic syndrome group and the metabolic syndrome group was 1.28 vs 1.14(males) and 2.55 vs 0.98(females). The OR values for ba PWV in the non-high-BP and high-BP, non-high-WC and high-WC, non-high-FPG and high-FPG, non-high-TG and high-TG, non-high-HDL and high-HDL, non-high-TC and high-TC, non-high-LDL and high-LDL, non-high-UA and high-UA groups were 3.38 vs 1.19, 3.50 vs 1.44, 2.80 vs 2.30, 3.29 vs 1.88, 3.03 vs 3.28, 3.35 vs 2.70, 3.93 vs 1.66, and 3.20 vs 2.34, respectively, in females(P < 0.001), and were 1.37 vs 1.34, 1.56 vs 1.26, 1.51 vs 1.28, 1.49 vs 1.52, 1.71 vs 1.61, 1.59 vs 1.74, 1.76 vs 1.47, and 1.73 vs 1.54, respectively, in males(P < 0.01). The OR value for ba PWV was still higher than 1.2(1.21 in males and 1.40 in females) after adjustment for the metabolic component(0, 1, 2, 3, 4, 5, 6 and above)(P < 0.01).CONCLUSION: NAFLD is closely correlated with ba PWV, particularly in females. NAFLD has a large impact on ba PWV, no matter whether the metabolic index is increased or not. NAFLD may be a useful indicator for assessing early arteriosclerosis.展开更多
The occurrence of Metabolic Syndrome (MS) represents an independent risk factor for developing cardiovascular disease states in patients suffering from type 2 diabetes mellitus. Moreover, both the size of LDL particle...The occurrence of Metabolic Syndrome (MS) represents an independent risk factor for developing cardiovascular disease states in patients suffering from type 2 diabetes mellitus. Moreover, both the size of LDL particles and liver dysfunction identified as non alcoholic fatty liver disease (NAFLD) represent important biomarkers for the development of cardiometabolic risk in patients with MS. Here we studied the effect of bergamot polyphenolic fraction (BPF) in patients with MS and NAFLD. 107 patients were enrolled at the San Raffaele IRCCS (Rome). All of them showed ultrasonografic evidences of NAFLD and at least three out of five previous identified criteria for the diagnosis of MS. Patients were divided into two groups: one receiving placebo and the second receiving BPF 650 mg twice a day for 120 consecutive days. In the group receiving BPF 650 mg twice a day, a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides alongside with an increase of HDL cholesterol was found. This effect was accompanied by significant reduction of both ultrasonographic and metabolic biomarkers of NAFLD. Moreover, a significant reduction of small dense LDL particles, as detected via proton NMR Spectroscopy, was found after BPF treatment. In conclusion, our data confirm the beneficial effect of bergamot-extract in patients with MS an effect highlighted by significant reduction of small dense LDL particles and by improvement of NAFLD biomarkers. This suggests a potential preventive role of bergamot derivatives in reducing cardiometabolic risk.展开更多
Non-alcoholic fatty liver disease(NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about ...Non-alcoholic fatty liver disease(NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis and advances on diagnosis and treatment.展开更多
AIM:To investigate the effect of alcohol on the metabolic syndrome (MS) and fatty liver in Japanese men and women.METHODS:A cross-sectional study was conducted in a medical health checkup program at a general hospital...AIM:To investigate the effect of alcohol on the metabolic syndrome (MS) and fatty liver in Japanese men and women.METHODS:A cross-sectional study was conducted in a medical health checkup program at a general hospital.This study involved 18 571 Japanese men and women,18-88 years of age,with a mean body mass index of 22.6 kg/m 2.A standardized questionnaire was administered.The total amount of alcohol consumed per week was calculated,and categorized into four grades.Fatty liver was examined by ultrasound modified criteria of the revised National Cholesterol Educa-tion Program Adult Treatment Panel Ⅲ and the new International Diabetes Federation.RESULTS:The prevalence of fatty liver decreased in men and women with light to moderate alcohol consumption,whereas the prevalence of MS was not so changed.The prevalence of fatty liver of any grade in men was lower than that in those with no or minimal alcohol consumption.In women with light to moderate alcohol consumption,prevalence of fatty liver was lower than that in women with no or minimal alcohol consumption.By logistic regression analysis,the odds ratio (OR) for MS in women with light alcohol consumption was decreased to < 1.0,but this change was not clear in men.The OR for fatty liver was clearly < 1.0 in men with any level of alcohol consumption and in women with light to moderate consumption.CONCLUSION:Light to moderate alcohol consumption has a favorable effect for fatty liver,but not for MS in Japanese men and women.展开更多
OBJECTIVE: To review the current state of research in non-alcoholic fatty liver disease (NAFLD). DATA RESOURCES: Searching Medline (1994-2002) and Chinese Medical Journals Index (1998- 2002) for articles on NAFLD. RES...OBJECTIVE: To review the current state of research in non-alcoholic fatty liver disease (NAFLD). DATA RESOURCES: Searching Medline (1994-2002) and Chinese Medical Journals Index (1998- 2002) for articles on NAFLD. RESULTS: NAFLD is a new and challenging field with increasing recognition although its pathogenesis is poorly understood. 'Two hits' hypothesis is still the leading theory guiding current research. CONCLUSIONS: Genetic study is a promising way that might lead to breakthrough in NAFLD research. NAFLD study in China is at an initial stage and there is a long way to go.展开更多
