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Sample records for alcoholic fatty liver

  1. Pathophysiology of Non Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Petta, Salvatore; Gastaldelli, Amalia; Rebelos, Eleni; Bugianesi, Elisabetta; Messa, Piergiorgio; Miele, Luca; Svegliati-Baroni, Gianluca; Valenti, Luca; Bonino, Ferruccio

    2016-01-01

    The physiopathology of fatty liver and metabolic syndrome are influenced by diet, life style and inflammation, which have a major impact on the severity of the clinicopathologic outcome of non-alcoholic fatty liver disease. A short comprehensive review is provided on current knowledge of the pathophysiological interplay among major circulating effectors/mediators of fatty liver, such as circulating lipids, mediators released by adipose, muscle and liver tissues and pancreatic and gut hormones in relation to diet, exercise and inflammation. PMID:27973438

  2. [Non-alcoholic fatty liver disease (NAFLD)].

    Science.gov (United States)

    Rau, Monika; Weiss, Johannes; Geier, Andreas

    2015-07-01

    Non-alcoholic fatty liver disease is the most common chronic liver disease in Europe and in the USA with rising prevalence. Patients with a metabolic syndrome (diabetes mellitus, obesity, dyslipidemia) are patients at risk with the highest prevalence for NAFLD. Progression from a non-alcoholic fatty liver (NAFL) to a non-alcoholic steatohepatitis (NASH) occurs in 5-20% of patients with the potential to develop a liver fibrosis/cirrhosis. NASH patients and NAFLD patients with higher fibrosis should be identified because they are at risk of a higher mortality. A specific treatment for NASH is not available at the moment. Therefore, the treatment of risk factors and metabolic syndrome has high priority.

  3. Pediatric Non-alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Uppal, Vikas; Mansoor, Sana; Furuya, Katryn N

    2016-05-01

    Childhood obesity has reached epidemic proportions, and by 2012, more than one third of American children were overweight or obese. As a result, increasingly, children are developing complications of obesity including liver disease. In fact, non-alcoholic fatty liver disease is the most common form of chronic liver disease seen in children today. Recently, there has been a burgeoning literature examining the pathogenesis, genetic markers, and role of the microbiome in this disease. On the clinical front, new modalities of diagnosing hepatic steatosis and hepatic fibrosis are being developed to provide non-invasive methods of surveillance in children. Lastly, the mainstay of treatment of pediatric non-alcoholic fatty liver disease (NAFLD) has been largely through lifestyle interventions, namely, dieting and exercise. Currently, there are a number of clinical trials examining novel lifestyle and drug therapies for NAFLD that are registered with the US National Institutes of Health ClinicalTrials.gov website.

  4. Managing non-alcoholic fatty liver disease

    Science.gov (United States)

    Ngu, Jing Hieng; Goh, George Boon Bee; Poh, Zhongxian; Soetikno, Roy

    2016-01-01

    The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly with the obesity and diabetes mellitus epidemics. It is rapidly becoming the most common cause of liver disease worldwide. NAFLD can progress to serious complications such as cirrhosis, hepatocellular carcinoma and death. Therefore, it is important to recognise this condition so that early intervention can be implemented. Lifestyle modifications and strict control of metabolic risk factors are the mainstay of treatment. As disease progression is slow in the majority of NAFLD patients, most can be managed well by primary care physicians. NAFLD patients with advanced liver fibrosis should be referred to specialist care for further assessment. PMID:27439352

  5. CEUS and Fibroscan in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

    OpenAIRE

    Cocciolillo, Sila; Parruti, Giustino; Marzio, Leonardo

    2014-01-01

    AIM: To determine intra-hepatic blood flow and liver stiffness in patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) using contrast-enhanced ultrasound and fibroscan.

  6. Non-Alcoholic Fatty Liver Disease: From patient to population

    NARCIS (Netherlands)

    E.M. Koehler (Edith)

    2013-01-01

    textabstractNon-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in Western countries, in parallel with epidemics in obesity and type 2 diabetes mellitus. NAFLD comprises a wide range of histological findings, extending from simple steatosis to nonalcoholic stea

  7. [Non-alcoholic fatty liver disease and steatohepatitis].

    Science.gov (United States)

    Pár, Gabriella; Horváth, Gábor; Pár, Alajos

    2013-07-21

    Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, the hepatic manifestations of metabolic syndrome with close association with inzulin resistance and obesity, are the most common liver diseases, affecting up to a third of the population worldwide. They confer increased risk for hepatocellular carcinoma as well as cardiovascular diseases. The review aims to summarize advances in epidemiology, pathogenesis and clinical management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Besides liver biopsy and biomarkers, a novel non-invasive diagnostic tool the called "controlled attenuation parameter" measuring the attenuation of ultrasound generated by the transient elastography transducer, can quantitatively assess the hepatic fat content and differentiate between steatosis grades. At the same time, liver stiffness (fibrosis) can also be evaluated. The authors present their own results obtained with the latter procedure. In non-alcoholic fatty liver disease, the lifestyle intervention, weight loss, diet and exercise supported by cognitive behavioural therapy represent the basis of management. Components of metabolic syndrome (obesity, dyslipidaemia, diabetes and arterial hypertension) have to be treated. Although there is no approved pharmacological therapy for NASH, it seems that long lasting administration of vitamin E in association with high dose ursodeoxycholic acid may be beneficial. In addition, omega-3 polyunsaturated fatty acid substitution can also decrease liver fat, however, the optimal dose is not known yet. Further controlled clinical studies are warranted to establish the real value of any suggested treatment modalities for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, although these are in experimental phase yet.

  8. Is nonalcoholic fatty liver disease an endogenous alcoholic fatty liver disease? - A mechanistic hypothesis.

    Science.gov (United States)

    de Medeiros, Ivanildo Coutinho; de Lima, Josivan Gomes

    2015-08-01

    Nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are so similar that only a detailed history of alcohol intake can distinguish one from the other. Because subjects with NAFLD produce significantly more endogenous ethanol (EE) than controls, some researchers suspected that these similarities are not merely coincidental. For this reason, it was attempted to show that NAFLD is actually an endogenous alcoholic fatty liver disease (EAFLD). However, negligible blood-alcohol concentration (BAC) and the inability of gut microbiota to produce hepatotoxic concentrations of EE rejected this hypothesis. To clarify these conflicting results, we provide a mechanistic framework explaining how NAFLD may be an EAFLD. First of all, the key finding is that ethanol is a prodrug, enabling the idea that AFLD may develop with negligible/absent BAC. Second, extrahepatic acetaldehyde (ACD) alone recapitulates AFLD and is about 330-fold more hepatotoxic than that generated inside the liver. Third, gut microbiota can even produce much larger amounts of EE than those currently considered cirrhotogenic for man. Fourth, an extensive gut-liver axis first-pass metabolism of ethanol prevents the development of significant BAC in NAFLD. Fifth, all genes involved in EE metabolism are upregulated in the livers of patients with nonalcoholic steatohepatitis (NASH). Last, overexpression of the gene encoding alcohol dehydrogenase (ADH) 4 implicates liver exposure to high concentrations of EE. In conclusion, this work provides mechanistic explanation supporting the assumption that NAFLD may indeed be an EAFLD. If validated by further testing, the hypothesis may help develop novel therapeutic and preventive strategies against this ubiquitous condition.

  9. Olive oil consumption and non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Nimer Assy; Faris Nassar; Gattas Nasser; Maria Grosovski

    2009-01-01

    The clinical implications of non-alcoholic fatty liver diseases (NAFLD) derive from their potential to progress to fibrosis and cirrhosis. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride (TG) accumulation. An olive oil-rich diet decreases accumulation of TGs in the liver, improves postprandial TGs, glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver. The principal mechanisms include: decreased nuclear factor-kappaB activation, decreased lowdensity lipoprotein oxidation, and improved insulin resistance by reduced production of inflammatory cytokines (tumor necrosis factor, interleukin-6) and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1. The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids, mainly from olive oil. In this review, we describe the dietary sources of the monounsaturated fatty acids, the composition of olive oil, dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis, clinical and experimental studies that assess the relationship between olive oil and NAFLD, and the mechanism by which olive oil ameliorates fatty liver, and we discuss future perspectives.

  10. Non-alcoholic Fatty Liver Disease (NAFLD)--A Review.

    Science.gov (United States)

    Karim, M F; Al-Mahtab, M; Rahman, S; Debnath, C R

    2015-10-01

    Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in Hepatology clinics. It is closely related to the increased frequency of overweight or obesity. It has recognised association with metabolic syndrome. Central obesity, diabetes mellitus, dyslipidemia are commonest risk factors. Association with hepatitis C genotype 3 is also recognised. NAFLD is an important cause of cyptogenic cirrhosis of liver. It affects all populations and all age groups. Most patients with NAFLD are asymptomatic or vague upper abdominal pain. Liver function tests are mostly normal or mild elevation of aminotranferases. Histological features almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. Two hit hypothesis is prevailing theory for the development of NAFLD. Diagnosis is usually made by imaging tools like ultrasonogram which reveal a bright liver while liver biopsy is gold standard for diagnosis as well as differentiating simple fatty liver and non-alcoholic steatohepatitis (NASH). Prognosis is variable. Simple hepatic steatosis generally has a benign long-term prognosis. However, one to two third of NASH progress to fibrosis or cirrhosis and may have a similar prognosis as cirrhosis from other liver diseases. Treatment is mostly control of underlying disorders and dietary advice, exercise, insulin sensitizers, antioxidants, or cytoprotective agents. The prevalence of NAFLD is increasing. So it needs more research to address this problem.

  11. NON-ALCOHOLIC FATTY LIVER DISEASE AT OUR INSTITUTE

    Directory of Open Access Journals (Sweden)

    Madhavi

    2015-12-01

    Full Text Available INTRODUCTION A Correlation clinical observational hospital based clinical study with 50 patients were undertaken to study the Clinical Profile of incidentally detected Non Alcoholic Fatty Liver Disease. The cases for the study were selected retrospectively who were diagnosed as fatty liver by ultrasound imaging who attended the Department of General Medicine, Government General Hospital Kakinada Rangaraya Medical College. Data has been enumerated for those who fulfilled the inclusion criteria. This study was conducted between January 2013-January 2015. The study has limitations of observer variant dependent diagnostic ultrasound for inclusion in to study. A BMI of>25 kg/m2 taken as definition for obesity for analysis.

  12. Non-alcoholic fatty liver disease in children.

    Science.gov (United States)

    Janczyk, Wojciech; Socha, Piotr

    2012-06-01

    Non-alcoholic fatty liver disease is increasingly prevalent in children, together with obesity. Transaminases, tests for insulin resistance, ultrasonography and MRI are variably used as surrogates markers of steatosis. Other liver diseases, such as Wilson disease, should be excluded. A liver biopsy is performed in selected cases: young children, familial history of severe disease, inconclusive tests for other pathologies, suspected advanced fibrosis, hypertransaminasemia despite weight loss and in clinical trials. Weight reduction, and changes in lifestyle, are the front-line treatment. Drug therapy is under evaluation.

  13. The Natural Course of Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Luis Calzadilla Bertot

    2016-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM. NAFLD exhibits a histological spectrum, ranging from “bland steatosis” to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC, and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death.

  14. The Natural Course of Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Calzadilla Bertot, Luis; Adams, Leon Anton

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from “bland steatosis” to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death. PMID:27213358

  15. Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    McMahan, Rachel H; Porsche, Cara E; Edwards, Michael G; Rosen, Hugo R

    2016-01-01

    Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC) have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1), CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease.

  16. Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Rachel H McMahan

    Full Text Available Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1, CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease.

  17. Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    McMahan, Rachel H.; Porsche, Cara E.; Edwards, Michael G.; Rosen, Hugo R.

    2016-01-01

    Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC) have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1), CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an anti-inflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease. PMID:27454769

  18. Translational approaches: from fatty liver to non-alcoholic steatohepatitis.

    Science.gov (United States)

    Rosso, Natalia; Chavez-Tapia, Norberto C; Tiribelli, Claudio; Bellentani, Stefano

    2014-07-21

    Over the past few decades, non-alcoholic fatty liver disease (NAFLD) has become one, if not the most common, cause of chronic liver disease affecting both adults and children. The increasing number of cases at an early age is the most worrying aspect of this pathology, since it provides more time for its evolution. The spectrum of this disease ranges from liver steatosis to steatohepatitis, fibrosis and in some cases, hepatocellular carcinoma. NAFLD may not always be considered a benign disease and hepatologists must be cautious in the presence of fatty liver. This should prompt the use of the available experimental models to understand better the pathogenesis and to develop a rational treatment of a disease that is dangerously increasing. In spite of the growing efforts, the pathogenesis of NAFLD is still poorly understood. In the present article we review the most relevant hypotheses and evidence that account for the progression of NAFLD to non-alcoholic steatohepatitis (NASH) and fibrosis. The available in vitro and in vivo experimental models of NASH are discussed and revised in terms of their validity in translational studies. These studies must be aimed at the discovery of the still unknown triggers or mediators that induce the progression of hepatic inflammation, apoptosis and fibrosis.

  19. [Non-alcoholic fatty liver disease--new view].

    Science.gov (United States)

    Raszeja-Wyszomirska, Joanna; Lawniczak, Małgorzata; Marlicz, Wojciech; Miezyńska-Kurtycz, Joanna; Milkiewicz, Piotr

    2008-06-01

    Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology--from steatosis alone, through the necroinflammatory disorder of non-alcoholic steatohepatitis (NASH) to cirrhosis and liver cancer. NAFLD/NASH is mostly related with visceral adiposity, obesity, type 2 diabetes melitus (DM t.2) and metabolic syndrome. Pathogenetic concepts of NAFLD include overnutrition and underactivity, insulin resistance (IR) and genetic factor. The prevalence of NAFLD has been estimated to be 17-33% in some countries, NASH may be present in about 1/3 of such cases, while 20-25% of NASH cases could progress to cirrhosis. NAFLD is now recognized as one of the most frequent reason of liver tests elevation without clinical symptoms. Insulin resistance is considering as having a central role in NAFLD pathogenesis. In hepatocytes, IR is related to hyperglycaemia and hyperinsulinaemia, formation of advanced glycation end-products, increased free fatty acids and their metabolites, oxidative stress and altered profiles of adipocytokines. Early stages of fatty liver are clinically silent and include elevation of ALT and GGTP, hyperechogenic liver in USG and/or hepatomegaly. Among clinical symptoms, abdominal discomfort is relatively common as well as chronic fatigue. NAFLD/NASH is not a benign disease, progressive liver biopsy have shown histological progression of fibrosis in 32%, the estimated rate of cirrhosis development is 20% and a liver--related death is 12% over 10 years. No treatment has scientifically proved to ameliorate NAFLD or to avoid its progression. The various therapeutic alternatives are aimed at interfering with the risk factors involved in the pathogenesis of the disorder in order to prevent the progression to end-stage liver disease. The most important therapeutic measure is increasing insulin sensitivity by an attempt to change a lifestyle mostly by dieting and physical activity in order to loose weight. The most used agent is metformin, the others

  20. Noninvasive investigations for non alcoholic fatty liver disease and liver fi brosis

    Institute of Scientific and Technical Information of China (English)

    Carmen; Fierbinteanu-Braticevici; Ion; Dina; Ana; Petrisor; Laura; Tribus; Lucian; Negreanu; Catalin; Carstoiu

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that have insulin resistance in common and are associated with metabolic conditions such as obesity, type 2 diabetes mellitus, and dyslipidemia. NAFLD ranges from simple liver steatosis, which follows a benign course, to nonalcoholic steatohepatitis (NASH), a more severe entity, with necroinflmmation and f ibrosis, which can progress to cryptogenic cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evalu...

  1. Glycosyltransferases and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Zhan, Yu-Tao; Su, Hai-Ying; An, Wei

    2016-02-28

    Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases (GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized.

  2. Nutritional recommendations for patients with non-alcoholic fatty liver diseases

    Institute of Scientific and Technical Information of China (English)

    Nimer Assy

    2011-01-01

    Fatty liver is the most common liver disease worldwide.Patients with fatty liver disease die primarily from cardiovascular disease and not from chronic liver diseases. Hyperglycemia and hyperinsulinemia induce lipogenesis, thereby increasing the hepatic pool of fatty acids. This pool is also increased by increased delivery of fatty acids through the diet or lipolysis in adipose tissue. Nutritional consultations and lifestyle modification are important in the treatment of non-alcoholic fatty liver disease (NAFLD). Among the dietary constituents, combination of vitamin D, vitamin E, and omega-3 fatty acids shows promise for the treatment of NAFLD.

  3. Non-alcoholic fatty liver disease in 2015

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    There is worldwide epidemic of non-alcoholic fatty liverdisease (NAFLD). NAFLD is a clinical entity related tometabolic syndrome. Majority of the patients are obesebut the disease can affect non-obese individuals aswell. Metabolic factors and genetics play important rolesin the pathogenesis of this disorder. The spectrum ofdisorders included in NAFLD are benign macrovesicularhepatic steatosis, non-alcoholic steatohepatitis, hepaticfibrosis, cirrhosis of liver and hepatocellular carcinoma.Although the disease remains asymptomatic mostof the time, it can slowly progress to end stage liverdisease. It will be the most common indication of livertransplantation in the future. It is diagnosed by abnormalliver chemistry, imaging studies and liver biopsy. Asthere are risks of potential complications during liverbiopsy, many patients do not opt for liver biopsy. Thereare some noninvasive scoring systems to find outwhether patients have advanced hepatic fibrosis. At thepresent time, there are limited treatment options whichinclude lifestyle modification to loose weight, vitaminE and thioglitazones. Different therapeutic agents arebeing investigated for optimal management of thisentity. There are some studies done on incretin basedtherapies in patients with NAFLD. Other potential agentswill be silent information regulator protein Sirtuin andantifibrotic monoclonal antibody Simtuzumab againstlysyl oxidase like molecule 2. But they are still in theinvestigational phase.

  4. Differential DNA methylation of genes involved in fibrosis progression in non-alcoholic fatty liver disease and alcoholic liver disease.

    OpenAIRE

    Zeybel, Müjdat; Hardy, Timothy; Robinson, Stuart M.; Fox, Christopher; Anstee, Quentin M.; Ness, Thomas; Masson, Steven; Masson, Steven; French, Jeremy; White, Steve; Mann, Jelena

    2015-01-01

    RESEARCH Open Access Differential DNA methylation of genes involved in fibrosis progression in non-alcoholic fatty liver disease and alcoholic liver disease Müjdat Zeybel1, Timothy Hardy1, Stuart M Robinson1, Christopher Fox1, Quentin M Anstee1, Thomas Ness2, Steven Masson1, John C Mathers1, Jeremy French1, Steve White1 and Jelena Mann1* Abstract Background: Chronic liver injury can lead to the development of liver fibrosis and cirrhosis but only in a minority of patie...

  5. Non-alcoholic fatty liver disease, diet and gut microbiota.

    Science.gov (United States)

    Finelli, Carmine; Tarantino, Giovanni

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a severe liver disease that is increasing in prevalence with the worldwide epidemic of obesity and its related insulin-resistance state. Evidence for the role of the gut microbiota in energy storage and the subsequent development of obesity and some of its related diseases is now well established. More recently, a new role of gut microbiota has emerged in NAFLD. The gut microbiota is involved in gut permeability, low-grade inflammation and immune balance, it modulates dietary choline metabolism, regulates bile acid metabolism and produces endogenous ethanol. All of these factors are molecular mechanisms by which the microbiota can induce NAFLD or its progression toward overt non-alcoholic steatohepatitis. Modification of the gut microbiota composition and/or its biochemical capacity by specific dietary or pharmacological interventions may advantageously affect host metabolism. Large-scale intervention trials, investigating the potential benefit of prebiotics and probiotics in improving cardiometabolic health in high-risk populations, are fervently awaited.

  6. Non-alcoholic fatty liver disease: is iron relevant?

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    O'Brien, Julia; Powell, Lawrie W

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a common and ubiquitous disorder (Bedogni et al. in Hepatology 42:44-52, 2005; Bellentani et al. in Ann Intern Med 132:112-117, 2000) which in a proportion of subjects leads to non-alcoholic steatohepatitis (NASH), advanced liver disease and hepatocellular carcinoma. Although the factors responsible for progression of disease are still uncertain, there is evidence that insulin resistance (IR) is a key operative mechanism (Angulo et al. in Hepatology 30:1356-1362, 1999) and that two stages are involved. The first is the accumulation of triglycerides in hepatocytes followed by a "second hit" which promotes cellular oxidative stress. Several factors may be responsible for the induction of oxidative stress but hepatic iron has been implicated in various studies. The topic is controversial, however, with early studies showing an association between hepatic iron (with or without hemochromatosis gene mutations) and the progression to hepatic fibrosis. Subsequent studies, however, could not confirm an association between the presence of hepatic iron and any of the histological determinants of NAFLD or NASH. Recent studies have reactivated interest in this subject firstly, with the demonstration that hepatic iron loading increases liver cholesterol synthesis with increased lipid deposition in the liver increasing the cellular lipid burden and secondly, a large clinical study has concluded that hepatocellular iron deposition is associated with an increased risk of hepatic fibrosis, thus, strongly supporting the original observation made over a decade ago. An improvement in insulin sensitivity has been demonstrated following phlebotomy therapy but a suitably powered controlled clinical trial is required before this treatment can be implemented.

  7. Iron and non-alcoholic fatty liver disease

    Science.gov (United States)

    Britton, Laurence J; Subramaniam, V Nathan; Crawford, Darrell HG

    2016-01-01

    The mechanisms that promote liver injury in non-alcoholic fatty liver disease (NAFLD) are yet to be thoroughly elucidated. As such, effective treatment strategies are lacking and novel therapeutic targets are required. Iron has been widely implicated in the pathogenesis of NAFLD and represents a potential target for treatment. Relationships between serum ferritin concentration and NAFLD are noted in a majority of studies, although serum ferritin is an imprecise measure of iron loading. Numerous mechanisms for a pathogenic role of hepatic iron in NAFLD have been demonstrated in animal and cell culture models. However, the human data linking hepatic iron to liver injury in NAFLD is less clear, with seemingly conflicting evidence, supporting either an effect of iron in hepatocytes or within reticulo-endothelial cells. Adipose tissue has emerged as a key site at which iron may have a pathogenic role in NAFLD. Evidence for this comes indirectly from studies that have evaluated the role of adipose tissue iron with respect to insulin resistance. Adding further complexity, multiple strands of evidence support an effect of NAFLD itself on iron metabolism. In this review, we summarise the human and basic science data that has evaluated the role of iron in NAFLD pathogenesis. PMID:27688653

  8. [Non-alcoholic fatty liver disease (NAFLD) /non-alcoholic steatohepatitis (NASH) and nutrition].

    Science.gov (United States)

    Ishii, Kiyo-aki; Takamura, Toshinari

    2016-03-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the form of triglycerides in the hepatocytes. A more severe form of NAFLD with necrosis, inflammation, and fibrosis is called non-alcoholic steatohepatitis (NASH). The liver is located in the center of the body's organ network and acts as a coordinator of glucose and lipid metabolism. Therefore, it is important to perform nutritional therapy of patients with NAFLD/NASH while maintaining the energy balance in the entire body.

  9. Orthotopic liver transplantation in non-alcoholic fatty liver disease patients.

    Science.gov (United States)

    Burra, Patrizia; Germani, Giacomo

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a frequent etiology of liver disease in Western Countries and non-alcoholic steato-hepatitis (NASH) is becoming a leading indication for liver transplantation in US, with constant increase overtime. Specific co-morbidities correlated to the presence of obesity and associated with metabolic syndrome should always be ruled out in patients affected by NASH-related end-stage liver disease, who are potential candidates for liver transplantation. Patients transplanted for NAFLD present similar outcomes compared with patients transplanted for other indications. With regards to post-transplant outcomes in obese patients, available data are contradictory, with reported increased mortality only in patients with BMI >40. A new multidisciplinary protocol of liver transplantation and sleeve gastrectomy seems to be effective and safe in obese patients who were not able to lose weight before liver transplantation. However prospective studies are needed. The NASH recurrence rate after liver transplantation ranges between 20-40%, but its variability largely depends on the methodology used for the diagnosis (i.e. liver tests, liver histology or imaging technique).

  10. Elevated endotoxin levels in non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Kumar Sudhesh

    2010-03-01

    Full Text Available Abstract Background Emerging data indicate that gut-derived endotoxin may contribute to low-grade systemic inflammation in insulin resistant states. This study aimed to examine the importance of serum endotoxin and inflammatory markers in non-alcoholic fatty liver disease (NAFLD patients, with and without type 2 diabetes mellitus (T2DM, and to explore the effect of treatment with a lipase inhibitor, Orlistat, on their inflammatory status. Methods Fasted serum from 155 patients with biopsy proven NAFLD and 23 control subjects were analysed for endotoxin, soluble CD14 (sCD14, soluble tumour necrosis factor receptor II (sTNFRII and various metabolic parameters. A subgroup of NAFLD patients were re-assessed 6 and 12 months after treatment with diet alone (n = 6 or diet plus Orlistat (n = 8. Results Endotoxin levels were significantly higher in patients with NAFLD compared with controls (NAFLD: 10.6(7.8, 14.8 EU/mL; controls: 3.9(3.2, 5.2 EU/mL, p Sub-cohort treatment with Orlistat in patients with NAFLD showed significant decreases in ALT (p = 0.006, weight (p = 0.005 and endotoxin (p = 0.004 compared with the NAFLD, non-Orlistat treated control cohort at 6 and 12 months post therapy, respectively. Conclusions Endotoxin levels were considerably increased in NAFLD patients, with marked increases noted in early stage fibrosis compared with controls. These results suggest elevated endotoxin may serve as an early indicator of potential liver damage, perhaps negating the need for invasive liver biopsy. As endotoxin may promote insulin resistance and inflammation, interventions aimed at reducing endotoxin levels in NAFLD patients may prove beneficial in reducing inflammatory burden.

  11. Experimental study of osthole on treatment of hyperlipidemic and alcoholic fatty liver in animals

    Institute of Scientific and Technical Information of China (English)

    Fang Song; Mei-Lin Xie; Lu-Jia Zhu; Ke-Ping Zhang; Jie Xue; Zhen-Lun Gu

    2006-01-01

    AIM: To evaluate the effects of osthole on fatty liver,and investigate the possible mechanism.METHODS: A quail model with hyperlipidemic fatty liver and rat model with alcoholic fatty liver were set up by feeding high fat diet and alcohol, respectively. These experimental animals were then treated with osthole 5-20 mg/kg for 6 wk, respectively. Whereafter, the lipid in serum and hepatic tissue, and coefficient of hepatic weight were measured.RESULTS: After treatment with osthole the levels of serum total cholesterol (TC), triglyceride (TG), lower density lipoprotein-cholesterol (LDL-C), coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased. The activity of superoxide dismutase (SOD) in liver was improved.In alcohol-induced fatty liver rats, the level of malondialdehyde (MDA) in liver was decreased. In high fat-induced fatty liver quails, glutathione peroxidase (GSH-PX) in liver was significantly improved. The histological evaluation of liver specimens demonstrated that the osthole dramatically decreased lipid accumulation.CONCLUSION: These results suggested that osthole had therapeutic effects on both alcohol and high fatinduced fatty liver. The mechanism might be associated with its antioxidation.

  12. [Retinal and carotid changes in non-alcoholic fatty liver disease].

    Science.gov (United States)

    Baloşeanu, Cristina; Rogoveanu, I; Mocanu, Carmen

    2013-01-01

    This article presents the results of a study on 85 patients with non-alcoholic fatty liver disease (NAFLD). We evaluate the retinal vascular changes using retinal photography and carotid vascular changes, by ultrasounds, occured in this group of patients.

  13. Sex Difference in the Association between Serum Homocysteine Level and Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Won, Bo-Youn; Lee, Soo-Hyun; Yun, Sung-Hwan; Kim, Moon-Jong; Park, Kye-Seon; Kim, Young-Sang; Haam, Ji-Hee; Kim, Hyung-Yuk; Kim, Hye-Jung; Park, Ki-Hyun

    2016-01-01

    Background The relationship between serum homocysteine levels and non-alcoholic fatty liver disease is poorly understood. This study aims to investigate the sex-specific relationship between serum homocysteine level and non-alcoholic fatty liver disease in the Korean population. Methods This cross-sectional study included 150 men and 132 women who participated in medical examination programs in Korea from January 2014 to December 2014. Patients were screened for fatty liver by abdominal ultrasound and patient blood samples were collected to measure homocysteine levels. Patients that consumed more than 20 grams of alcohol per day were excluded from this study. Results The homocysteine level (11.56 vs. 8.05 nmol/L) and the proportion of non-alcoholic fatty liver disease (60.7% vs. 19.7%) were significantly higher in men than in women. In men, elevated serum homocysteine levels were associated with a greater prevalence of non-alcoholic fatty liver disease (quartile 1, 43.6%; quartile 4, 80.6%; P=0.01); however, in females, there was no significant association between serum homocysteine levels and the prevalence of non-alcoholic fatty liver disease. In the logistic regression model adjusted for age and potential confounding parameters, the odds ratio for men was significantly higher in the uppermost quartile (model 3, quartile 4: odds ratio, 6.78; 95% confidential interval, 1.67 to 27.56); however, serum homocysteine levels in women were not associated with non-alcoholic fatty liver disease in the crude model or in models adjusted for confounders. Conclusion Serum homocysteine levels were associated with the prevalence of non-alcoholic fatty liver disease in men. PMID:27468343

  14. 'Non-alcoholic fatty liver disease' bij kinderen : een nieuwe complicatie van obesitas

    NARCIS (Netherlands)

    Bocca, Gianni; Stolk, R.P.; Scheenstra, R.; Sauer, P.J.

    2008-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases from simple steatosis to steatohepatitis and cirrhosis with liver failure. In children, NAFLD is mainly associated with obesity and metabolic syndrome, the results of an unhealthy lifestyle. Insulin resistance and

  15. Protective effect of alcohol consumption for fatty liver but not metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    Masahide Hamaguchi; Takao Kojima; Akihiro Ohbora; Noriyuki Takeda; Michiaki Fukui; Takahiro Kato

    2012-01-01

    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/m2. 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 Education 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.

  16. Multicausality in fatty liver disease: Is there a rationale to distinguish between alcoholic and non-alcoholic origin?

    Institute of Scientific and Technical Information of China (English)

    Henry V(o)lzke

    2012-01-01

    Apart from alcohol,there are other factors that may induce complications,which resemble alcohol-related liver disorders.In particular,obesity has been brought into focus as a risk factor for fatty liver disease.The term "non-alcoholic" fatty liver disease is commonly used to distinguish between obesity-related and alcohol-related hepatic steatosis.This review uses the epidemiological perspective to critically assess whether it is necessary and useful to differentiate between alcoholic and "non-alcoholic" fatty liver disease.The MEDLINE database was searched using the PubMed search engine,and a review of reference lists from original research and review articles was conducted.The concept to distinguish between alcoholic and "non-alcoholic" fatty liver disease is mainly based on specific pathomechanisms.This concept has,however,several limitations including the common overlap between alcohol misuse and obesityrelated metabolic disorders and the non-consideration of additional causal factors.Both entities share similar histopathological patterns.Studies demonstrating differences in clinical presentation and outcome are often biased by selection.Risk factor reduction is the main principle of prevention and treatment of both disease forms.In conclusion,alcoholic and "non-alcoholic" fatty liver diseases are one and the same disease caused by different risk factors.A shift from artificial categories to a more general approach to fatty liver disease as a multicausal disorder may optimize preventive strategies and help clinicians more effectively treat patients at the individual level.

  17. Induction of CYP2E1 in non-alcoholic fatty liver diseases.

    Science.gov (United States)

    Aljomah, Ghanim; Baker, Susan S; Liu, Wensheng; Kozielski, Rafal; Oluwole, Janet; Lupu, Benita; Baker, Robert D; Zhu, Lixin

    2015-12-01

    Mounting evidence supports a contribution of endogenous alcohol metabolism in the pathogenesis of non-alcoholic steatohepatitis (NASH). However, it is not known whether the expression of alcohol metabolism genes is altered in the livers of simple steatosis. There is also a current debate on whether fatty acids induce CYP2E1 in fatty livers. In this study, expression of alcohol metabolizing genes in the liver biopsies of simple steatosis patients was examined by quantitative real-time PCR (qRT-PCR), in comparison to biopsies of NASH livers and normal controls. Induction of alcohol metabolizing genes was also examined in cultured HepG2 cells treated with ethanol or oleic acid, by qRT-PCR and Western blots. We found that the mRNA expression of alcohol metabolizing genes including ADH1C, ADH4, ADH6, catalase and CYP2E1 was elevated in the livers of simple steatosis, to similar levels found in NASH livers. In cultured HepG2 cells, ethanol induced the expression of CYP2E1 mRNA and protein, but not ADH4 or ADH6; oleic acid did not induce any of these genes. These results suggest that elevated alcohol metabolism may contribute to the pathogenesis of NAFLD at the stage of simple steatosis as well as more severe stages. Our in vitro data support that CYP2E1 is induced by endogenous alcohol but not by fatty acids.

  18. Novel Action of Carotenoids on Non-Alcoholic Fatty Liver Disease: Macrophage Polarization and Liver Homeostasis

    Science.gov (United States)

    Ni, Yinhua; Zhuge, Fen; Nagashimada, Mayumi; Ota, Tsuguhito

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is considered a hepatic manifestation of metabolic syndrome; however, mechanisms underlying the onset and progression of NAFLD are still unclear. Resident and recruited macrophages are key players in the homeostatic function of the liver and in the progression of NAFLD to NASH. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of macrophages. New NAFLD therapies will likely involve modification of macrophage polarization by restraining M1 activation or driving M2 activation. Carotenoids are potent antioxidants and anti-inflammatory micronutrients that have been used to prevent and treat NAFLD. In addition to their antioxidative action, carotenoids can regulate macrophage polarization and thereby halt the progression of NASH. In this review, we summarize the molecular mechanisms of macrophage polarization and the function of liver macrophages/Kupffer cells in NAFLD. From our review, we propose that dietary carotenoids, such as β-cryptoxanthin and astaxanthin, be used to prevent or treat NAFLD through the regulation of macrophage polarization and liver homeostasis. PMID:27347998

  19. Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Hannele Yki-Järvinen

    2015-11-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD covers a spectrum of disorders ranging from simple steatosis (non-alcoholic fatty liver, NAFL to non-alcoholic steatohepatitis (NASH and cirrhosis. NAFL increases the risk of liver fibrosis. If the liver is fatty due to causes of insulin resistance such as obesity and physical inactivity, it overproduces glucose and triglycerides leading to hyperinsulinemia and a low high-density lipoprotein (HDL cholesterol concentration. The latter features predispose to type 2 diabetes and cardiovascular disease (CVD. Understanding the impact of nutritional modulation of liver fat content and insulin resistance is therefore of interest for prevention and treatment of NAFLD. Hypocaloric, especially low carbohydrate ketogenic diets rapidly decrease liver fat content and associated metabolic abnormalities. However, any type of caloric restriction seems effective long-term. Isocaloric diets containing 16%–23% fat and 57%–65% carbohydrate lower liver fat compared to diets with 43%–55% fat and 27%–38% carbohydrate. Diets rich in saturated (SFA as compared to monounsaturated (MUFA or polyunsaturated (PUFA fatty acids appear particularly harmful as they increase both liver fat and insulin resistance. Overfeeding either saturated fat or carbohydrate increases liver fat content. Vitamin E supplementation decreases liver fat content as well as fibrosis but has no effect on features of insulin resistance.

  20. Amelioration effects of traditional Chinese medicine on alcohol-induced fatty liver

    Institute of Scientific and Technical Information of China (English)

    Hyun-Jeong Kwon; Yun-Young Kim; Se-Young Choung

    2005-01-01

    AIM: To examine the effects of traditional Chinese medicine (TCM) on alcohol-induced fatty liver in rats. TCM consists of Astragalus membranaceus, Morus alba, Crataegus pinnatifida,Alisma orientale, Salvia miltiorrhiza, and Pueraria lobata.METHODS: The rats were separated randomly into five groups. One (the CD group) was fed a control diet for 10 wk, another (the ED group) fed an ethanol-containing isocaloric liquid diet for 10 wk, and the last three (the TCM group) were fed an ethanol-containing isocaloric liquid TCM2000, respectively) weekly during the last 4 wk.RESULTS: ED group developed fatty liver according to lipid profile and liver histological findings. Compared with the control group, liver/body weight, serum triglyceride (TG) and total cholesterol (TC), liver TG and TC, serum alanine aminotransferase (ALT) and aspartic aminotransferase (AST) significantly increased in the ED group.Whereas, in the rats administered with TCM, liver/body weight, serum TG and TC, liver TG and TC, serum ALT and AST were significantly decreased, and the degree of hepatic lipid droplets was markedly improved compared with those in the ED group.CONCLUSION: TCM treatment causes significant reduction in alcohol-induced lipid hepatic accumulation,reversing fatty liver and liver damage, and can be usedas a remedy for alcoholic fatty liver.

  1. Peran Antioksidan pada Non Alcoholic Fatty Liver Disease (NAFLD

    Directory of Open Access Journals (Sweden)

    Yusri Diane Jurnalis

    2014-01-01

    Full Text Available AbstrakNonalcoholic Fatty Liver Disease (NAFLD merupakan penyebab tersering penyakit hati kronik pada anak dan remaja diseluruh dunia. NAFLD berhubungan dengan obesitas, diabetes melitus tipe 2 dan sindrom metabolik. Resistensi insulin memegang peranan penting dalam patogenesis molecular terjadinya NAFLD. Ketidakseimbangan prooksidan dan antioksidan pada sel hepatosis menentukan progresifitas penyakit ini. Sebagai antioksidan telah dilakukan penelitian mengenai efek antioksidan vitamin E, vitamin C, betaine, N-asetil sistein, probucol dan silymarin. Antioksidan tersebut memperlihatkan perbaikan fungsi hepar dan gambaran histopatologis.Kata kunci: Arial 9 NAFLD, resistensi insulin, antioksidanAbstractNonalcoholic fatty liver disease (NAFLD is the most common cause of liver disease in pediatric and adolescent population. NAFLD related with obesity, type 2 diabetes mellitus and metabolic syndrome. Insulin resistance and oxidative stress have important role in molecular pathogenesis of NAFLD. Prooxidant and antioxidant factor in hepatosit can determine progressivity of liver disease. As antioxidant agent for treatment NAFLD have been studied effect of vitamin E, vitamin C, betaine, N-acetyl cystein, probucol and sylimarin. They have been shown improvement of liver function test and histopathologycal feature.Keywords:NAFLD, insulin resistance, antioxidant

  2. The Potential of Flavonoids in the Treatment of Non-alcoholic Fatty Liver Disease

    NARCIS (Netherlands)

    van de Wier, B.; Koek, Ger H.; Bast, Aalt; Haenen, Guido R.M.

    2015-01-01

    The contemporary pathophysiological model of non-alcoholic fatty liver disease (NAFLD) consists of multiple parallel pathways with a dynamic cross talk that cumulate in steatosis and inflammation and ultimately fibrosis, cirrhosis, liver failure and hepatocellular carcinoma. So far, no pharmacologic

  3. Management of non-alcoholic fatty liver disease in 2015

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    There is no single pharmacologic therapy that hasbeen approved to treat nonalcoholic fatty liver diseasein the general population. The backbone of therapycurrently includes intensive lifestyle modification withestablished targets for diet and weight loss. The useof unsweetened, unfiltered coffee along with limitinghigh fructose corn syrup have emerged as beneficialdietary recommendations. The use of empiric oralhypoglycemic agents and vitamin E, however, has notbeen widely accepted. Developing bariatric surgicaltechniques are promising, but additional studies withlong-term follow up are needed before it can be widelyrecommended. Finally, liver transplantation is an increasinglyfrequent consideration once complications of endstagedisease have developed. The future treatmentof those with nonalcoholic fatty liver disease will likelyinvolve a personalized approach. The importance of thegut microbiome in mediating hepatocyte inflammationand intestinal permeability is emerging and may offeravenues for novel treatment. The study of anti-fibroticagents such as pentoxifylline and FXR agonists holdpromise and new pathways, such as hepatocyte cannabinoidreceptor antagonists are being studied. Withthe incidence of obesity and the metabolic syndromeincreasing throughout the developed world, the futurewill continue to focus on finding novel agents and newapplications of existing therapies to help prevent andto mediate the progression of nonalcoholic fatty liverdisease.

  4. Alcoholic fatty liver in rats: Role of fat and ethanol intake

    Energy Technology Data Exchange (ETDEWEB)

    Sankaran, H.; Deveney, C.W. (VA Medical Centers, Portland, OR (United States)); Larkin, E.C.; Rao, G.A. (VA Medical Centers, Martinez, CA (United States))

    1991-03-11

    The claim that high intake of both ethanol and fat is essential to induce fatty liver and high blood alcohol levels (BAL) was tested. Two groups of rats were fed liquid diets containing 26% and 36% of calories as ethanol respectively. After 4 weeks, all rats were bled for BAL and some were sacrificed to obtain liver morphology. Remaining rats in Group 1 (26% ethanol) were switched to 36% ethanol diet and Group 2 (36% ethanol) to 26% ethanol diet. All rats were sacrificed after 4 weeks to obtain blood for BAL and liver morphology. The results indicate that high ethanol intake and high fat ingestion is not the criterion for induction of fatty liver. Inadequate ingestion of macronutrients plays a major role in alcoholic fatty liver and BAL.

  5. Protection effect of trigonelline on liver of rats with non-alcoholic fatty liver diseases

    Institute of Scientific and Technical Information of China (English)

    Dong-Fang Zhang; Fan Zhang; Jin Zhang; Rui-Ming Zhang; Ran Li

    2015-01-01

    Objective:To study the effect of trigonelline on the change of indicators of serum transaminase, lipoprotein and liver lipid of model rats with non-alcoholic fatty liver diseases and on the expression level of Bcl-2 and Bax proteins.Methods:A total of 45 SD rats were randomly divided into Fthe control group, model group and trigonelline intervention group. Rats in the control group were fed with the common diet, while rats in the model group and intervention group were fed with the high fat diet. 8 weeks later, the intervention group received the intragastric administration of trigonellin e (with the dosage of 40 mg/kg/d) for 8 weeks; while control group and model group received the intragastric administration of saline with the equal dosage. Blood was taken from the abdominal aorta of rats 8 weeks later, detecting the level of a series of indicators of ALT, AST, TG, TC, HDL-C and LDL-C in the serum. After the rats were sacrificed, detect the indicators of TG, TC, SOD and MDA in the liver tissue of rats, as well as the expression of Bcl-2 and Bax in the liver tissue.Results: Results of histopathologic examination showed that the damage degree of liver for rats in the trigonellineintervention group was smaller than the one in the model group, with significantly reduced hepatic steatosis and the partially visible hepatic lobule. The levels of ALT, AST, TC and LDL-C in the serum of rats in the trigonelline group were significantly reduced, while the change in the levels of TG and HDL-C was not significantly different. The levels of TG, TC and MDA in the liver tissues were significantly decreased, while the level of SOD significantly increased; the expression of Bcl-2 protein in the liver tissues of rats in the trigonelline intervention group was significantly increased, while the expression of Bax protein significantly decreased.Conclusions: The trigonelline contributes to the therapeutic effect of non-alcoholic fatty liver diseases. It can also increase the

  6. Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids

    DEFF Research Database (Denmark)

    Orešic, Matej; Hyötyläinen, Tuulia; Kotronen, Anna

    2013-01-01

    We examined whether analysis of lipids by ultra-performance liquid chromatography (UPLC) coupled to MS allows the development of a laboratory test for non-alcoholic fatty-liver disease (NAFLD), and how a lipid-profile biomarker compares with the prediction of NAFLD and liver-fat content based...

  7. Non-alcoholic fatty liver disease: a new epidemic in children.

    Science.gov (United States)

    Ciocca, Mirta; Ramonet, Margarita; Álvarez, Fernando

    2016-12-01

    Non-alcoholic fatty liver disease is considered one of the most common causes of liver disease in adults and children, consistent with the increased prevalence of obesity in both populations worldwide. It is a multifactorial condition involving a broad spectrum of liver diseases than range from simple steatosis to steatohepatitis, and characterized by histological findings of inflammation and fibrosis. Its pathogenesis and progression are not fully understood yet, and a more complete understanding of liver disease may aid in developing new therapies and noninvasive diagnostic tools. Liver biopsy remains the gold standard for disease staging. Although lifestyle and diet modifications are the keys in non-alcoholic fatty liver disease treatment, the development of new drugs may be promising for patients failing first-line therapy.

  8. Gut-liver axis and probiotics: their role in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Paolella, Giulia; Mandato, Claudia; Pierri, Luca; Poeta, Marco; Di Stasi, Martina; Vajro, Pietro

    2014-11-14

    The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a "low bacterial richness" may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier ("leaky gut"), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.

  9. Diagnosis and classification of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: Current concepts and remaining challenges.

    Science.gov (United States)

    Hashimoto, Etsuko; Tokushige, Katsutoshi; Ludwig, Jurgen

    2015-01-01

    The high prevalence of non-alcoholic fatty liver disease (NAFLD) has made the condition an important public health issue. Two clinical entities are manifestations of NAFLD, namely, non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). The former tends to be benign and non-progressive while the latter can progress to cirrhosis, which in rare cases gives rise to hepatocellular carcinoma. The diagnosis of NAFLD is based on: (i) a history of no or limited daily alcohol intake (<20 g for women and <30 g for men); (ii) presence of hepatic steatosis by imaging or by histology; and (iii) exclusion of other liver diseases. NAFL is defined histologically by the presence of bland, primarily macrovesicular, hepatocellular fatty change, while NASH features fatty change with inflammation and evidence of hepatocyte injury, such as ballooning degeneration. Presence of fibrosis is a sign of chronicity. Thus, the diagnosis of NAFL/NASH rests on clinicopathological criteria; it always requires both clinical and biopsy-based information. NAFLD could be both the result and the cause of metabolic syndrome, with a vicious cycle operating between these conditions. Remaining challenges are: (i) the lack of a clear threshold alcohol intake for defining "non-alcoholic"; (ii) a lacking consensus for the classification of fatty liver disease; and (iii) absence of a histological definition of NASH, which currently remains the gold standard for the diagnosis. Further challenges include the overlap of the criteria for NAFLD and alcoholic liver disease as many obese individuals also consume considerable volumes of alcohol.

  10. NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Vikram, E-mail: prasadvm@ucmail.uc.edu [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Chirra, Shivani [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Kohli, Rohit [Department of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH 45267 (United States); Shull, Gary E. [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States)

    2014-07-25

    Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na{sup +}/H{sup +} exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors.

  11. WJH 6th Anniversary Special Issues(7): Nonalcoholic fatty liver disease Pathogenesis and therapeutic approaches for non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Hye-jin; Yoon; Bong; Soo; Cha

    2014-01-01

    Non-alcoholic fatty liver disease affects approximately one-third of the population worldwide, and its incidence continues to increase with the increasing prevalence of other metabolic disorders such as type 2 diabetes. As non-alcoholic fatty liver disease can progress to liver cirrhosis, its treatment is attracting greater attention. The pathogenesis of non-alcoholic fatty liver disease is closely associated with insulin resistance and dyslipidemia, especially hypertriglyceridemia. Increased serum levels of free fatty acid and glucose can cause oxidative stress in the liver and peripheral tissue, leading to ectopic fat accumulation, especially in the liver. In this review, we summarize the mechanism underlying the progression of hepatic steatosis to steatohepatitis and cirrhosis. We also discuss established drugs that are already being used to treat non-alcoholic fatty liver disease, in addition to newly discovered agents, with respect to their mechanisms of drug action, focusing mainly on hepatic insulin resistance. As well, we review clinical data that demonstrate the efficacy of these drugs, together with improvements in biochemical or histological parameters.

  12. Non-alcoholic fatty liver disease is associated with cardiovascular disease risk markers

    NARCIS (Netherlands)

    Edens, M. A.; Kuipers, F.; Stolk, R. P.

    2009-01-01

    Recognition of the link between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) has boosted research in this area. The main objective of this paper is to review the literature on NAFLD in the context of CVD, focussing on underlying mechanisms and treatment. Besides excessi

  13. Phenotyping the effect of diet on non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Wit, de N.J.W.; Afman, L.A.; Mensink, M.R.; Muller, M.R.

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with the growing incidence of metabolic syndrome. Diet is an important contributor to the pathogenesis of NAFLD. In this review, we focused on recent publications reporting on the effect of macro- and micronutrients on development and progressi

  14. Bioinformatics-Driven Identification and Examination of Candidate Genes for Non-Alcoholic Fatty Liver Disease

    DEFF Research Database (Denmark)

    Banasik, Karina; Justesen, Johanne M.; Hornbak, Malene

    2011-01-01

    Objective: Candidate genes for non-alcoholic fatty liver disease (NAFLD) identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes. Research Design and Methods: By integrating public database text mining, trans-organism protein...

  15. Naturally Occurring Stilbenoid TSG Reverses Non-Alcoholic Fatty Liver Diseases via Gut-Liver Axis.

    Directory of Open Access Journals (Sweden)

    Pei Lin

    Full Text Available The gut-liver axis is largely involved in the development of non-alcoholic fatty liver disease (NAFLD. We investigated whether 2, 3, 5, 4'-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG could reverse NAFLD induced by a high-fat diet (HFD and whether it did so via the gut-liver axis. Results showed that TSG could reduce the accumulation of FFA and it did so by reducing the expression of L-FABP and FATP4. TSG regulated gut microbiota balanced and increased the protein expression of ZO-1 and occludin, which could improve the function of the intestinal mucosal barrier and reduce serum LPS content by about 25%. TSG reduced TL4 levels by 56% and NF-κB expression by 23% relative to the NAFLD model group. This suggests that prevention of NAFLD by TSG in HFD-fed rats is mediated by modulation of the gut microbiota and TLR4/NF-κB pathway, which may alleviate chronic low-grade inflammation by reducing the exogenous antigen load on the host.

  16. Controversy in the diagnosis of pediatric non-alcoholic fatty liver disease

    OpenAIRE

    Marzuillo, Pierluigi; Grandone, Anna; Perrone, Laura; Miraglia del Giudice, Emanuele

    2015-01-01

    In the last years childhood obesity has reached epidemic diffusion with about 200 million school-age children worldwide being overweight or obese. Simultaneously, also the prevalence of obesity comorbidities has been increased and the non-alcoholic fatty liver disease (NAFLD) has become the most common form of liver disease in childhood. Also if there are some not-invasive diagnostic possibilities, the diagnostic gold standard is represented by hepatic biopsy giving to the clinicians the poss...

  17. Cardiovascular disease risk factors in patients with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Novaković Tatjana

    2013-01-01

    Full Text Available Introduction. Clinical, epidemiological and biochemical studies strongly support the concept that the non-alcoholic fatty liver disease is a hepatic manifestation of the metabolic syndrome. Insulin resistance is a common factor connecting obesity, diabetes, hypertension and dyslipidemia with fatty liver and the progression of hepatic disease to steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. Since identification of cardiovascular risk factors is the first step in their prevention, the aim of this study was to analyze the prevalence of some risk factors in patients with fatty liver. Material and Methods. The study included 130 patients who met metabolic syndrome criteria; their demographic and anthropometric characteristics were analyzed and some clinical characteristics were determined, such as smoking habit, arterial pressure and alcohol intake. Routine biochemical analyses were carried out by a standard laboratory procedure. Hepatic steatosis was detected by the abdominal ultrasound. Modified criteria of the National Cholesterol Education Program Adult Treatment Panel III were used to describe the metabolic syndrome. Results. The study group consisted of 72 subjects (55.38%, who had been found by ultrasound to have fatty liver, whereas the control group included 58 respondents (44.62% without pathological ultrasound findings. Differences in the number of fatty liver were highly statistically significant between the groups. The values of body mass index (33.56±6.05 vs 30.56±4.23 kg/m2; p = 0.001, glucose (6.23±0.95 vs 5.76±0.88 mmol/l; p<0.01 and cholesterol (6.66±1.30 vs 6.23±0.95; p <0.05 were significantly higher in the patients with fatty liver than in those without fatty liver. Conclusion. Our results indicate that the patients from the study group had a high percentage of cardiovascular risk factors.

  18. Efficacy of Qianggan capsule in treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia

    Institute of Scientific and Technical Information of China (English)

    Zhi-Jun He; Meng-Xian Wang; Min-Man Ning

    2016-01-01

    Objective:To observe the clinical effects of Qianggan capsule and silibinin capsule in the treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia. Methods:A total of 112 patients with non-alcoholic fatty liver disease were included in the study and divided into the control group (n=50) and the observation group (n=62). The patients in the control group were given silibinin capsule, while the patients in the observation group were given Qianggan capsule. The patients in the two groups were treated for 24 weeks. The liver/spleen CT was performed before and after treatment. BMI was measured. The liver function, serum lipid, and leptin were detected. Results:TG, LDL-C, BMI, and liver/spleen CT ratio in the observation group were significantly reduced when compared with the control group. The levels of HDL-C and adiponectin in the observation group were significantly elevated when compared with the control group. The differences of ALT, GGT, and AST after treatment between the two groups were not statistically significant. Conclusions:Qianggan capsule and silibinin capsule has an accurate efficacy and high safety in the treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia.

  19. [Role of the endocrine system in the pathogenesis of non-alcoholic fatty liver disease].

    Science.gov (United States)

    Hagymási, Krisztina; Reismann, Péter; Rácz, Károly; Tulassay, Zsolt

    2009-11-29

    The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing's syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.

  20. Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Matteo Nicola Dario Di Minno; Anna Russolillo; Roberta Lupoli; Pasquale Ambrosino; Alessandro Di Minno; Giovanni Tarantino

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) has been recognized as a major health burden.It is the most important cause of chronic liver disease and a major independent cardiovascular risk factor.Lacking a definite treatment for NAFLD,a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches.In this review,major literature data about the use of omega-3 polyunsaturated fatty acids (n-3 PUFAs) as a potential treatment of NAFLD have been described.n-3 PUFAs,besides having a beneficial impact on most of the cardio-metabolic risk factors (hypertension,hyperlipidemia,endothelial dysfunction and atherosclerosis) by regulating gene transcription factors [i.e.,peroxisome proliferator-activated receptor (PPAR)α,PPARγ,sterol regulatory element-binding protein-1,carbohydrate responsive element-binding protein],impacts both lipid metabolism and on insulin sensitivity.In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production,n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules (tumor necrosis factor-α and interleukin-6) and of oxygen reactive species.Further strengthening the results of the in vitro studies,both animal models and human intervention trials,showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory parameters and imaging measurements.Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans,well-designed randomized controlled trials of adequate size and duration,with histological endpoints,are needed to assess the long-term safety and efficacy of PUFA,as well as other therapies,for the treatment of NAFLD and non-alcoholic steatohepatitis patients.It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources (fish oil,flaxseeds,olive oil) which are typical foods

  1. Protective Effects of Korean Red Ginseng against Alcohol-Induced Fatty Liver in Rats

    Directory of Open Access Journals (Sweden)

    Hyo Jin Lee

    2015-06-01

    Full Text Available The present study tested the hypothesis that Korean red ginseng (KRG provides a protective effect against alcoholic fatty liver. Male Sprague-Dawley rats were divided into four groups and fed a modified Lieber-DeCarli diet containing 5% (w/v alcohol or an isocaloric amount of dextrin-maltose for the controls for 6 weeks: normal control (CON, alcohol control (ET, and ET treated with 125 or 250 mg/kg body weight/day of KRG (RGL or RGH, respectively. Compared with the CON group, the ET group exhibited a significant increase in triglycerides, total cholesterol and the presence of lipid droplets in the liver, and a decrease in fat mass, which were all attenuated by KRG supplementation in adose-dependent manner. The mitigation was accompanied by AMP-activated protein kinase (AMPK signaling pathways in the liver and adipose tissue. In addition, suppression in the alcohol-induced changes of adipose adipokine mRNA expression was also observed in KRG supplementation group. These findings suggest that KRG may have the potential to ameliorate alcoholic fatty liver by suppressing inappropriate lysis of adipose tissue and preventing unnecessary de novo lipogenesis in the liver, which are mediated by AMPK signaling pathways. A mechanism for an interplay between the two organs is still needed to be examined with further assays.

  2. Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of non-alcoholic fatty liver disease

    Science.gov (United States)

    Metabolic syndrome is often accompanied by development of hepatic steatosis and less frequently by nonalcoholic fatty liver disease (NAFLD) leading to nonalcoholic steatohepatitis (NASH). Replacement of corn oil with medium chain triacylglycerols (MCT) in the diets of alcohol-fed rats has been show...

  3. GLP-1 Receptor Agonist and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Jinmi Lee

    2012-08-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD, one of the most common liver diseases, is caused by the disruption of hepatic lipid homeostasis. It is associated with insulin resistance as seen in type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1 is an incretin that increases insulin sensitivity and aids glucose metabolism. In recent in vivo and in vitro studies, GLP-1 presents a novel therapeutic approach against NAFLD by increasing fatty acid oxidation, decreasing lipogenesis, and improving hepatic glucose metabolism. In this report, we provide an overview of the role and mechanism of GLP-1 in relieving NAFLD.

  4. The benefits of exercise for patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Keating, Shelley E; George, Jacob; Johnson, Nathan A

    2015-01-01

    As exercise is now an established therapy for the management of non-alcoholic fatty liver disease (NAFLD), recent investigations have sought to identify the optimal dose (type, intensity and amount) of exercise for hepatic benefit. Here, the authors discuss the following: the role of aerobic exercise for the modulation of hepatic steatosis; the limited evidence for the role of resistance training in reducing liver fat; the lack of evidence from clinical trials on the role of exercise in non-alcoholic steatohepatitis; and the benefits of exercise for patients with NAFLD, beyond steatosis. Based on current evidence, the authors provide recommendations for exercise prescription for patients with NAFLD.

  5. Non-alcoholic fatty liver disease: is bariatric surgery the answer?

    Science.gov (United States)

    Pillai, Anjana A; Rinella, Mary E

    2009-11-01

    As the worldwide obesity epidemic continues to increase, the prevalence of non-alcoholic fatty liver disease (NAFLD) and specifically non-alcoholic steatohepatitis (NASH) will become increasingly prominent. NASH will surpass chronic hepatitis C infection as the primary indication for orthotopic liver transplantation in the near future. With the evolution of surgical techniques, bariatric surgery is currently recognized as the most effective method for achieving sustained weight loss and reversing numerous comorbidities in severely obese individuals. This review focuses on the potential risks and benefits of bariatric surgery in subjects with NAFLD and explores its role in the management of NASH in the obese patient.

  6. Non-Alcoholic Fatty Liver Disease in Children: Focus on Nutritional Interventions

    Directory of Open Access Journals (Sweden)

    Min Yang

    2014-10-01

    Full Text Available With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention and treatment of NAFLD in children should be intensive lifestyle interventions such as changes in diet and physical activity. Recent advances have been focused on limitation of dietary fructose and supplementation of antioxidants, omega-3 fatty acids, and prebiotics/probiotics. Convincing evidences from both animal models and human studies have shown that reduction of dietary fructose and supplement of vitamin E, omega-3 fatty acids, and prebiotics/probiotics improve NAFLD.

  7. CEUS and Fibroscan in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Sila; Cocciolillo; Giustino; Parruti; Leonardo; Marzio

    2014-01-01

    AIM: To determine intra-hepatic blood flow and liver stiffness in patients with non-alcoholic fatty liver disease(NAFLD) and non-alcoholic steatohepatitis (NASH) using contrast-enhanced ultrasound and fibroscan.METHODS: This prospective study included 15 patients with NAFLD, 17 patients with NASH and 16 healthy controls.In each patient, real-time ultrasound was used to locate the portal vein (PV) and the right liver lobe, and 5 mL of SonoVue? was then injected intravenous in a peripheral vein of the left arm over a 4-s span. Digital recording was performed for 3 min thereafter. The recording was subsequently retrieved to identify an area of interest in the PV area and in the right liver parenchyma(LP) to assess the blood flow by processing the data using dedicated software (Qontrast?, Bracco, Italy).The following parameters were evaluated: percentage of maximal contrast activity (Peak%), time to peak (TTP, s), regional blood volume (RBV, cm3), regional blood flow (RBF, cm3/s) and mean transit time (MTT, s).At 24-48 h post-injection, liver stiffness was evaluated using Fibroscan and measured in kPa. The statistical evaluation was performed using Student’s t test.RESULTS: In the PV, the Peak%, RBV and RBF were significantly reduced in the NAFLD and NASH patientscompared with the controls (Peak%: NAFLD 26.3 ± 6.6,NASH 28.1 ± 7.3 vs controls 55.8 ± 9.9, P < 0.001;RBV: NAFLD 4202.3 ± 3519.7, NASH 3929.8 ± 1941.3vs controls 7473 ± 3281, P < 0.01; RBF: NAFLD 32.5± 10.8, NASH 32.7 ± 12.1 vs controls 73.1 ± 13.9, P< 0.001). The TTP in the PV was longer in both patient groups but reached statistical significance only in the NASH patients compared with the controls (NASH 79.5± 37.8 vs controls 43.2 ± 30, P < 0.01). In the LP,the Peak%, RBV and RBF were significantly reduced in the NAFLD and NASH patients compared with the controls (Peak%: NAFLD 43.2 ± 7.3, NASH 41.7 ± 7.7 vs controls 56.6 ± 6.3, P < 0.001; RBV: NAFLD 4851.5± 2009, NASH 5069.4 ± 2292.5 vs

  8. Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations.

    Science.gov (United States)

    Milić, Sandra; Lulić, Davorka; Štimac, Davor

    2014-07-28

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m(2). However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m(2)) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.

  9. Alanine Aminotransferase Elevation in Obese Infants and Children: A Marker of Early Onset Non Alcoholic Fatty Liver Disease

    OpenAIRE

    Engelmann, Guido; Hoffmann, Georg Friedrich; Grulich-Henn, Juergen; Teufel, Ulrike

    2014-01-01

    Background: Elevated aminotransferases serve as surrogate markers of non-alcoholic fatty liver disease, a feature commonly associated with the metabolic syndrome. Studies on the prevalence of fatty liver disease in obese children comprise small patient samples or focus on those patients with liver enzyme elevation. Objectives: We have prospectively analyzed liver enzymes in all overweight and obese children coming to our tertiary care centre. Patients and Methods: In a prospective study 224 h...

  10. Association between sonographic diagnosis of fatty liver with histopathologic abnormalities and liver biopsy findings in middle age patient with non-alcoholic fatty liver disease

    Science.gov (United States)

    Kalantari, Hamid; Moradi, Farhad; Hassanzade, Akbar

    2016-01-01

    Background: Liver biopsy is required to diagnose non-alcoholic steatohepatitis in patients with suspected non-alcoholic fatty liver disease (NAFLD). This study aimed to examine the relationship between sonographic diagnosis of fatty liver with histopathologic abnormalities and liver biopsy findings in patient with NAFLD. Materials and Methods: In this cross-sectional study, a total of 180 patients, with an age range of 18-60 year old, with NAFLD based on ultrasonograghic findings were evaluated. Age, sex, body mass index, diabetes mellitus, hypertension, family history of liver disease and laboratory parameters recorded for all patients. Hence, grade of steatosis and stage of fibrosis were evaluated by liver biopsy. Results: A total of 220 patients were enrolled. Liver biopsy was performed in 180 patients. Mean age was 43 ± 10.6 years old and 66% were male. Ultrasonograghic findings showed mild, moderate and severe NAFLD was define in 100 (55.5%), 72 (40%) and 8 (4.5%) of patients, respectively. Liver biopsies showed that steatosis scores of <5%, 5-33% and 33-66% was define in 56 (31%), 116 (64%) and 9 (5%) of patients, respectively. Furthermore, fibrosis was defined as follow; none 92 (51%), mild 68 (38%), moderate 11 (6%), bridging 5 (3%) and cirrhosis 3 (2%) patients. There was no statistically significant relationship between ultrasonograghic findings and steatosis scores (P = 0.44), but statistically significant relationship was found between ultrasonograghic findings and fibrosis stage (P = 0.017). Conclusion: Findings revealed that, in patients with NAFLD, ultrasonographic finding were not in associate to steatosis, but were in relation with fibrosis stage. PMID:27563632

  11. OXPHOS-Mediated Induction of NAD+ Promotes Complete Oxidation of Fatty Acids and Interdicts Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Akie, Thomas E; Liu, Lijun; Nam, Minwoo; Lei, Shi; Cooper, Marcus P

    2015-01-01

    OXPHOS is believed to play an important role in non-alcoholic fatty liver disease (NAFLD), however, precise mechanisms whereby OXPHOS influences lipid homeostasis are incompletely understood. We previously reported that ectopic expression of LRPPRC, a protein that increases cristae density and OXPHOS, promoted fatty acid oxidation in cultured primary hepatocytes. To determine the biological significance of that observation and define underlying mechanisms, we have ectopically expressed LRPPRC in mouse liver in the setting of NAFLD. Interestingly, ectopic expression of LRPPRC in mouse liver completely interdicted NAFLD, including inflammation. Consistent with mitigation of NAFLD, two markers of hepatic insulin resistance--ROS and PKCε activity--were both modestly reduced. As reported by others, improvement of NAFLD was associated with improved whole-body insulin sensitivity. Regarding hepatic lipid homeostasis, the ratio of NAD+ to NADH was dramatically increased in mouse liver replete with LRPPRC. Pharmacological activators and inhibitors of the cellular respiration respectively increased and decreased the [NAD+]/[NADH] ratio, indicating respiration-mediated control of the [NAD+]/[NADH] ratio. Supporting a prominent role for NAD+, increasing the concentration of NAD+ stimulated complete oxidation of fatty acids. Importantly, NAD+ rescued impaired fatty acid oxidation in hepatocytes deficient for either OXPHOS or SIRT3. These data are consistent with a model whereby augmented hepatic OXPHOS increases NAD+, which in turn promotes complete oxidation of fatty acids and protects against NAFLD.

  12. Pathology and biopsy assessment of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Straub, Beate Katharina; Schirmacher, Peter

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases in Western industrialized countries with dramatically rising incidence. The diagnosis of NAFLD requires the existence of steatosis in the absence of significant alcohol consumption. In cases of relevant inflammation pathogenetically linked to steatosis, it is termed non-alcoholic steatohepatitis (NASH). While pure steatosis represents a relatively harmless and rapidly reversible condition without a significant tendency to progression, NASH carries a significant morbidity and progression risk. Noninvasive methods neither reliably establish the diagnosis nor define the extent of disease in NASH, making histopathology the diagnostic gold standard. Since current therapeutic options in NASH are limited, indication for biopsy is made in the clinical context, predominantly in unclear clinical constellations, prior to invasive measures, for follow-up purposes and in the context of clinical studies. Histological hallmarks of NASH are steatosis, hepatocellular ballooning (with and without Mallory-Denk bodies), necroinflammation, and progressing disease a characteristic with perisinusoidal fibrosis. For semiquantitative assessment of necroinflammation (grading) and fibrosis (staging), a score has recently been implemented. Although histology does not reliably distinguish alcoholic steatohepatitis/alcoholic fatty liver disease from NASH/NAFLD, it may give valuable hints. NASH has a tendency for more steatosis, the so-called glycogenated nuclei, and less necroinflammatory activity. Future development of biopsy diagnosis will be coupled to the development of differential systemic therapeutic approaches. Especially in the context of clinical studies, detailed histological evaluation should be considered for the detection of predictive parameters.

  13. Genetics Home Reference: non-alcoholic fatty liver disease

    Science.gov (United States)

    ... PubMed Central Kahali B, Halligan B, Speliotes EK. Insights from Genome-Wide Association Analyses of Nonalcoholic Fatty ... healthcare professional . About Genetics Home Reference Site Map Customer Support Selection Criteria for Links USA.gov Copyright ...

  14. Impaired Insulin Suppression of VLDL-Triglyceride Kinetics in Non-alcoholic Fatty Liver Disease

    DEFF Research Database (Denmark)

    Poulsen, Marianne K; Nellemann, Birgitte; Stødkilde-Jørgensen, Hans;

    2016-01-01

    CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of VLDL-triglyceride (VLDL-TG) kinetics is not fully understood. OBJECTIVE: To determine VLDL-TG, glucose and palmitate kinetics during fasting and hyperin......CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of VLDL-triglyceride (VLDL-TG) kinetics is not fully understood. OBJECTIVE: To determine VLDL-TG, glucose and palmitate kinetics during fasting...... and hyperinsulinemia in men with (NAFLD+) and without NAFLD (NAFLD-). DESIGN: 27 non-diabetic, upper-body obese (WHR >0.9, BMI >28 kg/m(2)) men, 18 NAFLD+ and 9 NAFLD- determined by magnetic resonance spectroscopy, were enrolled.(14)C-labeled VLDL-TG and (3)H-labeled glucose and palmitate tracers were applied...... metabolic abnormalities associated with NAFLD and presumably diabetes....

  15. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008075 Effect of Jiangzhi granules on expression of leptin receptor mRNA, P-JAK2 and P-STAT3 in rats with non-alcoholic fatty liver disease. MA Zansong(马赞颂), et al. Dept Gastroenterol, Instit Spleen and Stomach Dis, Longhua Hosp. Shanghai TCM Univ, Shanghai 200032.World Chin J Digestol 2007;15(32):3360-3366. Objective To study the effect of Jiangzhi granules on non-alcoholic fatty liver disease in rats, and on the expression of

  16. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice

    OpenAIRE

    Le Roy, Tiphaine; Llopis, Marta; Lepage, Patricia; Bruneau, Aurelia; Rabot, Sylvie; Bevilacqua, Claudia; Martin, Patrice; Philippe, Catherine; Walker, Francine; Bado, Andre; Perlemuter, Gabriel; Cassard-Doulcier, Anne-Marie

    2013-01-01

    Objective: Non-alcoholic fatty liver disease (NAFLD) is prevalent among obese people and is considered the hepatic manifestation of metabolic syndrome. However, not all obese individuals develop NAFLD. Our objective was to demonstrate the role of the gut microbiota in NAFLD development using transplantation experiments in mice. [br/] Design: Two donor C57BL/6J mice were selected on the basis of their responses to a high-fat diet (HFD). Although both mice displayed similar body weight gain, on...

  17. Systems biology elucidates common pathogenic mechanisms between nonalcoholic and alcoholic-fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Silvia Sookoian

    Full Text Available The abnormal accumulation of fat in the liver is often related either to metabolic risk factors associated with metabolic syndrome in the absence of alcohol consumption (nonalcoholic fatty liver disease, NAFLD or to chronic alcohol consumption (alcoholic fatty liver disease, AFLD. Clinical and histological studies suggest that NAFLD and AFLD share pathogenic mechanisms. Nevertheless, current data are still inconclusive as to whether the underlying biological process and disease pathways of NAFLD and AFLD are alike. Our primary aim was to integrate omics and physiological data to answer the question of whether NAFLD and AFLD share molecular processes that lead to disease development. We also explored the extent to which insulin resistance (IR is a distinctive feature of NAFLD. To answer these questions, we used systems biology approaches, such as gene enrichment analysis, protein-protein interaction networks, and gene prioritization, based on multi-level data extracted by computational data mining. We observed that the leading disease pathways associated with NAFLD did not significantly differ from those of AFLD. However, systems biology revealed the importance of each molecular process behind each of the two diseases, and dissected distinctive molecular NAFLD and AFLD-signatures. Comparative co-analysis of NAFLD and AFLD clarified the participation of NAFLD, but not AFLD, in cardiovascular disease, and showed that insulin signaling is impaired in fatty liver regardless of the noxa, but the putative regulatory mechanisms associated with NAFLD seem to encompass a complex network of genes and proteins, plausible of epigenetic modifications. Gene prioritization showed a cancer-related functional map that suggests that the fatty transformation of the liver tissue is regardless of the cause, an emerging mechanism of ubiquitous oncogenic activation. In conclusion, similar underlying disease mechanisms lead to NAFLD and AFLD, but specific ones depict a

  18. Genetics of non-alcoholic fatty liver disease: From susceptibility and nutrient interactions to management

    Science.gov (United States)

    Ravi Kanth, Vishnubhotla Venkata; Sasikala, Mitnala; Sharma, Mithun; Rao, Padaki Nagaraja; Reddy, Duvvuru Nageshwar

    2016-01-01

    Genetics plays an important role in determining the susceptibility of an individual to develop a disease. Complex, multi factorial diseases of modern day (diabetes, cardiovascular disease, hypertension and obesity) are a result of disparity between the type of food consumed and genes, suggesting that food which does not match the host genes is probably one of the major reasons for developing life style diseases. Non-alcoholic fatty liver is becoming a global epidemic leading to substantial morbidity. While various genotyping approaches such as whole exome sequencing using next generation sequencers and genome wide association studies have identified susceptibility loci for non-alcoholic fatty liver disease (NAFLD) including variants in patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 genes apart from others; nutrient based studies emphasized on a combination of vitamin D, E and omega-3 fatty acids to manage fatty liver disease. However majority of the studies were conducted independent of each other and very few studies explored the interactions between the genetic susceptibility and nutrient interactions. Identifying such interactions will aid in optimizing the nutrition tailor made to an individual’s genetic makeup, thereby aiding in delaying the onset of the disease and its progression. The present topic focuses on studies that identified the genetic susceptibility for NAFLD, nutritional recommendations, and their interactions for better management of NAFLD. PMID:27458502

  19. Genetics of non-alcoholic fatty liver disease: From susceptibility and nutrient interactions to management

    Institute of Scientific and Technical Information of China (English)

    Vishnubhotla; Venkata; Ravi; Kanth; Mitnala; Sasikala; Mithun; Sharma; Padaki; Nagaraja; Rao; Duvvuru; Nageshwar; Reddy

    2016-01-01

    Genetics plays an important role in determining the susceptibility of an individual to develop a disease. Complex, multi factorial diseases of modern day(diabetes, cardiovascular disease, hypertension and obesity) are a result of disparity between the type of food consumed and genes, suggesting that food which does not match the host genes is probably one of the major reasons for developing life style diseases. Non-alcoholic fatty liver is becoming a global epidemic leading to substantial morbidity. While various genotyping approaches such as whole exome sequencing using next generation sequencers and genome wide association studies have identified susceptibility loci for non-alcoholic fatty liver disease(NAFLD) including variants in patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 genes apart from others; nutrient based studies emphasized on a combination of vitamin D, E and omega-3 fatty acids to manage fatty liver disease. However majority of the studies were conducted independent of each other and very few studies explored the interactions between the genetic susceptibility and nutrient interactions. Identifying such interactions will aid in optimizing the nutrition tailor made to an individual’s genetic makeup, thereby aiding in delaying the onset of the disease and its progression. The present topic focuses on studies that identified the genetic susceptibility for NAFLD, nutritional recommendations, and their interactions for better management of NAFLD.

  20. Th17 involvement in nonalcoholic fatty liver disease progression to non-alcoholic steatohepatitis.

    Science.gov (United States)

    Chackelevicius, Carla Melisa; Gambaro, Sabrina Eliana; Tiribelli, Claudio; Rosso, Natalia

    2016-11-07

    The nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD encompasses a wide histological spectrum ranging from benign simple steatosis to non-alcoholic steatohepatitis (NASH). Sustained inflammation in the liver is critical in this process. Hepatic macrophages, including liver resident macropaghes (Kupffer cells), monocytes infiltrating the injured liver, as well as specific lymphocytes subsets play a pivotal role in the initiation and perpetuation of the inflammatory response, with a major deleterious impact on the progression of fatty liver to fibrosis. During the last years, Th17 cells have been involved in the development of inflammation not only in liver but also in other organs, such as adipose tissue or lung. Differentiation of a naïve T cell into a Th17 cell leads to pro-inflammatory cytokine and chemokine production with subsequent myeloid cell recruitment to the inflamed tissue. Th17 response can be mitigated by T regulatory cells that secrete anti-inflammatory cytokines. Both T cell subsets need TGF-β for their differentiation and a characteristic plasticity in their phenotype may render them new therapeutic targets. In this review, we discuss the role of the Th17 pathway in NAFLD progression to NASH and to liver fibrosis analyzing different animal models of liver injury and human studies.

  1. Breath biomarkers and non-alcoholic fatty liver disease: preliminary observations.

    Science.gov (United States)

    Solga, S F; Alkhuraishe, A; Cope, K; Tabesh, A; Clark, J M; Torbenson, M; Schwartz, P; Magnuson, T; Diehl, A M; Risby, T H

    2006-01-01

    Breath biomarkers have the potential to offer information that is similar to conventional clinical tests or they are entirely unique. Preliminary data support the use of breath biomarkers in the study of liver disease, in particular non-alcoholic fatty liver disease (NAFLD). It was evaluated whether breath ethanol, ethane, sulfur compounds and acetone would be associated with hepatic histopathology amongst morbidly obese patients presenting for bariatric surgery. Breath samples were collected during a preoperative visit and compared with liver biopsies obtained during the surgery. A Student's two-tailed t-test was used to compare differences between the two groups. Linear regression was used to analyse associations between the concentrations of breath molecules and independent predictor variables. It was found that breath ethanol, ethane and acetone can be useful biomarkers in patients with NAFLD. In particular, breath ethanol can be associated with hepatic steatosis, and breath acetone can be associated with non-alcoholic steatohepatitis.

  2. Type 2 diabetic patients with non-alcoholic fatty liver disease exhibit significant haemorheological abnormalities

    Institute of Scientific and Technical Information of China (English)

    Hui Dong; Fu'er Lu; Nan Wang; Xin Zou; Jingjing Rao

    2011-01-01

    Haemorheological abnormalities have been described in diabetes mellitus,as well as in non-alcoholic fatty liver disease (NAFLD).However,the relationship between the changes in liver fat content and haemorheology is unknown.The current study aims to show the correlation between haemorheological parameters and intrahepatic lipid content (IHLC) in patients with type 2 diabetes.The serum biochemical markers,such as fasting plasma glucose (FPG),haemoglobin A1c (HbA1c),liver enzymes,lipid profiles,and haemorheological properties,were examined.IHLC was quantified using proton magnetic resonance spectroscopy (1H-MRS) scanning of the liver.A significant correlation was observed between IHLC and whole blood viscosity at high,middle,and low shear rates.IHLC also positively correlated with haematocrit,the reduced whole blood viscosity at low and middle shear rates,and the erythrocyte aggregation index.Diabetic patients with NAFLD exhibited significant haemorheological abnormalities compared with patients without NAFLD.In summary,haemorheological disorders are linked to non-alcoholic fatty liver in type 2 diabetes.

  3. Metabolic syndrome and risk factors for non-alcoholic fatty liver disease

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    Mônica Rodrigues de Araújo Souza

    2012-03-01

    Full Text Available CONTEXT: Non-alcoholic fatty liver disease (NAFLD, hepatic manifestation of metabolic syndrome, has been considered the most common liver disease nowadays, which is also the most frequent cause of elevated transaminases and cryptogenic cirrhosis. The greatest input of fatty acids into the liver and consequent increased beta-oxidation contribute to the formation of free radicals, release of inflammatory cytokines and varying degrees of hepatocytic aggression, whose histological expression may vary from steatosis (HS to non-alcoholic steatohepatitis (NASH. The differentiation of these forms is required by the potential risk of progression to cirrhosis and development of hepatocellular carcinoma. OBJECTIVE: To review the literature about the major risk factors for NAFLD in the context of metabolic syndrome, focusing on underlying mechanisms and prevention. METHOD: PubMed, MEDLINE and SciELO data basis analysis was performed to identify studies describing the link between risk factors for metabolic syndrome and NAFLD. A combination of descriptors was used, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolic syndrome and risk factors. At the end, 96 clinical and experimental studies, cohorts, meta-analysis and systematic reviews of great impact and scientific relevance to the topic, were selected. RESULTS: The final analysis of all these data, pointed out the central obesity, type 2 diabetes, dyslipidemia and hypertension as the best risk factors related to NAFLD. However, other factors were highlighted, such as gender differences, ethnicity, genetic factors and the role of innate immunity system. How these additional factors may be involved in the installation, progression and disease prognosis is discussed. CONCLUSION: Risk factors for NAFLD in the context of metabolic syndrome expands the prospects to 1 recognize patients with metabolic syndrome at high risk for NAFLD, 2 elucidate pathways common to other co-morbidities, 3

  4. Comparing Effects of Medication Therapy and Exercise Training with Diet on Liver enzyme Levels and Liver Sonography in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD

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    Azadeh Nabizadeh Haghighi

    2016-03-01

    Full Text Available Background & Objectives: Non-alcoholic fatty liver disease, characterized by the deposition of fat in liver cells, can cause fibrosis, cirrhosis, and liver cell damage if not controlled. The aim of this study is to compare the effects of medication therapy and exercise training with diet on liver enzyme levels and liver sonography in patients with non-alcoholic fatty liver disease (NAFLD. Materials & Methods :In this quasi-experimental study, female patients with non-alcoholic fatty liver were randomly divided into two groups: medication therapy (n = 10 and exercise therapy (n = 10 for 8 weeks. During this period, the exercise group performed exercise training three days a week for 90 minutes per session. The drug was given to the medication group. In both groups, the diet was 500 calories less than their daily energy. Before and after intervention, blood tests and liver sonography were executed. All statistical analyses were done using SPSS for Windows version 20. Comparisons between and within groups were performed by Student's t-test and Wilcoxon test on paired and unpaired data. P < 0.05 was considered statistically significant. Results :In both groups, liver enzyme levels and disease severity in sonography reduced significantly (p<0.05. Conclusion: The findings of the present research showed that both methods of therapy have the same effect on reducing the severity of NAFLD.

  5. Effect of baicalin on toll-like receptor 4-mediated ischemia/reperfusion inflammatory responses in alcoholic fatty liver condition

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seok-Joo; Lee, Sun-Mee, E-mail: sunmee@skku.edu

    2012-01-01

    Alcoholic fatty liver is susceptible to secondary stresses such as ischemia/reperfusion (I/R). Baicalin is an active component extracted from Scutellaria baicalensis, which is widely used in herbal preparations for treatment of hepatic diseases and inflammatory disorders. This study evaluated the potential beneficial effect of baicalin on I/R injury in alcoholic fatty liver. Rats were fed an alcohol liquid diet or a control isocaloric diet for 5 weeks, and then subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Baicalin (200 mg/kg) was intraperitoneally administered 24 and 1 h before ischemia. After reperfusion, baicalin attenuated the increases in serum alanine aminotransferase activity, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels in alcoholic fatty liver. The increased levels of TNF-α and IL-6 mRNA expression and inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expressions increased after reperfusion, which were higher in ethanol-fed animals, were attenuated by baicalin. In ethanol-fed animals, baicalin attenuated the increases in toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 protein expressions and the nuclear translocation of NF-κB after reperfusion. In conclusion, our findings suggest that baicalin ameliorates I/R-induced hepatocellular damage by suppressing TLR4-mediated inflammatory responses in alcoholic fatty liver. -- Highlights: ► Baicalin attenuates hepatic I/R-induced inflammation in alcoholic fatty liver. ► Baicalin downregulates TLR4, MyD88 expression during I/R in alcoholic fatty liver. ► Baicalin attenuates NF-κB nuclear translocation during I/R in alcoholic fatty liver.

  6. Controversy in the diagnosis of pediatric non-alcoholic fatty liver disease.

    Science.gov (United States)

    Marzuillo, Pierluigi; Grandone, Anna; Perrone, Laura; Miraglia Del Giudice, Emanuele

    2015-06-07

    In the last years childhood obesity has reached epidemic diffusion with about 200 million school-age children worldwide being overweight or obese. Simultaneously, also the prevalence of obesity comorbidities has been increased and the non-alcoholic fatty liver disease (NAFLD) has become the most common form of liver disease in childhood. Also if there are some not-invasive diagnostic possibilities, the diagnostic gold standard is represented by hepatic biopsy giving to the clinicians the possibility to both diagnose the NAFLD and evaluate its progression to fibrosis or cirrhosis with greater certainty than other techniques. The use of liver biopsy in clinical practice causes debate among health care providers. Most patients with NAFLD have a good prognosis and, therefore, the risks of a liver biopsy seem to outweigh the clinical benefits. It represents an impractical screening procedure because it is both expensive and invasive and, moreover, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies because histological lesions of non-alcoholic steatohepatitis are unevenly distributed throughout the liver parenchyma. The liver biopsy limitations have led the clinicians to use, also if highly imperfect, non-invasive methods to diagnose and stage NAFLD. In this editorial the main diagnostic controversies in pediatric NAFLD are examined.

  7. Discrimination of individuals in a general population at high-risk for alcoholic and non-alcoholic fatty liver disease based on liver stiffness: a cross section study

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    Kasai Kenji

    2011-06-01

    Full Text Available Abstract Background Factors associated with liver stiffness (LS are unknown and normal reference values for LS have not been established. Individuals at high risk for alcoholic (ALD and non-alcoholic fatty (NAFLD liver disease need to be non-invasively discriminated during routine health checks. Factors related to LS measured using a FibroScan and normal reference values for LS are presented in this report. Methods We measured LS using a FibroScan in 416 consecutive individuals who presented for routine medical checks. We also investigated the relationship between LS and age, body mass index (BMI, liver function (LF, alcohol consumption, and fatty liver determined by ultrasonography. We identified individuals at high-risk for ALD and NAFLD as having a higher LS value than the normal upper limit detected in 171 healthy controls. Results The LS value for all individuals was 4.7 +/- 1.5 kPa (mean +/- SD and LS significantly and positively correlated with BMI and LF test results. The LS was significantly higher among individuals with, than without fatty liver. Liver stiffness in the 171 healthy controls was 4.3 +/- 0.81 kPa and the upper limit of LS in the normal controls was 5.9 kPa. We found that 60 (14.3% of 416 study participants had abnormal LS. The proportion of individuals whose LS values exceeded the normal upper limit was over five-fold higher among those with, than without fatty liver accompanied by abnormal LF test results. Conclusions Liver stiffness could be used to non-invasively monitor the progression of chronic liver diseases and to discriminate individuals at high risk for ALD and NAFLD during routine health assessments.

  8. Epidemiology and Natural History of Non-alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Mishra, Alita; Younossi, Zobair M

    2012-06-01

    Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease burden across the world. By definition, although the histopathologic features of NAFLD are identical to that of alcoholic liver disease, its diagnosis requires absence of significant alcohol use and absence of other causes of chronic liver disease. We now know that NAFLD is not simply a disease of the Western world. It is manifested across the world, in varying rates, across gender, across varying ethnicities, and in its association with other host factors. In this review article, the definition of NAFLD, its spectrum, ranging from mild steatosis to hepatocellular injury and inflammation defined as non-alcoholic steatohepatitis (NASH) is discussed. Mild steatosis is generally a stable disease whereas NASH can be progressive. Based on current published literature, current incidence and prevalence of NAFLD and NASH are discussed. It is also accepted that these processes will continue to increase in prevalence with the rise of obesity, type II diabetes, and associated metabolic syndrome. Some of the risk factors have been well-established and are discussed. In addition, this review also presents emerging associations with other risk factors for NAFLD. Natural history of NAFLD is variable depending upon the histologic subtypes and other underlying comorbidities and is discussed in this review as well.

  9. A new noninvasive technique for estimating hepatic triglyceride: will liver biopsy become redundant in diagnosing non-alcoholic fatty liver disease?

    NARCIS (Netherlands)

    Betzel, B.; Drenth, J.P.H.

    2014-01-01

    Obesity and metabolic syndrome are healthcare problems that continue to rise in frequency worldwide. Both phenotypes are a strong predictor for development of liver steatosis in the context of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Ultrasound may detect steatosis, but it

  10. PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Aragonès, Gemma; Auguet, Teresa; Armengol, Sandra; Berlanga, Alba; Guiu-Jurado, Esther; Aguilar, Carmen; Martínez, Salomé; Sabench, Fátima; Porras, José Antonio; Ruiz, Maikel Daniel; Hernández, Mercé; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2016-01-01

    Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) in the pathology of non-alcoholic fatty liver disease (NAFLD). Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR) analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18), simple steatosis (SS, n = 20), and non-alcoholic steatohepatitis (NASH, n = 17). Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis. PMID:27128907

  11. PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

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    Gemma Aragonès

    2016-04-01

    Full Text Available Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3 in the pathology of non-alcoholic fatty liver disease (NAFLD. Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18, simple steatosis (SS, n = 20, and non-alcoholic steatohepatitis (NASH, n = 17. Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis.

  12. Non-alcohol fatty liver disease in Asia: Prevention andplanning

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM To review all of epidemiological aspects of nonalcoholicfatty liver disease (NAFLD) and also preventthis disease is examined.METHODS: We conducted a systematic reviewaccording to the PRISMA guidelines. All searches forwriting this review is based on the papers was foundin PubMed (MEDLINE), Cochrane database and Scopusin August and September 2014 for topic of NAFLD inAsia and the way of prevention of this disease, with nolanguage limitations. All relevant articles were accessedin full text and all relevant materials was evaluated andreviewed.RESULTS: NAFLD is the most common liver disorder inworldwide, with an estimated with 20%-30% prevalencein Western countries and 2%-4% worldwide. Theprevalence of NAFLD in Asia, depending on location(urban vs rural), gender, ethnicity, and age is variablebetween 15%-20%. According to the many studies inthe world, the relationship between NAFLD, obesity,diabetes mellitus, and metabolic syndrome (MS) isquiet obvious. Prevalence of NAFLD in Asian countriesseems to be lower than the Western countries but, ithas increased recently due to the rise of obesity, type 2diabetes and MS in this region. One of the main reasonsfor the increase in obesity, diabetes and MS in Asia isa lifestyle change and industrialization. Today, NAFLDis recognized as a major chronic liver disease in Asia.Therefore, prevention of this disease in Asian countriesis very important and the best strategy for preventionand control of NAFLD is lifestyle modifications. Lifestylemodification programs are typically designed to changebad eating habits and increase physical activity that isassociated with clinically significant improvements inobesity, type 2 diabetes and MS.CONCLUSION: Prevention of NAFLD is very important in Asian countries particularly in Arab countries becauseof high prevalence of obesity, diabetes and MS.