OBJECTIVE To investigate the protective effect and potential mechanism of desmethylbellidifolin(DMB)in chronic alcoholic fatty liver disease.METHODS C57BL/6 mice were randomly divided into five groups.Control,metadoxi...OBJECTIVE To investigate the protective effect and potential mechanism of desmethylbellidifolin(DMB)in chronic alcoholic fatty liver disease.METHODS C57BL/6 mice were randomly divided into five groups.Control,metadoxine and DMB group(high dose and low dose)mice were fed with Lieber-DeCarli liquid diet containing 5%alcohol for six weeks.Pair-fed group mice were fed with a liquid diet containing the same calories.After treatment,serum GOT,GPT,TG and hepatic T-CHO,TG,GSH,GSH-Px,SOD and CAT levels were measured.Ectopic liver lipid deposition was determined by oil red O and hematoxylin-eosin(HE)staining.Lipid metabolism and autophagy related genes expression were determined by real-time PCR and Western blotting.Electron microscope and laser scanning confocal microscope were used to detect autophagosome and autophagy flux.RESULTS DMB treatment markedly reduced serum TG,GOT and GPT levels in alcohol-induced mice,as well as hepatic levels of T-CHO,TG and MDA,while increased the GSH,GSH-Px,SOD and CAT levels in the liver.Oil red O and HE staining showed that the alcohol-induced lipid accumulation and hepatocyte morphology changes were significantly improved by DMB treatment.Mechanistically,the expression of stearoyl-CoA desaturase 1 and fatty acid synthase were significantly decreased,while lipolysis related hormone-sensitive lipase was elevated in mouse liver by DMB treatment.In addition,DMB could inhibit the phosphorylation of Akt and mTORC1,and activate autophagy process by inducing autophagy related genes expression,such as LC3,ATG5 and ATG7.Moreover,treatment with DMB notably increased the number of autolysosome and promote the autophagy flux,which may therefore induce the lipolysis and oxidation of lipids and prevent the alcohol-induced excessive lipid accumulation in the liver.CONCLUSION DMB exerts a protective role in alcoholic fatty liver disease by regulating the Akt-mTORC1 pathway mediated autophagy activation.展开更多
“Non-alcoholic fatty liver disease” is the alarming health risk around the world today. Nearly 1/3 of the world’s population is affected by non-alcoholic fatty liver disease. Many scientists put forward two hit hyp...“Non-alcoholic fatty liver disease” is the alarming health risk around the world today. Nearly 1/3 of the world’s population is affected by non-alcoholic fatty liver disease. Many scientists put forward two hit hypotheses to explain the pathophysiology of non-alcoholic fatty liver disease. With the aid of trials using Biopsy, ultrasound scan and molecular techniques, scientists explained an authentic evidence of non-alcoholic fatty liver disease progression is ultimately because of obesity and its commodities, such as Cardio vascular diseases, Diabetes and Metabolic syndrome. This review mainly focuses on how obesity leads to non-alcoholic fatty liver disease based on statistical analysis of different research studies conducted by the research scientists. In the analysis of 1980-2003, out of 505 individuals, 305 were affected with NAFLD and among them, 64.3% were obese. In the analysis of the period of 1996-2002, out of 550 NAFLD patients, 70.36% were obese. Also in the analysis of 2010-2015 period of time, mostly 90% of the NAFLD patients were obese. It was also revealed that, along with NAFLD and obesity, diabetes and hyperlipidemia also exist as the commodities of obesity. Attention of medical field is towards the treatment and analysis of non-alcoholic fatty liver disease which is expected to be the reason of liver transplant by 2020.展开更多
In the last years new evidence has accumulated on nonalcoholic fatty liver disease(NAFLD)challenging the paradigms that had been holding the scene over the previous 30 years.NAFLD has such an epidemic prevalence as to...In the last years new evidence has accumulated on nonalcoholic fatty liver disease(NAFLD)challenging the paradigms that had been holding the scene over the previous 30 years.NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases.Conversely,focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach.NAFLD,which can be diagnosed with either non-invasive strategies or through liver biopsy,is a pathogenically complex and clinically heterogeneous disease.The existence of metabolic as opposed to genetic-associated disease,notably including"lean NAFLD"has recently been recognized.Moreover,NAFLD is a systemic condition,featuring metabolic,cardiovascular and(hepatic/extrahepatic)cancer risk.Among the clinico-laboratory features of NAFLD we discuss hyperuricemia,insulin resistance,atherosclerosis,gallstones,psoriasis and selected endocrine derangements.NAFLD is a precursor of type 2 diabetes(T2D)and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD.Finally,lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed.In conclusion,this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD,a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations.It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies,intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible.展开更多