  13. Liver regeneration in nonalcoholic fatty liver disease

    OpenAIRE

    Aldo Lagomarsino

    2012-01-01

    Steatosis is the accumulation of fat in hepatocytes, which may be the result of liver regeneration or pathological processes such as alcoholic and nonalcoholic fatty liver disease. Despite its importance, in both cases the exact mechanism that prevails in fatty liver regeneration is poorly understood. Previous studies have shown that patients with fatty liver express dispar regeneration, possibly due to the accumulation of reactive oxygen species generated by inflammatory processes caused by ...

  14. A STUDY OF NON ALCOHOLIC FATTY LIVER DISEASE IN PAT IENTS WITH METABOLIC SYNDROME

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    Vasundhara Devi

    2013-01-01

    Full Text Available ABSTRACT: This study was conducted to know the relation of no n- alcoholic fatty liver disease (non-alcoholic steatohepatitis & cirrhosis with met abolic syndrome. MATERIAL AND METHODS: 60 cases were selected. Out of them 30 were non-al coholic steatohepatitis and 30 cirrhosis along with 30 healthy controls. Parameter s of metabolic syndrome and liver function which are waist circumference, blood pressure, fasti ng plasma glucose, total triglycerides, high density lipo- protein cholesterol, total bilirubin, a lanine amino transferase, alkaline phosphotase, total proteins and albumin were measured. STATISTICAL ANALYSIS : All values were expressed as mean ± SD. The results obtained we re analyzed statistically using the unpaired student ‘t‘test to evaluate the significanc e of differences between the mean values. RESULTS: The values of waist circumference, fasting plasma g lucose, systolic blood pressure, total triglycerides, total bilirubin, alanine-amino -transferase and alkaline phosphotase were raised in non-alcoholic steatohepatitis and cirrhosi s patients. The level of high density lipoprotein cholesterol was decreased in non-alcoholi c steatohepatitis and cirrhosis patients. The level of albumin was decreased in cirrhosis pati ents. CONCLUSION: On the basis of our results it may be concluded that metabolic syndrome causes nonalcoholic fatty liver disease.

  15. Non-alcoholic fatty liver disease: An early mediator predicting metabolic syndrome in obese children?

    Institute of Scientific and Technical Information of China (English)

    Jun-Fen Fu; Hong-Bo Shi; Li-Rui Liu; Ping Jiang; Li Liang; Chun-Lin Wang; Xi-Yong Liu

    2011-01-01

    AIM: To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome, and if liver B-ultrasound can be used for its diagnosis.METHODS: We classified 861 obese children (6-16 years old) into three subgroups: group 0 (normal liver in ultrasound and normal transaminases); group 1 (fatty liver in ultrasound and normal transaminases); and group 2 (fatty liver in ultrasound and elevated transaminases).We measured the body mass index, waist and hip circumference,blood pressure, fasting blood glucose, insulin,homeostasis model assessment of insulin resistance (HOMA-IR), whole-body insulin sensitivity index (WBISI),lipid profile and transaminases in all the participants.The risk of developing metabolic syndrome (MS) was assessed according to the degree of liver fatty infiltration based on the B-ultrasound examination.RESULTS: Among the 861 obese children, 587 (68.18%)were classified as having NAFLD, and 221 (25.67%)as having MS. The prevalence of MS in NAFLD children (groups 1 and 2) was 37.64% (221/587), which was much higher than that in non-NAFLD group (group 0,12.04%) (P < 0.01). There were significantly higher incidences concerning every component of MS in group 2 compared with group 0 (P < 0.05). The incidence of NAFLD in MS patients was 84.61% (187/221), which was significantly higher than that of hypertension (57.46%,127/221) and glucose metabolic anomalies (22.62%,50/221), and almost equal to the prevalence of dyslipidemia (89.14%, 197/221). Based on the B-ultrasound scales, the presence of moderate and severe liver fatty infiltration carried a high risk of hypertension [odds ratio (OR): 2.18, 95% confidence interval (95% CI):1.27-3.75], dyslipidemia (OR: 7.99, 95% CI: 4.34-14.73),impaired fasting glucose (OR: 3.65, 95% CI: 1.04-12.85),and whole MS (OR: 3.77; 95% CI: 1.90-7.47, P < 0.01).The state of insulin resistance (calculated by HOMA-IR and WBISI) deteriorated as the degree of fatty infiltration increased

  16. Activation of CDK4 Triggers Development of Non-alcoholic Fatty Liver Disease

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    Jingling Jin

    2016-07-01

    Full Text Available The development of non-alcoholic fatty liver disease (NAFLD is a multiple step process. Here, we show that activation of cdk4 triggers the development of NAFLD. We found that cdk4 protein levels are elevated in mouse models of NAFLD and in patients with fatty livers. This increase leads to C/EBPα phosphorylation on Ser193 and formation of C/EBPα-p300 complexes, resulting in hepatic steatosis, fibrosis, and hepatocellular carcinoma (HCC. The disruption of this pathway in cdk4-resistant C/EBPα-S193A mice dramatically reduces development of high-fat diet (HFD-mediated NAFLD. In addition, inhibition of cdk4 by flavopiridol or PD-0332991 significantly reduces development of hepatic steatosis, the first step of NAFLD. Thus, this study reveals that activation of cdk4 triggers NAFLD and that inhibitors of cdk4 may be used for the prevention/treatment of NAFLD.

  17. Experimental models of non-alcoholic fatty liver disease in rats.

    Science.gov (United States)

    Kucera, Otto; Cervinkova, Zuzana

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and it persists at a high prevalence. NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings, ranging from simple fatty liver through non-alcoholic steatohepatitis (NASH) to fibrosis and ultimately cirrhosis, which may progress to hepatocellular carcinoma. The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance. Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models. The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages. Within the past several years, great emphasis has been placed on the development of an appropriate model for human NASH. This paper reviews the widely used experimental models of NAFLD in rats. We discuss nutritional, genetic and combined models of NAFLD and their pros and cons. The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies. Considering the legislative, ethical, economical and health factors of NAFLD, animal models are essential tools for the research of this disease.

  18. Clinical assessment of hepatic de novo lipogenesis in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Paglialunga, Sabina; Dehn, Clayton A

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is heralded as the next big global epidemic. Hepatic de novo lipogenesis (DNL), the synthesis of new fatty acids from non-lipid sources, is thought to play a pivotal role in the development of NAFLD. While there is currently no NAFLD-specific therapeutic agent available, pharmaceutical drugs aimed at reducing hepatic fat accretion may prove to be a powerful ally in the treatment and management of this disease. With a focus on NAFLD, the present review summarizes current techniques examining DNL from a clinical perspective, and describes the merits and limitations of three commonly used assays; stable-label isotope tracer studies, fatty acid indexes and indirect calorimetry as non-invasive measures of hepatic DNL. Finally, the application of DNL assessments in the pharmacological and nutraceutical treatment of NAFLD/NASH is summarized. In a clinical research setting, measures of DNL are an important marker in the development of anti-NAFLD treatments.

  19. Gut microbiota and non-alcoholic fatty liver disease: new insights.

    Science.gov (United States)

    Aron-Wisnewsky, J; Gaborit, B; Dutour, A; Clement, K

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is a severe liver disease that is increasing in prevalence with the worldwide epidemic of obesity and its related insulin-resistance state. A 'two-hit' mechanism has been proposed; however, the complete physiopathogenesis remains incompletely understood. Evidence for the role of the gut microbiota in energy storage and the subsequent development of obesity and some of its related diseases is now well established. More recently, a new role of gut microbiota has emerged in NAFLD. The gut microbiota is involved in gut permeability, low-grade inflammation and immune balance, it modulates dietary choline metabolism, regulates bile acid metabolism and produces endogenous ethanol. All of these factors are molecular mechanisms by which the microbiota can induce NAFLD or its progression toward overt non-alcoholic steatohepatitis.

  20. Is there any progress in the treatment of non-alcoholic fatty liver disease?

    Institute of Scientific and Technical Information of China (English)

    Emmanuel; A; Tsochatzis; George; V; Papatheodoridis

    2011-01-01

    Despite the fact that non-alcoholic fatty liver disease(NAFLD) and its severe clinical form,non-alcoholic steatohepatitis,are becoming increasingly prevalent in the industrialised countries,there are no licensed pharmacological treatments for them.Weight loss and life modifications,antioxidant therapies and insulin-sensitising agents are the current treatment strategies and have all been tested with inconclusive results.Low sample numbers,inadequate treatment duration and invalid surrogate markers for treatment response might all account for these results.As NAFLD is a systemic rather than a liver disease,future trials should address the patient as a whole and also address cardiovascular risk factors.

  1. Does Lysosomial Acid Lipase Reduction Play a Role in Adult Non-Alcoholic Fatty Liver Disease?

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    Francesco Baratta

    2015-11-01

    Full Text Available Lysosomal Acid Lipase (LAL is a key enzyme involved in lipid metabolism, responsible for hydrolysing the cholesteryl esters and triglycerides. Wolman Disease represents the early onset phenotype of LAL deficiency rapidly leading to death. Cholesterol Ester Storage Disease is a late onset phenotype that occurs with fatty liver, elevated aminotransferase levels, hepatomegaly and dyslipidaemia, the latter characterized by elevated LDL-C and low HDL-C. The natural history and the clinical manifestations of the LAL deficiency in adults are not well defined, and the diagnosis is often incidental. LAL deficiency has been suggested as an under-recognized cause of dyslipidaemia and fatty liver. Therefore, LAL activity may be reduced also in non-obese patients presenting non-alcoholic fatty liver disease (NAFLD, unexplained persistently elevated liver transaminases or with elevation in LDL cholesterol. In these patients, it could be indicated to test LAL activity. So far, very few studies have been performed to assess LAL activity in representative samples of normal subjects or patients with NAFLD. Moreover, no large study has been carried out in adult subjects with NAFLD or cryptogenic cirrhosis.

  2. C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients

    DEFF Research Database (Denmark)

    Zimmermann, Esther; Anty, Rodolphe; Tordjman, Joan

    2011-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a major hepatic consequence of obesity. It has been suggested that the high sensitivity C-reactive protein (hs-CRP) is an obesity-independent surrogate marker of severity of NAFLD, especially development of non-alcoholic steato-hepatitis (NASH...

  3. Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease

    Science.gov (United States)

    Shoji, Hirotaka; Yoshio, Sachiyo; Mano, Yohei; Kumagai, Erina; Sugiyama, Masaya; Korenaga, Masaaki; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Aikata, Hiroshi; Hyogo, Hideyuki; Chayama, Kazuaki; Ohashi, Tomohiko; Ito, Kiyoaki; Yoneda, Masashi; Nozaki, Yuichi; Kawaguchi, Takumi; Torimura, Takuji; Abe, Masanori; Hiasa, Yoichi; Fukai, Moto; Kamiyama, Toshiya; Taketomi, Akinobu; Mizokami, Masashi; Kanto, Tatsuya

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. Activation of macrophages and hepatic stellate cells is a critical step that promotes liver fibrosis. We aimed to explore the feasibility of interleukin-34 (IL-34), a key regulator of macrophages, as a fibrosis marker in patients with NAFLD. We enrolled 197 liver biopsy-proven NAFLD patients. We evaluated the serum levels of IL-34, macrophage-colony stimulating factor (M-CSF), soluble CD163 (sCD163), 40 cytokines/chemokines, hyaluronic acid, type IV collagen 7s, and clinically-approved fibrosis scores. IL-34 increased with the progression of fibrosis and was an independent marker for liver fibrosis. Immunostaining experiments, using resected liver specimens from NAFLD patients, revealed that IL-34 was mainly expressed on liver fibroblasts. IL-34 based fibrosis score (0.0387*IL-34 (pg/ml) + 0.3623*type IV collagen 7s (ng/ml) + 0.0184*age (year)–1.1850) was a practical predictive model of liver fibrosis. Using receiver-operating characteristic analyses, the area under the curve, sensitivity, and specificity of IL-34 based fibrosis score were superior or comparable to the other fibrosis biomarkers and scores. In conclusion, the IL-34 based fibrosis score, including serum IL-34, type IV collagen 7s and age, is a feasible diagnostic marker of liver fibrosis in NAFLD patients. PMID:27363523

  4. Alcohol consumption and risk of fatty liver disease: a meta-analysis

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    Guoli Cao

    2016-10-01

    Full Text Available Background Observational studies have shown inconsistent results regarding alcohol consumption and risk of fatty liver. We performed a meta-analysis of published literature to investigate the association between alcohol consumption and fatty liver disease (FLD. Methods We searched Medline, Embase, Web of Science, and several Chinese databases, identifying studies that reported an association between alcohol consumption and the risk of FLD. Results A total of 16 studies with 76,608 participants including 13 cross-sectional studies, two cross-sectional following longitudinal studies, and one cohort study met the inclusion criteria. For light to moderate alcohol consumption (LMAC, there was a 22.6% reduction in risk of FLD (odds ratio [OR] = 0.774, 95% confidence interval CI [0.695–0.862], P <0.001, and subgroup analysis showed that a greater reduction in risk of FLD was found in the female drinkers (30.2% and the drinkers with BMI ≥25 kg/m2(31.3% compared with the male drinkers (22.6% and the drinkers with BMI <25 kg/m2(21.3%, respectively. For heavy alcohol consumption, there was no significant influence on risk of FLD (OR = 0.869, 95% CI [0.553–1.364], P = 0.541 in Japanese women, but there was a 33.7% reduction in risk of FLD (OR = 0.663, 95% CI [0.574–0.765], P < 0.001 in Japanese men and a significant increased risk of FLD (OR = 1.785, 95% CI [1.064–2.996], P = 0.028 in Germans. Conclusion LMAC is associated with a significant protective effect on FLD in the studied population, especially in the women and obese population. However, the effect of heavy alcohol consumption on FLD remains unclear due to limited studies and small sample sizes.

  5. Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers

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    Claudia Sanna

    2016-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas and extra-intestinal sites (kidney in men, and breast in women. Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC, but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites.

  6. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant.

    Science.gov (United States)

    Gitto, Stefano; Villa, Erica

    2016-04-02

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis.

  7. Non-alcoholic fatty liver disease in obese adults: clinical aspects and current management strategies.

    Science.gov (United States)

    Pallayova, M; Taheri, S

    2014-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder whose prevalence is strongly linked to the current epidemic of obesity in many western countries. The prevalence of NAFLD is two to four times higher in populations with pre-existing metabolic comorbidities than in the general population. The diagnosis of primary NAFLD involves establishing the presence of hepatic steatosis or steatohepatitis by imaging or histology, along with establishing the non-alcoholic nature of the disease process and excluding competing aetiologies for hepatic steatosis. Among the indirect serum biomarkers, the NAFLD fibrosis score can help to identify patients with NAFLD and with higher likelihood of having fibrosis or cirrhosis. A liver biopsy should be considered in NAFLD patients at increased risk for steatohepatitis/advanced fibrosis and in cases where a liver biopsy is necessary to exclude co-existing chronic liver diseases and other aetiologies for hepatic steatosis. The treatment and management recommendations for obesity-associated NAFLD are aimed towards weight reduction. The currently available interventions employed to promote weight loss and improve the metabolic responses in NAFLD include lifestyle modification, pharmacotherapy and bariatric surgery.

  8. Beneifcial mechanisms of aerobic exercise on hepatic lipid metabolism in non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Rui Guo; Emily C Liong; Kwok Fai So; Man-Lung Fung; George L Tipoe

    2015-01-01

    BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) refers to any fatty liver disease that is not due to excessive use of alcohol. NAFLD probably results from abnormal hepatic lipid metabolism and insulin resistance. Aerobic exercise is shown to improve NAFLD. This review aimed to evaluate the molecular mechanisms involved in the beneifcial effects of aerobic exercise on NAFLD. DATA SOURCE:We searched articles in English on the role of aerobic exercise in NAFLD therapy in PubMed. RESULTS:The mechanisms of chronic aerobic exercise in regulating the outcome of NAFLD include: (i) reducing in-trahepatic fat content by down-regulating sterol regulatory element-binding protein-1c and up-regulating peroxisome proliferator-activated receptorγ expression levels; (ii) decreas-ing hepatic oxidative stress through modulating the reactive oxygen species, and enhancing antioxidant enzymes such as catalase and glutathione peroxidase; (iii) ameliorating hepatic inlfammation via the inhibition of pro-inlfammatory media-tors such as tumor necrosis factor-alpha and interleukin-1 beta; (iv) attenuating mitochondrial dependent apoptosis by reducing cytochrome C released from the mitochondria to the cytosol; and (v) inducing hepato-protective autophagy. CONCLUSION:Aerobic exercise, via different mechanisms, signiifcantly decreases the fat content of the liver and improves the outcomes of patients with NAFLD.

  9. Gut-liver axis, nutrition, and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Kirpich, Irina A; Marsano, Luis S; McClain, Craig J

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases involving hepatic fat accumulation, inflammation with the potential progression to fibrosis and cirrhosis over time. NAFLD is often associated with obesity, insulin resistance, and diabetes. The interactions between the liver and the gut, the so-called "gut-liver axis", play a critical role in NAFLD onset and progression. Compelling evidence links the gut microbiome, intestinal barrier integrity, and NAFLD. The dietary factors may alter the gut microbiota and intestinal barrier function, favoring the occurrence of metabolic endotoxemia and low grade inflammation, thereby contributing to the development of obesity and obesity-associated fatty liver disease. Therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain intestinal barrier integrity are potential agents for NAFLD management. This review summarizes the current knowledge regarding the complex interplay between the gut microbiota, intestinal barrier, and dietary factors in NAFLD pathogenesis. The concepts addressed in this review have important clinical implications, although more work needs to be done to understand how dietary factors affect the gut barrier and microbiota, and to comprehend how microbe-derived components may interfere with the host's metabolism contributing to NAFLD development.

  10. Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease.

    Science.gov (United States)

    Zaitone, Sawsan; Hassan, Neven; El-Orabi, Naglaa; El-Awady, El-Sayed

    2011-07-15

    Insulin resistance, oxidative stress and cytokine imbalance are key pathophysiological mechanisms in non-alcoholic fatty liver disease (NAFLD). This study aimed at evaluating the effect of treatment with the insulin sensitizer, pioglitazone, the tumor necrosis factor-α inhibitor, pentoxifylline, and the antioxidant, melatonin and their combinations in rats with NAFLD. Rats were fed a high-fat diet (HFD) for eight weeks to induce NAFLD. For an additional eight weeks, rats were fed the HFD along with pioglitazone, pentoxifylline, melatonin alone or in combination. Liver index and insulin resistance index were calculated. Serum liver enzyme activities, total cholesterol, triglycerides and tumor necrosis factor-α (TNF-α) were determined. Tissue triglycerides, malondialdehyde and reduced glutathione were measured and liver injury was evaluated by histopathological examination. HFD induced severe hepatic steatosis, inflammation and fibrosis. In addition, liver index, insulin resistance index, activities of liver enzymes and serum level of total cholesterol, triglycerides and TNF-α were elevated. This was coupled with an increase in tissue triglycerides, malondialdehyde and depletion of reduced glutathione. Pioglitazone, pentoxifylline and melatonin, alone or in combination; reduced the insulin resistance index, activities of liver enzymes, hepatic malondialdehyde and increased hepatic reduced glutathione level. Pentoxifylline led to a decrease in serum TNF-α level, however, pioglitazone and melatonin reduced serum total cholesterol and triglycerides. In conclusion, data in this study indicate that pentoxifylline and melatonin can be used as promising adjuvant therapies to pioglitazone in the clinical management of NAFLD.

  11. Role of diet on non-alcoholic fatty liver disease: An updatednarrative review

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Papandreou; Eleni Andreou

    2015-01-01

    The purpose of this article review is to update whatis known about the role of diet on non-alcoholic fattyliver disease (NAFLD). NAFLD is the most commoncause of chronic liver disease in the developed worldand is considered to be a spectrum, ranging from fattyinfiltration of the liver alone (steatosis), which may leadto fatty infiltration with inflammation known as nonalcoholic steatohepatitis While the majority of individualswith risk factors like obesity and insulin resistance havesteatosis, only few people may develop steatohepatitis.Current treatment relies on weight loss and exercise,although various insulin-sensitizing medications appearpromising. Weight loss alone by dietary changeshas been shown to lead to histological improvementin fatty liver making nutrition therapy to become acornerstone of treatment for NAFLD. Supplementationof vitamin E, C and omega 3 fatty acids are underconsideration with some conflicting data. Moreover,research has been showed that saturated fat, trans-fattyacid, carbohydrate, and simple sugars (fructose andsucrose) may play significant role in the intrahepatic fataccumulation. However, true associations with specificnutrients yet to be clarified.

  12. Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents.

    Science.gov (United States)

    Nadeau, Kristen J; Ehlers, Lindsay B; Zeitler, Philip S; Love-Osborne, Kathy

    2009-02-01

    The presence of fatty liver per ultrasound and liver-associated enzymes were measured in a select cohort of youth with both obesity and insulin resistance, and the effect of metformin on these parameters evaluated. Fifty obese, multiethnic, insulin-resistant adolescents (mean age 15.1 yr, mean body mass index 39.8 kg/m2) were randomized to receive lifestyle recommendations plus either twice per day doses of 850 mg of metformin or placebo. Fasting and post-glucose challenge biochemistries and liver ultrasounds were compared at baseline and 6 months. The prevalence of fatty liver was 74%, elevated alanine aminotransferase (ALT) 14%, aspartate aminotransferase (AST) 14%, and gamma-glutamyl transferase (GGT) 17%. Fatty liver was mild in 23%, moderate in 31%, and severe in 46%. Fatty liver was more common in male and Hispanic subjects and elevated ALT more common in Hispanic subjects. Subjects with fatty liver appeared more insulin resistant (higher fasting insulin and triglycerides, lower high-density lipoprotein cholesterol) and had higher ALT and AST. At 6 months, mean ALT, GGT, and fasting insulin improved significantly in all subjects. Fatty liver prevalence (p metformin compared to placebo. Non-alcoholic fatty liver disease (NAFLD) occurs with a high prevalence and severity in obese, insulin-resistant adolescents. While metformin plus lifestyle intervention appears promising, defining NAFLD therapies capable of preventing fibrosis and cirrhosis requires further study.

  13. 内生性乙醇与非酒精性脂肪性肝病研究进展%Endogenous alcohol in non -alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    何崇信; 徐正婕(综述); 范建高(审校)

    2016-01-01

    非酒精性脂肪性肝病和酒精性肝病具有相似的病理学特征,使得内生性乙醇在非酒精性脂肪性肝病的进展中可能扮演的重要角色成为肝病学家们关注的新方向。内生性乙醇与肝脏、肠道和肠道细菌以及非酒精性脂肪性肝病的关系密切,给我们提供了解释非酒精性脂肪性肝病病因的新视角。%Similar pathologic characteristics between non-alcoholic fatty liver disease and alcoholic liver disease presents a new direction for the hepatologists worldwide that endogenous alcohol may play important role in the development of non-alcoholic fatty liver disease. The closed relationship among endogenous alcohol and liver,intestine,intestinal flora and non-alcoholic fatty liver disease provides a new sight to explain the pathogenesis of non-alcoholic fatty liver diseases.

  14. Presence of fatty liver and the relationship between alcohol consumption and markers of inflammation.

    Science.gov (United States)

    Kächele, Martin; Wolff, Stefan; Kratzer, Wolfgang; Haenle, Mark; Homann, Jörg; Trischler, Gerlinde; Koenig, Wolfgang; Imhof, Armin

    2015-01-01

    Background and Aims. Local and systemic inflammation represent a major feature of atherosclerotic cardiovascular disease (CVD) and are also linked to nonalcoholic fatty liver disease (NAFLD). Studies indicate that NAFLD might be a risk factor for CVD whereas low-to-moderate alcohol consumption is associated with lower cardiovascular morbidity and mortality compared to abstainers and heavy drinkers. We hypothesize that FLD interacts with the effect of alcohol intake on markers of inflammation, and thus potentially on cardiovascular risk. Methods and Results. We evaluated alcohol consumption, markers of inflammation and sonographic criteria of FLD in 515 subjects, representing a subsample of a cross-sectional population based study (Echinococcus multilocularis and Internal Diseases in Leutkirch (EMIL) Study). Presence of FLD was markedly reduced in subjects drinking 0-20 g alcohol/d (19%), compared to nondrinkers (35%) and heavy drinkers (34-44.9%). Serum concentrations of inflammatory markers were substantially higher in subjects with FLD. However, presence of FLD showed no effect on the association between alcohol consumption and inflammatory biomarkers. Conclusions. Based on data from a population-based sample, there is no evidence for a link between FLD, alcohol consumption, and inflammatory cardiovascular risk markers. However, larger prospective studies are needed to confirm this.

  15. Presence of Fatty Liver and the Relationship between Alcohol Consumption and Markers of Inflammation

    Directory of Open Access Journals (Sweden)

    Martin Kächele

    2015-01-01

    Full Text Available Background and Aims. Local and systemic inflammation represent a major feature of atherosclerotic cardiovascular disease (CVD and are also linked to nonalcoholic fatty liver disease (NAFLD. Studies indicate that NAFLD might be a risk factor for CVD whereas low-to-moderate alcohol consumption is associated with lower cardiovascular morbidity and mortality compared to abstainers and heavy drinkers. We hypothesize that FLD interacts with the effect of alcohol intake on markers of inflammation, and thus potentially on cardiovascular risk. Methods and Results. We evaluated alcohol consumption, markers of inflammation and sonographic criteria of FLD in 515 subjects, representing a subsample of a cross-sectional population based study (Echinococcus multilocularis and Internal Diseases in Leutkirch (EMIL Study. Presence of FLD was markedly reduced in subjects drinking 0–20 g alcohol/d (19%, compared to nondrinkers (35% and heavy drinkers (34–44.9%. Serum concentrations of inflammatory markers were substantially higher in subjects with FLD. However, presence of FLD showed no effect on the association between alcohol consumption and inflammatory biomarkers. Conclusions. Based on data from a population-based sample, there is no evidence for a link between FLD, alcohol consumption, and inflammatory cardiovascular risk markers. However, larger prospective studies are needed to confirm this.

  16. Epigenetic Mechanisms Underlying the Link between Non-Alcoholic Fatty Liver Diseases and Nutrition

    Directory of Open Access Journals (Sweden)

    Joo Ho Lee

    2014-08-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is defined as a pathologic accumulation of fat in the form of triglycerides (TG in the liver (steatosis that is not caused by alcohol. A subgroup of NAFLD patients shows liver cell injury and inflammation coupled with the excessive fat accumulation (steatohepatitis, which is referred to as non-alcoholic steatohepatitis (NASH. Patients with NASH may develop cirrhosis and hepatocellular carcinoma (HCC. NAFLD shares the key features of metabolic syndrome including obesity, hyperlipidemia, hypertension, and insulin resistance. The pathogenesis of NAFLD is multi-factorial, however the oxidative stress seems to plays a major role in the development and progression of the disease. The emerging field of epigenetics provides a new perspective on the pathogenesis of NAFLD. Epigenetics is an inheritable but reversible phenomenon that affects gene expression without altering the DNA sequence and refers to DNA methylation, histone modifications and microRNAs. Epigenetic manipulation through metabolic pathways such as one-carbon metabolism has been proposed as a promising approach to retard the progression of NAFLD. Investigating the epigenetic modifiers in NAFLD may also lead to the development of preventive or therapeutic strategies for NASH-associated complications.

  17. Three-dimensional perfused human in vitro model of non-alcoholic fatty liver disease

    Science.gov (United States)

    Kostrzewski, Tomasz; Cornforth, Terri; Snow, Sophie A; Ouro-Gnao, Larissa; Rowe, Cliff; Large, Emma M; Hughes, David J

    2017-01-01

    AIM To develop a human in vitro model of non-alcoholic fatty liver disease (NAFLD), utilising primary hepatocytes cultured in a three-dimensional (3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids (FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factor-binding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantly reduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known anti-steatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium. CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds. PMID:28127194

  18. The inflammasome in liver injury and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Mehal, Wajahat Zafar

    2014-01-01

    The liver possesses a strong inflammatory response, as seen experimentally and clinically with liver inflammation due to toxic and metabolic stress, sepsis and ischemia. Initiation of this inflammatory response requires the interaction of two types of extracellular signals which collectively upregulate and activate a cytosolic molecular complex termed the inflammasome. Signal 1 is via activation of pattern recognition receptors, and signal 2 is delivered by diverse stimuli including particulates and adenosine triphosphate. The common end result of inflammasome activation is the activation of the protease caspase-1 with release of active interleukin-1β. The inflammasome is important in a wide range of conditions including alcoholic and non-alcoholic steatohepatitis. Kupffer cells are known to be important, but the consequences of inflammasome activation in other hepatic immune cells have not been well characterized. The inflammasome pathway is also known to be required for a full fibrotic response, as demonstrated by reduced lung, skin and liver fibrosis in inflammasome-deficient mice. Identification of the inflammasome machinery has opened up novel therapeutic avenues by the use of antagonists for Toll-like receptors as well as the adenosine triphosphate receptor P2X7, and the interleukin-1 receptor. There is now great interest in how inflammasome pathways are regulated. The initial challenge is to understand how an acute inflammatory response is sustained. This is a significant issue as the known stimuli result in an acute response that is self-limited to under 24 h. This suggests that there are significant regulators which allow sustained inflammasome activation in conditions such as non-alcoholic steatohepatitis and alcoholic hepatitis.

  19. Proteomic and genomic studies of non-alcoholic fatty liver disease--clues in the pathogenesis.

    Science.gov (United States)

    Lim, Jun Wei; Dillon, John; Miller, Michael

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patient-disease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) anti-inflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production.

  20. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

    Science.gov (United States)

    Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

    2016-01-01

    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

  1. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions.

    Science.gov (United States)

    Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

    2016-09-28

    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

  2. The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Pietrobattista Andrea

    2009-05-01

    Full Text Available Abstract Background Liver fibrosis is a stage of non-alcoholic fatty liver disease (NAFLD which is responsible for liver-related morbidity and mortality in adults. Accordingly, the search for non-invasive markers of liver fibrosis has been the subject of intensive efforts in adults with NAFLD. Here, we developed a simple algorithm for the prediction of liver fibrosis in children with NAFLD followed at a tertiary care center. Methods The study included 136 male and 67 female children with NAFLD aged 3.3 to 18.0 years; 141 (69% of them had fibrosis at liver biopsy. On the basis of biological plausibility, readily availability and evidence from adult studies, we evaluated the following potential predictors of liver fibrosis at bootstrapped stepwise logistic regression: gender, age, body mass index, waist circumference, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase, albumin, prothrombin time, glucose, insulin, triglycerides and cholesterol. A final model was developed using bootstrapped logistic regression with bias-correction. We used this model to develop the 'pediatric NAFLD fibrosis index' (PNFI, which varies between 0 and 10. Results The final model was based on age, waist circumference and triglycerides and had a area under the receiver operating characteristic curve of 0.85 (95% bootstrapped confidence interval (CI with bias correction 0.80 to 0.90 for the prediction of liver fibrosis. A PNFI ≥ 9 (positive likelihood ratio = 28.6, 95% CI 4.0 to 201.0; positive predictive value = 98.5, 95% CI 91.8 to 100.0 could be used to rule in liver fibrosis without performing liver biopsy. Conclusion PNFI may help clinicians to predict liver fibrosis in children with NAFLD, but external validation is needed before it can be employed for this purpose.

  3. Relationship between alcohol consumption and clinical manifestation of patients with fatty liver:a single-center study

    Institute of Scientific and Technical Information of China (English)

    Xiu-FangWang; MinYue

    2011-01-01

    BACKGROUND: Fatty liver is a common chronic liver disease worldwide. It is associated with an increasing morbidity in China in recent years. The aim of this study was to analyze the effect of drinking alcohol on the hemoglobin and biochemical values of patients with fatty liver. METHODS: We investigated the clinical and laboratory data of 669 patients with fatty liver. Of the 669 patients, 166 consumed alcohol more than 60 g per week for at least 2 years, and 503 did not have a history of long-term alcohol consumption. We further analyzed the relationship between alcohol consumption and clinicalcharacteristicsofthesepatients. RESULTS: The values of aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), and hemoglobin in the long-term consumption group were significantly higher than those in the non long-term consumption group (P CONCLUSION: Alcohol consumption is associated with significantly increased values of AST, GGT, and hemoglobin in patients with fatty liver, suggesting their potential roles in hepatic steatosis.

  4. Pentoxifylline ameliorates non-alcoholic fatty liver disease in hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation.

    Science.gov (United States)

    Ye, Jia-Hung; Chao, Jung; Chang, Ming-Ling; Peng, Wen-Huang; Cheng, Hao-Yuan; Liao, Jiunn-Wang; Pao, Li-Heng

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), which includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis, is characterised by abnormal fat accumulation in the liver in the absence of excessive alcohol intake. In patients with type 2 diabetes (T2D), concurrent NAFLD might increase the risk of chronic kidney disease and the mortality rate. Although several studies have examined the effectiveness of pentoxifylline (PTX) in NAFLD treatment, no results are available to verify the effectiveness of PTX in treating T2D associated with NAFLD. In this study, we developed a combined high-fat diet-induced obesity and low-dose streptozocin-induced hyperglycaemia mouse model to mimic the concurrent NAFLD and T2D pathological condition. By combining physiological assessments, pathological examinations, metabolomics studies on blood, urine, and liver, and measurements of gene and protein expression, we elucidated the effectiveness and the underlying mechanism of action of PTX in the hyperglycaemic and dyslipidaemic mice. Our results revealed that PTX ameliorated NAFLD in the hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation. Furthermore, the glycolysis pathway and branched-chain amino acid-related pathways in these mice were restored by PTX.

  5. Pentoxifylline ameliorates non-alcoholic fatty liver disease in hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation

    Science.gov (United States)

    Ye, Jia-Hung; Chao, Jung; Chang, Ming-Ling; Peng, Wen-Huang; Cheng, Hao-Yuan; Liao, Jiunn-Wang; Pao, Li-Heng

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), which includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis, is characterised by abnormal fat accumulation in the liver in the absence of excessive alcohol intake. In patients with type 2 diabetes (T2D), concurrent NAFLD might increase the risk of chronic kidney disease and the mortality rate. Although several studies have examined the effectiveness of pentoxifylline (PTX) in NAFLD treatment, no results are available to verify the effectiveness of PTX in treating T2D associated with NAFLD. In this study, we developed a combined high-fat diet-induced obesity and low-dose streptozocin-induced hyperglycaemia mouse model to mimic the concurrent NAFLD and T2D pathological condition. By combining physiological assessments, pathological examinations, metabolomics studies on blood, urine, and liver, and measurements of gene and protein expression, we elucidated the effectiveness and the underlying mechanism of action of PTX in the hyperglycaemic and dyslipidaemic mice. Our results revealed that PTX ameliorated NAFLD in the hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation. Furthermore, the glycolysis pathway and branched-chain amino acid-related pathways in these mice were restored by PTX. PMID:27612024

  6. Non-alcoholic fatty liver disease and psoriasis: So far, sonear

    Institute of Scientific and Technical Information of China (English)

    Giulia Ganzetti; Anna Campanati; Annamaria Offidani

    2015-01-01

    Psoriasis is a chronic inflammatory immune-mediatedskin diseases which is frequently associated tocomorbidities. Non-alcoholic fatty liver disease (NAFLD)is defined as an excessive accumulation of triglyceridesin hepatocytes and includes a wide spectrum of liverconditions ranging from relatively benign steatosisto non-alcoholic steatohepatitis with fatty infiltrationand lobular inflammation and to cirrhosis and endstageliver disease. Actually, psoriasis is considereda systemic diseases associated to comorbidities, asmetabolic syndrome and NAFLD is seen the hepaticmanifestation of the metabolic syndrome. The possiblelink between psoriasis, obesity and metabolic syndrome,which are known risk factors for NAFLD has beenrecently documented focusing in the crucial role of theadipose tissue in the development of the inflammatorybackground sharing by the above entities. Accordingto recent data, patients with psoriasis show a greaterprevalence of NAFLD and metabolic syndrome thanthe general population. Moreover, patients with NAFLDand psoriasis are at higher risk of severe liver fibrosisthan those with NAFLD and without psoriasis. The linkbetween these pathological conditions appears to be achronic low-grade inflammatory status. The aim of thisreview is to focus on the multiple aspects linking NAFLDand psoriasis, only apparently far diseases.

  7. Observation on Effect of Treatment of Alcoholic Fatty Liver by Traditional Medical Therapy of Liver-Clearing, Dampness-Removing and Collaterals-Dredging

    Institute of Scientific and Technical Information of China (English)

    张诗军; 陈泽雄; 劳绍贤; 黄必军

    2002-01-01

    @@ Spirits of wine is one of the pathogenetic factors of liver damage which is merely secondary to hepatitis virus. The incidence of fatty liver in Chinese adults is 5%-9% now. It is reported that interleukin-8 (IL-8) and lipid peroxidation play an important role in development of alcoholic fatty liver and liver damage(1-3). The authors have observed the therapeutic effect in 30 patients of alcoholic fatty liver treated with Chinese herbal drugs for Liver-clearing, Dampness-removing and Collaterals-dredging (abbre. as CHD) from Aug. 1999 to June 2001 and explored the relationship between the effects of treatment and some indices, including IL-8, malonyldialdehyde (MDA) and superoxide dismutase (SOD).

  8. Adipose Tissue, Metabolic Syndrome, and Non-Alcoholic Fatty Liver Disease – A Short Review

    Directory of Open Access Journals (Sweden)

    Panayiotis Kouis

    2014-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most common chronic liver disease globally, and it is expected to rise even further as a result of the increase in obesity and related risk factors. This short review summarises current evidence on the role of adipose tissue and insulin resistance in NAFLD and the interrelationship between NAFLD and the metabolic syndrome (MetS, considering central adiposity is a major feature of both the MetS and NAFLD, and that NAFLD has been previously described as the hepatic manifestation of the MetS. In addition, genetic studies of NAFLD with relation to adiposity and insulin resistance are reviewed, and up-to-date diagnostic and therapeutic tools are also discussed.

  9. Imaging of non alcoholic fatty liver disease: A road less travelled

    Directory of Open Access Journals (Sweden)

    Divya Singh

    2013-01-01

    Full Text Available Non alcoholic fatty liver disease (NAFLD is a spectrum that includes simple steatosis, nonalcoholic steatohepatitis and cirrhosis. It is increasingly emerging as a cause of elevated liver enzymes, cryptogenic cirrhosis and hepatocellular carcinoma. The morbidity and mortality related to NAFLD is expected to rise with the upsurge of obesity and type 2 diabetes mellitus. The need of the hour is to devise techniques to estimate and then accurately follow-up hepatic fat content in patients with NAFLD. There are lots of imaging modalities in the radiological armamentarium, namely, ultrasonography with the extra edge of elastography, computed tomography, and magnetic resonance imaging with chemical shift imaging and spectroscopy to provide an estimation of hepatic fat content.

  10. Non-alcoholic fatty liver disease - the heart of the matter

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of themost common forms of chronic liver disease in theWestern world. There is a close association with themetabolic syndrome and NAFLD is considered to bethe hepatic manifestation of the metabolic syndrome.The components of the metabolic syndrome includehypertension, obesity and insulin resistance whichare well established cardiovascular risk factors. Themortality rate of NAFLD patients from myocardialinfarction is higher than that in the general United Statespopulation and there is also an increased risk of nonfatalcardiovascular events. This article reviews thecardiovascular complications associated with NAFLD. Inorder to provide comprehensive care of NAFLD patients,physicians need to be aware of, and search for, thecardiac morbidity associated with NAFLD.

  11. Correlation of HIFs/PPAR signaling pathway activation degree and lipid metabolism in liver tissue of alcoholic fatty liver rat model

    Institute of Scientific and Technical Information of China (English)

    Li-Ying Guo; Ya-Min Li; Qing-Chun Li

    2015-01-01

    Objective:To study the correlation of HIFs/PPAR signaling pathway activation degree and lipid metabolism in liver tissue of alcoholic fatty liver rat model.Methods:Adult SD rats were selected and alcoholic fatty liver rat models were established by alcohol administration and high-fat diet feeding. Liver tissue was collected and contents of HIF-1α, PPARγ and lipid metabolism-related enzymes were detected; serum was collected and contents of lipid metabolism indexes and liver cell damage indexes were detected.Results:(1) one week, two weeks, three weeks and four weeks after models were established, HIF-1αα in livers of the model group showed an increasing trend and PPARγ showed a decreasing trend; HIF-1α content was higher than that of the control group and PPARγ content was lower than that of the control group; (2) contents of apoCII, apoCIII,α-GST and GLDH in serum as well as levels of FAT, FABP1, FAS, ACC and ACAT-2 in liver tissue of the model group all significantly increased, and were positively correlated with HIF-1α and negatively correlated with PPARγ.Conclusion:Transcription factor HIF-1α content abnormally increases and PPARγ content abnormally decreases in liver tissue of alcoholic fatty liver rat models; it results in abnormal lipid metabolism and liver cell damage through increasing the expression of lipid metabolism-related enzymes in the liver.

  12. Role of cytokines and chemokines in non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Vincent Braunersreuther; Giorgio Luciano Viviani; Fran(c)ois Mach; Fabrizio Montecucco

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis,to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver.The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state.Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease,inflammatory processes in NAFLD might influence its pathophysiology and prognosis.In particular,nonalcoholic steatohepatitis (the most inflamed condition in NAFLDs,which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators.Among several mediators,cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets.In this review,we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD.

  13. A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence

    Science.gov (United States)

    Temple, Jonathan L.; Cordero, Paul; Li, Jiawei; Nguyen, Vi; Oben, Jude A.

    2016-01-01

    Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, ”paediatric” NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic tools, enabling early diagnosis and appropriate therapeutic intervention. PMID:27314342

  14. Relevant Aspects of Nutritional and Dietary Interventions in Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Maria Catalina Hernandez-Rodas

    2015-10-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the main cause of liver disease worldwide. NAFLD is linked to circumstances such as type 2 diabetes, insulin resistance, obesity, hyperlipidemia, and hypertension. Since the obesity figures and related comorbidities are increasing, NAFLD has turned into a liver problem that has become progressively more common. Currently, there is no effective drug therapy for NAFLD; therefore, interventions in lifestyles remain the first line of treatment. Bearing in mind that adherence rates to this type of treatment are poor, great efforts are currently focused on finding novel therapeutic agents for the prevention in the development of hepatic steatosis and its progression to nonalcoholic steatohepatitis and cirrhosis. This review presents a compilation of the scientific evidence found in the last years showing the results of interventions in lifestyle, diet, and behavioral therapies and research results in human, animal and cell models. Possible therapeutic agents ranging from supplementation with vitamins, amino acids, prebiotics, probiotics, symbiotics, polyunsaturated fatty acids and polyphenols to interventions with medicinal plants are analyzed.

  15. Toll-like receptor 7 affects the pathogenesis of non-alcoholic fatty liver disease

    Science.gov (United States)

    Kim, Sokho; Park, Surim; Kim, Bumseok; Kwon, Jungkee

    2016-01-01

    Recently, a possible link between toll-like receptor 7 (TLR7) and liver disease was suggested, although it was limited to fibrosis. Based on this report, we investigated whether TLR7 has a pivotal role in non-alcoholic fatty liver disease (NAFLD). The TLR7 signaling pathway, which is activated by imiquimod (TLR7 ligand) naturally, induced autophagy and released insulin-like growth factor 1 (IGF-1) into medium from hepatocytes. Lipid accumulation induced by unsaturated fatty acid (UFA; arachidonic acid:oleic acid = 1:1) in hepatocytes, was attenuated in TLR7 and autophagy activation. Interestingly, TLR7 activation attenuated UFA-induced lipid peroxidation products, such as malondialdehyde (MDA) and 4-Hydroxy-2-Nonenal (4-HNE). To clarify a possible pathway between TLR7 and lipid peroxidation, we treated hepatocytes with MDA and 4-HNE. MDA and 4-HNE induced 2-folds lipid accumulation in UFA-treated hepatocytes via blockade of the TLR7 signaling pathway’s IGF-1 release compared to only UFA-treated hepatocytes. In vivo experiments carried out with TLR7 knockout mice produced results consistent with in vitro experiments. In conclusion, TLR7 prevents progression of NAFLD via induced autophagy and released IGF-1 from liver. These findings suggest a new therapeutic strategy for the treatment of NAFLD. PMID:27279075

  16. Toll-like receptor 7 affects the pathogenesis of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Kim, Sokho; Park, Surim; Kim, Bumseok; Kwon, Jungkee

    2016-06-09

    Recently, a possible link between toll-like receptor 7 (TLR7) and liver disease was suggested, although it was limited to fibrosis. Based on this report, we investigated whether TLR7 has a pivotal role in non-alcoholic fatty liver disease (NAFLD). The TLR7 signaling pathway, which is activated by imiquimod (TLR7 ligand) naturally, induced autophagy and released insulin-like growth factor 1 (IGF-1) into medium from hepatocytes. Lipid accumulation induced by unsaturated fatty acid (UFA; arachidonic acid:oleic acid = 1:1) in hepatocytes, was attenuated in TLR7 and autophagy activation. Interestingly, TLR7 activation attenuated UFA-induced lipid peroxidation products, such as malondialdehyde (MDA) and 4-Hydroxy-2-Nonenal (4-HNE). To clarify a possible pathway between TLR7 and lipid peroxidation, we treated hepatocytes with MDA and 4-HNE. MDA and 4-HNE induced 2-folds lipid accumulation in UFA-treated hepatocytes via blockade of the TLR7 signaling pathway's IGF-1 release compared to only UFA-treated hepatocytes. In vivo experiments carried out with TLR7 knockout mice produced results consistent with in vitro experiments. In conclusion, TLR7 prevents progression of NAFLD via induced autophagy and released IGF-1 from liver. These findings suggest a new therapeutic strategy for the treatment of NAFLD.

  17. Circulating sCD36 levels in patients with non-alcoholic fatty liver disease and controls

    DEFF Research Database (Denmark)

    Heebøll, S; Poulsen, M K; Ornstrup, M J;

    2016-01-01

    . An unhealthy and unbalanced CD36 expression in adipose and hepatic tissue may shift the fatty acid load to the liver.Clinical Trials.gov (NCT01464801, NCT01412645, NCT01446276).International Journal of Obesity accepted article preview online, 05 December 2016. doi:10.1038/ijo.2016.223.......BACKGROUND AND OBJECTIVE: CD36 is implicated in fatty acid uptake in multiple tissues, including hepatocytes and adipocytes. Circulating CD36 (sCD36) is increased in non-alcoholic fatty liver disease (NAFLD).We explored this association further by investigating correlations between sCD36 levels...

  18. Circulating sCD36 levels in patients with non-alcoholic fatty liver disease and controls

    DEFF Research Database (Denmark)

    Heebøll, Sara; Poulsen, Marianne Kjær; Ørnstrup, Marie Juul

    2017-01-01

    BACKGROUND AND OBJECTIVE: CD36 is implicated in fatty acid uptake in multiple tissues, including hepatocytes and adipocytes. Circulating CD36 (sCD36) is increased in non-alcoholic fatty liver disease (NAFLD).We explored this association further by investigating correlations between sCD36 levels....... An unhealthy and unbalanced CD36 expression in adipose and hepatic tissue may shift the fatty acid load to the liver.Clinical Trials.gov (NCT01464801, NCT01412645, NCT01446276).International Journal of Obesity accepted article preview online, 05 December 2016. doi:10.1038/ijo.2016.223....

  19. Non-alcoholic fatty liver disease and metabolic syndrome in obese children

    Institute of Scientific and Technical Information of China (English)

    Mehmet Emre Atabek

    2011-01-01

    I read with great interest the article of Fu et al who investigated whether non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome, and whether liver B-ultrasound could be used for its diagnosis, in a study involving 861 obese children (6-16 years old). In this study, it was reported that NAFLD is not only a liver disease, but also an early mediator that reflects metabolic disorder, and that liver B-ultrasound can be a useful tool for metabolic syndrome (MS) screening.Theauthorsreportedthat The authorsreportedthat reported that NAFLD and MS were present in 68.18% and 25.67% of obese children, respectively. Moreover, they observed that the prevalence of MS in NAFLD children was 37.64%, which was much higher than that in the non-NAFLD group. Criteria analogous to those of the Adult Treatment Panel Ⅲ definition for MS were used for children in this study. The reported prevalence data on MS in the young has varied markedly, in large part because of disagreement among the variously proposed definitions of MS. Therefore, in my opinion, a study aiming to assess the association between MS components and NAFLD in obese children has to take into account a simple, easy-to-apply clinical definition proposed by the international diabetes federation for MS. Interpretation of the results of the Fu et al study are limited by another major caveat: that the diagnosis or exclusion of NAFLD was based on liver enzymes and ultrasound imaging, but was not confirmed by liver biopsy. Indeed, it is known that liver enzymes may be within the reference interval in up to 70% of patients with diagnosed NAFLD and that the full histopathological spectrum of NAFLD may be present in patients with normal liver enzymes, which therefore cannot be reliably used to exclude the presence of NAFLD.

  20. Non-alcoholic fatty liver disease and diabetes: from physiopathological interplay to diagnosis and treatment.

    Science.gov (United States)

    Leite, Nathalie C; Villela-Nogueira, Cristiane A; Cardoso, Claudia R L; Salles, Gil F

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2 diabetes are at a particularly high risk for developing the progressive forms of NAFLD, non-alcoholic steatohepatitis and associated advanced liver fibrosis. Moreover, diabetes is an independent risk factor for NAFLD progression, and for hepatocellular carcinoma development and liver-related mortality in prospective studies. Notwithstanding, patients with NAFLD have an elevated prevalence of prediabetes. Recent studies have shown that NAFLD presence predicts the development of type 2 diabetes. Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients. The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods, although histopathological evaluation is still considered the gold standard diagnostic method. An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking. We sought to outline the published data including epidemiology, pathogenesis, diagnosis and treatment of NAFLD in diabetic patients, in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus.

  1. Epigenetic mechanisms in non-alcoholic fatty liver disease: An emerging field.

    Science.gov (United States)

    Gallego-Durán, Rocío; Romero-Gómez, Manuel

    2015-10-28

    Non-alcoholic fatty liver disease (NAFLD) is an emerging health concern in both developed and non-developed world, encompassing from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and liver cancer. Incidence and prevalence of this disease are increasing due to the socioeconomic transition and change to harmful diet. Currently, gold standard method in NAFLD diagnosis is liver biopsy, despite complications and lack of accuracy due to sampling error. Further, pathogenesis of NAFLD is not fully understood, but is well-known that obesity, diabetes and metabolic derangements played a major role in disease development and progression. Besides, gut microbioma and host genetic and epigenetic background could explain considerable interindividual variability. Knowledge that epigenetics, heritable events not caused by changes in DNA sequence, contribute to development of diseases has been a revolution in the last few years. Recently, evidences are accumulating revealing the important role of epigenetics in NAFLD pathogenesis and in NASH genesis. Histone modifications, changes in DNA methylation and aberrant profiles or microRNAs could boost development of NAFLD and transition into clinical relevant status. PNPLA3 genotype GG has been associated with a more progressive disease and epigenetics could modulate this effect. The impact of epigenetic on NAFLD progression could deserve further applications on therapeutic targets together with future non-invasive methods useful for the diagnosis and staging of NAFLD.

  2. Association between serum irisin levels and non-alcoholic fatty liver disease in health screen examinees.

    Directory of Open Access Journals (Sweden)

    Eun Sung Choi

    Full Text Available Irisin is a recently found myokine that aids obesity control and improves glucose homeostasis by acting on white adipose tissue cells and increases total energy consumption. The aim of this study was to evaluate serum irisin levels in patients with non-alcoholic fatty liver disease (NAFLD and to compare these levels with those of normal controls. Among 595 health screen examinees who had visited our institute between January 2013 to March 2013, 355 patients (84 NAFLD patients and 271 normal controls were enrolled depending on whether they gave written informed consents and their history of alcohol intake, blood tests, and abdominal ultrasonographic findings. Age; sex; laboratory test parameters; homeostasis model assessment-insulin resistance; and levels of leptin, adiponectin, and irisin were assessed. Serum irisin levels (ng/ml were significantly higher in the NAFLD group than in normal controls (63.4 ± 32.6 vs. 43.0 ± 29.7, p<0.001 and higher in the mild fatty liver group than in the moderate-to-severe fatty liver group (68.3 ± 38.2 vs. 56.6 ± 21.2, p<0.001. Additionally, serum irisin levels were not different between the non-obese and obese groups (48.4 ± 34.2 vs. 45.8 ± 22.9, p = 0.492; however, the levels were significantly lowest in normal controls and highest in the mild fatty liver group in the non-obese (44.9 ± 31.7 vs. 73.1 ± 48.5 vs 59.7 ± 18.0, p<0.001 and obese groups (35.0 ± 17.0 vs. 62.9 ± 21.2 vs. 54.6 ± 23.3, p<0.001. Serum irisin levels were significantly higher in NAFLD patients, which is not consistent with the results of previously published studies. Therefore, more studies are needed to confirm the role of irisin in NAFLD.

  3. Novel antidiabetic medications for non-alcoholic fatty liver disease with type 2 diabetes mellitus.

    Science.gov (United States)

    Sumida, Yoshio; Seko, Yuya; Yoneda, Masashi

    2016-12-26

    Liver-related diseases are the leading causes of death in patients with type 2 diabetes mellitus (T2DM) in Japan. Type 2 diabetes mellitus is closely associated with non-alcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Non-alcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma and hepatic failure. Non-alcoholic steatohepatitis can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM. Although metformin is established as the first-line therapy for T2DM, given its relative safety and beneficial effects on glycosylated hemoglobin, weight, and cardiovascular mortality, this agent is not recommended as specific therapy for NASH/NAFLD due to lack of clinical evidence. The effects of pioglitazone on NASH histology with T2DM have been extensively proved, but several concerns exist, such as body weight gain, fluid retention, cancer incidence, and bone fracture. In recent years, novel antidiabetic medications have been approved for T2DM, such as glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and sodium/glucose cotransporter 2 inhibitors. A key clinical question for hepatologists is what kinds of antidiabetic medications are the most appropriate for the treatment of NAFLD accompanied by T2DM, to prevent progression of hepatic fibrosis resulting in HCC/liver-related mortality without increased risk of cardiovascular events. This review focuses on novel antidiabetic agents and future perspectives on the treatment of NAFLD/NASH with T2DM.

  4. Hypoxia and fatty liver.

    Science.gov (United States)

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-11-07

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease.

  5. Understanding the pathophysiological mechanisms inthe pediatric non-alcoholic fatty liver disease: The role ofgenetics

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Classically, the non-alcoholic fatty liver disease (NAFLD)physiopathology and progression has been summarizedin the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resistance,accompanying obesity, that leads to liver steatosisincreasing the absolute non esterified fatty acids uptakein the liver and the esterification to form triacylglycerol.The oxidative stress is involved in the second hit leadingto the progression to nonalcoholic steatohepatitis(NASH) because of its harmful action on steatosichepatocytes. However, at the present time, the two hitshypothesis needs to be updated because of the discoverof genetic polymorphisms involved both in the liver fataccumulation and progression to NASH that make moreintriguing understanding the NAFLD pathophysiologicalmechanisms. In this editorial, we want to underline therole of PNPLA3 I148M, GPR120 R270H and TM6SF2E167K in the pediatric NAFLD development becausethey add new pieces to the comprehension of theNAFLD pathophysiological puzzle. The PNPLA3 I148Mpolymorphism encodes for an abnormal protein whichpredisposes to intrahepatic triglycerides accumulationboth for a loss-of-function of its triglyceride hydrolaseactivity and for a gain-of-function of its lipogenic activity.Therefore, it is involved in the first hit, such as TM6SF2E167K polymorphisms that lead to intrahepatic fat accumulationthrough a reduced very low density lipoproteinsecretion. On the other hand, the GPR120 R270H variant,reducing the anti-inflammatory action of the GPR120receptor expressed by Kuppfer cells, is involved in thesecond hit leading to the liver injury.

  6. EXPERIENCE OF ORNITHINE ASPARTATE (HEPA-MERZ) AND PROBIOTICS BIOFLORUM FORTE IN THE TREATMENT OF NON-SEVERE FORMS OF ALCOHOLIC AND NON-ALCOHOLIC FATTY LIVER DISEASE

    OpenAIRE

    2016-01-01

    Aim: to evaluate the efficacy and tolerability of ornithine aspartate, probiotic Bioflorum Forte and their combination with steatosis and steatohepatitis in patients  with alcohol and non-alcoholic  fatty  liver disease. Materials and methods.  An open, randomized,  comparative  clinical study, which included 30 outpatients and inpatients with a diagnosis of steatosis, steatohepatitis. We analyzed the clinical symptoms, functional state of the liver. With the help of questionnaires  (Grids Le...

  7. Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Marialena Mouzaki

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is characterized by dysbiosis. The bidirectional effects between intestinal microbiota (IM and bile acids (BA suggest that dysbiosis may be accompanied by an altered bile acid (BA homeostasis, which in turn can contribute to the metabolic dysregulation seen in NAFLD. This study sought to examine BA homeostasis in patients with NAFLD and to relate that with IM data.This was a prospective, cross-sectional study of adults with biopsy-confirmed NAFLD (non-alcoholic fatty liver: NAFL or non-alcoholic steatohepatitis: NASH and healthy controls (HC. Clinical and laboratory data, stool samples and 7-day food records were collected. Fecal BA profiles, serum markers of BA synthesis 7-alpha-hydroxy-4-cholesten-3-one (C4 and intestinal BA signalling, as well as IM composition were assessed.53 subjects were included: 25 HC, 12 NAFL and 16 NASH. Levels of total fecal BA, cholic acid (CA, chenodeoxycholic acid (CDCA and BA synthesis were higher in patients with NASH compared to HC (p<0.05 for all comparisons. The primary to secondary BA ratio was higher in NASH compared to HC (p = 0.004, but ratio of conjugated to unconjugated BAs was not different between the groups. Bacteroidetes and Clostridium leptum counts were decreased in in a subset of 16 patients with NASH compared to 25 HC, after adjusting for body mass index and weight-adjusted calorie intake (p = 0.028 and p = 0.030, respectively. C. leptum was positively correlated with fecal unconjugated lithocholic acid (LCA (r = 0.526, p = 0.003 and inversely with unconjugated CA (r = -0.669, p<0.0001 and unconjugated CDCA (r = - 0.630, p<0.0001. FGF19 levels were not different between the groups (p = 0.114.In adults with NAFLD, dysbiosis is associated with altered BA homeostasis, which renders them at increased risk of hepatic injury.

  8. Dietary sodium and potassium intake in relation to non-alcoholic fatty liver disease.

    Science.gov (United States)

    Choi, Yuni; Lee, Jung Eun; Chang, Yoosoo; Kim, Mi Kyung; Sung, Eunju; Shin, Hocheol; Ryu, Seungho

    2016-10-01

    A few epidemiological data are available assessing the associations of intakes of sodium (Na) and potassium (K) with non-alcoholic fatty liver disease (NAFLD). We aimed to examine the associations of dietary intake of Na and K with the prevalence of ultrasound-diagnosed NAFLD. We performed a cross-sectional study of 100 177 participants (46 596 men and 53 581 women) who underwent a health screening examination and completed a FFQ at the Kangbuk Samsung Hospital Total Healthcare Centers, South Korea, between 2011 and 2013. NAFLD was defined by ultrasonographic detection of fatty liver in the absence of excessive alcohol intake or other known causes of liver disease. The proportion of NAFLD was 35·6 % for men and 9·8 % for women. Increasing prevalence of NAFLD was observed with increasing Na intake. The multivariable-adjusted prevalence ratios (PR) of NAFLD comparing the highest with the lowest quintile of energy-adjusted Na intake were 1·25 (95 % CI 1·18, 1·32; P trend<0·001) in men and 1·32 (95 % CI 1·18, 1·47; P trend <0·001) in women. However, when we additionally adjusted for body fat percentage, the association became attenuated; the corresponding PR of NAFLD were 1·15 (95 % CI 1·09, 1·21) in men and 1·06 (95 % CI 0·95, 1·17) in women. No inverse association was observed for energy-adjusted K intake. Our findings suggest that higher Na intake is associated with a greater prevalence of NAFLD in young and middle-aged asymptomatic adults, which might be partly mediated by adiposity.

  9. Manifestation of Non-Alcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Different Dietary Mouse Models

    Directory of Open Access Journals (Sweden)

    Vera HI Fengler

    2016-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH, which are usually associated with obesity and metabolic syndrome, are considerable health and economic issues due to the rapid increase of their prevalence in Western society. Histologically, the diseases are characterised by steatosis, hepatic inflammation, and if further progressed, fibrosis. Dietary-induced mouse models are widely used in investigations of the development and progression of NAFLD and NASH; these models attempt to mimic the histological and metabolic features of the human diseases. However, the majority of dietary mouse models fail to reflect the whole pathophysiological spectrum of NAFLD and NASH. Some models exhibit histological features similar to those seen in humans while lacking the metabolic context, while others resemble the metabolic conditions leading to NAFLD in humans but fail to mimic the whole histological spectrum, including progression from steatosis to liver fibrosis, and thus fail to mimic NASH. This review summarises the advantages and disadvantages of the different dietary-induced mouse models of NAFLD and NASH, with a focus on the genetic background of several commonly used wild-type mouse strains as well as gender and age, which influence the development and progression of these liver diseases.

  10. An Animal Model for the Juvenile Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

    Science.gov (United States)

    Marin, Veronica; Rosso, Natalia; Dal Ben, Matteo; Raseni, Alan; Boschelle, Manuela; Degrassi, Cristina; Nemeckova, Ivana; Nachtigal, Petr; Avellini, Claudio; Tiribelli, Claudio; Gazzin, Silvia

    2016-01-01

    Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches. PMID:27391242

  11. Targeting Kupffer cells in non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: Why and how?

    Institute of Scientific and Technical Information of China (English)

    Nicolas; Lanthier

    2015-01-01

    Mechanisms for non-alcoholic steatohepatitis(NASH)development are under investigation in an era of increased prevalence of obesity and metabolic syndrome. Previous findings have pointed to the role of adipose tissue, adipose tissue macrophages and their secretory products in the development of a chronic inflammatory status inducing insulin resistance and a higher risk of liver steatosis called non-alcoholic fatty liver disease. The activation of resident macrophages [Kupffer cells(KC)] and the recruitment of blood derived monocytes/macrophages into the diseased liver have now been identified as key elements for disease initiation and progression. Those cells could be activated through gut flora modifications and an altered gut barrier function but also through the internalization of toxic lipid compounds in adjacent hepatocytes or in KC themselves. Due to the role of activated KC in insulin resistance, fibrosis development and inflammation amplification, they became a target in clinical trials. A shift towards an anti-inflammatory KC phenotype through peroxisome proliferator activator-receptorδ agonists, an inhibition of macrophage recruitment through anti-C-C chemokine receptor 2 action and a specific blocking of internalization of toxic lipoxidation or glycation compounds into KC by galectin-3 receptor inhibitors are now under investigation in human NASH.

  12. Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice.

    Directory of Open Access Journals (Sweden)

    Yvonne Ritze

    Full Text Available OBJECTIVE: Experimental evidence revealed that obesity-associated non-alcoholic fatty liver disease (NAFLD is linked to changes in intestinal permeability and translocation of bacterial products to the liver. Hitherto, no reliable therapy is available except for weight reduction. Within this study, we examined the possible effect of the probiotic bacterial strain Lactobacillus rhamnosus GG (LGG as protective agent against experimental NAFLD in a mouse model. METHODS: Experimental NAFLD was induced by a high-fructose diet over eight weeks in C57BL/J6 mice. Fructose was administered via the drinking water containing 30% fructose with or without LGG at a concentration resulting in approximately 5×10(7 colony forming units/g body weight. Mice were examined for changes in small intestinal microbiota, gut barrier function, lipopolysaccharide (LPS concentrations in the portal vein, liver inflammation and fat accumulation in the liver. RESULTS: LGG increased beneficial bacteria in the distal small intestine. Moreover, LGG reduced duodenal IκB protein levels and restored the duodenal tight junction protein concentration. Portal LPS (P≤0.05 was reduced and tended to attenuate TNF-α, IL-8R and IL-1β mRNA expression in the liver feeding a high-fructose diet supplemented with LGG. Furthermore liver fat accumulation and portal alanine-aminotransferase concentrations (P≤0.05 were attenuated in mice fed the high-fructose diet and LGG. CONCLUSIONS: We show for the first time that LGG protects mice from NAFLD induced by a high-fructose diet. The underlying mechanisms of protection likely involve an increase of beneficial bacteria, restoration of gut barrier function and subsequent attenuation of liver inflammation and steatosis.

  13. Assessment of the co-incidence between non alcoholic fatty liver disease and carotid atherosclerosis.

    Science.gov (United States)

    El-Sayed, Sohair Abd El-Kader; El-Folly, Runia Fouad; Ahmed, Amr Mahmmoud

    2014-04-01

    Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of abnormal liver biochemistry and cryptogenic cirrhosis. Those with NAFLD have a higher prevalence of atherosclerosis, as shown by increased carotid artery intimal media thickness (CIMT). The aim of this study is to assess the co-incidence and prevalence between NAFLD and carotid atherosclerosis. In this study seventy-two subjects were categorized into 2 groups. GI: 52 patients diagnosed as NAFLD with diabetes mellitus type 2 or obesity or hyperlipedemia. GII: 20 diseased controls diagnosed as NAFLD without other predisposing factor. CIMT and plaque prevalence were estimated by carotid ultrasonography as a single trained operator who was blind to clinical characteristics of participants. The results showed that CIMT by carotid duplex ultrasonography was significantly higher in group A than group B but CIMT did not reveal any significant difference as regards to the etiology of NAFLD. CIMT was significantly higher in cases with bright liver than those with homogenous liver (by abdominal US) in group I and II. CIMT was significantly higher in those with moderate steatosis than those with mild steatosis (in GI & GII).

  14. Monounsaturated fat decreases hepatic lipid content in non-alcoholic fatty liver disease in rats

    Institute of Scientific and Technical Information of China (English)

    Osamah Hussein; Masha Grosovski; Etti Lasri; Sergio Svalb; Uzi Ravid; Nimer Assy

    2007-01-01

    AIM: To evaluate the effects of different types of dietary fats on the hepatic lipid content and oxidative stress parameters in rat liver with experimental non-alcoholic fatty liver disease (NAFLD).METHODS: A total of 32 Sprague-Dawley rats were randomly divided into five groups. The rats in the control group (n = 8) were on chow diet (Group 1), rats (n =6) on methionine choline-deficient diet (MCDD) (Group 2), rats (n = 6) on MCDD enriched with olive oil (Group 3), rats (n = 6) on MCDD with fish oil (Group 4) and rats (n = 6) on MCDD with butter fat (Group 5). After 2 mo, blood and liver sections were examined for lipids composition and oxidative stress parameters.RESULTS: The liver weight/rat weight ratio increased in all treatment groups as compared with the control group. Severe fatty liver was seen in MCDD + fish oil and in MCDD + butter fat groups, but not in MCDD and MCDD + olive oil groups. The increase in hepatic triglycerides (TG) levels was blunted by 30% in MCDD+ olive oil group (0.59 ± 0.09) compared with MCDD group (0.85 ± 0.04, P < 0.004), by 37% compared with MCDD + fish oil group (0.95±0.07, P < 0.001), and by 33% compared with MCDD + butter group (0.09±0.1,P < 0.01). The increase in serum TG was lowered by10% in MCDD + olive oil group (0.9 ± 0.07) compared with MCDD group (1.05 ± 0.06). Hepatic cholesterol increased by 15-fold in MCDD group [(0.08 ± 0.02, this increment was blunted by 21% in MCDD + fish oil group(0.09 ± 0.02)]. In comparison with the control group,ratio of long-chain polyunsaturated fatty acids omega-6/omega-3 increased in MCDD + olive oil, MCDD + fish oil and MCDD + butter fat groups by 345-, 30- and 397-fold, respectively. In comparison to MCDD group(1.58±0.08), hepatic MDA contents in MCDD + olive oil(3.3±0.6), MCDD + fish oil (3.0±0.4), and MCDD +butter group (2.9±0.36) were increased by 108%, 91%and 87%, respectively (P < 0.004). Hepatic paraoxonase activity decreased significantly in all treatment groups

  15. Pathogenesis, diagnosis and treatment of non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Verónica Martín-Domínguez

    2013-08-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD includes a broad spectrum of alterations that go from simple steatosis to steatohepatitis and cirrhosis. Type 2 diabetes mellitus (DM-2 and obesity are the principle factors associated to NAFLD. A 20-30 % prevalence in general population has been described. The survival of this type of patient is lower than the general population's, showing a higher incidence of hepatic and cardiovascular complications. The aetiopathogenesis is still unclear, but we know the intervention of different factors that produce fatty-acid accumulation in hepatic parenchyma, causing oxidative stress, oxygen-free radicals and the synthesis of an inflammatory cascade, that determine the progression of this disease from steatosis up to advanced fibrosis. The diagnostic gold-standard is still the liver biopsy, even though the development of newer non-invasive techniques, like serological and imaging (radiology, have opened a new field for research that allows bloodless testing of these patients and better study of the natural history of this disease. Nowadays, there is still no specific treatment for NAFLD. The development of healthy life habits and moderate exercise continue to be the pillars of treatment. Different pharmacological approaches have been studied and applied, such as the control of insulin resistance, lowering cholesterol levels, antioxidants, and other alternatives in experimental trials.

  16. Lifestyle intervention for non-alcoholic fatty liver disease: prospective cohort study of its efficacy and factors related to improvement.

    NARCIS (Netherlands)

    Koot, B.G.P.; Baan-Slootweg, O.H. van der; Tamminga-Smeulders, C.L.J.; Pels Rijcken, T.H.; Korevaar, J.C.; Aalderen, W.M. van; Jansen, P.L.M.; Benninga, M.A.

    2011-01-01

    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obese children. Lifestyle intervention is the primary treatment for NAFLD. However, limited data are available regarding the efficacy of lifestyle interventions. OBJECTIVES: To prospectively determine the efficacy of a li

  17. Lifestyle intervention for non-alcoholic fatty liver disease: prospective cohort study of its efficacy and factors related to improvement

    NARCIS (Netherlands)

    Koot, B.G.P.; van der Baan-Slootweg, O.H.; Tamminga-Smeulders, C.L.J.; Pels Rijcken, T.H.; Korevaar, J.C.; van Aalderen, W.M.; Jansen, P.L.M.; Benninga, M.A.

    2011-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obese children. Lifestyle intervention is the primary treatment for NAFLD. However, limited data are available regarding the efficacy of lifestyle interventions. Objectives To prospectively determine the efficacy of a life

  18. The association of serum uric acid level with prevalence of non-alcoholic fatty liver in Uyghur and Han ethnicities

    Institute of Scientific and Technical Information of China (English)

    蔡雯

    2013-01-01

    Objective To explore the association of serum uric acid level with non-alcoholic fatty liver disease(NAFLD) in Han and Uyghur ethnic groups. Methods A cross-sectional study was performed in the population in 2011 in the First Affiliated Hospital of Xinjiang Medical University.

  19. Effects of glucagon-like peptide-1 on glucagon secretion in patients with non-alcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Junker, Anders E; Gluud, Lise L; van Hall, Gerrit

    2016-01-01

    BACKGROUND & AIMS: We evaluated the glucagon-suppressive effect of glucagon-like peptide-1 (GLP-1) and its potential effects on endogenous glucose production and whole body lipolysis in non-diabetic patients with non-alcoholic fatty liver disease (NAFLD). METHODS: On two separate days 10 non...

  20. SREBP-2 1784 G/C Genotype is Associated with Non-Alcoholic Fatty Liver Disease in North Indians

    Directory of Open Access Journals (Sweden)

    Surya Prakash Bhatt

    2011-01-01

    Full Text Available Background: Genetics of non-alcoholic fatty liver (NAFLD in Asian Indians has been inadequately investigated. This study aims to determine the association of the 1784G > C polymorphism in the SREBP-2 gene with NAFLD in Asian Indians in north India.

  1. MicroRNAs as controlled systems and controllers in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Panera, Nadia; Gnani, Daniela; Crudele, Annalisa; Ceccarelli, Sara; Nobili, Valerio; Alisi, Anna

    2014-11-07

    Non-alcoholic fatty liver disease (NAFLD) is a multi-faceted condition including simple steatosis alone or associated with inflammation and ballooning (non-alcoholic steatohepatitis) and eventually fibrosis. The NAFLD incidence has increased over the last twenty years becoming the most frequent chronic liver disease in industrialized countries. Obesity, visceral adiposity, insulin resistance, and many other disorders that characterize metabolic syndrome are the major predisposing risk factors for NAFLD. Furthermore, different factors, including genetic background, epigenetic mechanisms and environmental factors, such as diet and physical exercise, contribute to NAFLD development and progression. Several lines of evidence demonstrate that specific microRNAs expression profiles are strongly associated with several pathological conditions including NAFLD. In NAFLD, microRNA deregulation in response to intrinsic genetic or epigenetic factors or environmental factors contributes to metabolic dysfunction. In this review we focused on microRNAs role both as controlled and controllers molecules in NAFLD development and/or their eventual value as non-invasive biomarkers of disease.

  2. Serum parameters predict the severity of ultrasonographicifndingsinnon-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Mohsen Razavizade; Raika Jamali; Abbas Arj; Hamidreza Talari

    2012-01-01

    BACKGROUND: Controversy exists about the correlation between liver ultrasonography and serum parameters for evaluating the severity of liver involvement in non-alcoholic fatty liver disease (NAFLD). This study was designed to determine the association between liver ultrasonography staging in NAFLD and serum parameters correlated with disease severity in previous studies; and set optimal cut-off points for those serum parameters correlated with NAFLD staging at ultrasonography, in order to differentiate ultrasonographic groups (USGs). METHODS: This cross-sectional study evaluated outpatients with evidence of NAFLD in ultrasonography referred to a general hospital. Those with positive viral markers, abnormal serum ceruloplasmin or gamma-globulin concentrations were excluded. A radiologist performed the ultrasonography staging and stratiifed the patients into mild, moderate, and severe groups. Fasting serum alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, triglyceride (TG), high and low density lipoprotein (HDL, LDL), and cholesterol were checked. RESULTS:Two hundred and forty-ifve patients with a mean age (±standard deviation) of 41.63(±11.46) years were included. There were no signiifcant differences when mean laboratory concentrations were compared between moderate and severe USGs. Therefore, these groups were combined to create revised USGs ("mild"versus"moderate or severe"). There were associations between the revised USGs, and ALT, TG, HDL levels, and diabetes mellitus [odds ratios=2.81 (95%conifdence interval (CI):1.37-5.76), 2.48 (95%CI:1.29-4.78), 0.36 (95%CI:0.18-0.74), and 5.65 (95%CI:2.86-11.16) respectively;all P values CONCLUSIONS: Serum ALT, TG, and HDL concentrations seem to be associated with the staging by liver ultrasonography in NAFLD. They might be used to predict the staging of liver ultrasonography in these patients.

  3. Oral probiotic microcapsule formulation ameliorates non-alcoholic fatty liver disease in Bio F1B Golden Syrian hamsters.

    Directory of Open Access Journals (Sweden)

    Jasmine Bhathena

    Full Text Available The beneficial effect of a microencapsulated feruloyl esterase producing Lactobacillus fermentum ATCC 11976 formulation for use in non-alcoholic fatty liver disease (NAFLD was investigated. For which Bio F1B Golden Syrian hamsters were fed a methionine deficient/choline devoid diet to induce non-alcoholic fatty liver disease. Results, for the first time, show significant clinical benefits in experimental animals. Examination of lipids show that concentrations of hepatic free cholesterol, esterified cholesterol, triglycerides and phospholipids were significantly lowered in treated animals. In addition, serum total cholesterol, triglycerides, uric acid and insulin resistance were found to decrease in treated animals. Liver histology evaluations showed reduced fat deposits. Western blot analysis shows significant differences in expression levels of key liver enzymes in treated animals. In conclusion, these findings suggest the excellent potential of using an oral probiotic formulation to ameliorate NAFLD.

  4. Sarcopenia and non-alcoholic fatty liver disease: Is there a relationship? A systematic review

    Science.gov (United States)

    Tovo, Cristiane V; Fernandes, Sabrina A; Buss, Caroline; de Mattos, Angelo A

    2017-01-01

    AIM To perform a systematic review to evaluate the incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) in adult patients with sarcopenia. METHODS Randomized clinical trials, cross-sectional or cohort studies including adult patients (over 18 years) with sarcopenia were selected. The primary outcomes of interest were the prevalence or incidence of NAFLD in sarcopenic patients. In the screening process, 44 full-text articles were included in the review and 41 studies were excluded. RESULTS Three cross-sectional studies were included. The authors attempted to perform a systematic review, but due to the differences between the studies, a qualitative synthesis was provided. The diagnosis of NAFLD was made by non-invasive methods (image methods or any surrogate markers) in all three evaluated studies. All the studies suggested that there was an independent association between sarcopenia and NAFLD. CONCLUSION Sarcopenia is independently associated with NAFLD and possibly to an advanced fibrosis. PMID:28293382

  5. Reducing Liver Fat by Low Carbohydrate Caloric Restriction Targets Hepatic Glucose Production in Non-Diabetic Obese Adults with Non-Alcoholic Fatty Liver Disease

    OpenAIRE

    Haoyong Yu; Weiping Jia; ZengKui Guo

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective: this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans w...

  6. Liver glycerol permeability and aquaporin-9 are dysregulated in a murine model of Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Patrizia Gena

    Full Text Available One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD, is a worrisome health problem worldwide characterized by intrahepatic triacylglycerol (TG overaccumulation. NAFLD is a common feature of metabolic syndrome being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import of glycerol, the other primary source (as glycerol-3-phosphate of increased TG in hepatocytes. Obese leptin-deficient (ob/ob mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9, the major pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33% than lean mice, a finding fully confirmed by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly lower (53% than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased level of plasma glycerol characterizing obese mice. In summary, our results suggest implication of AQP9 in liver steatosis. The reduction of hepatocyte AQP9 and, consequently, glycerol permeability might be a defensive mechanism to counteract further fat infiltration in liver parenchyma.

  7. Metformin in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

    Science.gov (United States)

    Li, Yan; Liu, Lei; Wang, Bin; Wang, Jun; Chen, Dongfeng

    2013-01-01

    Non-alcoholic fatty liver disease (NAFLD) related to insulin resistance (IR) is a growing global health concern. Recent studies have indicated that metformin could improve IR and may be beneficial in the treatment of NAFLD. This study aimed to assess the beneficial or harmful effects of metformin in NAFLD. We searched Medline and four other databases during April 2012. Selection criteria were randomized clinical trials comparing metformin with placebo or other interventions for treating NAFLD patients. The primary outcome was histological response. The secondary outcomes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), homeostasis model assessment of IR (HOMA-IR), body mass index (BMI) and adverse events. Dichotomous data were reported as odds ratio (OR), while continuous data were calculated as the mean difference (MD), both with 95% confidence intervals (CI). Random and fixed effects meta-analyses were performed. Nine studies were included, involving 417 participants, and conducted for a time period ranging from 4 to 12 months. In the treated participants, improvements were observed in ALT (MD, -8.12 U/l; P=0.03), AST (MD, -4.52 U/l; P=0.04), HOMA-IR (MD, -0.61; P=0.005) and BMI (MD, -0.82 kg/m(2); P=0.04), but not in histological response: steatosis (P=0.66), inflammation (P=0.91), hepatocellular ballooning (P= 0.25) and fibrosis (P= 0.90). Sub-analysis of non-alcoholic fatty steatohepatitis showed that metformin failed to improve any pooled outcome. Adverse events were poorly reported. Current information indicates that metformin improves liver function, HOMA-IR and BMI to some extent, but not histological response in NAFLD patients. This finding could serve as a stimulus for future studies investigating issues such as dose-responsiveness, safety and patient tolerance to metformin therapy.

  8. Mediterranean diet and non-alcoholic fatty liver disease: new therapeutic option around the corner?

    Science.gov (United States)

    Sofi, Francesco; Casini, Alessandro

    2014-06-21

    Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in Western countries, being considered as the hepatic manifestation of metabolic syndrome. NAFLD has a common pathogenic background to that of metabolic syndrome, and shares many risk factors such as obesity, hypertension, insulin resistance and dyslipidemia. Although there is no currently available evidence-based established treatment for NAFLD, all the recommendations from the medical associations indicate that the most effective treatment is to reduce weight through lifestyle modifications. Diet, indeed, plays a key role in the management of NAFLD patients, as both the quantity and quality of the diet have been reported to have a beneficial role in the onset and severity of the liver disease. Among all the diets that have been proposed, a Mediterranean diet was the most effective dietary option for inducing weight loss together with beneficial effects on all the risk factors associated with metabolic syndrome and NAFLD. Over the last few years, research has demonstrated a beneficial effect of a Mediterranean diet in NAFLD. In this review, we will examine all the available data on the association between diet, nutrients and the Mediterranean diet in association with onset and severity of NAFLD.

  9. GLP-1 receptor agonists: effects on the progression of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Liu, Jia; Wang, Guang; Jia, Yumei; Xu, Yuan

    2015-05-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, and its incidence has been increasing recently. In addition to hepatic complications, NAFLD is also recognized as an independent risk factor for cardiovascular disease. Unfortunately, the current therapies for NAFLD display variable efficacy; a novel and effective drug is urgently needed. Glucagon-like peptide-1 (GLP-1), a receptor agonist is a new drug approved for treating type 2 diabetes. Recently, these types of agents have shown a novel therapeutic effect on NAFLD. However, the mechanisms of GLP-1 receptor agonists on the treatment of NAFLD have not yet been explained precisely. Recent studies have demonstrated that GLP-1 reverses the progression of NAFLD not only indirectly through an incretin effect that improves key parameters involved in NAFLD, but also a direct effect on lipid metabolism of hepatocytes and inflammation in liver. In this review, we provided an overview of the role and mechanisms of GLP-1 in the therapy of NAFLD.

  10. Epigenetic mechanisms in non-alcoholic fatty liver disease:An emerging field

    Institute of Scientific and Technical Information of China (English)

    Rocío; Gallego-Durán; Manuel; Romero-Gómez

    2015-01-01

    Non-alcoholic fatty liver disease(NAFLD) is an emerging health concern in both developed and non-developed world, encompassing from simple steatosis to nonalcoholic steatohepatitis(NASH), cirrhosis and liver cancer. Incidence and prevalence of this disease are increasing due to the socioeconomic transition and change to harmful diet. Currently, gold standard method in NAFLD diagnosis is liver biopsy, despite complications and lack of accuracy due to sampling error. Further, pathogenesis of NAFLD is not fully understood, but is well-known that obesity, diabetes and metabolic derangements played a major role in disease development and progression. Besides, gut microbioma and host genetic and epigenetic background could explain considerable interindividual variability. Knowledge that epigenetics, heritable events not caused by changes in DNA sequence, contribute to development of diseases has been a revolution in the last few years. Recently, evidences are accumulating revealing the important role of epigenetics in NAFLD pathogenesis and in NASH genesis. Histone modifications, changes in DNA methylation and aberrant profiles or micro RNAs could boost development of NAFLD and transition into clinical relevant status. PNPLA3 genotype GG has been associated with a more progressive disease and epigenetics could modulate this effect. The impact of epigenetic on NAFLD progression could deserve further applications on therapeutic targets together with future non-invasive methods useful for the diagnosis and staging of NAFLD.

  11. Therapeutic options in pediatric non alcoholic fatty liver disease: current status and future directions

    Directory of Open Access Journals (Sweden)

    Vajro Pietro

    2012-10-01

    Full Text Available Abstract The epidemics of overweight and obesity has resulted in a significant increase of non alcoholic fatty liver disease (NAFLD, a potentially progressive condition. Currently, obesity related hepatopathy represents therefore the main cause of pediatric chronic liver disease. The first choice treatment at all ages is weight loss and/or lifestyle changes, however compliance is very poor and a pharmacological approach has become necessary. In the present article we present a systematic literature review focusing on established pediatric NALFD drugs (ursodeoxycholic acid, insulin sensitizers, and antioxidants and on innovative therapeutic options as well. Regarding the former ones, a pediatric pilot study highlighted that ursodeoxycholic acid is not efficient on transaminases levels and bright liver. Similarly, a recent large scale, multicenter randomized clinical trial (TONIC study showed that also insulin sensitizers and antioxidant vitamin E have scarce effects on serum transaminase levels. Among a large series of novel therapeutic approaches acting on recently proposed different pathomechanisms, probiotics seem hitherto the most interesting and reasonable option for their safety and tolerability. Toll-like receptors modifiers, Pentoxifylline, and Farnesoid X receptors agonists have been still poorly investigated, and will need further studies before becoming possible promising innovative therapeutic strategies.

  12. Effectiveness of exercise in hepatic fat mobilization in non-alcoholic fatty liver disease: Systematic review

    Science.gov (United States)

    Golabi, Pegah; Locklear, Cameron T; Austin, Patrick; Afdhal, Sophie; Byrns, Melinda; Gerber, Lynn; Younossi, Zobair M

    2016-01-01

    AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease (NAFLD) patients. METHODS: Ovid-Medline, PubMed, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: “NASH”, “NAFLD”, “non-alcoholic steatohepatitis”, “non-alcoholic fatty liver disease”, “fat”, “steatosis”, “diet”, “exercise”, “MR spectroscopy” and “liver biopsy”. NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy (H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. RESULTS: Eight studies met selection criteria (6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared the two interventions. The beneficial effects of exercise on intrahepatic triglyceride (IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents

  13. Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

    Science.gov (United States)

    Leung, Christopher; Herath, Chandana B; Jia, Zhiyuan; Andrikopoulos, Sof; Brown, Bronwyn E; Davies, Michael J; Rivera, Leni R; Furness, John B; Forbes, Josephine M; Angus, Peter W

    2016-01-01

    AIM To determine if manipulation of dietary advanced glycation end product (AGE), intake affects non-alcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/- animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD. PMID:27672297

  14. Prevalence of Non-alcoholic Fatty Liver Disease and Its Related Factors in Iran

    Science.gov (United States)

    Moghaddasifar, I.; Lankarani, K. B.; Moosazadeh, M.; Afshari, M.; Ghaemi, A.; Aliramezany, M.; Afsar Gharebagh, R.; Malary, M.

    2016-01-01

    Background: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in developing and developed countries. Estimating the total prevalence of NAFLD by means of appropriate statistical methods can provide reliable evidence for health policy makers. Objective: To determine the prevalence of NAFLD in Iran using a systematic review and meta-analysis. Methods: We identified relevant studies by searching national and international databases. Standard error of the prevalence reported in each study was calculated assuming a binomial distribution. The heterogeneity between the results of the studies was determined using Cochran’s Q and I square indices. We used a random effect model to combine the prevalence rates reported in the studies. Results: We entered 23 eligible studies in this systematic review investigated NAFLD among 25,865 Iranian people. The total prevalence of NAFLD, prevalence of mild, moderate and severe fatty liver disease were estimated at 33.9% (95% CI 26.4%–41.5%), 26.7% (95% CI 21.7%–31.7%), 7.6% (95% CI 5.7%–9.4%), and 0.5% (95% CI 0.1%–0.9%), respectively. The majority of studies reported that NAFLD was more common among men (seven of eight studies), obese person (15 of 15 studies), older people (10 of 10 studies), patients with systolic hypertension (5 of 8 studies), patients with diastolic hypertension (7 of 9 studies), patients with hypertriglyceridemia (14 of 16 studies), patients with high HOMA level (4 of 4 studies), patients with metabolic syndrome (4 of 4 studies), and those with elevated serum ALT (8 of 12 studies). Conclusion: Our study showed that the prevalence of NAFLD in Iran was relatively high and male gender, old age, diabetes, metabolic syndrome, systolic/diastolic hypertension, high serum ALT, and hypertriglyceridemia may be determinants of NAFLD.

  15. Non-Alcoholic Fatty Liver Disease (NAFLD and Its Connection with Insulin Resistance, Dyslipidemia, Atherosclerosis and Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Amalia Gastaldelli

    2013-05-01

    Full Text Available Non-alcoholic fatty liver disease is marked by hepatic fat accumulation not due to alcohol abuse. Several studies have demonstrated that NAFLD is associated with insulin resistance leading to a resistance in the antilipolytic effect of insulin in the adipose tissue with an increase of free fatty acids (FFAs. The increase of FFAs induces mitochondrial dysfunction and development of lipotoxicity. Moreover, in subjects with NAFLD, ectopic fat also accumulates as cardiac and pancreatic fat. In this review we analyzed the mechanisms that relate NAFLD with metabolic syndrome and dyslipidemia and its association with the development and progression of cardiovascular disease.