Non-alcoholic fatty liver disease(NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among child...Non-alcoholic fatty liver disease(NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance(IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis(NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data(BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR(acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy(the "imperfect" gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention.Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle changes. When morbid obesity prevails, bariatric surgery should be considered.展开更多
Non-alcoholic fatty liver disease(NAFLD)is one of the most prevalent causes of chronic liver disease worldwide.In the last decade it has become the third most common indication for liver transplantation in the United ...Non-alcoholic fatty liver disease(NAFLD)is one of the most prevalent causes of chronic liver disease worldwide.In the last decade it has become the third most common indication for liver transplantation in the United States.Increasing prevalence of NAFLD in the general population also poses a risk to organ donation,as allograft steatosis can be associated with non-function of the graft.Post-transplant survival is comparable between NAFLD and non-NAFLD causes of liver disease,although long term outcomes beyond 10 year are lacking.NAFLD can recur in the allograft frequently although thus far post transplant survival has not been impacted.De novo NAFLD can also occur in the allograft of patients transplanted for non-NAFLD liver disease.Predictors for NAFLD post-transplant recurrence include obesity,hyperlipidemia and diabetes as well as steroid dose after liver transplantation.A polymorphism in PNPLA3 that mediates triglyceride hydrolysis and is linked to pre-transplant risk of obesity and NAFLD has also been linked to post transplant NAFLD risk.Although immunosuppression side effects potentiate obesity and the metabolic syndrome,studies of immunosuppression modulation and trials of specific immunosuppression regimens post-transplant are lacking in this patient population.Based on pre-transplant data,sustained weight loss through diet and exercise is the most effective therapy for NAFLD.Other agents occasionally utilized in NAFLD prior to transplantation include vitamin E and insulin-sensitizing agents.Studies of these therapies are lacking in the post-transplant population.A multimodality and multidisciplinary approach to treatment should be utilized in management of post-transplant NAFLD.展开更多
Emerging data have highlighted the co-existence of nonalcoholic fatty liver disease(NAFLD) and inflammatory bowel disease; both of which are increasingly prevalent disorders with significant complications and impact o...Emerging data have highlighted the co-existence of nonalcoholic fatty liver disease(NAFLD) and inflammatory bowel disease; both of which are increasingly prevalent disorders with significant complications and impact on future health burden. Cross-section observational studies have shown widely variable prevalence rates of co-existing disease,largely due to differences in disease definition and diagnostic tools utilised in the studies. Age,obesity,insulin resistance and other metabolic conditions are common risks factors in observational studies. However,other studies have also suggested a more dominant role of inflammatory bowel disease related factors such as disease activity,duration,steroid use and prior surgical intervention,in the development of NAFLD. This suggests a potentially more complex pathogenesis and relationship between the two diseases which may be contributed by factors including altered intestinal permeability,gut dysbiosis and chronic inflammatory response. Commonly used immunomodulation agents pose potential hepatic toxicity,however no definitive evidence exist linking them to the development of hepatic steatosis,nor are there any data on the impact of therapy and prognosis in patient with co-existent diseases. Further studies are required to assess the impact and establish appropriate screening and management strategies in order to allow early identification,intervention and improve patient outcomes.展开更多
obesity is a global epidemic contributing to an increas-ing prevalence of obesity-related systemic disorders, including nonalcoholic fatty liver disease. The rising prevalence of nonalcoholic steatohepatitis(NASh) wil...obesity is a global epidemic contributing to an increas-ing prevalence of obesity-related systemic disorders, including nonalcoholic fatty liver disease. The rising prevalence of nonalcoholic steatohepatitis(NASh) will in the near future lead to end-stage liver disease in a large cohort of patients with NASh-related cirrhosis and NASh is predicted to be a leading indication for liver transplantation in the coming decade. however, the prevalence of obesity and the progression of hepatic histological damage associated with NASh exhibit sig-nificant ethnic disparities. Despite a significantly lower body mass index and lower rates of obesity compared to other ethnic groups, Asians continue to demonstrate a significant prevalence of hypertension, diabetes, met-abolic syndrome and NASh. Ethnic disparities in central adiposity and visceral fat distribution have been hy-pothesized to contribute to these ethnic disparities. The current review focuses on the epidemiology of obesity and NASh among Asian populations.展开更多