  16. EXPERIENCE OF ORNITHINE ASPARTATE (HEPA-MERZ AND PROBIOTICS BIOFLORUM FORTE IN THE TREATMENT OF NON-SEVERE FORMS OF ALCOHOLIC AND NON-ALCOHOLIC FATTY LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    L. Yu. Ilchenko

    2016-01-01

    Full Text Available Aim: to evaluate the efficacy and tolerability of ornithine aspartate, probiotic Bioflorum Forte and their combination with steatosis and steatohepatitis in patients  with alcohol and non-alcoholic  fatty  liver disease. Materials and methods.  An open, randomized,  comparative  clinical study, which included 30 outpatients and inpatients with a diagnosis of steatosis, steatohepatitis. We analyzed the clinical symptoms, functional state of the liver. With the help of questionnaires  (Grids LeGo and post intoxication alcohol syndrome have established the presence of chronic alcohol intoxication. Test transmissions of numbers used to characterize the cognitive function, as well as detection  of minimal hepatic encephalopathy. Quality of life was assessed by questionnaire for patients with chronic liver disease — CLDQ (The chronic liver disease questionnaire. The duration of treatment was4 weeks. Results: all three treatment regimens have demonstrated therapeutic  efficacy: clinical improvement, recovery of liver function and results in cognitive function. When combined therapy also produced a significant improvement  in patients’ quality of life. It is shown that  the safety and tolerability of the means employed, adverse events were not reported. Conclusion: the results obtained allow us to recommend the use of ornithine aspartate (Hepa-Merz, both as monotherapy and as part of complex therapy of steatosis,  steatohepatitis with probiotic Bioflorum Forte in patients with alcoholic and non-alcoholic fatty liver disease.

  17. [Mechanisms of formation and progression of non-alcoholic fatty liver disease in type 2 diabetics].

    Science.gov (United States)

    Kravchun, N; Dorosh, E

    2014-03-01

    Currently, study of the mechanisms of formation and progression of non-alcoholic fatty liver disease (NAFLD) in the patients with type 2 diabetes mellitus (DM) is a topical problem in endocrinology. Prognosis for the disease depends on NAFLD stage and it determines the necessity to study the origin and mostly the progression in NAFLD course. It will favour the enhancement of efficacy of the treatment for this cohort of patients. The object of this work was to study the mechanisms of formation of NAFLD phasic course in type 2 diabetics via determining the levels of lipid peroxidation (LPO), 8-isoprostaglandin as components of oxidative stress. LPO indices and liver functional activity parameters (general cholesterol, high-density lipoproteids cholesterol, triglycerides, β-lipoproteids, very-low-density lipoproteids cholesterol, atherogenicity coefficient, thymol test, alanine aminotransferase, aspartate aminotransferase) were determined in the examined individuals. The carried research allowed, that changes in biochemical parameters levels is connected with increasing of diene conjugates (DC) activity and the carried correlation analysis of the studied values proved this relevance. The subgroup of the patients with DC levels of 200-400 nmol/l has no inflammatory alterations (cytolysis syndrome) that gives evidence of steatosis phase. The group of patients with DC levels of 400-600 nmol/l demonstrated the stage of non-alcoholic steatohepatitis with the most expressed shifts in functional liver condition. The greatest lipid, carbohydrate metabolic changes were found in the subgroup of the patients with DC level of 600 nmol/l and more that gives evidence of fibrotic processes.

  18. Hypoxia and fatty liver

    OpenAIRE

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-01-01

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty li...

  19. Cordyceps militaris alleviates non-alcoholic fatty liver disease in ob/ob mice

    Science.gov (United States)

    Choi, Ha-Neul; Jang, Yang-Hee; Kim, Min-Joo; Seo, Min Jeong; Kang, Byoung Won; Jeong, Yong Kee

    2014-01-01

    BACKGROUND/OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model. MATERIALS/METHODS Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free fatty acid (FFA), alanine transaminase (ALT), and proinflammatory cytokines were measured. Hepatic levels of lipids, glutathione (GSH), and lipid peroxide were determined. RESULTS Consumption of C. militaris significantly decreased serum glucose, as well as homeostasis model assessment for insulin resistance (HOMA-IR), in ob/ob mice. In addition to lowering serum FFA levels, C. militaris also significantly decreased hepatic total lipids and triglyceride contents. Serum ALT activities and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were reduced by C. militaris. Consumption of C. militaris increased hepatic GSH and reduced lipid peroxide levels. CONCLUSIONS These results indicate that C. militaris can exert protective effects against development of NAFLD, partly by reducing inflammatory cytokines and improving hepatic antioxidant status in ob/ob mice. PMID:24741401

  20. Hepatoprotective and antioxidant effects of lycopene on non-alcoholic fatty liver disease in rat

    Science.gov (United States)

    Jiang, Wei; Guo, Mei-Hua; Hai, Xin

    2016-01-01

    AIM To evaluate the hepatoprotective effect of lycopene (Ly) on non-alcoholic fatty liver disease (NAFLD) in rat. METHODS A rat model of NAFLD was first established by feeding a high-fat diet for 14 wk. Sixty-five rats were randomly divided into normal group, model group and Ly treatment groups. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC) in serum and low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), free fatty acid (FFA), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) in liver tissue were evaluated, respectively. While the hepatoprotective effect was also confirmed by histopathological analysis, the expression levels of TNF-α and cytochrome P450 (CYP) 2E1 in rat liver were determined by immunohistochemistry analysis. RESULTS A significant decrease was observed in the levels of serum AST (2.07-fold), ALT (2.95-fold), and the blood lipid TG (2.34-fold) and TC (1.66-fold) in the dose of 20 mg/kg Ly-treated rats (P < 0.01), compared to the model group. Pretreatment with 5, 10 and 20 mg/kg of Ly significantly raised the levels of antioxidant enzyme SOD in a dose-dependent manner, to 90.95 ± 9.56, 109.52 ± 11.34 and 121.25 ± 10.68 (P < 0.05, P < 0.01), as compared with the model group. Similarly, the levels of GSH were significantly increased (P < 0.05, P < 0.01) after the Ly treatment. Meanwhile, pretreatment with 5, 10 and 20 mg/kg of Ly significantly reduced MDA amount by 30.87, 45.51 and 54.49% in the liver homogenates, respectively (P < 0.01). The Ly treatment group showed significantly decreased levels of lipid products LDL-C (P < 0.05, P < 0.01), improved HDL-C level and significantly decreased content of FFA, compared to the model group (P < 0.05, P < 0.01). Furthermore, the Ly-treated group also exhibited a down-regulated TNF-α and CYP2E1 expression, decreased infiltration of liver fats and reversed histopathological changes, all

  1. Serum procalcitonin and CRP levels in non-alcoholic fatty liver disease: a case control study

    Directory of Open Access Journals (Sweden)

    Ersoz Galip

    2009-02-01

    Full Text Available Abstract Background Both C reactive protein (CRP and procalcitonin (PCT are well known acute phase reactant proteins. CRP was reported to increase in metabolic syndrome and type-2 diabetes. Similarly altered level of serum PCT was found in chronic liver diseases and cirrhosis. The liver is considered the main source of CRP and a source of PCT, however, the serum PCT and CRP levels in non-alcoholic fatty liver disease (NAFLD were not compared previously. Therefore we aimed to study the diagnostic and discriminative role of serum PCT and CRP in NAFLD. Methods Fifty NAFLD cases and 50 healthy controls were included to the study. Liver function tests were measured, body mass index was calculated, and insulin resistance was determined by using a homeostasis model assessment (HOMA-IR. Ultrasound evaluation was performed for each subject. Serum CRP was measured with nephalometric method. Serum PCT was measured with Kryptor based system. Results Serum PCT levels were similar in steatohepatitis (n 20 and simple steatosis (n 27 patients, and were not different than the control group (0.06 ± 0.01, 0.04 ± 0.01 versus 0.06 ± 0.01 ng/ml respectively. Serum CRP levels were significantly higher in simple steatosis, and steatohepatitis groups compared to healthy controls (7.5 ± 1.6 and 5.2 ± 2.5 versus 2.9 ± 0.5 mg/dl respectively p Conclusion Serum PCT was within normal ranges in patients with simple steatosis or steatohepatitis and has no diagnostic value. Serum CRP level was increased in NAFLD compared to controls. CRP can be used as an additional marker for diagnosis of NAFLD but it has no value in discrimination of steatohepatitis from simple steatosis.

  2. Alcoholic liver disease: The gut microbiome and liver crosstalk

    OpenAIRE

    Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

    2015-01-01

    Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing ...

  3. Circulating microRNAs in patients with non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Serkan; Dogan; Gokmen; Zararsiz; Sebnem; Gursoy; Kadri; Guven; Omer; Ozbakir; Munis; Dundar; Mehmet; Yucesoy

    2014-01-01

    AIM: To identify novel non-invasive biomarkers for non-alcoholic fatty liver disease(NAFLD). METHODS: Twenty patients with histologically proven NAFLD and 20 controls were included. All NAFLD cases were scored using the NAFLD activity score. The rela-tive expressions of miR-197, miR-146 b, miR-10 b, miR-181d, miR-34 a, miR-122, miR-99 a and miR-29 a were analyzed using real-time polymerase chain reaction. RESULTS: Serum levels of miR-181 d, miR-99 a, miR-197 and miR-146 b were significantly lower in biopsy-proven NAFLD patients than in the healthy controls. Serum lev-els of miR-197 and miR-10 b were inversely correlated with degree of inflammation and miR-181 d and miR-99 a were inversely correlated with serum gamma glu-tamyl transferase levels in non-alcoholic steatohepatitis patients. CONCLUSION: NAFLD is associated with altered se-rum miRNA expression pattern. This study provides clues for defining the non-invasive diagnosis of NAFLD.

  4. Bioinformatics-driven identification and examination of candidate genes for non-alcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Karina Banasik

    Full Text Available OBJECTIVE: Candidate genes for non-alcoholic fatty liver disease (NAFLD identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes. RESEARCH DESIGN AND METHODS: By integrating public database text mining, trans-organism protein-protein interaction transferal, and information on liver protein expression a protein-protein interaction network was constructed and from this a smaller isolated interactome was identified. Five genes from this interactome were selected for genetic analysis. Twenty-one tag single-nucleotide polymorphisms (SNPs which captured all common variation in these genes were genotyped in 10,196 Danes, and analyzed for association with NAFLD-related quantitative traits, type 2 diabetes (T2D, central obesity, and WHO-defined metabolic syndrome (MetS. RESULTS: 273 genes were included in the protein-protein interaction analysis and EHHADH, ECHS1, HADHA, HADHB, and ACADL were selected for further examination. A total of 10 nominal statistical significant associations (P<0.05 to quantitative metabolic traits were identified. Also, the case-control study showed associations between variation in the five genes and T2D, central obesity, and MetS, respectively. Bonferroni adjustments for multiple testing negated all associations. CONCLUSIONS: Using a bioinformatics approach we identified five candidate genes for NAFLD. However, we failed to provide evidence of associations with major effects between SNPs in these five genes and NAFLD-related quantitative traits, T2D, central obesity, and MetS.

  5. Flaxseed supplementation in non-alcoholic fatty liver disease: a pilot randomized, open labeled, controlled study.

    Science.gov (United States)

    Yari, Zahra; Rahimlou, Mehran; Eslamparast, Tannaz; Ebrahimi-Daryani, Naser; Poustchi, Hossein; Hekmatdoost, Azita

    2016-06-01

    A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Participants were assigned to take either a lifestyle modification (LM), or LM +30 g/day brown milled flaxseed for 12 weeks. At the end of the study, body weight, liver enzymes, insulin resistance and hepatic fibrosis and steatosis decreased significantly in both groups (p< 0.05); however, this reduction was significantly greater in those who took flaxseed supplementation (p < 0.05). The significant mean differences were reached in hepatic markers between flaxseed and control group, respectively: ALT [-11.12 compared with -3.7 U/L; P< 0.001], AST [-8.29 compared with -4 U/L; p < 0.001], GGT [-15.7 compared with -2.62 U/L; p < 0.001], fibrosis score [-1.26 compared with -0.77 kPa; p = 0.013] and steatosis score [-47 compared with -15.45 dB/m; p = 0.022]. In conclusion, flaxseed supplementation plus lifestyle modification is more effective than lifestyle modification alone for NAFLD management.

  6. Non-alcoholic fatty liver and metabolic syndrome in children: a vicious circle.

    Science.gov (United States)

    Alterio, Arianna; Alisi, Anna; Liccardo, Daniela; Nobili, Valerio

    2014-01-01

    During the last decade, paediatricians have observed a dramatic increase of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) in children. Furthermore, several lines of evidence have reported that a large part of children with NAFLD presents one or more traits of MS making plausible that, in the coming years, these subjects may present a rapid course of disease towards more severe cirrhosis and cardiovascular disease. Genetic susceptibility and the pressure of intrauterine environment and lifestyle are all crucial to activate molecular machinery that leads to development of NAFLD and MS in childhood. In this scenario, central obesity and consequent adipose tissue inflammation are critical to promote both MS-associated metabolic dysfunctions and NAFLD-related hepatic damage. An excessive dietary intake may in fact cause a specific lipid partitioning and induce metabolic stressors, which in turn promote insulin resistance and the release of several circulating factors. These molecules, on the one hand, trigger steatosis and the inflammatory response that characterize liver damage in NAFLD, and on the other hand contribute to the onset of other features of MS. This review provides an overview of current genetic, pathogenetic and clinical evidence of the vicious circle created by NAFLD and MS in children.

  7. Non-alcoholic fatty liver disease in the Philippines:Comparable with other nations?

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM:To evaluate the prevalence and determined the common characteristics of patients diagnosed with non alcoholic fatty liver disease (NAFLD) at the Philippine General Hospital,Manila,from January 1999 to December 2004.METHODS:NAFLD was diagnosed in 134 from a total of 1102 patients,based on clinical,ultrasonographic and/or histopathological findings.Patients with conditions associated with secondary NAFLD were excluded.Chart review was done to note demographics,comorbid illnesses,physical characteristics,hepatomegaly,aspartate/alanine aminotransferase (AST/ALT) levels,albumin,lipid levels,alkaline phosphatase,prothrombin time,and partial thromboplastin time.Data obtained were analyzed using the statistical program SPSS version 10.RESULTS:Of the 134 patients included,71% were female and 29% male.Mean patient age was 42.2years.Sixty percent of patients were obese,56% had hepatomegaly,and 69% had diabetes.AST levels were elevated in 45% of subjects and ALT levels in 64%.CONCLUSION:The prevalence of NAFLD at our institution was 12.2%.Patients diagnosed appear to be younger in age in contrast to previous studies.Female sex,obesity,elevated liver enzymes,and diabetes were characteristic features of our NAFLD patients,which is comparable to previous studies from other countries.

  8. Prevalence and determinants of non-alcoholic fatty liver disease in lifelines: A large Dutch population cohort

    Science.gov (United States)

    Schreuder, Tim C. M. A.; Dullaart, Robin P. F.; Faber, Klaas Nico; Alizadeh, Behrooz Z.; Blokzijl, Hans

    2017-01-01

    Background & aims Non-alcoholic fatty liver disease is an increasing health issue that develops rather unnoticed with obesity, type 2 diabetes mellitus and metabolic syndrome. We investigated prevalence, determinants and associated metabolic abnormalities of non-alcoholic fatty liver disease in the largest population-based cohort to date. Methods Biochemical characteristics, type 2 diabetes mellitus and metabolic syndrome were determined in the Lifelines Cohort Study (N = 167,729), a population-based cohort in the North of the Netherlands. Non-alcoholic fatty liver disease was defined as Fatty Liver Index (FLI)≥60. Exclusion criteria were age obese, had higher levels of hemoglobinA1c, fasting glucose, liver enzymes, total cholesterol, low-density lipoprotein cholesterol, triglycerides, c-reactive protein and leucocytes and lower high-density lipoprotein cholesterol (all P<0.0001). Participants with a FLI≥60 showed higher prevalence of type 2 diabetes mellitus (9.3% vs. 1.4%), metabolic syndrome (54.2% vs. 6.2%), impaired renal function (20.1% vs. 8.7%) and cardiovascular disease (4.6% vs. 1.6%) (all P<0.0001). Multivariable logistic analysis showed that smoking, hemoglobin, leucocytes, c-reactive protein, platelets, alanine aminotransferase, alkaline phosphatase, albumin, impaired renal function (OR 1.27, 95%CI 1.15–1.41), metabolic syndrome (OR 11.89, 95%CI 11.03–12.82) and its individual components hyperglycemia (OR 2.53, 95%CI 2.34–2.72), hypertension (OR 1.89, 95%CI 1.77–2.01) and reduced high-density lipoprotein cholesterol (OR 3.44, 95%CI 3.22–3.68) were independently associated with suspected non-alcoholic fatty liver disease (all P<0.0001). Conclusion Twenty-two percent (22.0%) of the population in the North of the Netherlands is suspected to suffer from non-alcoholic fatty liver disease, coinciding with a significant increased risk of type 2 diabetes mellitus, metabolic syndrome, cardiovascular disease and impaired renal function. PMID

  9. Lifestyle changes associated with a new antioxidant formulation in non-alcoholic fatty liver disease: a case series.

    Science.gov (United States)

    Abenavoli, Ludovico; Peta, Valentina; Milic, Natasa

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a relevant issue in public health owing to its epidemiological burden. It represents the most common chronic liver disease in the general population and is expected to increase in future as a result of an ageing population. The only currently recommended treatment for NAFLD is lifestyle modification. However, literature reports pre-clinical and clinical studies on the use of antioxidant supplementation in NAFLD. A new antioxidant complex, called Bilirel (BIL) (Pharmaluce, Republic of San Marino), have recently introduced in the Italian market. However no data are reported on his effects on liver steatosis. Here we report on a cases series of seven overweight patients with NAFLD, in which the association of an Italian Mediterranean diet, increased physical activity, and daily administration of two pills of BIL for 6 weeks, have induced the rapid improvement of fatty liver accumulation, glucose and lipid metabolism, and weight reduction.

  10. Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease

    Science.gov (United States)

    Wang, Baohong; Jiang, Xiangyang; Cao, Min; Ge, Jianping; Bao, Qiongling; Tang, Lingling; Chen, Yu; Li, Lanjuan

    2016-01-01

    Increasing evidence suggests a role of intestinal dysbiosis in obesity and non-alcoholic fatty liver disease (NAFLD). But it remains unknown in nonobese NAFLD. This prospective, cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression. A total of 126 nonobese subjects were enrolled: 43 NAFLD and 83 healthy controls (HC). The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region. Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD. Compared with HC, patients had 20% more phylum Bacteroidetes (p = 0.005) and 24% less Firmicutes (p = 0.002). Within Firmicutes, four families and their 8 genera, which were short-chain fatty acids-producing and 7α-dehydroxylating bacteria, were significantly decreased. Moreover, Gram-negative (G−) bacteria were prevalent in NAFLD (p = 0.008). Furthermore, a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD. This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression. PMID:27550547

  11. Treatment of Non-alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo-controlled Trial.

    Science.gov (United States)

    Rahmani, Sepideh; Asgary, Sedigheh; Askari, Gholamreza; Keshvari, Mahtab; Hatamipour, Mahdi; Feizi, Awat; Sahebkar, Amirhossein

    2016-09-01

    Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Although many aspects of NAFLD pathogenesis have been understood, there is a paucity of effective treatments to be used as the second line when lifestyle modification is insufficient. Curcumin, a natural polyphenol from turmeric, has been shown to be effective against development of hepatic steatosis and its progression to steatohepatitis, yet these beneficial effects have not been explored in clinical practice. The aim of this study is to investigate the effects of curcumin on hepatic fat content as well as biochemical and anthropometric features of patients with NAFLD. In this randomized double-blind placebo-controlled trial, patients with ultrasonographic evidence of NAFLD were randomly assigned to receive an amorphous dispersion curcumin formulation (500 mg/day equivalent to 70-mg curcumin) or matched placebo for a period of 8 weeks. Liver fat content (assessed through ultrasonography), glycemic and lipid profile, transaminase levels, and anthropometric indices were evaluated at baseline and at the end of follow-up period. The clinical trial protocol was registered under the Iranian Registry of Clinical Trials ID: IRCT2014110511763N18. Compared with placebo, curcumin was associated with a significant reduction in liver fat content (78.9% improvement in the curcumin vs 27.5% improvement in the placebo group). There were also significant reductions in body mass index and serum levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, glucose, and glycated hemoglobin compared with the placebo group. Curcumin was safe and well tolerated during the course of trial. Findings of the present proof-of-concept trial suggested improvement of different features of NAFLD after a short-term supplementation with curcumin. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Activation of proteinase 3 contributes to Non-alcoholic Fatty Liver Disease (NAFLD) and insulin resistance.

    Science.gov (United States)

    Toonen, Erik J M; Mirea, Andreea-Manuela; Tack, Cees J; Stienstra, Rinke; Ballak, Dov B; van Diepen, Janna A; Hijmans, Anneke; Chavakis, Triantafyllos; Dokter, Wim H; Pham, Christine T N; Netea, Mihai G; Dinarello, Charles A; Joosten, Leo A B

    2016-05-24

    Activation of inflammatory pathways is known to accompany development of obesity-induced non-alcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes. In addition to caspase-1, the neutrophil serine proteases proteinase 3, neutrophil elastase and cathepsin G are able to process the inactive pro-inflammatory mediators IL-1β and IL-18 to their bioactive forms, thereby regulating inflammatory responses. In the present study, we investigated whether proteinase 3 is involved in obesity-induced development of insulin resistance and NAFLD. We investigated the development of NAFLD and insulin resistance in mice deficient for neutrophil elastase/proteinase 3 and neutrophil elastase/cathepsin G and in wild-type mice treated with the neutrophil serine proteinase inhibitor human alpha-1 antitrypsin. Expression profiling of metabolically relevant tissues obtained from insulin resistant mice showed that expression of proteinase 3 was specifically upregulated in the liver, whereas neutrophil elastase, cathepsin G and caspase-1 were not. Neutrophil elastase/proteinase 3 deficient mice showed strongly reduced levels of lipids in the liver after fed a high fat diet. Moreover, these mice were resistant to high fat diet-induced weight gain, inflammation and insulin resistance. Injection of proteinase 3 exacerbated insulin resistance in caspase-1(-/-) mice, indicating that proteinase 3 acts independently of caspase-1. Treatment with alpha-1 antitrypsin during the last 10 days of a 16 week high fat diet reduced hepatic lipid content and decreased fasting glucose levels. We conclude that proteinase 3 is involved in NAFLD and insulin resistance and that inhibition of proteinase 3 may have therapeutic potential.

  13. A "systems medicine" approach to the study of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Petta, Salvatore; Valenti, Luca; Bugianesi, Elisabetta; Targher, Giovanni; Bellentani, Stefano; Bonino, Ferruccio

    2016-03-01

    The prevalence of fatty liver (steatosis) in the general population is rapidly increasing worldwide. The progress of knowledge in the physiopathology of fatty liver is based on the systems biology approach to studying the complex interactions among different physiological systems. Similarly, translational and clinical research should address the complex interplay between these systems impacting on fatty liver. The clinical needs drive the applications of systems medicine to re-define clinical phenotypes, assessing the multiple nature of disease susceptibility and progression (e.g. the definition of risk, prognosis, diagnosis criteria, and new endpoints of clinical trials). Based on this premise and in light of recent findings, the complex mechanisms involved in the pathology of fatty liver and their impact on the short- and long-term clinical outcomes of cardiovascular, metabolic liver diseases associated with steatosis are presented in this review using a new "systems medicine" approach. A new data set is proposed for studying the impairments of different physiological systems that have an impact on fatty liver in different subsets of subjects and patients.

  14. Macrophage activation marker soluble CD163 and non-alcoholic fatty liver disease in morbidly obese patients undergoing bariatric surgery

    DEFF Research Database (Denmark)

    Kazankov, Konstantin; Tordjman, Joan; Møller, Holger Jon

    2015-01-01

    BACKGROUND AND AIMS: Macrophages play an important role in non-alcoholic fatty liver disease (NAFLD). Soluble CD163 (sCD163) is a specific marker of macrophage activation. We aimed to measure sCD163 in morbidly obese patients with varying degrees of NAFLD before and after bariatric surgery (BS...... (NAS), Kleiner fibrosis score, and the fatty liver inhibition of progression (FLIP) algorithm. In a subset, CD163 immunohistochemistry and real-time quantitative polymerase chain reaction for CD163 mRNA were performed. RESULTS: sCD163 was higher in patients with NAS ≥ 5 compared with those with NAS ... decreased after BS and was greatly reduced after 12 months, more rapidly so in patients with NAS ≥ 5 (P alcoholic steatohepatitis (NASH) according to the FLIP algorithm (P = 0.03). Immunohistochemistry showed CD163-positive macrophages aligning fat-laden hepatocytes and forming...

  15. Obesity in children and adolescents: the relation between metabolic syndrome and non-alcoholic fatty-liver disease

    OpenAIRE

    DUARTE, Maria Amélia Soares de Melo; Silva,Giselia Alves Pontes da

    2010-01-01

    This article aims to review clinical and diagnostic aspects of non-alcoholic fatty liver disease associated with obesity and its relation to metabolic syndrome in children and adolescents. An on-line search was carried out of original articles in the Medical Literature Analysis and Retrieval System Online (MEDLINE), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Scientific Eletronic Library Online (SciELO) databases, using the following key words: "hepatic steatosis...

  16. Insidensi dan Faktor Risiko Non Alcoholic Fatty Liver Disease (NAFLD) di RSUP HAM Medan Tahun 2011-2014

    OpenAIRE

    Lubis, Siti Khadijatul Yazrah

    2016-01-01

    Introduction: Non Alcoholic Fatty Liver Disease (NAFLD) is hepatic manifestation that having close relation with metabolic syndrome which affected 30% people in Indonesia. The increasing of metabolic syndrome incidence in few years indirectly will be followed by the increasing of incidence of NAFLD. Method: The aim of this study for doing investigation of frequency and risk factors of NAFLD patients in RSUP H. Adam Malik Medan from 2011-2014 by collecting data from patient medical records....

  17. Application of Weka environment to determine factors that stand behind non-alcoholic fatty liver disease (NAFLD)

    Science.gov (United States)

    Plutecki, Michal M.; Wierzbicka, Aldona; Socha, Piotr; Mulawka, Jan J.

    2009-06-01

    The paper describes an innovative approach to discover new knowledge in non-alcoholic fatty liver disease (NAFLD). In order to determine the factors that may cause the disease a number of classification and attribute selection algorithms have been applied. Only those with the best classification results were chosen. Several interesting facts associated with this unclear disease have been discovered. All data mining computations were made in Weka environment.

  18. The effects of PCB126 on intra-hepatic mechanisms associated with non alcoholic fatty liver disease

    OpenAIRE

    Boucher, Marie-Pier; Lefebvre, Caroline; Chapados, Natalie Ann

    2015-01-01

    Background Non alcoholic fatty liver disease (NAFLD) results from alteration in lipid synthesis and elimination mechanisms such as very-low density lipoprotein (VLDL) production and de novo lipogenesis. Persistent organic pollutants (POPs) are chemicals that were mostly used historically as pesticides, solvents, flame retardant, and other applications. Among POPs, polychlorinated biphenyls (PCB) have been recognized to be of environmental and potential toxicologic concerns. Specifically, PCB1...

  19. Psoriasis,non-alcoholic fatty liver disease,and cardiovascular disease:Three different diseases on a unique background

    Institute of Scientific and Technical Information of China (English)

    Giulia Ganzetti; Anna Campanati; Elisa Molinelli; Annamaria Offidani

    2016-01-01

    Psoriasis is a chronic inflammatory immune-mediated skin disease, frequently associated with systemic comorbidities. According to recent data, patients with psoriasis show a greater prevalence of metabolic syndrome, which confers a higher cardiovascular risk. The link between these pathological conditions appears to be a chronic low-grade inflammatory status. The aim of this review is to focus on the multiple epidemiological and physio-pathogenetic aspects linking non-alcoholic fatty liver disease, psoriasis, and cardiovascular disease.

  20. A switch in hepatic cortisol metabolism across the spectrum of non alcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Adeeba Ahmed

    Full Text Available CONTEXT: Non alcoholic fatty liver disease (NAFLD is the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of liver disease ranging from reversible hepatic steatosis, to non alcoholic steato-hepatitis (NASH and cirrhosis. The potential role of glucocorticoids (GC in the pathogenesis of NAFLD is highlighted in patients with GC excess, Cushing's syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol availability is controlled by enzymes that regenerate cortisol (F from inactive cortisone (E (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1, or inactivate cortisol through A-ring metabolism (5α- and 5β-reductase, 5αR and 5βR. OBJECTIVE AND METHODS: In vitro studies defined 11β-HSD1 expression in normal and NASH liver samples. We then characterised hepatic cortisol metabolism in 16 patients with histologically proven NAFLD compared to 32 obese controls using gas chromatographic analysis of 24 hour urine collection and plasma cortisol generation profile following oral cortisone. RESULTS: In patients with steatosis 5αR activity was increased, with a decrease in hepatic 11β-HSD1 activity. Total cortisol metabolites were increased in this group consistent with increased GC production rate. In contrast, in patients with NASH, 11β-HSD1 activity was increased both in comparison to patients with steatosis, and controls. Endorsing these findings, 11β-HSD1 mRNA and immunostaining was markedly increased in NASH patients in peri septal hepatocytes and within CD68 positive macrophages within inflamed cirrhotic septa. CONCLUSION: Patients with hepatic steatosis have increased clearance and decreased hepatic regeneration of cortisol and we propose that this may represent a protective mechanism to decrease local GC availability to preserve hepatic metabolic phenotype. With progression to NASH, increased 11

  1. Peroxisome proliferator-activated receptors as targets totreat non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Lately, the world has faced tremendous progress in theunderstanding of non-alcoholic fatty liver disease (NAFLD)pathogenesis due to rising obesity rates. Peroxisomeproliferator-activated receptors (PPARs) are transcriptionfactors that modulate the expression of genes involved inlipid metabolism, energy homeostasis and inflammation,being altered in diet-induced obesity. Experimentalevidences show that PPAR-alpha is the master regulatorof hepatic beta-oxidation (mitochondrial and peroxisomal) and microsomal omega-oxidation, being markedlydecreased by high-fat (HF) intake. PPAR-beta/delta iscrucial to the regulation of forkhead box-containing proteinO subfamily-1 expression and, hence, the modulationof enzymes that trigger hepatic gluconeogenesis. Inaddition, PPAR-beta/delta can activate hepatic stellatecells aiming to the hepatic recovery from chronic insult.On the contrary, PPAR-gamma upregulation by HF dietsmaximizes NAFLD through the induction of lipogenicfactors, which are implicated in the fatty acid synthesis.Excessive dietary sugars also upregulate PPAR-gamma,triggering de novo lipogenesis and the consequent lipiddroplets deposition within hepatocytes. Targeting PPARsto treat NAFLD seems a fruitful approach as PPAR-alphaagonist elicits expressive decrease in hepatic steatosis byincreasing mitochondrial beta-oxidation, besides reducedlipogenesis. PPAR-beta/delta ameliorates hepatic insulinresistance by decreasing hepatic gluconeogenesis atpostprandial stage. Total PPAR-gamma activation canexert noxious effects by stimulating hepatic lipogenesis.However, partial PPAR-gamma activation leads to benefits,mainly mediated by increased adiponectin expressionand decreased insulin resistance. Further studies arenecessary aiming at translational approaches useful totreat NAFLD in humans worldwide by targeting PPARs.

  2. Risk Score Model for Predicting Sonographic Non-Alcoholic Fatty Liver Disease in Children and Adolescents

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    Parinaz Poursafa

    2011-06-01

    Full Text Available Objective: This study aimed to develop and test the validity of a risk score to be used as a simple tool to identify those children at high risk of sonographic non-alcoholic fatty liver disease (NAFLD. Methods:This cross-sectional study was conducted among 962 participants aged 6-18 years in Isfahan, Iran. They consisted of three groups of nearly equal number of normal-weight, overweight and obese individuals. Coefficients of the logistic regression models were used to assign a score value for each variable and the composite sonographic NAFLD risk score was calculated as the sum of those scores. Performance of model was assessed by receiver operating characteristic (ROC curve procedure. Findings:Data of 931 participants was included in the analysis. The sonographic findings of 16.8% of participants were compatible with NAFLD. Age, sex, body mass index, waist circumference and serum triglycerides level were diagnosed as factors associated with NAFLD. The risk score was calculated as 50 for sonographic NAFLD. Conclusion:This study, to the best of our knowledge is the first of its kind in the pediatric age group, focuses on predicting sonographic NAFLD from easily-measured factors. It may suggest an association of hypertriglyceridemic-waist phenotype with NAFLD in the pediatric age group.

  3. The Role of Dietary Sugars and De novo Lipogenesis in Non-Alcoholic Fatty Liver Disease

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    J. Bernadette Moore

    2014-12-01

    Full Text Available Dietary sugar consumption, in particular sugar-sweetened beverages and the monosaccharide fructose, has been linked to the incidence and severity of non-alcoholic fatty liver disease (NAFLD. Intervention studies in both animals and humans have shown large doses of fructose to be particularly lipogenic. While fructose does stimulate de novo lipogenesis (DNL, stable isotope tracer studies in humans demonstrate quantitatively that the lipogenic effect of fructose is not mediated exclusively by its provision of excess substrates for DNL. The deleterious metabolic effects of high fructose loads appear to be a consequence of altered transcriptional regulatory networks impacting intracellular macronutrient metabolism and altering signaling and inflammatory processes. Uric acid generated by fructose metabolism may also contribute to or exacerbate these effects. Here we review data from human and animal intervention and stable isotope tracer studies relevant to the role of dietary sugars on NAFLD development and progression, in the context of typical sugar consumption patterns and dietary recommendations worldwide. We conclude that the use of hypercaloric, supra-physiological doses in intervention trials has been a major confounding factor and whether or not dietary sugars, including fructose, at typically consumed population levels, effect hepatic lipogenesis and NAFLD pathogenesis in humans independently of excess energy remains unresolved.

  4. Metabolic syndrome and non-alcoholic fatty liver disease:Asian deifnitions and Asian studies

    Institute of Scientific and Technical Information of China (English)

    Jian-Gao Fan; Yong-De Peng

    2007-01-01

    BACKGROUND:Non-alcoholic fatty liver disease (NAFLD), as conventionally recognized, is a metabolic disorder largely conifned to residents of aflfuent 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-Paciifc 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 deifnitions 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 identiifcation and appropriate treatment of the components of metabolic syndrome are crucial to reduce hepatic as well as cardiovascular morbidity and mortality.

  5. Editor’s Pick: Non-Alcoholic Fatty Liver Disease – Changing the Prevalence of Liver Cancer?

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    Benedetta Campana

    2015-01-01

    Full Text Available Due to its increasing prevalence, exceeding 25% of the Western population, non-alcoholic fatty liver disease (NAFLD merits recognition as one of the most frequent chronic liver diseases (CLD and requires consideration of the associated disease-related complications and their consequences for the surveillance and treatment of patients and the socio-economy worldwide. Along with the increasing incidence of NAFLD-related cirrhosis and end-stage liver disease, the frequency of NAFLD-related hepatocellular carcinoma (HCC is rising and expected to surpass HCC related to chronic hepatitis C in the upcoming future. These epidemiologic changes will impact on the overall mortality of CLD and the requirement of organs for transplantation. Although the risk of HCC in NAFLD, similar to other CLD, is related to fibrosis (advanced fibrosis increases the risk of HCC 25-fold, there are reports suggesting a considerable rate of HCC also developing in simple hepatic steatosis. Moreover, HCC is nowadays the leading cause of obesity-related cancer mortality; cancers of other origin such as colorectal cancer are more prevalent in patients with NAFLD and obesity. The pathophysiology of HCC has mainly been studied in models of viral hepatitis. Given the expected raise in NAFLD-related HCC, a better understanding of the pathophysiology of carcinogenesis in NAFLD and obesity is desired in order to better define chemopreventive strategies. Here we review the epidemiology, aetiology, and pathogenesis of HCC on the background of NAFLD and deduce potential consequences for the management of patients in respect to the NAFLD epidemic.

  6. Effect of lifestyle intervention on non-alcoholic fatty liver disease in Chinese obese children

    Institute of Scientific and Technical Information of China (English)

    Chun-Lin Wang; Li Liang; Jun-Fen Fu; Chao-Chun Zou; Fang Hong; Jin-Zheng Xue; Jin-Rui Lu; Xiang-Min Wu

    2008-01-01

    AIM:To investigate the effect of lifestyle intervention on non-alcoholic fatty liver disease(NAFLD)in Chinese obese children.METHODS:Seventy-six obese children aged from 10 to 17 years with NAFLD were enrolled for a one-month intervention and divided randomly into three groups.Group1,consisting of 38 obese children,was an untreated control group without any intervention.Group 2,consisting of 19 obese children in summer camp,was strictly controlled only by life style intervention.Group 3,consisting of 19 obese children,received oral vitamin E therapy at a dose of 100 mg/d.The height,weight,fasting blood glucose(FBG),fasting serum insulin(FINS),plasma alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TCHO)and homeostasis model assentinsulin resistance(HOMA-IR)were measured at baseline and after one month.All patients were underwent to an ultrasonographic study of the liver performed by one operator who was blinded to the groups.RESULTS:The monitor indices of BMI,ALT,AST,TG,TCHO and HOMA-IR were successfully improved except in group 1.BMI and ALT in group 2 were reduced more significantly than in group 3 (2.44±0.82 vs 1.45±0.80,P=0.001;88.58±39.99 vs 63.69±27.05,P=0.040,respectively).CONCLUSION:Both a short-term lifestyle intervention and vitamin E therapy have an effect on NAFLD in obese children.Compared with vitamin E,lifestyle intervention is more effective.Therefore,lifestyle intervention should represent the first step in the management of children with NAFLD.

  7. Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Huang; Yan Fan; Hen Zhang; Ping Wang; Jing Ping Yuan; Ming-Jie Li; Xi-Yan Zhan

    2008-01-01

    AIM: To determine the role of leptin system in non-alcoholic fatty liver disease (NAFLD) development by delineating the changes in serum levels of leptin and soluble leptin receptor (sOB-R).METHODS: Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 patients with cholecystolithiasis (stationary phase) as controls. Serum leptin levels were determined by radioimmunoassay and concentration of sOB-R was measured by ELISA. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected.RESULTS: Mean serum leptin level and BMI in the NAFLD group were significantly higher than in the controls (both P < 0.001), but mean sOB-R level was lower in the NAFLD group when compared to the controls. Both men and women in the NAFLD group had higher mean serum leptin levels and lower sOB-R levels than did the men and women in the control group (all P < 0.001). There was a significant negative correlation between serum leptin and sOB-R levels (r = -0.725, P < 0.001). Multivariate analysis showed that the percentage of hepatocyte steatosis, sex, BMI, and homeostasis model assessment of insulin resistance (HOMA IR) were independently related to serum leptin levels.CONCLUSION: Elevated serum leptin seems to be a feature of steatosis, and serum leptin seems to increase as hepatocyte steatosis develops. An enhanced release of ieptin is accompanied by an decrease in sOB-R concentration, which suggests higher resistance of peripheral tissues towards the action of leptin.

  8. Adipose tissue-derived stem cells promote the reversion of non-alcoholic fatty liver disease: An in vivo study.

    Science.gov (United States)

    Liao, Naishun; Pan, Fan; Wang, Yingchao; Zheng, Youshi; Xu, Bo; Chen, Wenwei; Gao, Yunzhen; Cai, Zhixiong; Liu, Xiaolong; Liu, Jingfeng

    2016-05-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver injury and seriously affects human health. In the present study, we aimed to investigate whether adipose tissue-derived stem cell (ADSC) transplantation in combination with dietary modification was capable of reversing the progression of NAFLD. After establishing a rat model of NAFLD by feeding them a high-fat diet (HFD), ADSCs were transplanted via the portal vein into rats with HFD-induced NAFLD, and simultaneously fed a modified diet. Thereafter, gross liver morphology, the hepatosomatic (HSI) index and indicators of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were evaluated. Subsequently, the serum levels of total cholesterol (TC), triglycerides (TGs) and fatty acids (FAs) were also assayed. Furthermore, H&E and oil red O staining were used to confirm the pathological effects of NAFLD in the rat livers. Although dietary modification alone caused liver function to recover, ADSC transplantation in combination with dietary modification further decreased the HSI index, the serum levels of ALT, TBIL, TC, TGs, FAs, reduced lipid accumulation to normal levels, and reversed the hepatic pathological changes in the rat livers. Taken together, these findings suggest that ADSC transplantation assists in the reversion of NAFLD by improving liver function and promoting lipid metabolism, thereby exerting hepatoprotective effects. Thus, we suggest that ADSC transplantation is a promising, potential therapeutic strategy for NAFLD treatment.

  9. Predictors for advanced fibrosis in morbidly obese non-alcoholic fatty liver patients

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    Zelber-Sagi, Shira; Shoham, Dafna; Zvibel, Isabel; Abu-Abeid, Subhi; Shibolet, Oren; Fishman, Sigal

    2017-01-01

    AIM To investigate predictors for fibrosis specifically in a high risk population of morbidly obese patients, including detailed evaluation of lifestyle. METHODS We conducted a cross-sectional study among morbidly obese patients attending the bariatric clinic at the Tel-Aviv Medical Center between the years 2013-2014 with body mass index (BMI) above 40 or above 35 with co-morbidity. Patients with serum hepatitis B surface antigen or anti-hepatitis C virus antibodies, genetic liver diseases, autoimmune disease or high alcohol intake (≥ 30 g/d in men or ≥ 20 g/d in women) were excluded from the study. Liver fibrosis was estimated by transient elastography (FibroScan®), using the ‘‘XL’’ probe. We collected data on age and gender, education, smoking status and amount, medical history, nutrition and lifestyle habits. All these data were collected using structured and validated questionnaires. Fasting blood test were available for a subsample. RESULTS Fibroscan was performed on a total of 91 patients, of which 77 had a valid examination according to the accepted criteria. Of those, 21% had significant fibrosis (F2) and 39% had advanced or severe fibrosis (F3 or F4). In multivariate analysis, male gender and BMI had a positive association with advanced fibrosis; the OR for fibrosis F ≥ 2 was 7.93 (95%CI: 2.36-26.64, P = 0.001) for male gender and 1.33 (1.11-1.60 kg/m2, P = 0.002) for BMI. The OR for fibrosis F ≥ 3 was 2.92 (1.08-7.91, P = 0.035) for male gender and 1.17 (1.03-1.33, P = 0.018) for BMI. Subjects were categorized to subgroups based on the combination of male gender and BMI of 40 and above. A significant dose response association with stiffness level was noted across these categories, with the highest stiffness among men with a higher BMI (P = 0.001). In addition, a significant positive correlation between pack-years cigarette smoking and liver stiffness was demonstrated among men (r = 0.54, P = 0.012). CONCLUSION In the morbidly obese

  10. Barley Sprouts Extract Attenuates Alcoholic Fatty Liver Injury in Mice by Reducing Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Yun-Hee Lee

    2016-07-01

    Full Text Available It has been reported that barley leaves possess beneficial properties such as antioxidant, hypolipidemic, antidepressant, and antidiabetic. Interestingly, barley sprouts contain a high content of saponarin, which showed both anti-inflammatory and antioxidant activities. In this study, we evaluated the effect of barley sprouts on alcohol-induced liver injury mediated by inflammation and oxidative stress. Raw barley sprouts were extracted, and quantitative and qualitative analyses of its components were performed. The mice were fed a liquid alcohol diet with or without barley sprouts for four weeks. Lipopolysaccharide (LPS-stimulated RAW 264.7 cells were used to study the effect of barley sprouts on inflammation. Alcohol intake for four weeks caused liver injury, evidenced by an increase in serum alanine aminotransferase and aspartate aminotransferase activities and tumor necrosis factor (TNF-α levels. The accumulation of lipid in the liver was also significantly induced, whereas the glutathione (GSH level was reduced. Moreover, the inflammation-related gene expression was dramatically increased. All these alcohol-induced changes were effectively prevented by barley sprouts treatment. In particular, pretreatment with barley sprouts significantly blocked inducible nitric oxide synthase (iNOS and cyclooxygenase (COX-2 expression in LPS-stimulated RAW 264.7. This study suggests that the protective effect of barley sprouts against alcohol-induced liver injury is potentially attributable to its inhibition of the inflammatory response induced by alcohol.

  11. Barley Sprouts Extract Attenuates Alcoholic Fatty Liver Injury in Mice by Reducing Inflammatory Response

    Science.gov (United States)

    Lee, Yun-Hee; Kim, Joung-Hee; Kim, Sou Hyun; Oh, Ji Youn; Seo, Woo Duck; Kim, Kyung-Mi; Jung, Jae-Chul; Jung, Young-Suk

    2016-01-01

    It has been reported that barley leaves possess beneficial properties such as antioxidant, hypolipidemic, antidepressant, and antidiabetic. Interestingly, barley sprouts contain a high content of saponarin, which showed both anti-inflammatory and antioxidant activities. In this study, we evaluated the effect of barley sprouts on alcohol-induced liver injury mediated by inflammation and oxidative stress. Raw barley sprouts were extracted, and quantitative and qualitative analyses of its components were performed. The mice were fed a liquid alcohol diet with or without barley sprouts for four weeks. Lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were used to study the effect of barley sprouts on inflammation. Alcohol intake for four weeks caused liver injury, evidenced by an increase in serum alanine aminotransferase and aspartate aminotransferase activities and tumor necrosis factor (TNF)-α levels. The accumulation of lipid in the liver was also significantly induced, whereas the glutathione (GSH) level was reduced. Moreover, the inflammation-related gene expression was dramatically increased. All these alcohol-induced changes were effectively prevented by barley sprouts treatment. In particular, pretreatment with barley sprouts significantly blocked inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression in LPS-stimulated RAW 264.7. This study suggests that the protective effect of barley sprouts against alcohol-induced liver injury is potentially attributable to its inhibition of the inflammatory response induced by alcohol. PMID:27455313

  12. Increase of S-100 protein-positive stellate cells in the anterior pituitary of chronic alcoholic patients with fatty liver or fatty cirrhosis.

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    Ishikawa T

    2003-04-01

    Full Text Available Healthy subjects 40 years old were used as controls in a study of stellate cells (S-100 protein-containing cells, or S-100 cells in subjects with chronic alcoholism and fatty liver or fatty cirrhosis. S-100 cells were sparsely found in the adenohypophysis of control subjects, and these cells sometimes formed small clusters. However, in chronic alcoholics with fatty liver or fatty cirrhosis, the number of stellate cells in the anterior pituitary tended to be 17 times higher than it was in the control group. No increase in the number of S-100 positive cells that constitute the large and small follicles in the intermediate pituitary. The physiological function of the S-100 protein has not yet been identified. The fact that an increase in prolactin-secreting and growth hormone-secreting cells, as well as a decrease in gonadotrophs were observed in the hypophysis of alcoholics suggests that the function of stellate cells may be closely related to these phenomena. Our results also imply that the stellate cells found in the anterior and intermediate pituitary differ in function although they both produce S-100 proteins.

  13. Non-alcoholic fatty liver disease (NAFLD) potentiates autoimmune hepatitis in the CYP2D6 mouse model.

    Science.gov (United States)

    Müller, Peter; Messmer, Marie; Bayer, Monika; Pfeilschifter, Josef M; Hintermann, Edith; Christen, Urs

    2016-05-01

    Non-alcoholic fatty liver disease (NAFLD) and its more severe development non-alcoholic steatohepatitis (NASH) are increasing worldwide. In particular NASH, which is characterized by an active hepatic inflammation, has often severe consequences including progressive fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). Here we investigated how metabolic liver injury is influencing the pathogenesis of autoimmune hepatitis (AIH). We used the CYP2D6 mouse model in which wild type C57BL/6 mice are infected with an Adenovirus expressing the major liver autoantigen cytochrome P450 2D6 (CYP2D6). Such mice display several features of human AIH, including interface hepatitis, formation of LKM-1 antibodies and CYP2D6-specific T cells, as well as hepatic fibrosis. NAFLD was induced with a high-fat diet (HFD). We found that pre-existing NAFLD potentiates the severity of AIH. Mice fed for 12 weeks with a HFD displayed increased cellular infiltration of the liver, enhanced hepatic fibrosis and elevated numbers of liver autoantigen-specific T cells. Our data suggest that a pre-existing metabolic liver injury constitutes an additional risk for the severity of an autoimmune condition of the liver, such as AIH.

  14. Shear Wave Elastography for Assessment of Steatohepatitis and Hepatic Fibrosis in Rat Models of Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Kang, Bo-Kyeong; Lee, Seung Soo; Cheong, Hyunhee; Hong, Seung Mo; Jang, Kiseok; Lee, Moon-Gyu

    2015-12-01

    The purpose of this study was to evaluate shear wave elastography (SWE) as a method for determining the severity of non-alcoholic fatty liver disease (NAFLD) and the stage of hepatic fibrosis, as well as the major determinants of liver elasticity among the various histologic and biomolecular changes associated with NAFLD. Rat NAFLD models with various degrees of NAFLD severity were created and imaged using SWE. The explanted livers were subjected to histopathologic evaluation and RNA expression analysis. Among the histologic and biomolecular findings, the fibrosis stage and the collagen RNA level were significant independent factors associated with liver elasticity (p steatohepatitis (NASH) and in determining fibrosis stage, and the corresponding areas under the receiver operating characteristic curves were 0.963 and 0.927-0.997, respectively. In conclusion, SWE is a potential non-invasive method for the detection of NASH and staging of hepatic fibrosis in patients with NAFLD.

  15. Editorial: Magnetic Resonance Elastography and Non-Alcoholic Fatty Liver Disease: Time for an Upgrade?

    Science.gov (United States)

    Flores, Avegail; Asrani, Sumeet K

    2016-07-01

    Elastography techniques, such as two-dimensional magnetic resonance elastography (2D-MRE) are increasingly used for the non-invasive assessment of liver fibrosis in patients with nonalchoholic fatty liver disease (NAFLD). Loomba et al. demonstrate that 3D-MRE (shear wave frequency 40 Hz) had even greater diagnostic accuracy than the commercially available 2D-MRE (shear wave frequency 60 Hz) in diagnosing advanced fibrosis (area under the receiver operator curve, AUROC 0.981 vs. 0.921, P<0. 05) using liver biopsy as reference standard. Despite limitations, MRE serves as an important tool in risk stratification for patients with NAFLD.

  16. Prevalence and predictors of non-alcoholic fatty liver disease as defined by the fatty liver index in a type 2 diabetes population

    Science.gov (United States)

    SILAGHI, CRISTINA ALINA; SILAGHI, HORATIU; COLOSI, HORATIU ALEXANDRU; CRACIUN, ANCA ELENA; FARCAS, ANCA; COSMA, DANIEL TUDOR; HANCU, NICOLAE; PAIS, RALUCA; GEORGESCU, CARMEN EMANUELA

    2016-01-01

    Background and aims We aimed to study the prevalence and the predictive factors of non-alcoholic fatty liver disease (NAFLD) defined by the fatty liver index (FLI) in type 2 diabetic patients (T2DM). Methods Three hundred and eighty-one T2DM outpatients who regularly attended a Consulting Clinic in Cluj were retrospectivelly included. FLI, a surrogate steatosis biomarker based on body mass index (BMI), waist circumference (WC), triglycerides (TGL) and gammaglutamyl-transferase (GGT) was used to assess NAFLD in all patients. Anthropometric and biochemical parameters were measured. Hepatic steatosis (HS) was evaluated by ultrasonography. Results NAFLD-FLI (defined as FLI>60) was correlated with HS evaluated by ultrasound (r=0.28; p<0.001). NAFLD-FLI was detected in 79% of T2DM. The prevalence of obesity in NAFLD-FLI patients was 80%. Of the patients with normal alanine aminotransferase (ALAT), 73.8 % had NAFLD. At univariate analysis, NAFLD-FLI was correlated with age (r= −0.14; p=0.007), sex (r=0.20; p<0.001), LDL cholesterol (r=0.12; p=0.032), HDL cholesterol (r = −0.13; p=0.015), ALAT (r=0.20; p<0.001) and ASAT (r=0.19; p<0.001). At multiple regression analysis, sex, ALAT and LDL-cholesterol were independent predictors of NAFLD-FLI. After logistic regression model, ALAT, LDL-cholesterol, HOMA-IR were good independent predictors of NAFLD-FLI. Conclusions NAFLD-FLI could be useful to identify NAFLD in T2DM patients. Subjects with T2DM had a high prevalence of NADLD-FLI even with normal ALAT levels. Our findings showed that sex, ALAT, LDL cholesterol and IR were significant and independent factors associated with the presence of NAFLD in T2DM subjects. PMID:27004029

  17. Association between non-alcoholic fatty liver disease and coronary artery disease severity

    Institute of Scientific and Technical Information of China (English)

    SUN Ling; L(U) Shu-zheng

    2011-01-01

    Background Both non-alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) are closely associated with many metabolic disorders. Invasive coronary angiography (CAG) is a common approach as an intervention for CAD.However, the association between angiographic severity of coronary artery and NAFLD remains controversial. This study aimed to evaluate the relationship between NAFLD and CAD.Methods Totally 542 consecutive patients who planned to undergo CAG due to a suspected CAD were enrolled.Abdominal computed tomography (CT) was performed before angiography to detect NAFLD. CAD was defined as stenosis of at least 50% in at least one major coronary artery. The severity of CAD was assessed by the number of vessels affected and the vessel score multiplied by the severity score (Gensini score). Significant stenosis was defined as 70% or greater reduction in lumen diameter. A probability value of P <0.05 was considered statistically significant.Results Of 542 patients studied, 248 (45.8%) were found to have NAFLD by abdominal CT, and 382 patients (88%)were found to have significant CAD by CAG. Age, diabetes mellitus, waist circumference, body mass index, and obesity were associated with NAFLD. According to the results of Logistic regression analysis, the presence of NAFLD independently increased the risk for CAD, as seen in CAG (odds ratio (OR), 95% confidence interval (CI): 7.585(4.617-12.461); P <0.001). NAFLD was significantly more common in patients as CAD severity increased (P<0.001).Conclusions The presence of NAFLD is associated with high severity of CAD, requiring that patients with abdominal obesity be also investigated for NAFLD. Patients with NAFLD should be closely followed up for the presence and severity of CAD.

  18. Clinical guidelines of non-alcoholic fatty liver disease: A systematic review

    Science.gov (United States)

    Zhu, Jin-Zhou; Hollis-Hansen, Kelseanna; Wan, Xing-Yong; Fei, Su-Juan; Pang, Xun-Lei; Meng, Fan-Dong; Yu, Chao-Hui; Li, You-Ming

    2016-01-01

    AIM To perform a systematic review to grade guidelines and present recommendations for clinical management of non-alcoholic fatty liver disease (NAFLD). METHODS A database search was conducted on PubMed for guidelines published before May 2016, supplemented by reviewing relevant websites. The Appraisal of Guidelines for Research and Evaluation (ARGEE) Instrument II was a tool designed to appraise the methodological rigor and transparency in which a clinical guideline is developed and it is used internationally. It was used to appraise the quality of guidelines in this study. The inclusion criteria include: clinical NAFLD guidelines for adults, published in English, and released by governmental agencies or key organizations. RESULTS Eleven guidelines were included in this study. Since 2007, guidelines have been released in Asia (3 in China, 1 in South Korea, and 1 in Japan), Europe (1 in Italy), America (1 in United States and 1 in Chile) and three international agencies [European associations joint, Asia-Pacific Working Party and World Gastroenterology Organization (WGO)]. Using the ARGEE II instrument, we found US 2012 and Europe 2016 had the highest scores, especially in the areas of rigor of development and applicability. Additionally, Italy 2010 and Korea 2013 also presented comprehensive content, rigorous procedures and good applicability. And WGO 2014 offered various algorithms for clinical practice. Lastly, a practical algorithm for the clinical management was developed, based on the recommended guidelines. CONCLUSION This is the first systematic review of NAFLD guidelines. It may yield insights for physicians and policy-makers in the development and application of guidelines. PMID:27688665

  19. Comparative Effect of Insulin Sensitizers and Statin on Metabolic Profile and Ultrasonographical Score in Non Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Yadav, Suraj Singh; Reddy, Himanshu D.; Singhal, Shubham; Singh, Dinesh Kumar; Usman, Kauser

    2016-01-01

    Introduction Non Alcoholic Fatty Liver Disease (NAFLD) is a metabolic disorder involving fat accumulation in the liver. The initial management for patients with NAFLD includes lifestyle modification and weight loss in overweight or obese patients. Aim The present study was conducted to compare the efficacy of insulin sensitizers and statin in the patients of NAFLD. Materials and Methods The study included 98 patients diagnosed with NAFLD on USG (Ultrasonography) abdomen, divided into three Groups randomly and administered Metformin (Group I), Rosuvastatin (Group II) or Pioglitazone (Group III) along with dietary intervention and lifestyle modification. Their Body Mass Index (BMI), liver function tests, fasting lipid profile, USG scores for fatty liver were done and followed up at 4 weeks, 12 weeks and 24 week for change in above parameters. Results Out of the three Groups, Group II showed a maximum improvements in usg scores for NAFLD (p<0.001) and fasting lipid profile. Group II also showed maximum derangement of liver enzymes at 24 weeks though none of the subjects had more than three times elevation of liver enzymes. Conclusion Rosuvastatin may be an effective therapy as add on treatment to dietary and lifestyle intervention in patients of NAFLD. As an add-on treatment Rosuvastatin was superior to Pioglitazone or Metformin and acute decompensation is unlikely with this drug. Metformin was not effective as add on therapy for NAFLD, rather rapid weight loss in short period of time resulted in worsening of hepatic steatosis. PMID:27656480

  20. Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal

    Science.gov (United States)

    Cavalcante, Lourianne Nascimento; Stefano, Jose Tadeu; Machado, Mariana V; Mazo, Daniel F; Rabelo, Fabiola; Sandes, Kiyoko Abe; Carrilho, Flair José; Cortez-Pinto, Helena; Lyra, Andre Castro; de Oliveira, Claudia P

    2015-01-01

    AIM: To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. METHODS: We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnic-geographical differential frequencies (≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant (P 2.5 [NASH 5.3 (70.8%) vs S. Steatosis 4.6 (29.2%) P = 0.04]. In the Portuguese study population, dyslipidemia was present in all patients with NASH (P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group (P = 0.003, respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH

  1. Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B

    Directory of Open Access Journals (Sweden)

    Alexander Hodge

    2017-01-01

    Full Text Available There is emerging evidence for the positive effects or benefits of coffee in patients with liver disease. We conducted a retrospective cross-sectional study on patients with non-alcoholic fatty liver disease (NAFLD, hepatitis C virus (HCV, and hepatitis B virus (HBV infection to determine the effects of coffee intake on a non-invasive marker of liver fibrosis: liver stiffness assessed by transient elastography (TE. We assessed coffee and tea intake and measured TE in 1018 patients with NAFLD, HCV, and HBV (155 with NAFLD, 378 with HCV and 485 with HBV. Univariate and multivariate regression models were performed taking into account potential confounders. Liver stiffness was higher in males compared to females (p < 0.05. Patients with HBV had lower liver stiffness than those with HCV and NAFLD. After adjustment for age, gender, smoking, alcohol consumption, M or XL probe, and disease state (NAFLD, HCV, and HBV status, those who drank 2 or more cups of coffee per day had a lower liver stiffness (p = 0.044. Tea consumption had no effect (p = 0.9. Coffee consumption decreases liver stiffness, which may indicate less fibrosis and inflammation, independent of disease state. This study adds further evidence to the notion of coffee maybe beneficial in patients with liver disease.

  2. Pathogenesis and management issues for non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Marko Duvnjak; Ivan Leroti(c); Neven Bar(s)i(c); Vedran Toma(s)i(c); Lucija Virovi(c) Juki(c); Vedran Velagi(c)

    2007-01-01

    Nonalcoholic fatty liver disease (NAFLD) has, although it is a very common disorder, only relatively recently gained broader interest among physicians and scientists.Fatty liver has been documented in up to 10 to 15percent of normal individuals and 70 to 80 percent of obese individuals. Although the pathophysiology of NAFLD is still subject to intensive research, several players and mechanisms have been suggested based on the substantial evidence. Excessive hepatocyte triglyceride accumulation resulting from insulin resistance is the first step in the proposed 'two hit' model of the pathogenesis of NAFLD. Oxidative stress resulting from mitochondrial fatty acids oxidation, NF-κB-dependent inflammatory cytokine expression and adipocytokines are all considered to be the potential factors causing second hits which lead to hepatocyte injury, inflammation and fibrosis. Although it was initially believed that NAFLD is a completely benign disorder, histologic follow-up studies have showed that fibrosis progression occurs in about a third of patients. A small number of patients with NAFLD eventually ends up with end-stage liver disease and even hepatocellular carcinoma. Although liver biopsy is currently the only way to confirm the NAFLD diagnosis and distinguish between fatty liver alone and NASH, no guidelines or firm recommendations can still be made as for when and in whom it is necessary. Increased physical activity, gradual weight reduction and in selected cases bariatric surgery remain the mainstay of NAFLD therapy. Studies with pharmacologic agents are showing promising results, but available data are still insufficient to make specific recommendations; their use therefore remains highly individual.

  3. Reducing Liver Fat by Low Carbohydrate Caloric Restriction Targets Hepatic Glucose Production in Non-Diabetic Obese Adults with Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Yu, Haoyong; Jia, Weiping; Guo, ZengKui

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective: this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans with NAFLD. Methods: eight non-diabetic obese adults were restricted for daily energy intake (800 kcal) and low carbohydrate ( 0.05). Liver fat is the only independent variable highly correlated to HGP after the removal of confounders. Conclusion: NAFLD impairs HGP but not peripheral glucose disposal; low carbohydrate caloric restriction effectively lowers liver fat which appears to directly correct the HGP impairment. PMID:25411646

  4. Non-alcoholic fatty liver disease and beneficial effects ofdietary supplements

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    I read with great interest the review published byEslamparast et al , on the dietary supplements withhepato-protective properties, and their proposedmechanisms to protect against non-alcoholic fatty liverdisease. In this way, recently, our study group reportedthe efficacy of the Mediterranean diet associated to anantioxidant complex, to improve in overweight patientsnot only anthropometric parameters, but also insulinresistance,lipid serum levels, and intra-hepatic fataccumulation.

  5. Prevalence of nonalcoholic fatty liver disease and alcoholism in the participants of the Physical Activity in Community Project

    Directory of Open Access Journals (Sweden)

    Gisele L. N. Soler

    2011-02-01

    Full Text Available Screening image studies have shown that the frequency of hepatic steatosis findings has been progressivly increasing. The risk of developing NAFLD has been described and associated with obesity, insulin resistance and metabolic syndrome. There seems to be a correlation between NAFLD, alcohol e hepatic fibrosis. Our objective was to describe the prevalence of NAFLD and alcoholism in the participants of the of the Physical Activity in Community Project and to evaluate the associations between hepatic steatosis and presence of obesity and visceral obesity. Abdominal ultrasound was performed in 69 patients, 53.02±1.26 years old, looking for the presence and for the degree of fatty liver as well as subcutaneous and visceral fat. Patients with viral hepatitis and significant alcoholism were excluded after the AUDIT test. After this analysis, 60 patients were evaluated according to their anthropometrics data and were allocated into two groups: with and without fatty liver disease. The prevalence of alcoholism was 8.7%. Thirty seven percent of the patients showed up with NAFLD and were considered low to moderate risk (91%. The NAFLD showed a significant rise in the body mass index (34.1±8.7 versus 29.8±6.5kg/m2, waist circumference (102,6±12,7 versus 95.3±12.3cm, overall weight, (85,8±18,7 versus 74,5± 17.7kg, and visceral fat (47.9±10.5 versus 36.0±12.7mm. Hepatic steatosis is common in obese, especially in those with visceral obesity. We know that alcohol and visceral obesity are involved in the physiopathologic process of hepatic steatosis. For this reason, patients with Hepatic steatosis and excessive alcohol consumption may be at greater risk for Cirrhossis and hepatic insufficiency.

  6. Determining the association between adipokine expression in multiple tissues and phenotypic features of non-alcoholic fatty liver disease in obesity

    NARCIS (Netherlands)

    Wolfs, M. G. M.; Gruben, N.; Rensen, S. S.; Verdam, F. J.; Greve, J. W.; Driessen, A.; Wijmenga, C.; Buurman, W. A.; Franke, L.; Scheja, L.; Koonen, D. P. Y.; Shiri-Sverdlov, R.; van Haeften, T. W.; Hofker, M. H.; Fu, J.

    2015-01-01

    OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is an obesity-associated disease, and in obesity adipokines are believed to be involved in the development of NAFLD. However, it is still not clear whether adipokines in the liver and/or adipose tissues can be related to the development of specif

  7. The effect of resveratrol on experimental non-alcoholic fatty liver disease depends on severity of pathology and timing of treatment

    DEFF Research Database (Denmark)

    Heebøll, Sara; El-Houri, Rime Bahij; Hellberg, Ylva Erika Kristina

    2016-01-01

    BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with few therapeutic options. RSV prevents the development of steatosis in a number of experimental fatty liver (NAFL) models but the preventive or therapeutic effects on experimental NASH...

  8. Non-Alcoholic Fatty Liver Disease as a Predictor of Atrial Fibrillation in Middle-Aged Population (OPERA Study).

    Science.gov (United States)

    Käräjämäki, Aki J; Pätsi, Olli-Pekka; Savolainen, Markku; Kesäniemi, Y Antero; Huikuri, Heikki; Ukkola, Olavi

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) are widespread diseases and have multiple common risk factors and comorbidities. No studies of association between ultrasonography-diagnosed NAFLD and AF exist in other than diabetic population. The goal of this prospective study was to study the value of NAFLD as a predictor of atrial fibrillation. This study had 958 subjects from the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort, and the mean follow-up time was 16.3 years. NAFLD was diagnosed if the subject had fatty liver in ultrasonography and no excess alcohol intake. AF was followed in the National Registers. In this study 249 subjects (26.0%) had NAFLD and 37 (14.9%) of these had AF whereas only 56 (7.9%) of those without NAFLD experienced AF during the follow-up time (p = 0.001). In the multiple Cox regression analysis including potential confounders (age, sex, study group, diabetes, body mass index (BMI), waist circumference, alcohol consumption, smoking, serum alanine aminotransferase concentration (ALT), systolic blood pressure, quick index, left ventricular mass index, left atrial diameter, coronary artery disease (CAD), atrial natriuretic peptide (ANP) and high sensitive C-reactive protein (hs-CRP)), NAFLD remained as an independent predictor of AF (Adjusted OR, 1.88 (95% Confidence interval (CI) 1.03-3.45)). In conclusion, our data shows that NAFLD is independently associated with the risk of AF.

  9. Increased Circulating Levels of Alpha-Ketoglutarate in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Berlanga, Alba; Guiu-Jurado, Esther; Martinez, Salomé; Armengol, Sandra; Sabench, Fàtima; Ras, Rosa; Hernandez, Mercè; Aguilar, Carmen; Colom, Josep; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2016-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) causes a wide spectrum of liver damage, ranging from simple steatosis to cirrhosis. However, simple steatosis (SS) and steatohepatitis (NASH) cannot yet be distinguished by clinical or laboratory features. The aim of this study was to assess the relationship between alpha-ketoglutarate and the degrees of NAFLD in morbidly obese patients. Materials and Methods We used a gas chromatography-quadruple time-of-flight-mass spectrometry analysis to quantify alpha-ketoglutarate in serum from normal-weight subjects (n = 30) and morbidly obese women (n = 97) with or without NAFLD. Results We found that serum levels of alpha-ketoglutarate were significantly higher in morbidly obese women than in normal-weight women. We showed that circulating levels of alpha-ketoglutarate were lower in lean controls and morbidly obese patients without NAFLD. We also found that alpha-ketoglutarate serum levels were higher in both SS and NASH than in normal liver of morbidly obese patients. However, there was no difference between SS and NASH. Moreover, we observed that circulating levels of alpha-ketoglutarate were associated with glucose metabolism parameters, lipid profile, hepatic enzymes and steatosis degree. In addition, diagnostic performance of alpha-ketoglutarate has been analyzed in NAFLD patients. The AUROC curves from patients with liver steatosis exhibited an acceptable clinical utility. Finally, we showed that the combination of biomarkers (AST, ALT and alpha-ketoglutarate) had the highest accuracy in diagnosing liver steatosis. Conclusion These findings suggest that alpha-ketoglutarate can determine the presence of non-alcoholic fatty liver in morbidly obese patients but it is not valid a biomarker for NASH. PMID:27123846

  10. Increased Circulating Levels of Alpha-Ketoglutarate in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Gemma Aragonès

    Full Text Available Non-alcoholic fatty liver disease (NAFLD causes a wide spectrum of liver damage, ranging from simple steatosis to cirrhosis. However, simple steatosis (SS and steatohepatitis (NASH cannot yet be distinguished by clinical or laboratory features. The aim of this study was to assess the relationship between alpha-ketoglutarate and the degrees of NAFLD in morbidly obese patients.We used a gas chromatography-quadruple time-of-flight-mass spectrometry analysis to quantify alpha-ketoglutarate in serum from normal-weight subjects (n = 30 and morbidly obese women (n = 97 with or without NAFLD.We found that serum levels of alpha-ketoglutarate were significantly higher in morbidly obese women than in normal-weight women. We showed that circulating levels of alpha-ketoglutarate were lower in lean controls and morbidly obese patients without NAFLD. We also found that alpha-ketoglutarate serum levels were higher in both SS and NASH than in normal liver of morbidly obese patients. However, there was no difference between SS and NASH. Moreover, we observed that circulating levels of alpha-ketoglutarate were associated with glucose metabolism parameters, lipid profile, hepatic enzymes and steatosis degree. In addition, diagnostic performance of alpha-ketoglutarate has been analyzed in NAFLD patients. The AUROC curves from patients with liver steatosis exhibited an acceptable clinical utility. Finally, we showed that the combination of biomarkers (AST, ALT and alpha-ketoglutarate had the highest accuracy in diagnosing liver steatosis.These findings suggest that alpha-ketoglutarate can determine the presence of non-alcoholic fatty liver in morbidly obese patients but it is not valid a biomarker for NASH.

  11. Prevalence of biopsy-proven non-alcoholic fatty liver disease in severely obese subjects without metabolic syndrome.

    Science.gov (United States)

    Qureshi, K; Abrams, G A

    2016-04-01

    Obesity is a major risk factor for non-alcoholic fatty liver disease (NAFLD). NAFLD encompasses simple fatty liver (FL) and non-alcoholic steatohepatitis (NASH) in its spectrum. NASH can progress to liver cirrhosis and is associated with liver cancer. Not all obese subjects have insulin resistance (IR) or develop metabolic syndrome (MS). This study evaluates the prevalence of NAFLD in severely obese subjects without MS. We retrospectively reviewed 445 charts from our database of severely obese subjects with clinical suspicion of NAFLD and who were selected for laparoscopic Roux-en-Y gastric bypass surgery. One hundred five subjects who did not have MS, as defined by the International Diabetes Foundation, based on comprehensive pre-operative metabolic evaluation were included. Liver biopsy specimens were evaluated for NAFLD. 24% of morbidly obese (mean body mass index [BMI] 48 kg m(-2) ) adult subjects (mean age 38 years) who underwent bariatric surgery did not have MS. NAFLD was identified in 77 (73%) on liver biopsy, out of which 59 (56%) were labelled as FL and 18 (17%) had histological diagnosis of NASH. Age, gender, race and BMI were the same among all groups. Among NAFLD subjects, 22% did not have any additional metabolic component of MS, while 36% had low high-density lipoprotein, 27% had hypertension, 8% had high triglycerides and 6% had hyperglycaemia. IR calculated by HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) and diagnosis of hyperglycaemia was statistically higher in NASH group compared to those who did not have NASH. NAFLD is highly prevalent in morbidly obese individuals who undergo bariatric surgery despite the absence of MS. Diagnosis of hyperglycaemia in such subjects suggests the presence of IR and may have underlying NASH, which is a progressive form of NAFLD.

  12. Fatty liver in children

    OpenAIRE

    Rafeey, Mandana; Mortazavi, Fakhrossadat; Mogaddasi, Nafiseh; Robabeh, Ghergherehchi; Ghaffari, Shamsi; Hasani, Alka

    2009-01-01

    Aims: The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran. Methods: In this cross-sectional study all subjects aged between six months to 15 years that were referred to the sonography unit, were investigated for fatty liver from March 2005 to August 2006. Patients with fatty liver change underwent detailed clinical and laboratory evaluation. Results: From 150...

  13. Non-invasive imaging techniques in assessing non-alcoholic fatty liver disease: a current status of available methods.

    Science.gov (United States)

    Lăpădat, A M; Jianu, I R; Ungureanu, B S; Florescu, L M; Gheonea, D I; Sovaila, S; Gheonea, I A

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is an ailment affecting and increasing a number of people worldwide diagnosed via non-invasive imaging techniques, at a time when a minimum harm caused by medical procedures is rightfully emphasized, more sought after, than ever before. Liver steatosis should not be taken lightly even if its evolution is largely benign as it has the potential to develop into non-alcoholic steatohepatitis (NASH) or even more concerning, hepatic cirrhosis, and hepatocellular carcinoma (HCC). Traditionally, liver biopsy has been the standard for diagnosing this particular liver disease, but nowadays, a consistent number of imagistic methods are available for diagnosing hepatosteatosis and choosing the one appropriate to the clinical context is the key. Although different in sensitivity and specificity when it comes to determining the hepatic fat fraction (FF), these imaging techniques possessing a diverse availability, operating difficulty, cost, and reproducibility are invaluable to any modern physician. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), elastography, and spectroscopy will be discussed in order to lay out the advantages and disadvantages of their diagnostic potential and application. Although imagistics has given physicians a valuable insight into the means of managing NAFLD, the current methods are far from perfect, but given the time, they will surely be improved and the use of liver biopsy will be completely removed.

  14. Prevalence and factors associated with the presence of non alcoholic fatty liver disease in an apparently healthy adult population in primary care units

    OpenAIRE

    Pizarro Gregorio; Aubà Josep; Bernad Jesús; Canut Santiago; Planas Jaume; Muñoz Laura; Gil Dolors; Pera Guillem; Aznar Jesús; Miranda Dolores; Torán Pere; Auladell Ma Antonia; Caballería Llorenç; Aizpurua Miren; Altaba Anna

    2007-01-01

    Abstract Background Fatty liver disease is characterized by the accumulation of fat vacuoles inside of the hepatocytes. Non alcoholic fatty liver is associated with obesity, type 2 diabetes, dyslipemia, the intake of certain drugs and with the so-called metabolic syndrome. However, there is little information on the clinical relevance of this disorder as a healthcare problem in the general population, since the studies published generally include a limited number of patients and the diagnosis...

  15. Alcoholic liver disease

    Science.gov (United States)

    Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Over time, scarring and cirrhosis can occur. Cirrhosis is the ...

  16. Comparison of lipid profile in different grades of non-alcoholic fatty liver disease diagnosed on ultrasound

    Institute of Scientific and Technical Information of China (English)

    Dhumal Uttareshvar Mahaling; Madole Mahesh Basavaraj; Aher Jagdish Bika

    2013-01-01

    Objective: To detect and compare serum lipid abnormalities in patients diagnosed with different grades of non-alcoholic fatty liver on ultrasonography.Methods:A total of 70 cases which included 30 males and 40 females, diagnosed as non-alcoholic 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 test (ANOVA) and P value <0.05 was considered as statistically significant.Results:Out of 70 cases which were diagnosed as NAFLD cases were 47.15%, grade II were 42.85% and grade III were 10%. The mean age of the patients was 49.14 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 on ultrasonography, grade I NAFLD non-hypertensive. Though liver biopsy is the gold standard method for diagnosis of NAFLD, Ultrasonography which is non-invasive, simple tool, can be used for the early detection of NAFLD in asymptomatic patients.

  17. Reducing Liver Fat by Low Carbohydrate Caloric Restriction Targets Hepatic Glucose Production in Non-Diabetic Obese Adults with Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Haoyong Yu

    2014-09-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective: this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans with NAFLD. Methods: eight non-diabetic obese adults were restricted for daily energy intake (800 kcal and low carbohydrate (<10% for 8 weeks. Body compositions, liver fat and hepatic glucose production (HGP and peripheral glucose disposal before and after the intervention were determined. Results: the caloric restriction reduced liver fat content by 2/3 (p = 0.004. Abdominal subcutaneous and visceral fat, body weight, BMI, waist circumference and fasting plasma triglyceride and free fatty acid concentrations all significantly decreased (p < 0.05. The suppression of post-load HGP was improved by 22% (p = 0.002 whereas glucose disposal was not affected (p = 0.3. Fasting glucose remained unchanged and the changes in the 2-hour plasma glucose and insulin concentration were modest and statistically insignificant (p > 0.05. Liver fat is the only independent variable highly correlated to HGP after the removal of confounders. Conclusion: NAFLD impairs HGP but not peripheral glucose disposal; low carbohydrate caloric restriction effectively lowers liver fat which appears to directly correct the HGP impairment.

  18. Research on the protection effect of pioglitazone for non-alcoholic fatty liver disease (NAFLD) in rats

    Institute of Scientific and Technical Information of China (English)

    XU Ping; ZHANG Xing-guo; LI You-ming; YU Chao-hui; XU Lei; XU Gen-yun

    2006-01-01

    Objective: The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone (PGZ) acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding. Methods: The rats were separated randomly into 6 groups: model group I were fed high simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group Ⅱ were fed normal food for 16 weeks.The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), tumor necrosis factor alpha (TNL-α), fasting blood glucose (FBG), fasting plasma insulin (FINS), HOMA (homeostasis model assessment) insulin resistance index (HOMA-IR), and the liver histology of rats of all groups were assayed. Results: After 8 weeks, the liver in model group I showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT,AST, ALP, TNF-α were significantly increased (P<0.05) compared with control group I. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased (P<0.05)compared with model group Ⅰ. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group Ⅱ rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels of ALT, AST, ALP,FINS and HOMA-IR were significantly increased (P<0.05) in model group Ⅱ compared with control group Ⅱ. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT

  19. New Era for Usage of Serum Liver Enzymes as A Promising Horizon for the Prediction of Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Salman, Ahmed Abd Allah; Aboelfadl, Soheir Abd Elfattah; Heagzy, Mona Abd Elmenem

    2016-01-01

    BACKGROUND: Liver histology remains the gold standard for assessing non-alcoholic fatty liver disease (NAFLD). Noninvasive serological markers and radiological methods have been developed to evaluate steatosis to avoid biopsy. AIM: To put cutoff value for liver enzymes that could predict non-alcoholic steatohepatitis (NASH). PATIENTS AND METHODS: This study was conducted on 54 patients (with NAFLD diagnosed by the US). Patients were subjected to history, physical, anthropometric measurements, investigations including liver enzymes, abdominal US, and liver biopsy. According to biopsy results, patients were subdivided according to NASH development. Also, biopsy results were correlated to the levels of liver enzymes. RESULTS: Forty-seven patients who were suspected to have NAFLD by sonar were confirmed by biopsy. There was a significant correlation between steatosis degree in biopsy and sonar. Correlation study between steatosis in biopsy and ALT level showed highly significant positive correlation. Correlation study between steatosis in biopsy on one side & AST and GGT on the other side showed significant positive correlation. Cutoff value for detection of NASH using ALT & AST & and GGT were 50.5, 56, 60.5 respectively with sensitivity = 95.5, 90.5, 86.4 % and specificity = 93.8, 100, 87.5%. CONCLUSION: Cut off values of liver enzymes can be combined with abdominal sonar to predict NASH.

  20. The absence of obstructive sleep apnea may protect against non-alcoholic fatty liver in patients undergoing bariatric surgery.

    Directory of Open Access Journals (Sweden)

    Kathleen E Corey

    Full Text Available BACKGROUND: Non-alcoholic fatty liver disease (NAFLD is the most common cause of liver disease worldwide and its progressive form, steatohepatitis, will be the leading indication for liver transplant by 2020. While risk factors for steatohepatitis have been identified, little work has been performed to identify factors protective against NAFLD development. AIM: This study sought to identify factors predictive of normal liver histology in a bariatric cohort. METHODS: Patients undergoing weight loss surgery with liver biopsies at the time of surgery were included. Patients with other causes of chronic liver disease were excluded. RESULTS: One hundred fifty-nine patients were included. Forty-nine patients had normal liver histology and 110 patients had NAFLD. Several previously identified factors associated with normal liver histology were found. Black race was the strongest predictor of the absence of NAFLD with an odds ratio (OR of 6.8, 95% confidence interval (CI 2.4-18.9. Low HOMA-IR was also associated with normal histology (OR 1.4, 95% CI 1.03-1.9. In contrast, low HDL was associated with a decreased chance of normal histology (OR 0.38, 95% CI 0.05-0.83. Interestingly, a novel protective factor, the absence of obstructive sleep apnea (OSA was strongly associated with normal histology (OR 5.6, 95% CI 2.0-16.1. In multivariate regression controlling for BMI, black race, absence of OSA, low HOMA-IR and low ALT independently predicted normal liver histology with an area under the ROC curve of 0.85. CONCLUSIONS: Our study confirmed several factors associated with normal liver histology, including black race and identified a novel factor, absence of OSA. Further evaluation of these factors will allow for improved understanding of the pathogenesis of NAFLD.

  1. Ameliorative effects of Compound K and ginsenoside Rh1 on non-alcoholic fatty liver disease in rats

    Science.gov (United States)

    Chen, Xu-Jia; Liu, Wen-Jing; Wen, Meng-Liang; Liang, Hong; Wu, Shao-Mei; Zhu, Yun-Zhen; Zhao, Jiang-Yuan; Dong, Xiang-Qian; Li, Ming-Gang; Bian, Li; Zou, Cheng-Gang; Ma, Lan-Qing

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a common liver disease, which has no standard treatment available. Panax notoginseng saponines (PNS) have recently been reported to protect liver against hepatocyte injury induced by ethanol or high fat diet (HFD) in rats. Compound K and ginsenoside Rh1 are the main metabolites of PNS. In this study, we evaluated the effects of CK and Rh1 on NAFLD. Rats fed HFD showed significant elevations in liver function markers, lipids, glucose tolerance, and insulin resistance. Treatment with CK or Rh1 either alone or in combination dramatically ameliorated the liver function impairment induced by HFD. Histologically, CK and Rh1 significantly reversed HFD-induced hepatocyte injury and liver fibrosis. In vitro experiments demonstrated that treatment with CK or Rh1 alone or in combination markedly induced cell apoptosis, and inhibited cell proliferation and activation in HSC-T6 cells. Additionally, CK and Rh1, either alone or in combination, also repressed the expression of fibrotic factors TIMP-1, PC-I, and PC-III. Taken together, our results demonstrate that CK and Rh1 have positive effects on NAFLD via the anti-fibrotic and hepatoprotective activity. PMID:28106137

  2. Expression of p53, Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Anatol Panasiuk; Janusz Dzieciol; Bozena Panasiuk; Danuta Prokopowicz

    2006-01-01

    AIM: To analyze the protein expression essential for apoptosis in liver steatosis.METHODS: The expression of proapoptotic proteinsp53, Bax, and antiapoptotic Bcl-2 in hepatocytes with steatosis (SH) and without steatosis (NSH) was evaluated in 84 patients at various stages of non-alcoholic fatty liver disease (NAFLD).RESULTS: Immunohistochemical staining of liver tissue showed the activation of p53 protein in SH and NSH with increased liver steatosis, diminished Bcl-2 and slightly decreased Bax protein. Positive correlation was found between the stage of liver steatosis with p53 expression in SH (r = 0.54, P < 0.01) and NSH (r = 0.49,P < 0.01).The antiapoptotic protein Bcl-2 was diminished together with the advancement of liver steatosis, especially in non-steatosed hepatocytes (r =0.43, P < 001).CONCLUSION: Apoptosis is one of the most important mechanisms leading to hepatocyte elimination in NAFLD. The intensification of inflammation in NAFLD induces proapoptotic protein p53 with the inhibition of antiapoptotic Bcl-2.

  3. [The unity of pathogenesis of insulin resistance syndrome and non-alcoholic fatty disease of liver. The metabolic disorder of fatty acids and triglycerides].

    Science.gov (United States)

    Titov, V N; Ivanova, K V; Malyshev, P P; Kaba, S I; Shiriaeva, Iu K

    2012-11-01

    The pathogenesis of non-alcoholic fatty disease of liver (steatosis) is still as unclear as a loss of hepatocytes similar to apoptosis, development of biological reaction of inflammation, its transformation into steatohepatitis with subsequent fibrosis and formation of atrophic cirrhosis. The article suggests that steatosis is developed due to higher concentration of palmitic saturated fatty acid (C 16:0) in food, intensification of its endogenic synthesis from food carbohydrates and glucose and development of insulin resistance. It is displayed in in hormone ability to activate both oxidation in cells of glucose and synthesis of oleic monoene fatty acid from palmitic saturated fatty acid (C 18:1). The insulin resistance initiates pathologic process on the level of paracrine associations of cells resulting in permanent increase of concentration of non-etherified fatty acids in intercellular medium and intensification of their passive absorption by cells. The phylogenetically ancient mitochondrions will not to oxidize glucose until non-etherified fatty acids are present in cytosol and hence there is an opportunity to oxidize them. To eliminate undesirable action of polar saturated palmitic fatty acid, the cells etherify it by spirit glyceride into triglycerides to deposit in cytosol or to secrete into blood in a form of lipoproteins of very low density. Under insulin resistance, saturated palmitic fatty acid synthesized by hepatocytes from glucose, does not further transform into oleic monoenic fatty acid. The cells are to etherify endogenic (exogenic) palmnitic saturated fatty acid into composition of aphysiologic palmitic triglycerides (saturated palmitic fatty acid in position sn-2 of spirit glyceride). At that, triglycerides of palmitat-palmitat-oleat and even tripalmitat type are formed. The melting temperature of tripalmitat is 48 degrees C and melting temperature of physiologic trioletat is 13 degrees C. The intracellular lipases factually can't hydrolyze

  4. Prevalence and factors associated with the presence of non alcoholic fatty liver disease in an apparently healthy adult population in primary care units

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    Pizarro Gregorio

    2007-11-01

    Full Text Available Abstract Background Fatty liver disease is characterized by the accumulation of fat vacuoles inside of the hepatocytes. Non alcoholic fatty liver is associated with obesity, type 2 diabetes, dyslipemia, the intake of certain drugs and with the so-called metabolic syndrome. However, there is little information on the clinical relevance of this disorder as a healthcare problem in the general population, since the studies published generally include a limited number of patients and the diagnosis is established on the basis of clear biochemical alterations and liver biopsy. Methods/Design The aim of the study is the prevalence of non-alcoholic fatty liver disease in a general adult population by hepatic ultrasonography. A population-based, descriptive, transversal, multicentre study. Eighteen primary care centres of the north of Barcelona and the Maresme Areas of Healthcare Management attending an urban and semi-urban population of 360.000 inhabitants. A randomized sample of 786 subjects of 15 years or older were selected from the population and assigned to the participating centres according to the Primary Care Information System (SIAP: This population is practically the same as the general population of the area. The following determinations will be carried out in all the participants: hepatic ultrasonography to detect fatty liver, a questionnaire concerning liver diseases, alcohol intake, smoking and drug use, physical examination including abdominal perimeter and body mass index and biochemical analysis including liver function tests and parameters related to the metabolic syndrome and the HAIR score. Ultrasonographic diagnosis of fatty liver will be made according to established criteria (American Gastroenterology Association and diagnosis of metabolic syndrome according to the criteria of the European Group for the Study of Insulin Resistance. Discussion This study will attempt to determine the prevalence of non alcoholic fatty liver disease

  5. Association between thrombotic risk factors and extent of fibrosis in patients with non-alcoholic fatty liver diseases

    Institute of Scientific and Technical Information of China (English)

    N Assy; I Bekirov; Y Mejritsky; L Solomon; S Szvalb; O Hussein

    2005-01-01

    AIM: To evaluate the prevalence of genetic and acquired prothrombotic risk factors and their association with the extent of fibrosis and fatty infiltration in patients with non-alcoholic fatty liver disease (NAFLD).METHODS: Forty-four patients with chronic hepatitis (28 men and 16 women, with mean age of 45±11 and 49±12 years, respectively) constituted the patient population of this study. The groups were divided as follows: 15 patients with fatty liver (FL); 15 with non-alcoholic steatohepatitis (NASH); 14 with chronic viral hepatitis (CH) diagnosed by histology and liver technetium scan or ultrasound; and 10 healthy individuals. Thrombophilic, coagulation factors and genetic mutations were diagnosed by standard hemostatic and molecular coagulation assays.RESULTS: Activated protein C (APC) resistance and protein S were the most prevalent thrombotic risk factors (6% and 10% in NAFLD vs 21% and 14% in CH; P<0.01 and P<0.05, respectively). One thrombotic risk factor was identified in 41% of patients (23% mild fibrosis, 18% severe fibrosis) and two thrombotic risk factors in 6% of patients with NAFLD and severe fibrosis. While no differences in APC ratio, lupus anticoagulant, fibrinogen, factor V Leiden,prothrombin, and MTHFR mutation were found. Protein S levels were significantly lower in NASH patients than in patients with FL alone (92±19 vs106±2, P<0.01). Protein C levels were markedly higher in patients with NAFLD and mild or severe fibrosis as compared to the patients with CH, respectively (128±40 vs96±14, P<0.001 or 129±36 vs 88±13, P<0.01).CONCLUSION: Up to 46% of patients with NAFLD may have thrombotic risk factors, and the presence of thrombotic risk factors is correlated with the extent of hepatic fibrosis,suggesting a crucial role of the coagulation system in the pathogenesis of hepatic fibrosis.