The intestine of the human contains a dynamic population of microbes that have a symbiotic relationship with the host. In addition, there is an effect of the intestinal microbiota on metabolism and digestion. Non-alco...The intestine of the human contains a dynamic population of microbes that have a symbiotic relationship with the host. In addition, there is an effect of the intestinal microbiota on metabolism and digestion. Non-alcoholic fatty liver disease(NAFLD) is a common cause worldwideof hepatic pathology and is thought to be the hepatic manifestation of the metabolic syndrome. In this review we examine the effect of the human microbiome on the components and pathogenesis of the metabolic syndrome. We are now on the threshold of therapeutic interventions on the human microbiome in order to effect human disease including NAFLD.展开更多
BACKGROUND Zinc-α2-glycoprotein 1 (AZGP1) plays important roles in metabolism-related diseases. The underlying molecular mechanisms and therapeutic effects of AZGP1 remain unknown in non-alcoholic fatty liver disease...BACKGROUND Zinc-α2-glycoprotein 1 (AZGP1) plays important roles in metabolism-related diseases. The underlying molecular mechanisms and therapeutic effects of AZGP1 remain unknown in non-alcoholic fatty liver disease (NAFLD). AIM To explore the effects and potential mechanism of AZGP1 on NAFLD in vivo and in vitro. METHODS The expression of AZGP1 and its effects on hepatocytes were examined in NAFLD patients, CCl4-treated mice fed a high fat diet (HFD), and human LO2 cells. RESULTS AZGP1 levels were significantly decreased in liver tissues of NAFLD patients and mice. AZGP1 knockdown was found to activate inflammation;enhance steatogenesis, including promoting lipogenesis [sterol regulatory elementbinding protein (SREBP)-1c, liver X receptor (LXR), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl CoA desaturase 1 (SCD)-1], increasing lipid transport and accumulation [fatty acid transport protein (FATP), carnitine palmitoyl transferase (CPT)-1A, and adiponectin], and reducing fatty acid β-oxidation [farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR)-α];accelerate proliferation;and reverse apoptosis in LO2 cells. AZGP1 overexpression (OV-AZGP1) had the opposite effects. Furthermore, AZGP1 alleviated NAFLD by blocking TNF-α-mediated inflammation and intracellular lipid deposition, promoting proliferation, and inhibiting apoptosis in LO2 cells. Finally, treatment with OV-AZGP1 plasmid dramatically improved liver injury and eliminated liver fat in NAFLD mice. CONCLUSION AZGP1 attenuates NAFLD with regard to ameliorating inflammation, accelerating lipolysis, promoting proliferation, and reducing apoptosis by negatively regulating TNF-α. AZGP1 is suggested to be a novel promising therapeutic target for NAFLD.展开更多
文摘As a result of the obesity epidemic,Nonalcoholic fatty liver disease(NAFLD)and its complications have increased among millions of people.Consequently,a group of experts recommended changing the term NAFLD to an inclusive terminology more reflective of the underlying pathogenesis;metabolic-associated fatty liver disease(MAFLD).This new term of MAFLD has its own disease epidemiology and clinical outcomes prompting efforts in studying its differences from NAFLD.This article discusses the rationale behind the nomenclature change,the main differences,and its clinical implications.
文摘AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review.METHODS: The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur.RESULTS: We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148M variant, TM6SF2, particularly the p. E167K variant, and on variants in FTO, LIPA, IFNλ4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine.CONCLUSION: Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management.
基金Supported by National Natural Science Fund of China,No.81130049,No.8120218412~(th) China Five-Year Scientific and Technical Plan,No.2012BAI02B02
文摘AIM: To study the prevalence and clinical biochemical, blood cell and metabolic features of lean-non-alcoholic fatty liver disease (lean-NAFLD) and its association with other diseases.
文摘BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), as conventionally recognized, is a metabolic disorder largely confined to residents of affluent industrialized Western countries. However, obesity and insulin resistance are not restricted to the West, as witnessed by their increasingly universal distribution. In particular, there has been an upsurge in metabolic syndrome in the Asia-Pacific region, although there are critical differences in the extent of adiposity between Eastern and Western populations. DATA SOURCES: An English-language literature search using PubMed (1999-2007) on obesity, metabolic syndrome and NAFLD, focusing on Asian definitions and Asian studies. RESULTS: NAFLD appears to be of long-standing insulin resistance and likely represents the hepatic manifestation of the metabolic syndrome. With insulin resistance as a common factor, the disease is associated with atherosclerosis and cardiovascular risk. All features of the metabolic syndrome and related events are assessed for practical management of NAFLD, although the criteria for the diagnosis of obesity and central obesity differ across racial groups. CONCLUSIONS: The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension and ultimately metabolic syndrome, puts a very large population at risk of developing NAFLD in the coming decades. The simultaneous identification and appropriate treatment of the components of metabolic syndrome are crucial to reduce hepatic as well as cardiovascular morbidity and mortality.