  6. Connection of Nicotine to Diet-Induced Obesity and Non-Alcoholic Fatty Liver Disease: Cellular and Mechanistic Insights

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    Sinha-Hikim, Amiya P.; Sinha-Hikim, Indrani; Friedman, Theodore C.

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) poses a serious health hazard affecting 20–40% of adults in the general population in the USA and over 70% of the obese and extremely obese people. In addition to obesity, nicotine is recognized as a risk factor for NAFLD, and it has been reported that nicotine can exaggerate obesity-induced hepatic steatosis. The development of NAFLD has serious clinical complications because of its potential progression from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. Multiple mechanisms can be involved in nicotine plus high-fat diet-induced (HFD) hepatic steatosis. Emerging evidence now suggests that nicotine exacerbates hepatic steatosis triggered by HFD, through increased oxidative stress and hepatocellular apoptosis, decreased phosphorylation (inactivation) of adenosine-5-monophosphate-activated protein kinase and, in turn, up-regulation of sterol response-element binding protein 1-c, fatty acid synthase, and activation of acetyl-coenzyme A-carboxylase, leading to increased hepatic lipogenesis. There is also growing evidence that chronic endoplasmic reticulum stress through regulation of several pathways leading to oxidative stress, inflammation, perturbed hepatic lipid homeostasis, apoptosis, and autophagy can induce hepatic steatosis and its progression to NASH. Evidence also suggests a central role of the gut microbiota in obesity and its related disorders, including NAFLD. This review explores the contribution of nicotine and obesity to the development of NAFLD and its molecular underpinning. PMID:28239368

  7. Non-alcoholic fatty liver disease in a rural, physically active, low income population in Sri Lanka

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    Pinidiyapathirage M

    2011-11-01

    Full Text Available Abstract Background Non-alcoholic fatty liver disease (NAFLD is recognized as a metabolic disorder largely seen in urbanized populations. The purpose of this study was to assess prevalence and risk factors for NAFLD in a rural, physically active, economically deprived population in Sri Lanka. Methods By visiting individual households in the community, 35-64 year old adults resident in two selected estates in the Nuwara Eliya District of Sri Lanka, were invited to participate in the study. Blood pressure and anthropometric measurements were made on all participants. Blood samples were obtained for the assay of fasting glucose, serum lipids, serum insulin and alanine aminotransferase. NAFLD was diagnosed on established ultrasound criteria for fatty liver in the absence of hepatitis B and C markers and high alcohol consumption. Results Of those invited, 403 (65% participated in the study. Almost all participants were either Indian or Sri Lankan Tamils and 53% were females. Prevalence of NAFLD was 18% in this population. Twice as many males were diagnosed as having NAFLD compared to females. Male sex, high BMI, high waist circumference, high diastolic blood pressure and high plasma glucose levels were significant predictors of NAFLD. Conclusion Nearly one in five people in this predominantly Indian Tamil, rural, physically active, economically deprived population had NAFLD. The condition was associated with constituent features of the metabolic syndrome. These results support studies reporting ethnic variations in disease susceptibility and suggest that genetic factors may also play a role in determining disease risk.

  8. Non-alcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians

    Institute of Scientific and Technical Information of China (English)

    Kaushal Madan; Yogesh Batra; S Datta Gupta; Bal Chander; K D Anand Rajan; M S Tewatia; S K Panda; S K Acharya

    2006-01-01

    AIM: To evaluate the clinical and biochemical profile of patients with non alcoholic fatty liver disease (NAFLD)and to assess their histological severity at presentation.METHODS: Consecutive patients presenting to the liver clinic of All India Institute of Medical Sciences (AIIMS)with raised transaminases to at least 1.5 times upper limit of normal, and histologically confirmed non-alcoholic fatty liver disease were included. Patients who had significant alcohol intake or positive markers of other liver diseases or who were taking drugs known to produce fatty liver were excluded. The clinical, biochemical and histological profile of this group was studied.RESULTS: Fifty-one patients with NAFLD formed the study population. Their median age and BMI were 34(17-58) years and 26.7(21.3-32.5) kg/m2 respectively and 46 (90.1%) were males. The majority of the patients had mild inflammation, either grade 1 [32 (63%)] or grade 2 [16 (31%)] and only 3 (6%) patients had severe (grade 3) inflammation. Twenty-three (45%), 19 (37%),8(16%) and 1(2%) patienthad stage 0, 1, 2 and 3 fibrosis respectively on index biopsy and none had cirrhosis.On univariate analysis, triglyceride levels more than 150 mg % (OR = 7.1; 95% CI: 1.6-31.5, P = 0.002) and AST/ALT ratio > 1 (OR = 14.3; 95% CI: 1.4-678.5, P = 0.008)were associated with high grades of inflammation and none was associated with advanced fibrosis. On multivariate logistic regression analysis, hypertriglyceridemia >150 mg% was the only factor independently associated with presence of high grade of inflammation (OR = 1.6;95% CI: 1.3-22.7, P = 0.02), while none was associated with advanced fibrosis. Triglyceride levels correlated positively with inflammatory grade (r = 0.412; P = 0.003).CONCLUSION: NAFLD in North Indian patients is a disease of young over-weight males, most of whom are insulin resistant and they tend to have a mild histological disease at presentation.

  9. Treatment with a novel oleic-acid–dihydroxyamphetamine conjugation ameliorates non-alcoholic fatty liver disease in obese Zucker rats

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    Juan M. Decara

    2015-10-01

    Full Text Available Fatty liver disease is one of the main hepatic complications associated with obesity. To date, there are no effective treatments for this pathology apart from the use of classical fibrates. In this study, we have characterized the in vivo effects of a novel conjugation of oleic acid with an amphetamine derivative (OLHHA in an animal model of genetic obesity. Lean and obese Zucker rats received a daily intraperitoneal administration of OLHHA (5 mg kg−1 for 15 days. Plasma and liver samples were collected for the biochemical and molecular biological analyses, including both immunohistochemical and histological studies. The expression of key enzymes and proteins that are involved in lipid metabolism and energy homeostasis was evaluated in the liver samples. The potential of OLHHA to produce adverse drug reactions or toxicity was also evaluated through the monitoring of interactions with hERG channel and liver cytochrome. We found that OLHHA is a drug with a safe pharmacological profile. Treatment for 15 days with OLHHA reduced the liver fat content and plasma triglyceride levels, and this was accompanied by a general improvement in the profile of plasma parameters related to liver damage in the obese rats. A decrease in fat accumulation in the liver was confirmed using histological staining. Additionally, OLHHA was observed to exert anti-apoptotic effects. This hepatoprotective activity in obese rats was associated with an increase in the mRNA and protein expression of the cannabinoid type 1 receptor and a decrease in the expression of the lipogenic enzymes FAS and HMGCR primarily. However, changes in the mRNA expression of certain proteins were not associated with changes in the protein expression (i.e. L-FABP and INSIG2. The present results demonstrate that OLHHA is a potential anti-steatotic drug that ameliorates the obesity-associated fatty liver and suggest the potential use of this new drug for the treatment of non-alcoholic fatty

  10. The level of plasma homocysteine in patients with non-alcoholic fatty liver disease in combination with type 2 diabetes

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    V. F. Orlovskiy

    2015-06-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is one of the major causes of chronic diseases of the hepatobiliary zone. Aim. In order to explore new pathogenetic factors of NAFLD examined the level of plasma homocysteine in 110 patients. Methods and results. Patients were divided into two groups - the isolated NAFLD and in combination with Diabetes mellitus type 2. Found a significant increase in homocysteine level in all patients with NAFLD compared with the control group. High homocysteine concentration was in patients with comorbidity. There was positive correlation between levels of homocysteine and lipid components and cytolytic syndrome in all patients. Conclusion. The data obtained allow us to consider homocysteine as one of the factors in the pathological changes development in the liver.

  11. Non-alcoholic fatty liver disease and the metabolic syndrome: An update

    Institute of Scientific and Technical Information of China (English)

    R Scott Rector; John P Thyfault; Yongzhong Wei; Jamal A Ibdah

    2008-01-01

    Sedentary lifestyle and poor dietary choices are leading to a weight gain epidemic in westernized countries,subsequently increasing the risk for developing the metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). NAFLD is estimated to affect approximate 30% of the general US population and is considered the hepatic manifestation of the metabolic syndrome.Recent findings linking the components of the metabolic syndrome with NAFLD and the progression to nonalcoholic steatohepatitis (NASH) will be reviewed;in particular, the role of visceral adipose tissue, insulin resistance, and adipocytokines in the exacerbation of these conditions. While no therapy has been proven effective for treating NAFLD/NASH, common recommendations will be discussed.

  12. Assessment of Portal Venous and Hepatic Artery Haemodynamic Variation in Non-Alcoholic Fatty Liver Disease (NAFLD) Patients

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    Balasubramanian, Padhmini; Govindasamy, Ezhumalai; Venkatesh, Basavaiya Prabhu

    2016-01-01

    Introduction Non-Alcoholic Fatty Liver Disease (NAFLD) has various spectrums of liver diseases like isolated fatty liver, steatohepatitis and cirrhosis usually progressing in a linear fashion. In this process they are known to cause certain haemodynamic changes in the portal flow and hepatic artery flow. Aim The aim of the study was to study these haemodynamic changes in patients with NAFLD and to correlate it with the disease severity. Materials and Methods Ninety patients diagnosed to have NAFLD based on ultrasound abdomen (30 each in grade1, grade2 and grade3 NAFLD) and 30 controls (Normal liver on ultrasound abdomen) were subjected to portal vein and hepatic artery Doppler study. Peak maximum velocity (Vmax), Peak minimum velocity (Vmin), Mean flow velocity (MFV), and Vein pulsality index (VPI) of the portal vein and hepatic artery resistivity index (HARI) of the hepatic artery were the doppler parameters which were assessed. Liver span was also assessed both for the fatty liver and controls. Results The mean Vmax, Vmin, MFV and VPI of the portal vein in patients with NAFLD was 12.23±1.74cm/sec, 9.31±1.45cm/sec, 10.76±1.48cm/sec, and 0.24±0.04 as compared to 14.05±2.43cm/sec, 10.01±2.27cm/sec, 12.23±2.47cm/sec, 0.3±0.08 in controls respectively. All these differences were statistically significant except for Vmin. The Mean HARI in patients with fatty liver was 0.65±0.06 when compared to controls of 0.75±0.06 (p=0.001). HARI (r-value of -0.517) had a better negative correlation followed by VPI (r-value of -0.44) and Vmax (r-value of -0.293) with the severity of NAFLD. MFV had a very weak negative correlation (r-value of -0.182) with the severity of NAFLD. Conclusion The Vmax, MFV, VPI and HARI were significantly less when compared to controls suggesting a reduced portal flow and an increased hepatic arterial flow in patients with NAFLD. Among the parameters, HARI correlated better with the severity of NAFLD followed by VPI. PMID:27656524

  13. Influence of Ethnicity on the Accuracy of Non-Invasive Scores Predicting Non-Alcoholic Fatty Liver Disease

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    Xia, Ming-Feng; Yki-Järvinen, Hannele; Bian, Hua; Lin, Huan-Dong; Yan, Hong-Mei; Chang, Xin-Xia; Zhou, You; Gao, Xin

    2016-01-01

    Objectives Presence of non-alcoholic fatty liver disease (NAFLD) can predict risks for diabetes, cardiovascular disease and advanced liver disease in the general population. We aimed to establish a non-invasive score for prediction of NAFLD in Han Chinese, the largest ethnic group in the world, and detect whether ethnicity influences the accuracy of such a score. Methods Liver fat content (LFAT) was measured by quantitative ultrasound in 3548 subjects in the Shanghai Changfeng Community and a Chinese score was created using multivariate logistic regression analyses. This new score was internally validated in Chinese and externally in Finns. Its diagnostic performance was compared to the NAFLD liver fat score, fatty liver index (FLI) and hepatic steatosis index (HSI) developed in Finns, Italians and Koreans. We also analyzed how obesity related to LFAT measured by 1H-MRS in 79 Finns and 118 Chinese with type 2 diabetes (T2D). Results The metabolic syndrome and T2D, fasting serum insulin, body mass index (BMI) and AST/ALT ratio were independent predictors of NAFLD in Chinese. The AUROC in the Chinese validation cohort was 0.76 (0.73–0.78) and in Finns 0.73 (0.68–0.78) (p<0.0001). 43%, 27%, 32% and 42% of Chinese had NAFLD when determined by the Chinese score, NAFLD liver fat score (p<0.001 vs. Chinese score), FLI (p<0.001) and HSI (NS). For any given BMI and waist circumference, the Chinese had a markedly higher LFAT than the Finns. Conclusion The predictors of NAFLD in Han Chinese are as in Europids but the Chinese have more LFAT for any given degree of obesity than Europids. Ethnicity needs to be considered when NAFLD is predicted using risk scores. PMID:27579785

  14. Quantitative MRI for hepatic fat fraction and T2* measurement in pediatric patients with non-alcoholic fatty liver disease

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    Deng, Jie; Rigsby, Cynthia K.; Donaldson, James S. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Fishbein, Mark H. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Gastroenterology, Hepatology, and Nutrition, Chicago, IL (United States); Zhang, Gang [Ann and Robert H. Lurie Children' s Hospital of Chicago, Biostatistics Research Core, Chicago, IL (United States); Schoeneman, Samantha E. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States)

    2014-11-15

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The gold standard for diagnosis is liver biopsy. MRI is a non-invasive imaging method to provide quantitative measurement of hepatic fat content. The methodology is particularly appealing for the pediatric population because of its rapidity and radiation-free imaging techniques. To develop a multi-point Dixon MRI method with multi-interference models (multi-fat-peak modeling and bi-exponential T2* correction) for accurate hepatic fat fraction (FF) and T2* measurements in pediatric patients with NAFLD. A phantom study was first performed to validate the accuracy of the MRI fat fraction measurement by comparing it with the chemical fat composition of the ex-vivo pork liver-fat homogenate. The most accurate model determined from the phantom study was used for fat fraction and T2* measurements in 52 children and young adults referred from the pediatric hepatology clinic with suspected or identified NAFLD. Separate T2* values of water (T2*{sub W}) and fat (T2*{sub F}) components derived from the bi-exponential fitting were evaluated and plotted as a function of fat fraction. In ten patients undergoing liver biopsy, we compared histological analysis of liver fat fraction with MRI fat fraction. In the phantom study the 6-point Dixon with 5-fat-peak, bi-exponential T2* modeling demonstrated the best precision and accuracy in fat fraction measurements compared with other methods. This model was further calibrated with chemical fat fraction and applied in patients, where similar patterns were observed as in the phantom study that conventional 2-point and 3-point Dixon methods underestimated fat fraction compared to the calibrated 6-point 5-fat-peak bi-exponential model (P < 0.0001). With increasing fat fraction, T2*{sub W} (27.9 ± 3.5 ms) decreased, whereas T2*{sub F} (20.3 ± 5.5 ms) increased; and T2*{sub W} and T2*{sub F} became increasingly more similar when fat

  15. Chemokine ligand 2 and paraoxonase-1 in non-alcoholic fatty liver disease: The search for alternative causative factors.

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    Camps, Jordi; Joven, Jorge

    2015-03-14

    The incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) is constantly increasing. Despite this is apparently associated with the growing increase in obesity, insulin resistance and obesity-related metabolic disturbances their presence is not a necessary or sufficient condition to explain the accumulation of fat in the liver. Conversely, NAFLD is a predictor of other metabolic risks. NAFLD is currently the most frequent chronic liver disease but should not be considered benign or anecdotic because a considerable proportion of patients with NAFLD progress to cirrhosis and end-stage liver disease. Consequently, the search for alternative molecular mechanisms with therapeutic implications in NAFLD and associated disorders deserves a careful consideration. Mitochondria are possible targets as these organelles generate energy from nutrient oxidation. Some findings, generated in patients with extreme obesity and in murine models, support the notion that NAFLD could be a mitochondrial disease. This is plausible because mitochondrial dysfunction affects the accumulation of lipids in hepatocytes and promotes lipid peroxidation, the production of reactive oxygen species, the release of cytokines causing inflammation and cell death. Here we discuss basic research and mechanistic studies targeting the role of chemokine ligand 2 in liver inflammation and that of the paraoxonases in the oxidative stress. Their combination and association with mitochondrial dysfunction may uncover mechanisms underlying the progression of NAFLD and may help to identify novel therapeutic targets.

  16. The Association of Metabolic Syndrome, Insulin Resistance and Non-alcoholic Fatty Liver Disease in Overweight/Obese Children

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    El-Koofy, Nehal M.; Anwar, Ghada M.; El-Raziky, Mona S.; El-Hennawy, Ahmad M.; El-Mougy, Fatma M.; El-Karaksy, Hanaa M.; Hassanin, Fetouh M.; Helmy, Heba M.

    2012-01-01

    Background/Aim: To study the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT). Patients and Methods: Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and liver biochemical profile, in addition to liver ultrasound and liver biopsy. Results: Twenty patients (60.6%) were labeled with MS. IR was present in 16 (48.4%). Fifteen (44%) patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001). Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05) and fitted more with the criteria of MS (80% vs. 44%). IR was significantly more common among NAFLD patients (73% vs. 28%). Conclusion: There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD. PMID:22249092

  17. The association of metabolic syndrome, insulin resistance and non-alcoholic fatty liver disease in overweight/obese children

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    Nehal M El-Koofy

    2012-01-01

    Full Text Available Background/Aim: To study the prevalence of metabolic syndrome (MS, insulin resistance (IR and non-alcoholic fatty liver disease (NAFLD in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT. Patients and Methods: Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG, total cholesterol, high-density lipoprotein cholesterol (HDL-c, low-density lipoprotein cholesterol (LDL-c and liver biochemical profile, in addition to liver ultrasound and liver biopsy. Results: Twenty patients (60.6% were labeled with MS. IR was present in 16 (48.4%. Fifteen (44% patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001. Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05 and fitted more with the criteria of MS (80% vs. 44%. IR was significantly more common among NAFLD patients (73% vs. 28%. Conclusion: There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD.

  18. Non-Alcoholic Fatty Liver Disease: The Bile Acid-Activated Farnesoid X Receptor as an Emerging Treatment Target

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    Michael Fuchs

    2012-01-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is currently evolving as the most common liver disease worldwide. It may progress to liver cirrhosis and liver cancer and is poised to represent the most common indication for liver transplantation in the near future. The pathogenesis of NAFLD is multifactorial and not fully understood, but it represents an insulin resistance state characterized by a cluster of cardiovascular risk factors including obesity, dyslipidemia, hyperglycemia, and hypertension. Importantly, NAFLD also has evolved as independent risk factor for cardiovascular disease. Unfortunately thus far no established treatment does exist for NAFLD. The bile acid-activated nuclear farnesoid X receptor (FXR has been shown to play a role not only in bile acid but also in lipid and glucose homeostasis. Specific targeting of FXR may be an elegant and very effective way to readjust dysregulated nuclear receptor-mediated metabolic pathways. This review discusses the body's complex response to the activation of FXR with its beneficial actions but also potential undesirable side effects.

  19. The Potential of Non-Provitamin A Carotenoids for the Prevention and Treatment of Non-Alcoholic Fatty Liver Disease

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    Ana Gabriela Murillo

    2016-11-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is an obesity-associated spectrum of comorbidities defined by the presence of metabolic dysfunction, oxidative stress, inflammation, and fibrosis in the liver. If left untreated, NAFLD can progress to cirrhosis, liver failure, or hepatocellular carcinoma. NAFLD is recognized as the most common liver disease in the United States, affecting around 30% of the population. Identification of dietary components capable of reducing or preventing NAFLD is therefore essential to battle this condition. Dietary carotenoids including astaxanthin, lycopene, lutein, and zeaxanthin have been demonstrated to be potent antioxidants as well as to exhibit anti-inflammatory effects. Many studies report the protective effect(s of these carotenoids against different conditions such as atherosclerosis, diabetic complications, age-related macular degeneration, and liver diseases. In this review, we will focus on the effects of these carotenoids in the prevention or reduction of NAFLD as seen in epidemiological observations and clinical trials, as well as the suggested mechanism of action derived from animal and cell studies.

  20. Diagnosis and management of non-alcoholic fatty liver disease and related metabolic disorders: consensus statement from the Study Group of Liver and Metabolism, Chinese Society of Endocrinology.

    Science.gov (United States)

    Gao, Xin; Fan, Jian-Gao

    2013-12-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, affecting 20%-33% of the general population. Large population-based surveys in China indicate a prevalence of approximately 15%-30%. Worldwide, including in China, the prevalence of NAFLD has increased rapidly in parallel with regional trends of obesity, type 2 diabetes and metabolic syndrome. In addition, NAFLD has contributed significantly to increased overall, as well as cardiovascular and liver-related, mortality in the general population. In view of rapid advances in research into NAFLD in recent years, this consensus statement provides a brief update on the progress in the field and suggests preferred approaches for the comprehensive management of NAFLD and its related metabolic diseases.

  1. Therapeutic strategies for pediatric non-alcoholic fatty liver disease: A challenge for health care providers

    Institute of Scientific and Technical Information of China (English)

    Valerio Nobili; Melania Manco

    2007-01-01

    Non-alcoholic steato-hepatitis (NASH) is related to insulin resistance and, thus, frequently occurs as part of the metabolic changes that accompany obesity, diabetes and hyperlipidemia. In childhood, the overwhelming boost of obesity and its co-morbidities have lead to the extraordinarily increased prevalence of NASH.Establishing effective therapeutic strategies to treat the disease represents the challenge for hepatologists and gastroenterologists in the next decade. Therapeutic approaches have aimed at treating associated conditions (obesity, insulin resistance, hyperlipemia, etc) or reducing liver oxidative damage (vitamin E).

  2. Pharmacological and antioxidant actions of garlic and.or onion in non-alcoholic fatty liver disease (NAFLD) in rats.

    Science.gov (United States)

    El-Din, Sayed H Seif; Sabra, Abdel-Nasser A; Hammam, Olfat A; Ebeid, Fatma A; El-Lakkany, Naglaa M

    2014-08-01

    Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of fat-induced liver injury, ranging from mild steatosis to cirrhosis and liver failure. This study investigates the hepatoprotective properties of garlic and onion in NAFLD rat model. Ninety male Sprague-Dawley rats were randomly divided into 9 groups; normal (I), NAFLD induced with high fat diet (HFD; II), NAFLD switched to regular diet (RD; III), NAFLD-HFD or NAFLD-RD treated with garlic (IV, V), onion (VI, VII) or the combined garlic+onion (VIII, IX) respectively. A NAFLD rat model was established by feeding the animals with a high-fat diet for 12 wk. These animals were then treated with garlic or/and onion or vehicle for 8 wk (weeks 13-20) and then killed to obtain serum samples and liver tissues. Liver histology, lipids, parameters of oxidative stress, TNF-α and TGF-β were measured. The liver in NAFLD-HFD showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration. Serum levels of ALT, AST, ALP, leptin, cholesterol, triglycerides, TNF-α, TGF-β and hepatic MDA' were significantly increased (P NAFLD-RD group. Combined administration of garlic+onion produced a better and significant decrease in liver steatosis, serum liver enzymes, oxidative markers and lipid peroxidation versus each one alone. In the same time, NAFLD-induced inflammation was also mitigated via reduction of TNF-α and TGF-β. In addition, these results were better in the group IX versus group VIII.

  3. Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease: An update.

    Science.gov (United States)

    Athyros, Vasilios G; Tziomalos, Konstantinos; Katsiki, Niki; Doumas, Michael; Karagiannis, Asterios; Mikhailidis, Dimitri P

    2015-06-14

    Non-alcoholic fatty liver disease (NAFLD) is considered to be an independent cardiovascular disease (CVD) risk factor. However, simple steatosis has a benign clinical course without excess mortality. In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis (NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease (CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness (AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis (mainly by simple non-invasive tests), CKD, and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above.

  4. Exploring the molecular mechanisms underlying the potentiation of exogenous growth hormone on alcohol-induced fatty liver diseases in mice

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    Tian Ya-ping

    2010-11-01

    Full Text Available Abstract Background Growth hormone (GH is an essential regulator of intrahepatic lipid metabolism by activating multiple complex hepatic signaling cascades. Here, we examined whether chronic exogenous GH administration (via gene therapy could ameliorate liver steatosis in animal models of alcoholic fatty liver disease (AFLD and explored the underlying molecular mechanisms. Methods Male C57BL/6J mice were fed either an alcohol or a control liquid diet with or without GH therapy for 6 weeks. Biochemical parameters, liver histology, oxidative stress markers, and serum high molecular weight (HMW adiponectin were measured. Quantitative real-time PCR and western blotting were also conducted to determine the underlying molecular mechanism. Results Serum HMW adiponectin levels were significantly higher in the GH1-treated control group than in the control group (3.98 ± 0.71 μg/mL vs. 3.07 ± 0.55 μg/mL; P P P P P Conclusions GH therapy had positive effects on AFLD and may offer a promising approach to prevent or treat AFLD. These beneficial effects of GH on AFLD were achieved through the activation of the hepatic adiponectin-SIRT1-AMPK and PPARα-AMPK signaling systems.

  5. Type 2 Diabetes in Non-Alcoholic Fatty Liver Disease and Hepatitis C Virus Infection—Liver: The “Musketeer” in the Spotlight

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    Stefano Ballestri

    2016-03-01

    Full Text Available The pathogenesis of type 2 diabetes (T2D involves chronic hyperinsulinemia due to systemic and hepatic insulin resistance (IR, which if uncorrected, will lead to progressive pancreatic beta cell failure in predisposed individuals. Non-alcoholic fatty liver disease (NAFLD encompasses a spectrum of fatty (simple steatosis and steatohepatitis and non-fatty liver changes (NASH-cirrhosis with or without hepatocellular carcinoma (HCC that are commonly observed among individuals with multiple metabolic derangements, notably including visceral obesity, IR and T2D. Hepatitis C virus (HCV infection is also often associated with both hepatic steatosis and features of a specific HCV-associated dysmetabolic syndrome. In recent years, the key role of the steatotic liver in the development of IR and T2D has been increasingly recognized. Thus, in this comprehensive review we summarize the rapidly expanding body of evidence that links T2D with NAFLD and HCV infection. For each of these two liver diseases with systemic manifestations, we discuss the epidemiological burden, the pathophysiologic mechanisms and the clinical implications. To date, substantial evidence suggests that NAFLD and HCV play a key role in T2D development and that the interaction of T2D with liver disease may result in a “vicious circle”, eventually leading to an increased risk of all-cause mortality and liver-related and cardiovascular complications. Preliminary evidence also suggests that improvement of NAFLD is associated with a decreased incidence of T2D. Similarly, the prevention of T2D following HCV eradication in the era of direct-acting antiviral agents is a biologically plausible result. However, additional studies are required for further clarification of mechanisms involved.

  6. Strong association between non alcoholic fatty liver disease (NAFLD and low 25(OH vitamin D levels in an adult population with normal serum liver enzymes

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    Pozzilli Paolo

    2011-07-01

    Full Text Available Abstract Background Hypovitaminosis D has been recently recognized as a worldwide epidemic. Since vitamin D exerts significant metabolic activities, comprising free fatty acids (FFA flux regulation from the periphery to the liver, its deficiency may promote fat deposition into the hepatocytes. Aim of our study was to test the hypothesis of a direct association between hypovitaminosis D and the presence of NAFLD in subjects with various degree of insulin-resistance and related metabolic disorders. Methods We studied 262 consecutive subjects referred to the Diabetes and Metabolic Diseases clinics for metabolic evaluation. NAFLD (non-alcoholic fatty liver disease was diagnosed by upper abdomen ultrasonography, metabolic syndrome was identified according to the Third Report of National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATPIII modified criteria. Insulin-resistance was evaluated by means of HOMA-IR. Fatty-Liver-Index, a recently identified correlate of NAFLD, was also estimated. Serum 25(OHvitamin D was measured by colorimetric method. Results Patients with NAFLD (n = 162,61.8% had reduced serum 25(OH vitamin D levels compared to subjects without NAFLD (14.8 ± 9.2 vs 20.5 ± 9.7 ng/ml, p Conclusions Low 25(OHvitamin D levels are associated with the presence of NAFLD independently from metabolic syndrome, diabetes and insulin-resistance profile.

  7. Recent advances in dietary supplementation, in treatingnon-alcoholic fatty liver disease

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    Tannaz Eslamparast; Sareh Eghtesad; Hossein Poustchi; Azita Hekmatdoost

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is currentlyknown as the most common liver problem, characterizedby excessive lipid accumulation in hepatocytes,which may progress to other liver diseases such asnonalcoholic steatohepatitis, hepatic tissue fibrosis, livercirrhosis, and failure or hepatocellular carcinoma. SinceNAFLD is positively associated with the developmentof obesity, insulin resistance, and ultimately type2 diabetes mellitus, it is often regarded as thehepatic manifestation of the metabolic syndrome. Nopharmacologic treatment has yet been proven for thisdisease. For most patients with presumed or confirmedNAFLD, the only proven strategy is to offer lifestyleadvice that can lead to sustained weight loss. Sinceinsulin resistance, oxidative stress, inflammation, andnecro-apoptosis are involved in NAFLD pathogenesis,it seems that every potential therapeutic agent shouldtarget one or some of these pathologic events. Thereare many well known anti-oxidants, anti-inflammatory,and insulin sensitizer dietary supplements which haveshown beneficial effects on NAFLD improvementin animal and human studies. The purpose of thisreview is to explore the existing evidences on dietarysupplements considered to have hepatoprotectiveproperties, and to present some proposed mechanismsby which they may protect against NAFLD.

  8. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008447 Identification of gene expression patterns in a rat model of nonalcoholic fatty liver disease. ZHANG Xuequn(张雪群), et al. Dept Gastroenterol, 1st Hosp, Med Coll, Zhejiang Univ, Hangzhou 310003. Chin J Dig 2008;28(5):323-327. Objective To compare and analyze gene expression patterns in a rat model of nonalcoholic fatty liver disease (NAFLD). Methods Twelve male Sprague-Dawley rats were randomly given either general diet (control group) or a high-fat diet (model group) for 4 weeks.

  9. Predictors of non-alcoholic fatty liver disease in obese and overweight Egyptian children: Single center study

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    Hanaa M El-Karaksy

    2011-01-01

    Full Text Available Background/Aim: Pediatric non-alcoholic fatty liver disease (NAFLD is a global problem which has been increasingly recognized with the dramatic rise in pediatric obesity. The aim of the present study was to identify the clinical, sonographic, and biochemical predictors for NAFLD in obese children. Materials and Methods: Seventy-six children (2-15 years were included after an informed consent. All were subjected to full anthropometric assessment (including height, weight, body mass index, subscapular skin fold thickness, waist and hip circumference and calculation of waist: hip ratio, biochemical assessment of liver function tests, lipid profile and insulin resistance and sonographic assessment of hepatic echogenicity. Liver biopsy when indicated, was done in 33 patients. Results: Sixteen patients (21% had elevated ALT and 6 (7.9% had elevated AST. Significant dyslipidemia (low HDL-c, high total cholesterol, high LDL-c and triglycerides and higher insulin resistance were found in obese patients (P<0.01. The main sonographic findings were hepatomegaly in 20 patients (26.3% and echogenic liver in 41 patients (53.9%. Liver biopsy showed simple steatosis in eight cases (24.2% and non-alcoholic steatohepatitis (NASH in seven cases (21.2%. Anthropometric measurements, increased hepatic echogenicty by ultrasound, insulin resistance and lipid profile were good predictors of NAFLD in obese children if assessed together. However, LDL-c was the only sensitive predictor (independent variable for NAFLD in both uni- and multivariate logistic regression analyses. Conclusion : Dyslipidemia per se is a strong predictor of NAFLD among obese Egyptian children.

  10. Statins Increase Mitochondrial and Peroxisomal Fatty Acid Oxidation in the Liver and Prevent Non-Alcoholic Steatohepatitis in Mice

    Science.gov (United States)

    Park, Han-Sol; Jang, Jung Eun; Ko, Myoung Seok; Woo, Sung Hoon; Kim, Bum Joong; Kim, Hyun Sik; Park, Hye Sun; Park, In-Sun; Koh, Eun Hee

    2016-01-01

    Background Non-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH), but underlying mechanisms of this prevention are largely unknown. Methods Seven-week-old C57BL/6J mice were given normal chow or a methionine- and choline-deficient diet (MCDD) with or without various statins, fluvastatin, pravastatin, simvastatin, atorvastatin, and rosuvastatin (15 mg/kg/day), for 6 weeks. Histological lesions were analyzed by grading and staging systems of NASH. We also measured mitochondrial and peroxisomal FAO in the liver. Results Statin treatment prevented the development of MCDD-induced NASH. Both steatosis and inflammation or fibrosis grades were significantly improved by statins compared with MCDD-fed mice. Gene expression levels of peroxisomal proliferator-activated receptor α (PPARα) were decreased by MCDD and recovered by statin treatment. MCDD-induced suppression of mitochondrial and peroxisomal FAO was restored by statins. Each statin's effect on increasing FAO and improving NASH was independent on its effect of decreasing cholesterol levels. Conclusion Statins prevented NASH and increased mitochondrial and peroxisomal FAO via induction of PPARα. The ability to increase hepatic FAO is likely the major determinant of NASH prevention by statins. Improvement of peroxisomal function by statins may contribute to the prevention of NASH.

  11. Significant cohort of non-alcoholic fatty liver disease with portal vein thrombosis in transplant waiting list

    Institute of Scientific and Technical Information of China (English)

    Metin; Basaranoglu; Sonia; M; Najjar; Ali; Ebag; Demirbag; Hakan; Senturk

    2016-01-01

    AIM: To characterize non-alcoholic fatty liver disease(NAFLD) presentation with esophageal varices. METHODS: We carried out a retrospective cohort study on 258 patients with esophageal varices at a single tertiary referral center. These patients underwent diagnosis of several liver diseases, including: NAFLDassociated cirrhosis, hepatitis B, hepatitis C, Wilson disease, autoimune liver diseases, and others. RESULTS: Of the 258 patients, 39% of patients exhibited esophageal varices due to NAFLD-associated cirrhosis. Of the 38(14.7%) patients developed hepatocellular carcinoma during follow-up, 52% were due to hepatitis B, 26% due to hepatitis C and 13.2% due to NAFLD. Of the 258 patients, 50.0% with NAFLD, 33.3% with hepatitis B, 26.3% with hepatitis C, and 58.3% with other diseases were alive at the end of the 5-year period with a significant difference according to the Kaplan-Meier log Rank test(P = 0.040). Portal vein thrombosis was detected in 47.5% of patients with NAFLD, in 29% of patients with hepatitis B, in 17% of patients with hepatitis C, and in 62% of patients with other related diseases(P < 0.0001). CONCLUSION: Our study showed a proportionally greater elevation in liver transplant candidacy in patients with NAFLD and portal vein thrombosis. Older patients were more prone to developing cirrhosis, hepatocellular carcinoma and a high mortality rate. However, younger patients exhibited more portal vein thrombosis and gastric varices.

  12. Potential roles of glucagon-like peptide-1-based therapies in treating non-alcoholic fatty liver disease.

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    Liu, Ye; Wei, Rui; Hong, Tian-Pei

    2014-07-21

    Glucagon-like peptide-1 (GLP-1)-based therapies have demonstrated efficacy and safety in treating type 2 diabetes, which shares a similar pathophysiological mechanism with non-alcoholic fatty liver disease (NAFLD). Recent studies showed that glucose-induced GLP-1 secretion was decreased in patients with NAFLD and that the level of dipeptidyl peptidase-4, which inactivates intact GLP-1, was upregulated. Moreover, the expression of the GLP-1 receptor was downregulated in livers from patients with NAFLD, indicating an association of defective GLP-1 signalling with NAFLD. Notably, GLP-1-based therapies are reported to be effective in improving hepatic endpoints in patients with NAFLD, such as reducing hepatic fat content, hepatic steatosis and plasma transaminase levels, and preventing fibrosis. GLP-1-based therapies are beneficial for body weight control and glycaemic normalisation, which are important for the management of NAFLD. Moreover, clinical and preclinical studies showed that GLP-1-based agents might directly exert their actions on the liver through activation of functional GLP-1 receptors in hepatocytes. The possible mechanisms involve regulating gene expression that is associated with insulin resistance and lipid metabolism, and suppressing oxidative stress in the liver cells, thus preventing the development and progression of NAFLD. Based on these promising data, large-scale randomised controlled trials are warranted to assess the efficacy and safety of GLP-1-based therapies in treating NAFLD.

  13. Pediatric non alcoholic fatty liver disease: old and new concepts on development, progression, metabolic insight and potential treatment targets.

    Science.gov (United States)

    Giorgio, Valentina; Prono, Federica; Graziano, Francesca; Nobili, Valerio

    2013-03-25

    Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. NAFLD has emerged to be extremely prevalent, and predicted by obesity and male gender. It is defined by hepatic fat infiltration >5% hepatocytes, in the absence of other causes of liver pathology. It includes a spectrum of disease ranging from intrahepatic fat accumulation (steatosis) to various degrees of necrotic inflammation and fibrosis (non-alcoholic steatohepatatis [NASH]). NAFLD is associated, in children as in adults, with severe metabolic impairments, determining an increased risk of developing the metabolic syndrome. It can evolve to cirrhosis and hepatocellular carcinoma, with the consequent need for liver transplantation. Both genetic and environmental factors seem to be involved in the development and progression of the disease, but its physiopathology is not yet entirely clear. In view of this mounting epidemic phenomenon involving the youth, the study of NAFLD should be a priority for all health care systems. This review provides an overview of current and new clinical-histological concepts of pediatric NAFLD, going through possible implications into patho-physiolocical and therapeutic perspectives.

  14. Alcohol and liver

    Institute of Scientific and Technical Information of China (English)

    Natalia Osna

    2009-01-01

    @@ Liver is a primary site of ethanol metabolism, which makes this organ susceptible to alcohol-induced damage.Alcoholic liver disease (ALD) has many manifestations and complicated pathogenesis. In this Topic Highlight, we included the key reviews that characterize new findings about the mechanisms of ALD development and might be of strong interest for clinicians and researchers involved in liver alcohol studies.

  15. Meta-analysis reveals up-regulation of cholesterol processes in non-alcoholic and down-regulation in alcoholic fatty liver disease

    Science.gov (United States)

    Wruck, Wasco; Adjaye, James

    2017-01-01

    AIM To compare transcriptomes of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) in a meta-analysis of liver biopsies. METHODS Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD. RESULTS We observed predominating commonalities at the transcriptome level between ALD and NAFLD, most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction, phagosome and lysosome. However some pathways were regulated in opposite directions in ALD and NAFLD, for example, glycolysis was down-regulated in ALD and up-regulated in NAFLD. Interestingly, we found rate-limiting genes such as HMGCR, SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD (down-regulated) and NAFLD (up-regulated). We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE. Additionally, we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD. CONCLUSION Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile. Thus, it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile - also as possible drug targets. The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD. PMID:28357032

  16. Demethyleneberberine attenuates non-alcoholic fatty liver disease with activation of AMPK and inhibition of oxidative stress.

    Science.gov (United States)

    Qiang, Xiaoyan; Xu, Lulu; Zhang, Miao; Zhang, Pengcheng; Wang, Yinhang; Wang, Yongchen; Zhao, Zheng; Chen, Huan; Liu, Xie; Zhang, Yubin

    2016-04-15

    Non-alcoholic fatty liver disease (NAFLD) has reached an epidemic level globally, which is recognized to form non-alcoholic steatohepatitis (NASH) by the "two-hit" model, including oxidative stress and inflammation. AMP-activated protein kinase (AMPK) has long been regarded as a key regulator of energy metabolism, which is recognized as a critical target for NAFLD treatment. Here we introduce a natural product, demethyleneberberine (DMB), which potentially ameliorated NAFLD by activating AMPK pathways. Our study showed that the intraperitoneal injection of DMB (20 or 40 mg/kg body weight) decreased hepatic lipid accumulation in methionine and choline deficient (MCD) high-fat diet feeding mice and db/db mice. The further investigation demonstrated that DMB activated AMPK by increasing its phosphorylation in vitro and in vivo. Accompanied with AMPK activation, the expression of lipogenic genes were significantly reduced while genes responsible for the fatty acid β-oxidation were restored in DMB-treated NAFLD mice. In addition, the remarkable oxidative damage and inflammation induced by NAFLD were both attenuated by DMB treatment, which is reflected by decreased lipid oxidative product, malonaldehyde (MDA) and inflammatory factors, tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β). Based on all above, DMB could serve as a novel AMPK activator for treating NAFLD and preventing the pathologic progression from NAFLD to NASH by inhibiting the oxidative stress and inflammation.

  17. Additive Effect of Non-Alcoholic Fatty Liver Disease on Metabolic Syndrome-Related Endothelial Dysfunction in Hypertensive Patients.

    Science.gov (United States)

    Perticone, Maria; Cimellaro, Antonio; Maio, Raffaele; Caroleo, Benedetto; Sciacqua, Angela; Sesti, Giorgio; Perticone, Francesco

    2016-03-26

    Metabolic syndrome (MS) is characterized by an increased risk of incident diabetes and cardiovascular (CV) events, identifying insulin resistance (IR) and endothelial dysfunction as key elements. Moreover, non-alcoholic fatty liver disease (NAFLD) is bidirectionally linked with MS as a consequence of metabolic and inflammatory abnormalities. We addressed the question if the evolution in NAFLD might worsen endothelium-dependent vasodilating response in MS hypertensives. We recruited 272 Caucasian newly-diagnosed never-treated hypertensive outpatients divided into three groups according to the presence/absence of MS alone or in combination with NAFLD. MS and NAFLD were defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and non-invasive fatty liver index, respectively. We determined IR by using the homeostasis model assessment (HOMA) index. Vascular function, as forearm blood flow (FBF), was determined through strain-gauge plethysmography after intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside. MS+NAFLD+ group showed worse metabolic, inflammatory and vascular profiles compared with MS-NAFLD- and MS+NAFLD-. HOMA resulted in being the strongest predictor of FBF both in the MS+NAFLD- and in the MS+NAFLD+ groups, accounting for 20.5% and 33.2% of its variation, respectively. In conclusion, we demonstrated that MS+NAFLD+ hypertensives show a worse endothelium-dependent vasodilation compared with MS+NAFLD-, allowing for consideration of NAFLD as an early marker of endothelial dysfunction in hypertensives.

  18. Additive Effect of Non-Alcoholic Fatty Liver Disease on Metabolic Syndrome-Related Endothelial Dysfunction in Hypertensive Patients

    Directory of Open Access Journals (Sweden)

    Maria Perticone

    2016-03-01

    Full Text Available Metabolic syndrome (MS is characterized by an increased risk of incident diabetes and cardiovascular (CV events, identifying insulin resistance (IR and endothelial dysfunction as key elements. Moreover, non-alcoholic fatty liver disease (NAFLD is bidirectionally linked with MS as a consequence of metabolic and inflammatory abnormalities. We addressed the question if the evolution in NAFLD might worsen endothelium-dependent vasodilating response in MS hypertensives. We recruited 272 Caucasian newly-diagnosed never-treated hypertensive outpatients divided into three groups according to the presence/absence of MS alone or in combination with NAFLD. MS and NAFLD were defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII and non-invasive fatty liver index, respectively. We determined IR by using the homeostasis model assessment (HOMA index. Vascular function, as forearm blood flow (FBF, was determined through strain-gauge plethysmography after intra-arterial infusion of acetylcholine (ACh and sodium nitroprusside. MS+NAFLD+ group showed worse metabolic, inflammatory and vascular profiles compared with MS−NAFLD− and MS+NAFLD−. HOMA resulted in being the strongest predictor of FBF both in the MS+NAFLD− and in the MS+NAFLD+ groups, accounting for 20.5% and 33.2% of its variation, respectively. In conclusion, we demonstrated that MS+NAFLD+ hypertensives show a worse endothelium-dependent vasodilation compared with MS+NAFLD−, allowing for consideration of NAFLD as an early marker of endothelial dysfunction in hypertensives.