基金supported by the grant from Coordenacao de Aperfeicoamento de Pessoal de Nível Superior(CAPES)Grant no.Convênio PROAP 190/2014
文摘Background: Oxidative stress has been implicated in the progression of severe forms of non-alcoholic fatty liver disease(NAFLD). NADPH oxidase produces reactive oxygen species. In the present study, we investigated for the first time two single nucleotide polymorphisms(SNPs) in the regulatory region of genes encoding NADPH oxidase 4(NOX4) and p22 phox(CYBA) in NAFLD.Methods: A total of 207 biopsy-proven NAFLD patients [simple steatosis(n = 27); nonalcoholic steatohepatitis(NASH)(n = 180)] were evaluated. Genomic DNA was extracted from peripheral blood cells, and polymorphisms in CYBA(unregistered) and NOX4(rs3017887) were determined by direct sequencing of PCR.Results: Associations of CYBA-675 T/A with high-density lipoprotein(HDL)(TT vs TA vs AA; P < 0.01) and triglycerides(TGL)(TT vs XA; P < 0.01) were observed only in NASH patients. For polymorphisms in the NOX4 gene, NOX4(rs3017887) CA + AA genotypes was significant associated with alanine aminotransferase(ALT)(CA + AA vs CC; P = 0.02). However, there was no association of SNPs in the CYBA and NOX4 genes encoding the NADPH oxidase system proteins and the presence of NASH. Regarding the clinical results, it was observed that the most advanced degrees of fibrosis occurred in patients diagnosed with type 2 diabetes mellitus(66.9% vs 37.5%, P < 0.01) and those who were more obese(32.2 vs 29.0 kg/m2,P < 0.01). In addition, serum glucose and insulin levels increased significantly in the presence of NASH.Conclusions: There were associations between the presence of the allele A in the NOX4 SNP and a higher concentration of ALT in the NAFLD population; between the presence of the AA genotype in the polymorphism of the CYBA-675 T/A CYBA gene and a higher level of TGL and lower HDL in NASH patients. The presence of metabolic syndrome was associated with advanced degrees of fibrosis in NAFLD patients.
文摘Non-alcoholic fatty liver disease (NAFLD) is currently not a component of the diagnostic criteria for metabolic syndrome (MetS); however, the development of NAFLD has some common mechanisms with the development of MetS, as they share the pathophysiologic basis of insulin resistance. It is also recognized that NAFLD is the hepatic manifestation of MetS. To define MetS, the presence of at least three of the proposed criteria is required, and sometimes it is sufficient to have only one laboratory value, modified by diet or drugs, for the classification of MetS. Ultrasonographically-detected NAFLD (US-NAFLD) is more stable, only changing during the middleto long-term. Although controversies over MetS continue, and considering that abdominal ultrasonography for diagnosing NAFLD has high specificity and guidelines to modify the natural course of NAFLD by diet composition or lifestyle have not yet been established, why should we not introduce US-NAFLD as a new criterion to define MetS?
基金Supported by Grants from Public Interest Research and Social Development Program of Zhejiang Province,No.2011C23098Biomedical Science and Technology Foundation of Zhejiang Province,No.2012B20123Education bureau of Zhejiang Province,China,No.Y201223481
文摘AIM: To assess the relationship between non-alcoholic fatty liver disease(NAFLD) with metabolic risk factors and brachial ankle pulse wave velocity(ba PWV). METHODS: A total of 8603 subjects(6662 males and 1941 females) were enrolled during an annual health check-up. Fatty liver was examined using a Philips HD 11 XE multi-function color Doppler diagnostic instrument, and ba PWV was determined using a novel arteriosclerosis detection device. Blood pressure(BP), fasting plasma glucose(FPG), waist circumference( W C), p l a s m a t r i g l y c e r i d e s( TG), h i g h- d e n s i t y lipoprotein(HDL), total cholesterol(TC), low-density lipoprotein(LDL) and uric acid(UA) were measured using standard methods. The relationship between fatty liver with metabolic risk factors and ba PWV was analyzed using regression analysis and the χ2 test. RESULTS: The values and abnormal rates of ba PWV were significantly different between NAFLD patients and non-NAFLD subjects(P < 0.001). In addition, the values of ba PWV were different by gender between NAFLD patients and non-NAFLD subjects. The OR values in females, males, and the entire population were 3.33, 1.67, and 2.13, respectively(P < 0.001). The incidence of high ba PWV increased with increasing degree of NAFLD(levels 0, 1, 2, and 3)(P < 0.001), which was 45.9%, 54.5%, 60.2%, and 71.4% in malesand 27.0%, 49.1%, 55.60%, and 60.0% in females(P < 0.001), respectively. Logistic regression analysis showed that the OR value for ba PWV in the nonmetabolic syndrome group and the metabolic syndrome group was 1.28 vs 1.14(males) and 2.55 vs 0.98(females). The OR values for ba PWV in the non-high-BP and high-BP, non-high-WC and high-WC, non-high-FPG and high-FPG, non-high-TG and high-TG, non-high-HDL and high-HDL, non-high-TC and high-TC, non-high-LDL and high-LDL, non-high-UA and high-UA groups were 3.38 vs 1.19, 3.50 vs 1.44, 2.80 vs 2.30, 3.29 vs 1.88, 3.03 vs 3.28, 3.35 vs 2.70, 3.93 vs 1.66, and 3.20 vs 2.34, respectively, in females(P < 0.001), and were 1.37 vs 1.34, 1.56 vs 1.26, 1.51 vs 1.28, 1.49 vs 1.52, 1.71 vs 1.61, 1.59 vs 1.74, 1.76 vs 1.47, and 1.73 vs 1.54, respectively, in males(P < 0.01). The OR value for ba PWV was still higher than 1.2(1.21 in males and 1.40 in females) after adjustment for the metabolic component(0, 1, 2, 3, 4, 5, 6 and above)(P < 0.01).CONCLUSION: NAFLD is closely correlated with ba PWV, particularly in females. NAFLD has a large impact on ba PWV, no matter whether the metabolic index is increased or not. NAFLD may be a useful indicator for assessing early arteriosclerosis.
文摘The occurrence of Metabolic Syndrome (MS) represents an independent risk factor for developing cardiovascular disease states in patients suffering from type 2 diabetes mellitus. Moreover, both the size of LDL particles and liver dysfunction identified as non alcoholic fatty liver disease (NAFLD) represent important biomarkers for the development of cardiometabolic risk in patients with MS. Here we studied the effect of bergamot polyphenolic fraction (BPF) in patients with MS and NAFLD. 107 patients were enrolled at the San Raffaele IRCCS (Rome). All of them showed ultrasonografic evidences of NAFLD and at least three out of five previous identified criteria for the diagnosis of MS. Patients were divided into two groups: one receiving placebo and the second receiving BPF 650 mg twice a day for 120 consecutive days. In the group receiving BPF 650 mg twice a day, a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides alongside with an increase of HDL cholesterol was found. This effect was accompanied by significant reduction of both ultrasonographic and metabolic biomarkers of NAFLD. Moreover, a significant reduction of small dense LDL particles, as detected via proton NMR Spectroscopy, was found after BPF treatment. In conclusion, our data confirm the beneficial effect of bergamot-extract in patients with MS an effect highlighted by significant reduction of small dense LDL particles and by improvement of NAFLD biomarkers. This suggests a potential preventive role of bergamot derivatives in reducing cardiometabolic risk.
文摘Non-alcoholic fatty liver disease(NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis and advances on diagnosis and treatment.
基金Supported by A grant from the Gifu Medical AssociationYoung Scientists (B) from Japan Society for the Promotion of Science,No.23790791,in part
文摘AIM:To investigate the effect of alcohol on the metabolic syndrome (MS) and fatty liver in Japanese men and women.METHODS:A cross-sectional study was conducted in a medical health checkup program at a general hospital.This study involved 18 571 Japanese men and women,18-88 years of age,with a mean body mass index of 22.6 kg/m 2.A standardized questionnaire was administered.The total amount of alcohol consumed per week was calculated,and categorized into four grades.Fatty liver was examined by ultrasound modified criteria of the revised National Cholesterol Educa-tion Program Adult Treatment Panel Ⅲ and the new International Diabetes Federation.RESULTS:The prevalence of fatty liver decreased in men and women with light to moderate alcohol consumption,whereas the prevalence of MS was not so changed.The prevalence of fatty liver of any grade in men was lower than that in those with no or minimal alcohol consumption.In women with light to moderate alcohol consumption,prevalence of fatty liver was lower than that in women with no or minimal alcohol consumption.By logistic regression analysis,the odds ratio (OR) for MS in women with light alcohol consumption was decreased to < 1.0,but this change was not clear in men.The OR for fatty liver was clearly < 1.0 in men with any level of alcohol consumption and in women with light to moderate consumption.CONCLUSION:Light to moderate alcohol consumption has a favorable effect for fatty liver,but not for MS in Japanese men and women.
文摘OBJECTIVE: To review the current state of research in non-alcoholic fatty liver disease (NAFLD). DATA RESOURCES: Searching Medline (1994-2002) and Chinese Medical Journals Index (1998- 2002) for articles on NAFLD. RESULTS: NAFLD is a new and challenging field with increasing recognition although its pathogenesis is poorly understood. 'Two hits' hypothesis is still the leading theory guiding current research. CONCLUSIONS: Genetic study is a promising way that might lead to breakthrough in NAFLD research. NAFLD study in China is at an initial stage and there is a long way to go.
文摘OBJECTIVE To investigate the protective effect and potential mechanism of desmethylbellidifolin(DMB)in chronic alcoholic fatty liver disease.METHODS C57BL/6 mice were randomly divided into five groups.Control,metadoxine and DMB group(high dose and low dose)mice were fed with Lieber-DeCarli liquid diet containing 5%alcohol for six weeks.Pair-fed group mice were fed with a liquid diet containing the same calories.After treatment,serum GOT,GPT,TG and hepatic T-CHO,TG,GSH,GSH-Px,SOD and CAT levels were measured.Ectopic liver lipid deposition was determined by oil red O and hematoxylin-eosin(HE)staining.Lipid metabolism and autophagy related genes expression were determined by real-time PCR and Western blotting.Electron microscope and laser scanning confocal microscope were used to detect autophagosome and autophagy flux.RESULTS DMB treatment markedly reduced serum TG,GOT and GPT levels in alcohol-induced mice,as well as hepatic levels of T-CHO,TG and MDA,while increased the GSH,GSH-Px,SOD and CAT levels in the liver.Oil red O and HE staining showed that the alcohol-induced lipid accumulation and hepatocyte morphology changes were significantly improved by DMB treatment.Mechanistically,the expression of stearoyl-CoA desaturase 1 and fatty acid synthase were significantly decreased,while lipolysis related hormone-sensitive lipase was elevated in mouse liver by DMB treatment.In addition,DMB could inhibit the phosphorylation of Akt and mTORC1,and activate autophagy process by inducing autophagy related genes expression,such as LC3,ATG5 and ATG7.Moreover,treatment with DMB notably increased the number of autolysosome and promote the autophagy flux,which may therefore induce the lipolysis and oxidation of lipids and prevent the alcohol-induced excessive lipid accumulation in the liver.CONCLUSION DMB exerts a protective role in alcoholic fatty liver disease by regulating the Akt-mTORC1 pathway mediated autophagy activation.
文摘“Non-alcoholic fatty liver disease” is the alarming health risk around the world today. Nearly 1/3 of the world’s population is affected by non-alcoholic fatty liver disease. Many scientists put forward two hit hypotheses to explain the pathophysiology of non-alcoholic fatty liver disease. With the aid of trials using Biopsy, ultrasound scan and molecular techniques, scientists explained an authentic evidence of non-alcoholic fatty liver disease progression is ultimately because of obesity and its commodities, such as Cardio vascular diseases, Diabetes and Metabolic syndrome. This review mainly focuses on how obesity leads to non-alcoholic fatty liver disease based on statistical analysis of different research studies conducted by the research scientists. In the analysis of 1980-2003, out of 505 individuals, 305 were affected with NAFLD and among them, 64.3% were obese. In the analysis of the period of 1996-2002, out of 550 NAFLD patients, 70.36% were obese. Also in the analysis of 2010-2015 period of time, mostly 90% of the NAFLD patients were obese. It was also revealed that, along with NAFLD and obesity, diabetes and hyperlipidemia also exist as the commodities of obesity. Attention of medical field is towards the treatment and analysis of non-alcoholic fatty liver disease which is expected to be the reason of liver transplant by 2020.
文摘In the last years new evidence has accumulated on nonalcoholic fatty liver disease(NAFLD)challenging the paradigms that had been holding the scene over the previous 30 years.NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases.Conversely,focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach.NAFLD,which can be diagnosed with either non-invasive strategies or through liver biopsy,is a pathogenically complex and clinically heterogeneous disease.The existence of metabolic as opposed to genetic-associated disease,notably including"lean NAFLD"has recently been recognized.Moreover,NAFLD is a systemic condition,featuring metabolic,cardiovascular and(hepatic/extrahepatic)cancer risk.Among the clinico-laboratory features of NAFLD we discuss hyperuricemia,insulin resistance,atherosclerosis,gallstones,psoriasis and selected endocrine derangements.NAFLD is a precursor of type 2 diabetes(T2D)and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD.Finally,lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed.In conclusion,this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD,a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations.It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies,intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible.
文摘Non-alcoholic fatty liver disease(NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance(IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis(NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data(BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR(acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy(the "imperfect" gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention.Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle changes. When morbid obesity prevails, bariatric surgery should be considered.
文摘Non-alcoholic fatty liver disease(NAFLD)is one of the most prevalent causes of chronic liver disease worldwide.In the last decade it has become the third most common indication for liver transplantation in the United States.Increasing prevalence of NAFLD in the general population also poses a risk to organ donation,as allograft steatosis can be associated with non-function of the graft.Post-transplant survival is comparable between NAFLD and non-NAFLD causes of liver disease,although long term outcomes beyond 10 year are lacking.NAFLD can recur in the allograft frequently although thus far post transplant survival has not been impacted.De novo NAFLD can also occur in the allograft of patients transplanted for non-NAFLD liver disease.Predictors for NAFLD post-transplant recurrence include obesity,hyperlipidemia and diabetes as well as steroid dose after liver transplantation.A polymorphism in PNPLA3 that mediates triglyceride hydrolysis and is linked to pre-transplant risk of obesity and NAFLD has also been linked to post transplant NAFLD risk.Although immunosuppression side effects potentiate obesity and the metabolic syndrome,studies of immunosuppression modulation and trials of specific immunosuppression regimens post-transplant are lacking in this patient population.Based on pre-transplant data,sustained weight loss through diet and exercise is the most effective therapy for NAFLD.Other agents occasionally utilized in NAFLD prior to transplantation include vitamin E and insulin-sensitizing agents.Studies of these therapies are lacking in the post-transplant population.A multimodality and multidisciplinary approach to treatment should be utilized in management of post-transplant NAFLD.
文摘Emerging data have highlighted the co-existence of nonalcoholic fatty liver disease(NAFLD) and inflammatory bowel disease; both of which are increasingly prevalent disorders with significant complications and impact on future health burden. Cross-section observational studies have shown widely variable prevalence rates of co-existing disease,largely due to differences in disease definition and diagnostic tools utilised in the studies. Age,obesity,insulin resistance and other metabolic conditions are common risks factors in observational studies. However,other studies have also suggested a more dominant role of inflammatory bowel disease related factors such as disease activity,duration,steroid use and prior surgical intervention,in the development of NAFLD. This suggests a potentially more complex pathogenesis and relationship between the two diseases which may be contributed by factors including altered intestinal permeability,gut dysbiosis and chronic inflammatory response. Commonly used immunomodulation agents pose potential hepatic toxicity,however no definitive evidence exist linking them to the development of hepatic steatosis,nor are there any data on the impact of therapy and prognosis in patient with co-existent diseases. Further studies are required to assess the impact and establish appropriate screening and management strategies in order to allow early identification,intervention and improve patient outcomes.
文摘obesity is a global epidemic contributing to an increas-ing prevalence of obesity-related systemic disorders, including nonalcoholic fatty liver disease. The rising prevalence of nonalcoholic steatohepatitis(NASh) will in the near future lead to end-stage liver disease in a large cohort of patients with NASh-related cirrhosis and NASh is predicted to be a leading indication for liver transplantation in the coming decade. however, the prevalence of obesity and the progression of hepatic histological damage associated with NASh exhibit sig-nificant ethnic disparities. Despite a significantly lower body mass index and lower rates of obesity compared to other ethnic groups, Asians continue to demonstrate a significant prevalence of hypertension, diabetes, met-abolic syndrome and NASh. Ethnic disparities in central adiposity and visceral fat distribution have been hy-pothesized to contribute to these ethnic disparities. The current review focuses on the epidemiology of obesity and NASh among Asian populations.
文摘The intestine of the human contains a dynamic population of microbes that have a symbiotic relationship with the host. In addition, there is an effect of the intestinal microbiota on metabolism and digestion. Non-alcoholic fatty liver disease(NAFLD) is a common cause worldwideof hepatic pathology and is thought to be the hepatic manifestation of the metabolic syndrome. In this review we examine the effect of the human microbiome on the components and pathogenesis of the metabolic syndrome. We are now on the threshold of therapeutic interventions on the human microbiome in order to effect human disease including NAFLD.
基金Supported by the National Natural Science Foundation of China,No.81570547 and No.81770597the Development Program of China during the 13~(th) Five-year Plan Period,No.2017ZX10203202003005
文摘BACKGROUND Zinc-α2-glycoprotein 1 (AZGP1) plays important roles in metabolism-related diseases. The underlying molecular mechanisms and therapeutic effects of AZGP1 remain unknown in non-alcoholic fatty liver disease (NAFLD). AIM To explore the effects and potential mechanism of AZGP1 on NAFLD in vivo and in vitro. METHODS The expression of AZGP1 and its effects on hepatocytes were examined in NAFLD patients, CCl4-treated mice fed a high fat diet (HFD), and human LO2 cells. RESULTS AZGP1 levels were significantly decreased in liver tissues of NAFLD patients and mice. AZGP1 knockdown was found to activate inflammation;enhance steatogenesis, including promoting lipogenesis [sterol regulatory elementbinding protein (SREBP)-1c, liver X receptor (LXR), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl CoA desaturase 1 (SCD)-1], increasing lipid transport and accumulation [fatty acid transport protein (FATP), carnitine palmitoyl transferase (CPT)-1A, and adiponectin], and reducing fatty acid β-oxidation [farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR)-α];accelerate proliferation;and reverse apoptosis in LO2 cells. AZGP1 overexpression (OV-AZGP1) had the opposite effects. Furthermore, AZGP1 alleviated NAFLD by blocking TNF-α-mediated inflammation and intracellular lipid deposition, promoting proliferation, and inhibiting apoptosis in LO2 cells. Finally, treatment with OV-AZGP1 plasmid dramatically improved liver injury and eliminated liver fat in NAFLD mice. CONCLUSION AZGP1 attenuates NAFLD with regard to ameliorating inflammation, accelerating lipolysis, promoting proliferation, and reducing apoptosis by negatively regulating TNF-α. AZGP1 is suggested to be a novel promising therapeutic target for NAFLD.