  19. Non-alcoholic and alcoholic Fatty Liver Disease - two Diseases of Affluence associated with the Metabolic Syndrome and Type 2 Diabetes: the FIN-D2D Survey

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    Saltevo Juha

    2010-05-01

    Full Text Available Abstract Background Non-alcoholic fatty liver disease (NAFLD is known to be associated with the metabolic syndrome (MetS and abnormal glucose tolerance. Whether alcoholic fatty liver disease (AFLD is associated with similar metabolic abnormalities has not been examined in a population-based study. We aimed at assessing the prevalences of NAFLD and AFLD, and to examine to what extent these conditions are associated with MetS and abnormal glucose tolerance. Methods The cohort included 2766 Finnish subjects (45-74 years from the population-based FIN-D2D survey. Features of insulin resistance, components of the MetS, glucose tolerance status by oral glucose tolerance test, serum liver enzyme concentrations, and daily alcohol consumption were assessed. Results Subjects with NAFLD and AFLD were equally obese and had similar fasting and insulin concentrations. The prevalences of NAFLD and AFLD were 21% (95% CI: 19%-22% and 7% (95% CI: 6%-8%. The MetS was slightly more prevalent in AFLD (73% than in NAFLD (70%, p = 0.028, and type 2 diabetes was similarly prevalent in NAFLD and AFLD (24-25%. The MetS and type 2 diabetes were more prevalent in subjects with NAFLD or AFLD compared to subjects with normal LFTs (53% and 14%, p Discussion and conclusion In Finnish middle-aged population, the prevalence of NAFLD is 3-fold higher than that of AFLD. The prevalences of MetS and type 2 diabetes are, however, significantly increased in both NAFLD and AFLD compared to subjects with normal LFTs. Subjects with AFLD are thus similarly metabolically unhealthy as subjects with NAFLD.

  20. Correlation of severity of non-alcoholic fatty liver disease with viseral adipose tissue area,body mass index,and waist circumference

    Institute of Scientific and Technical Information of China (English)

    黄志鹏

    2013-01-01

    Objective To analyze the correlation of the severity of non-alcoholic fatty liver disease (NAFLD) with visceral adipose tissue area (VAT) ,body mass index (BMI) ,and waist circumference (WC) .Methods A total of 127NAFLD patients were divided into mild NAFLD group

  1. Influence of fat/carbohydrate ratio on progression of fatty liver disease and on development of osteopenia in male rats fed alcohol via total enteral nutrition (TEN)

    Science.gov (United States)

    Alcohol abuse is associated with the development of fatty liver disease and also with significant bone loss in both genders. In this study, we examined ethanol (EtOH)-induced pathology in response to diets with differing fat/carbohydrate ratios. Male Sprague-Dawley rats were fed intragastrically wit...

  2. Prevalence of non-alcoholic fatty liver disease and fibrosis in a large population cohort in the north of the Netherlands: A lifelines cohort study

    NARCIS (Netherlands)

    Van Den Berg, E.H.; Amini, M.; Schreuder, T.C.M.A.; Dullaart, R.P.F.; Faber, K.N.; Alizadeh, B.Z.; Blokzijl, H.

    2016-01-01

    Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is an increasing health issue, being part of the worldwide epidemic of obesity. The aim of this study was to investigate the prevalence of NAFLD and fibrosis and analyze biochemical characteristics in a large population-based cohort stud

  3. Body mass index in school-aged children and the risk of routinely diagnosed non-alcoholic fatty liver disease in adulthood

    DEFF Research Database (Denmark)

    Zimmermann, Esther; Gamborg, Michael; Holst, Claus

    2015-01-01

    OBJECTIVE: The relation between childhood overweight and adult non-alcoholic fatty liver disease (NAFLD) is largely unknown. We investigated if weight and weight gain in childhood increases the risk of being diagnosed with NAFLD in routine clinical settings in adulthood. PARTICIPANTS: We studied...

  4. Non-alcoholic fatty liver disease and the metabolic syndrome: Effects of weight loss and a review of popular diets. Are low carbohydrate diets the answer?

    Institute of Scientific and Technical Information of China (English)

    Harjot K Gill; George Y Wu

    2006-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of fat-induced liver injury, ranging from relatively benign steatosis to cirrhosis and liver failure.The presence of obesity and insulin resistance is strongly associated with non-alcoholic fatty liver and confers on it a greater risk of histologically advanced disease. There is a growing concern in the medical profession as the prevalence of this disease continues to rise in parallel with the rise in obesity and the metabolic syndrome.Treatment options are limited and dietary weight loss is often advised. Low fat diets are difficult to adhere to and recent studies have shown the potential of low carbohydrate diets for weight loss and improving insulin resistance. Thus far, no study has evaluated the effect of low carbohydrate diets on NAFLD. Future studies will be required to address this question and others with regards to the nutritional adequacy and long-term side effects of these diets.

  5. Comparison of low-calorie diet with and without sibutramine on body weight and liver function of patients with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Z bahmanabadi

    2011-06-01

    Full Text Available Introduction & Objective: Non-alcoholic fatty liver (NAFLD is defined as a spectrum of clinical scenarios which is pathological deposition of fat droplets in the liver of patients who have no history of alcohol use. This study compared the effect of low calorie diet with and without sibutramine on body weight and liver function in patients with NAFLD. Materials & Methods: This clinical trial study was conducted in 2010 at Tabriz University of Medical Sciences, on 40 obese patients with non-alcoholic fatty liver. Patients were randomly divided into two equal groups of intervention and control groups. Group one received 15 mg daily sibutramine capsules half an hour before lunch and a weight loss diet based on ideal body weight. The other group only had diet control for weight reduction. Before and after 3 months of intervention, weight changes, fasting glucose, glycosylated hemoglobin HbA1c, levels of liver enzymes and ultrasound evaluation was repeated. Data were analyzed using the SPSS software and the paired T test, Mann-Whitney and McNemar test. Results: The mean age of the subjects was 38.90 ± 7.00 in the sibutramine group and 36.55 ±7.87 for the control group. After three months, the average weight loss in sibutramine group was significantly more than the control group (sibutramine group13 kg and control group 4 kg (p<0.05. Improvement in liver echogenicity in sibutramine patients was 90% and 50% of diet group patients. ALT changes in the sibutramine group and control group was 7.50 ± 15.11 and 6.15 ± 28.23 respectively, which was statistically significant in the sibutramine group. AST changes were 4.38 ± 13.37 and 1.70 ± 18.37 in sibutramine and control group respectively. The changes were not statistically significant. Conclusion: Overall, findings of this study suggest that sibutramine is effective in liver function improvement and treatment of NAFLD patients.

  6. Cardiometabolic risk factors in different clinicomorphological stages of non-alcoholic fatty liver disease in patients with abdominal obesity

    Directory of Open Access Journals (Sweden)

    K A Komshilova

    2012-09-01

    Full Text Available The aim of the study was to compare clinical, laboratory and morphological parameters in patients with abdominal obesity and non-alcoholic fatty liver disease (NAFLD, and assessing the relationship between the degree of severity, stage NAFLD and cardiometabolic risk factors for type 2 diabetes mellitus and cardiovascular disease. The present study examined the content of adiponectin and rates of glucose and lipid metabolism in obese patients at different stages of NAFLD. According to the study, morphologically NAFLD was confirmed in 95.2% of patients. NAFLD was associated with various cardiometabolic disorders (dyslipidemia, disorders of glucose metabolism and insulin resistance, growing in frequency and severity with the progression NAFLD; and low levels of adiponectin decreasing with a deterioration NAFLD.

  7. High-normal levels of hs-CRP predict the development of non-alcoholic fatty liver in healthy men

    Science.gov (United States)

    Lee, Jieun; Yoon, Kijung; Ryu, Seungho; Chang, Yoosoo; Kim, Hyoung-Ryoul

    2017-01-01

    We performed a follow-up study to address whether high sensitivity C-reactive protein (hs-CRP) levels within the normal range can predict the development of non-alcoholic fatty liver disease (NAFLD) in healthy male subjects. Among15347 male workers between 30 and 59 years old who received annual health check-ups in 2002, a NAFLD-free cohort of 4,138 was followed through December 2009. Alcohol consumption was assessed with a questionnaire. At each visit, abdominal ultrasonography was performed to identify fatty liver disease. The COX proportional hazard model was used to evaluate the relationship between hs-CRP and incident NAFLD. During the follow-up period, 28.8% (1191 of 4138) of participants developed NAFLD. The hazard ratios of NAFLD were increased by hs-CRP categories within the normal range in the non-adjusted model and age-adjusted model. After adjusting for age, exercise, smoking, BMI, systolic BP, triglyceride, and fasting glucose, these incidences were only increased between the lowest and the highest hs-CRP categories. The risk for NAFLD increased as the hs-CRP level increased (p< 0.001). As the hs-CRP level increased within the healthy cohort, the risk of developing NAFLD increased. This trend remained true even if the hs-CRP level remained within the normal range. hs-CRP can be used as a predictor of NAFLD, as well as other obesity-associated diseases. Therefore, individuals with higher hs-CRP levels (even within the normal range) may require appropriate follow-up and management to prevent NAFLD development. PMID:28234943

  8. High-normal levels of hs-CRP predict the development of non-alcoholic fatty liver in healthy men.

    Science.gov (United States)

    Lee, Jieun; Yoon, Kijung; Ryu, Seungho; Chang, Yoosoo; Kim, Hyoung-Ryoul

    2017-01-01

    We performed a follow-up study to address whether high sensitivity C-reactive protein (hs-CRP) levels within the normal range can predict the development of non-alcoholic fatty liver disease (NAFLD) in healthy male subjects. Among15347 male workers between 30 and 59 years old who received annual health check-ups in 2002, a NAFLD-free cohort of 4,138 was followed through December 2009. Alcohol consumption was assessed with a questionnaire. At each visit, abdominal ultrasonography was performed to identify fatty liver disease. The COX proportional hazard model was used to evaluate the relationship between hs-CRP and incident NAFLD. During the follow-up period, 28.8% (1191 of 4138) of participants developed NAFLD. The hazard ratios of NAFLD were increased by hs-CRP categories within the normal range in the non-adjusted model and age-adjusted model. After adjusting for age, exercise, smoking, BMI, systolic BP, triglyceride, and fasting glucose, these incidences were only increased between the lowest and the highest hs-CRP categories. The risk for NAFLD increased as the hs-CRP level increased (phs-CRP level increased within the healthy cohort, the risk of developing NAFLD increased. This trend remained true even if the hs-CRP level remained within the normal range. hs-CRP can be used as a predictor of NAFLD, as well as other obesity-associated diseases. Therefore, individuals with higher hs-CRP levels (even within the normal range) may require appropriate follow-up and management to prevent NAFLD development.

  9. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis.

    Science.gov (United States)

    Koliaki, Chrysi; Szendroedi, Julia; Kaul, Kirti; Jelenik, Tomas; Nowotny, Peter; Jankowiak, Frank; Herder, Christian; Carstensen, Maren; Krausch, Markus; Knoefel, Wolfram Trudo; Schlensak, Matthias; Roden, Michael

    2015-05-05

    The association of hepatic mitochondrial function with insulin resistance and non-alcoholic fatty liver (NAFL) or steatohepatitis (NASH) remains unclear. This study applied high-resolution respirometry to directly quantify mitochondrial respiration in liver biopsies of obese insulin-resistant humans without (n = 18) or with (n = 16) histologically proven NAFL or with NASH (n = 7) compared to lean individuals (n = 12). Despite similar mitochondrial content, obese humans with or without NAFL had 4.3- to 5.0-fold higher maximal respiration rates in isolated mitochondria than lean persons. NASH patients featured higher mitochondrial mass, but 31%-40% lower maximal respiration, which associated with greater hepatic insulin resistance, mitochondrial uncoupling, and leaking activity. In NASH, augmented hepatic oxidative stress (H2O2, lipid peroxides) and oxidative DNA damage (8-OH-deoxyguanosine) was paralleled by reduced anti-oxidant defense capacity and increased inflammatory response. These data suggest adaptation of the liver ("hepatic mitochondrial flexibility") at early stages of obesity-related insulin resistance, which is subsequently lost in NASH.

  10. Effect of Tiaozhi Yanggan Decoction(调脂养肝汤)in Treating Patients with Non-alcoholic Fatty Liver

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To observe the clinical efficacy and safety of Tiaozhi Yanggan Decoction patients were enrolled and randomized into two groups according to the random number table in a ratio of 3:1,with 8 cases eventually dropping out.The symptoms,signs,liver function markers,blood lipids,iconographic indices and clinical comprehensive efficacy after a 12-week treatment course were assessed in 101 patients treated with TZYGD in the treated group and 29 patients treated with Thiola in the control group.Results:The total effective rate in the treated group and the control group was 81.19% and 68.97%,respectively,showing a significant difference between the two groups with the former being significantly higher than the latter(P<0.05).Moreover,the improvements in the symptoms,signs,liver function,blood lipids and iconographic indices in the treated group were favorable with no serious adverse reactions.Conclusion:TZYGD is effective and highly safe in treating non-alcoholic fatty liver.

  11. A comparison of the cardiometabolic profile of black South Africans with suspected non-alcoholic fatty liver disease (NAFLD) and excessive alcohol use.

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    Zatu, Mandlenkosi Caswell; van Rooyen, Johannes Marthinus; Loots, Du Toit; Greeff, Minrie; Schutte, Aletta Elisabeth

    2015-03-01

    Excessive alcohol use and non-alcoholic fatty liver disease (NAFLD) are putative cardiovascular disease risk factors. In order to ease the identification of these conditions on primary health care level, we aimed to determine and compare the demographic and cardiometabolic characteristics of excessive alcohol users and those with suspected NAFLD in black South Africans. In the Prospective Urban Rural Epidemiology study (North West Province, South Africa, N = 2021, collected in 2005) we selected 338 participants, namely: 1) alcohol users (N = 143) reporting 'yes' to alcohol intake, with high gamma-glutamyl transferase (GGT) ≥80 U/L and a percentage carbohydrate deficient transferrin (%CDT) ≥2%; 2) non-alcohol users (N = 127) self-reporting 'no' to alcohol intake with GGT ≤30 U/L and %CDT ≤2%; and 3) NAFLD group (N = 68) who were non-drinkers with GGT levels ≥60 U/L and %CDT ≤ 2%. The demographics indicated that the alcohol users were mostly men (73%) with a body mass index (BMI) of 19.8 (15.2-27.3) kg/m(2), 90% of which were smokers. Systolic blood pressure (SBP) of alcohol users significantly correlated with high-density lipoprotein cholesterol (HDL-C) (β = 0.24; p = 0.003) and waist circumference (WC) (β = 0.22; p = 0.006). Non-alcohol users were mostly women (84%) with a BMI of 26.0 (18.0-39.2) kg/m(2) and blood pressure in this group related positively with triglycerides. The NAFLD group were also mostly women (72%) with a comparatively larger WC (p NAFLD group associated positively with WC (β = 0.27; p = 0.018). We therefore found disparate gender and cardiometabolic profiles of black South Africans with suspected NAFLD and excessive alcohol use. The described profiles may aid health care practitioners in low resource settings when using these crude screening measures of gender, obesity indices (and self-reported alcohol use) to identify individuals at risk.

  12. Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease

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    Yoneda Masato

    2012-02-01

    Full Text Available Abstract Background Non-alcoholic fatty liver disease (NAFLD is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia and type 2 diabetes mellitus. However, other risk factors for the development of NAFLD are unclear. With the association between periodontal disease and the development of systemic diseases receiving increasing attention recently, we conducted this study to investigate the relationship between NAFLD and infection with Porphyromonas gingivalis (P. gingivalis, a major causative agent of periodontitis. Methods The detection frequencies of periodontal bacteria in oral samples collected from 150 biopsy-proven NAFLD patients (102 with non-alcoholic steatohepatitis (NASH and 48 with non-alcoholic fatty liver (NAFL patients and 60 non-NAFLD control subjects were determined. Detection of P. gingivalis and other periodontopathic bacteria were detected by PCR assay. In addition, effect of P. gingivalis-infection on mouse NAFLD model was investigated. To clarify the exact contribution of P. gingivalis-induced periodontitis, non-surgical periodontal treatments were also undertaken for 3 months in 10 NAFLD patients with periodontitis. Results The detection frequency of P. gingivalis in NAFLD patients was significantly higher than that in the non-NAFLD control subjects (46.7% vs. 21.7%, odds ratio: 3.16. In addition, the detection frequency of P. gingivalis in NASH patients was markedly higher than that in the non-NAFLD subjects (52.0%, odds ratio: 3.91. Most of the P. gingivalis fimbria detected in the NAFLD patients was of invasive genotypes, especially type II (50.0%. Infection of type II P. gingivalis on NAFLD model of mice accelerated the NAFLD progression. The non-surgical periodontal treatments on NAFLD patients carried out for 3 months ameliorated the liver function parameters, such as the serum levels of AST and ALT. Conclusions Infection with high-virulence P

  13. Relationship between Retinal Vascular Caliber and Coronary Artery Disease in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD

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    Marmor Alon

    2013-08-01

    Full Text Available Objective: To evaluate the relationship between retinal vascular caliber and cardiovascular disease in non-alcoholic fatty liver disease (NAFLD patients without diabetes and hypertension. Methods: Intention to treat study of individuals who underwent cardiac computed tomography (CT during a two year period. Coronary artery disease (CAD was defined as stenosis of >50% in at least one major coronary artery. Liver and spleen density were measured by abdominal (CT; intima-media thickness (IMT by Doppler ultrasound; retinal artery and vein diameter by colored-retinal angiography; and metabolic syndrome by ATP III guidelines. Serum biomarkers of insulin resistance, inflammation, and oxidant-antioxidant status were assessed. Results: Compared with 22 gender and age matched controls, the 29 NAFLD patients showed higher prevalence of coronary plaques (70% vs. 30%, p < 0.001, higher prevalence of coronary stenosis (30% vs. 15%, p < 0.001, lower retinal arteriole-to-venule ratio (AVR (0.66 ± 0.06 vs. 0.71 ± 0.02, p < 0.01, higher IMT (0.98 ± 0.3 vs. 0.83 ± 0.1, p < 0.04, higher carotid plaques (60% vs. 40%, p < 0.001, higher homeostasis model assessment of insulin resistance (HOMA (4.0 ± 3.4 vs. 2.0 ± 1.0, p < 0.005, and higher triglyceride levels (200 ± 80 vs. 150 ± 60, p < 0.005 than controls. Multivariate analysis showed fatty liver (OR 2.5; p < 0.01, IMT (OR 2.3 p < 0.001, and retinal AVR ratio (OR 1.5, p < 0.01 to be strongly associated with CAD independent of metabolic syndrome (OR 1.2, p < 0.05. Conclusions: Patients with smaller retinal AVR (<0.7 are likely to be at increased risk for CAD and carotid atherosclerosis in patients with NAFLD even without hypertension or diabetes.

  14. Hubungan Kadar Trigliserida dan Kolesterol-HDL Terhadap Kadar Alanine Aminotransferase pada Pasien Non Alcoholic Fatty Liver Disease

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    Bayu Gemilang

    2016-01-01

    Full Text Available AbstrakTrigliserida dan Kolesterol HDL (c-HDL merupakan beberapa dari komponen Sindroma Metabolik (SM. SM dipercaya merupakan faktor utama penyebab Non Alcoholic Fatty Liver Disease (NAFLD. NAFLD merupakan penyakit hati kronik yang nantinya dapat menyebabkan fibrosis sel-sel hepar dan juga keganasan. NAFLD tidak menunjukkan manifestasi klinis yang khas, sehingga diperlukan pemeriksaan penunjang seperti pemeriksaan enzim hati untuk menegakkan diagnosis. Alanine Aminotransferase (ALT menjadi pilihan sebagai marker pada penyakit NAFLD. Tujuan penelitian ini adalah menentukan hubungan antara trigliserida dan c-HDL dengan ALT pada penderita NAFLD. Ini merupakan penelitian analitik deskriptif dengan desain retrospektif menggunakan data pasien NAFLD di instalasi rekam medik RSUP dr.M.Djamil Padang. Sampel penelitian ini adalah 51 pasien NAFLD. Hasil penelitian didapatkan dari uji korelasi pearson terdapat derajat hubungan yang kuat (r=0,512 dan hubungan yang bermakna (p<0,001 antara kadar trigliserida dengan kadar ALT serum dan derajat hubungan yang sedang (r=0,26 dan hubungan yang tidak bermakna (p=0,065 antara c-HDL dengan ALT serum. Kesimpulan penelitian ini adalah kadar ALT berhubungan dengan kadar trigliserida pada penderita NAFLD, namun tidak dengan c-HDLKata kunci: NAFLD, trigliserida, HDL, ALT, sindroma metabolik AbstractTriglyceride and HDL Cholesterol (HDL-C are some of the Metabolic Syndrome (MS components. MS is believed as the main factor for the Non Alcoholic Fatty Liver Disease (NAFLD. NAFLD is a chronic liver disease, which later can cause hepatocyte fibrosis and also malignancy. NAFLD does not show a typical clinical appearance, so it is important to do workups such as liver enzyme test to make the diagnosis. Alanine Aminotransferase (ALT is considered as the marker of NAFLD.The objective of this study was to determine the relationship between triglycerides and HDL-C to ALT level in NAFLD patients.This  was a descriptive analytical

  15. Long Non-Coding RNA Profiling in a Non-Alcoholic Fatty Liver Disease Rodent Model: New Insight into Pathogenesis

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    Yi Chen

    2017-01-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is one of the most prevalent chronic liver diseases worldwide with an unclear mechanism. Long non-coding RNAs (lncRNAs have recently emerged as important regulatory molecules. To better understand NAFLD pathogenesis, lncRNA and messenger RNA (mRNA microarrays were conducted in an NAFLD rodent model. Potential target genes of significantly changed lncRNA were predicted using cis/trans-regulatory algorithms. Gene Ontology (GO analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analysis were then performed to explore their function. In the current analysis, 89 upregulated and 177 downregulated mRNAs were identified, together with 291 deregulated lncRNAs. Bioinformatic analysis of these RNAs has categorized these RNAs into pathways including arachidonic acid metabolism, circadian rhythm, linoleic acid metabolism, peroxisome proliferator-activated receptor (PPAR signaling pathway, sphingolipid metabolism, steroid biosynthesis, tryptophan metabolism and tyrosine metabolism were compromised. Quantitative polymerase chain reaction (qPCR of representative nine mRNAs and eight lncRNAs (named fatty liver-related lncRNA, FLRL was conducted and this verified previous microarray results. Several lncRNAs, such as FLRL1, FLRL6 and FLRL2 demonstrated to be involved in circadian rhythm targeting period circadian clock 3 (Per3, Per2 and aryl hydrocarbon receptor nuclear translocator-like (Arntl, respectively. While FLRL8, FLRL3 and FLRL7 showed a potential role in PPAR signaling pathway through interaction with fatty acid binding protein 5 (Fabp5, lipoprotein lipase (Lpl and fatty acid desaturase 2 (Fads2. Functional experiments showed that interfering of lncRNA FLRL2 expression affected the expression of predicted target, circadian rhythm gene Arntl. Moreover, both FLRL2 and Arntl were downregulated in the NAFLD cellular model. The current study identified lncRNA and corresponding mRNA in NAFLD

  16. Diagnosis and treatment for non-alcoholic fatty liver disease%非酒精性脂肪性肝病的诊断与治疗

    Institute of Scientific and Technical Information of China (English)

    范建高

    2006-01-01

    @@ 非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是指除外酒精和其他明确的损肝因素所致的,以弥漫性肝细胞大泡性脂肪变为病理特征的临床综合征,包括单纯性脂肪肝(simple fatty liver,SFL)以及由其演变的脂肪性肝炎(nonalcoholic steatohepatitis,NASH)和肝硬化.

  17. Update on fatty liver disease and steatohepatitis.

    Science.gov (United States)

    Aly, Fatima Zahra; Kleiner, David E

    2011-07-01

    Non-alcoholic fatty liver disease (NAFLD) is a broad term that includes liver diseases characterized by abnormal hepatocellular accumulations of lipid that cannot be related to alcohol abuse. It may be found in both adults and children, particularly those who are obese or have insulin resistance. Steatohepatitis is a specific pattern of injury within the spectrum of NAFLD and this pattern is associated with fibrotic progression and cirrhosis. In addition to steatohepatitis, a distinct form of fibrotic fatty liver disease exists in children. There have been a number of recent advances in the characterization of histologic changes in NAFLD. In light of these recent reports, this study will: (1) review the histologic features of steatosis and nonalcoholic steatohepatitis in adults; (2) review the variation of histologic patterns of pediatric fatty liver disease; and (3) discuss the validity and use of the nonalcoholic fatty liver disease Activity Score.

  18. Metabolic pathway of non-alcoholic fatty liver disease: Network properties and robustness

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    WenJun Zhang

    2017-03-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a systematic and complex disease involving various cytokines/metabolites. In present article, we use methodology of network biology to analyze network properties of NAFLD metabolic pathway. It is found that the metabolic pathway of NAFLD is not a typical complex network with power-law degree distribution, p(x=x^(-4.4275, x>=5. There is only one connected component in the metabolic pathway. The calculated cut cytokines/metabolites of the metabolic pathway are SREBP-1c, ChREBP, ObR, AMPK, IRE1alpha, ROS, PERK, elF2alpha, ATF4, CHOP, Bim, CASP8, Bid, CxII, Lipogenic enzymes, XBP1, and FFAs. The most important cytokine/metabolite for possible network robustness is FFAs, seconded by TNF-alpha. It is concluded that FFAs is the most important cytokine/metabolite in the metabolic pathway, seconded by ROS. FFAs, LEP, ACDC, CYP2E1, and Glucose are the only cytokines/metabolites that affect others without influences from other cytokines/metabolites. Finally, the IDs matrix for identifying possible sub-networks/modules is given. However, jointly combining the results of connectedness analysis and sub-networks/modules identification, we hold that there are not significant sub-networks/modules in the pathway.

  19. Relationship between Non-Alcoholic Fatty Liver Disease and Psoriasis: A Novel Hepato-Dermal Axis?

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    Mantovani, Alessandro; Gisondi, Paolo; Lonardo, Amedeo; Targher, Giovanni

    2016-02-05

    Over the past 10 years, it has become increasingly evident that nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects multiple extra-hepatic organ systems and interacts with the regulation of several metabolic and immunological pathways. In this review we discuss the rapidly expanding body of clinical and epidemiological evidence supporting a strong association between NAFLD and chronic plaque psoriasis. We also briefly discuss the possible biological mechanisms underlying this association, and discuss treatment options for psoriasis that may influence NAFLD development and progression. Recent observational studies have shown that the prevalence of NAFLD (as diagnosed either by imaging or by histology) is remarkably higher in psoriatic patients (occurring in up to 50% of these patients) than in matched control subjects. Notably, psoriasis is associated with NAFLD even after adjusting for metabolic syndrome traits and other potential confounding factors. Some studies have also suggested that psoriatic patients are more likely to have the more advanced forms of NAFLD than non-psoriatic controls, and that psoriatic patients with NAFLD have more severe psoriasis than those without NAFLD. In conclusion, the published evidence argues for more careful evaluation and surveillance of NAFLD among patients with psoriasis.

  20. Guidelines for Management of Non-alcoholic Fatty Liver Disease%非酒精性脂肪性肝病诊疗指南

    Institute of Scientific and Technical Information of China (English)

    中华医学会肝脏病学分会脂肪肝和酒精性肝病学组

    2010-01-01

    @@ 非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是一种与胰岛素抵抗(IR)和遗传易感性密切相关的代谢应激性肝损伤,病理学改变与酒精性肝病(ALD)相似,但患者无过量饮酒史,疾病谱包括非酒精性单纯性脂肪肝(non-alcoholic simple fatty liver,NAFL)、非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)及其相关肝硬化和肝细胞性肝癌[1,2].

  1. Profile of liver enzymes in non-alcoholic fatty liver disease in patients with impaired glucose tolerance and newly detected untreated type 2 diabetes

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    Debmalya Sanyal

    2015-01-01

    Full Text Available Context: The perception of non-alcoholic fatty liver disease (NAFLD as an uncommon and benign condition is rapidly changing. Approximately, 70% type 2 diabetes mellitus (T2DM patients have a fatty liver, which may follow an aggressive course with necroinflammation and fibrosis. Aims: To assess the profile of liver enzymes in subjects with impaired glucose tolerance (IGT, new onset treatment naive T2DM and normal glucose tolerance (NGT with and without NAFLD. Settings and Design: Cross-sectional clinic-based study. Subjects and Methods: 152 IGT and 158 recently detected T2DM subjects aged between 30 and 69 years, along with 160 age and gender matched controls with NGT. An ultrasonography scan of the upper abdomen was done in all patients in order to examine presence of fatty liver. Anthropometry, lipid profile, liver enzymes were also analyzed in all patients. Statistical Analysis Used: Unpaired t-test, Chi-square/Fisher Exact test (for categorical variables, Pearson/Spearmen correlation test to find significant difference, association and correlation between two or more groups respectively. Results: NAFLD was significantly associated with higher alanine aminotransferase (ALT and gamma-glutamyl transferase (GGT but not ALP levels in IGT and T2DM patients. ALT, GGT significant correlated with waist circumference, body mass index, fasting insulin, homeostatic model assessment- insulin resistance, fasting blood glucose, high density lipoprotein cholesterol, triglyceride. 57% of NAFLD patients had normal ALT between 25 and 40 U/L, 53% of NAFLD subjects had normal GGT between 15 and 30 U/L. ALT 40 U/L and GGT > 30 U/L had highest positive predictivity for presence of NAFLD in our study sample. Conclusions: Mild elevations of liver enzymes in the upper normal range are associated with features of metabolic syndrome and NAFLD even in IGT and recently detected T2DM patients. Novel cut-offs for liver enzymes are warranted in order to prevent unnecessary

  2. Amelioration of non-alcoholic fatty liver disease with NPC1L1-targeted IgY or n-3 polyunsaturated fatty acids in mice.

    Science.gov (United States)

    Bae, Jin-Sik; Park, Jong-Min; Lee, Junghoon; Oh, Byung-Chul; Jang, Sang-Ho; Lee, Yun Bin; Han, Young-Min; Ock, Chan-Young; Cha, Ji-Young; Hahm, Ki-Baik

    2017-01-01

    Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk for progression to hepatocellular carcinoma in addition to comorbidities such as cardiovascular and serious metabolic diseases; however, the current therapeutic options are limited. Based on our previous report that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can significantly ameliorate high fat diet (HFD)-induced NAFLD, we explored the therapeutic efficacy of n-3 PUFAs and N-IgY, which is a chicken egg yolk-derived IgY specific for the Niemann-Pick C1-Like 1 (NPC1L1) cholesterol transporter, on NAFLD in mice. We generated N-IgY and confirmed its efficient cholesterol transport-blocking activity in HepG2 and Caco-2 cells, which was comparable to the effect of ezetimibe (EZM). C57BL/6 wild type and fat-1 transgenic mice, capable of producing n-3 PUFAs, were fed a high fat diet (HFD) alone or supplemented with N-IgY. Endogenously synthesized n-3 PUFAs combined with N-IgY led to significant decreases in hepatic steatosis, fibrosis, and inflammation (pN-IgY and n-3 PUFAs resulted in significant upregulation of genes involved in cholesterol uptake (LDLR), reverse cholesterol transport (ABCG5/ABCG8), and bile acid metabolism (CYP7A1). Moreover, fat-1 transgenic mice treated with N-IgY showed significant downregulation of genes involved in cholesterol-induced hepatic stellate cell activation (Tgfb1, Tlr4, Col1a1, Col1a2, and Timp2). Collectively, these data suggest that n-3 PUFAs and N-IgY, alone or in combination, represent a promising treatment strategy to prevent HFD-induced fatty liver through the activation cholesterol catabolism to bile acids and by decreasing cholesterol-induced fibrosis.

  3. Contribution of Cyclooxygenase End Products and Oxidative Stress to Intrahepatic Endothelial Dysfunction in Early Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Morales Arraez, Dalia; Marcelino Reyes, Raquel; Abrante, Beatriz; Diaz-Flores, Felicitas; Salido, Eduardo; Quintero, Enrique; Hernández-Guerra, Manuel

    2016-01-01

    Introduction Metabolic syndrome induces endothelial dysfunction, a surrogate marker of cardiovascular disease. In parallel, metabolic syndrome is frequently associated with non-alcoholic fatty liver disease (NAFLD), which may progress to cirrhosis. The aim of the present study was to evaluate intrahepatic endothelial dysfunction related to cyclooxygenase end products and oxidative stress as possible mechanisms involved in the pathophysiology of NAFLD. Materials and Methods Sprague-Dawley rats were fed standard diet (control-diet, CD) or high-fat-diet (HFD) for 6 weeks. Metabolic syndrome was assessed by recording arterial pressure, lipids, glycemia and rat body weight. Splanchnic hemodynamics were measured, and endothelial dysfunction was evaluated using concentration-effect curves to acetylcholine. Response was assessed with either vehicle, L-NG-Nitroarginine (L-NNA), indomethacin, tempol, or a thromboxane receptor antagonist, SQ 29548. We quantified inflammation, fibrosis, oxidative stress, nitric oxide (NO) bioavailability and thromboxane B2 levels. Results HFD rats exhibited metabolic syndrome together with the presence of NAFLD. Compared to control-diet livers, HFD livers showed increased hepatic vascular resistance unrelated to inflammation or fibrosis, but with decreased NO activity and increased oxidative stress. Endothelial dysfunction was observed in HFD livers compared with CD rats and improved after cyclooxygenase inhibition or tempol pre-incubation. However, pre-incubation with SQ 29548 did not modify acetylcholine response. Conclusions Our study provides evidence that endothelial dysfunction at an early stage of NAFLD is associated with reduced NO bioavailability together with increased cyclooxygenase end products and oxidative stress, which suggests that both pathways are involved in the pathophysiology and may be worth exploring as therapeutic targets to prevent progression of the disease. PMID:27227672

  4. Contribution of Cyclooxygenase End Products and Oxidative Stress to Intrahepatic Endothelial Dysfunction in Early Non-Alcoholic Fatty Liver Disease.

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    Francisco Javier Gonzalez-Paredes

    Full Text Available Metabolic syndrome induces endothelial dysfunction, a surrogate marker of cardiovascular disease. In parallel, metabolic syndrome is frequently associated with non-alcoholic fatty liver disease (NAFLD, which may progress to cirrhosis. The aim of the present study was to evaluate intrahepatic endothelial dysfunction related to cyclooxygenase end products and oxidative stress as possible mechanisms involved in the pathophysiology of NAFLD.Sprague-Dawley rats were fed standard diet (control-diet, CD or high-fat-diet (HFD for 6 weeks. Metabolic syndrome was assessed by recording arterial pressure, lipids, glycemia and rat body weight. Splanchnic hemodynamics were measured, and endothelial dysfunction was evaluated using concentration-effect curves to acetylcholine. Response was assessed with either vehicle, L-NG-Nitroarginine (L-NNA, indomethacin, tempol, or a thromboxane receptor antagonist, SQ 29548. We quantified inflammation, fibrosis, oxidative stress, nitric oxide (NO bioavailability and thromboxane B2 levels.HFD rats exhibited metabolic syndrome together with the presence of NAFLD. Compared to control-diet livers, HFD livers showed increased hepatic vascular resistance unrelated to inflammation or fibrosis, but with decreased NO activity and increased oxidative stress. Endothelial dysfunction was observed in HFD livers compared with CD rats and improved after cyclooxygenase inhibition or tempol pre-incubation. However, pre-incubation with SQ 29548 did not modify acetylcholine response.Our study provides evidence that endothelial dysfunction at an early stage of NAFLD is associated with reduced NO bioavailability together with increased cyclooxygenase end products and oxidative stress, which suggests that both pathways are involved in the pathophysiology and may be worth exploring as therapeutic targets to prevent progression of the disease.

  5. The Effect of Chlorella vulgaris Supplementation on Liver Enzymes, Serum Glucose and Lipid Profile in Patients with Non-Alcoholic Fatty Liver Disease

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    Mehrangiz Ebrahimi-Mameghani

    2014-07-01

    Full Text Available Background: Non-alcoholic fatty liver disease (NAFLD is becoming a public health problem worldwide and using microalgae is a new approach on its treatment. The aim of this study was to investigate the effect of Chlorella vulgaris supplementation on liver enzymes, serum glucose and lipid profile in patients with NAFLD. Methods: This double-blind randomized placebo-controlled clinical trial was conducted on 60 NAFLD patients from specialized clinics of Tabriz University of Medical Sciences from December 2011 to July 2012. The subjects were randomly allocated into 2 groups: 1 “intervention” (n=30 received 400 mg/day vitamin E plus four 300 mg tablets of Chlorella vulgaris and, 2 “placebo” (n=30 received 400 mg/day vitamin E and four placebo tablets per day for 8 weeks. Weight, liver enzymes and metabolic factors were assessed in fasting serum and dietary data was collected at baseline and end of the study. Results: Weight, liver enzymes, fasting blood sugar (FBS and lipid profile decreased significantly in both groups (P<0.05. The differences in weight, ALP and FBS between the two groups were statistically significant (P=0.01, P=0.04 and P=0.02, respectively. Conclusion: C. vulgaris seems to improve FBS and lipid profile and therefore could be considered as an effective complementary treatment in NAFLD.

  6. Non-alcoholic fatty liver disease connections with fat-free tissues: A focus on bone and skeletal muscle

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    Poggiogalle, Eleonora; Donini, Lorenzo Maria; Lenzi, Andrea; Chiesa, Claudio; Pacifico, Lucia

    2017-01-01

    The estimates of global incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.

  7. Natural killer T cells and non-alcoholic fatty liver disease: Fat chews on the immune system

    Institute of Scientific and Technical Information of China (English)

    Michael Kremer; Ian N Hines

    2008-01-01

    Natural killer T cells (NKT) are an important subset of T lymphocytes. They are unique in their ability to produce both T helper 1 and T helper 2 associated cytokines, thus being capable of steering the immune system into either inflammation or tolerance. Disruption of NKT cell numbers or function results in severe deficits in immune surveillance against pathogens and tumor cells. Growing experimental evidence suggests that hepatosteatosis may reduce resident hepatic as well as peripheral NICE cells. Those models of hepatosteatosis and the change in NKT cell numbers are associated with a disruption of cytokine homeostasis, resulting in a more pronounced release of proinflammatory cytokines which renders the steatotic liver highly susceptible to secondary insults. In this letter to the editor, we focus on recently published data in the World Journal of Gastroenterology by Xu and colleagues demonstrating reduced peripheral NKT ceils in patients with non-alcoholic fatty liver disease, compare those findings with ours and others in different animal models of hepatosteatosis, and hypothesize about the potential underlying mechanism.

  8. Gene polymorphisms associated with non-alcoholic fatty liver disease and coronary artery disease: a concise review.

    Science.gov (United States)

    Li, Xiao-Lin; Sui, Jian-Qing; Lu, Lin-Lin; Zhang, Nan-Nan; Xu, Xin; Dong, Quan-Yong; Xin, Yong-Ning; Xuan, Shi-Ying

    2016-03-10

    Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease which represents a wide spectrum of hepatic damage. Several studies have reported that NAFLD is a strong independent risk factor for coronary artery disease (CAD). And patients with NAFLD are at higher risk and suggested undergoperiodic cardiovascular risk assessment. Cardiovascular disease (CVD) is responsible for the main cause of death in patients with NAFLD, and is mostly influenced by genetic factors. Both NAFLD and CAD are heterogeneous disease. Common pathways involved in the pathogenesis of NAFLD and CAD includes insulin resistance (IR), atherogenic dyslipidemia, subclinical inflammation, oxidative stress, etc. Genomic characteristics of these two diseases have been widely studied, further research about the association of these two diseases draws attention. The gene polymorphisms of adiponectin-encoding gene (ADIPOQ), leptin receptor (LEPR), apolipoprotein C3 (APOC3), peroxisome proliferator-activated receptors (PPAR), sterol regulatory elementbinding proteins (SREBP), transmembrane 6 superfamily member 2 (TM6SF2), microsomal triglyceride transfer protein (MTTP), tumor necrosis factors-alpha (TNF-α) and manganese superoxide dismutase (MnSOD) have been reported to be related to NAFLD and CAD. In this review, we aimed to provide an overview of recent insights into the genetic basis of NAFLD and CAD.

  9. Tree shrew (Tupaia belangeri chinensis), a novel non-obese animal model of non-alcoholic fatty liver disease

    Science.gov (United States)

    Zhang, Linqiang; Wu, Xiaoyun; Liao, Shasha; Li, Yunhai; Zhang, Zhiguo; Chang, Qing; Xiao, Ruyue

    2016-01-01

    ABSTRACT Non-alcoholic fatty liver disease (NAFLD) is becoming a severe public health problem that is affecting a large proportion of the world population. Generally, NAFLD in patients is usually accompanied by obesity, hyperglycemia, insulin resistance (IR) and type 2 diabetes (T2D), for which numerous animal models have been generated in order to explore the pathogenesis and therapies of NAFLD. On the contrary, quite a number of NAFLD subjects, especially in Asian regions, are non-obese and non-diabetic; however, few animal models are available for the research of non-obese NAFLD. Here, four approaches (here called approach 1 to 4) corresponding to the variable compositions of diets were used to treat tree shrews (Tupaia belangeri chinensis), which have a closer evolutionary relationship to primates than rodents. Analysis of plasma biochemical parameters, hepatic histology, and the expression of hepatic lipid metabolic genes revealed that all four approaches led to hepatic lipid accumulation, liver injury and hypercholesterolemia, but had no effect on body weight and adipose tissue generation, or glycemia. Hepatic gene expression in tree shrews treated by approach 4 might suggest a different or non-canonical pathway leading to hepatic steatosis. In conclusion, the tree shrew displays hepatic steatosis and dyslipidemia, but remains non-obese and non-diabetic under high energy diets, which suggests that the tree shrew may be useful as a novel animal model for the research of human non-obese NAFLD. PMID:27659689

  10. Tree shrew (Tupaia belangeri chinensis, a novel non-obese animal model of non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Linqiang Zhang

    2016-10-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is becoming a severe public health problem that is affecting a large proportion of the world population. Generally, NAFLD in patients is usually accompanied by obesity, hyperglycemia, insulin resistance (IR and type 2 diabetes (T2D, for which numerous animal models have been generated in order to explore the pathogenesis and therapies of NAFLD. On the contrary, quite a number of NAFLD subjects, especially in Asian regions, are non-obese and non-diabetic; however, few animal models are available for the research of non-obese NAFLD. Here, four approaches (here called approach 1 to 4 corresponding to the variable compositions of diets were used to treat tree shrews (Tupaia belangeri chinensis, which have a closer evolutionary relationship to primates than rodents. Analysis of plasma biochemical parameters, hepatic histology, and the expression of hepatic lipid metabolic genes revealed that all four approaches led to hepatic lipid accumulation, liver injury and hypercholesterolemia, but had no effect on body weight and adipose tissue generation, or glycemia. Hepatic gene expression in tree shrews treated by approach 4 might suggest a different or non-canonical pathway leading to hepatic steatosis. In conclusion, the tree shrew displays hepatic steatosis and dyslipidemia, but remains non-obese and non-diabetic under high energy diets, which suggests that the tree shrew may be useful as a novel animal model for the research of human non-obese NAFLD.

  11. Hepatic unsaturated fatty acids in patients with non-alcoholic fatty liver disease assessed by 3.0 T MR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Werven, J.R. van, E-mail: j.r.vanwerven@amc.uva.n [Department of Radiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Schreuder, T.C.M.A. [Department of Gastroenterology and Hepatology, VU Medical Center, Amsterdam (Netherlands); Nederveen, A.J.; Lavini, C. [Department of Radiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Jansen, P.L.M. [AMC Liver Center/Department of Hepatology, Academic Medical Center, Amsterdam (Netherlands); Stoker, J. [Department of Radiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands)

    2010-08-15

    Rationale and objective: Non-alcoholic fatty liver disease (NAFLD) is related to the metabolic syndrome and obesity. Proton magnetic resonance spectroscopy ({sup 1}H MRS) is a non-invasive technique to assess hepatic triglyceride content (HTGC) and allows assessment of unsaturated fatty acids (UFA). There is increasing evidence that hepatic UFA are associated with the development of NAFLD. Therefore the objective of this study was to assess hepatic UFA in patients with NAFLD using {sup 1}H MRS. Materials and methods: We included 26 consecutive patients with deranged liver enzymes, with and without type 2 diabetes mellitus (DM2), suspected for NAFLD. Liver function and metabolic parameters were assessed. {sup 1}H MRS measurements were performed at 3.0 T. From the {sup 1}H MR spectra two ratios were calculated: ratio 1 (UFA); unsaturated fatty acid peak vs. reference water peak and ratio 2 (HTGC); total fatty acid peak vs. reference water peak. Results: Twenty-six patients were included. In these patients hepatic UFA (ratio 1) correlated with AST/ALT ratio (r = -0.46, p = 0.02), glucose levels (r = 0.46, p = 0.018), HOMA-IR (r = 0.59, p = 0.004) and HTGC (r = 0.81, p < 0.001). In diabetic patients (n = 12) hepatic UFA correlated with alkaline phosphatase levels (r = 0.72, p = 0.01), HOMA-IR (r = 0.73, p = 0.01) and HTGC (r = 0.83, p = 0.002). Compared to non-diabetic patients with NAFLD, hepatic UFA levels were increased in patients with DM2 and NAFLD (0.032 vs. 0.014, p = 0.03). Conclusion: Hepatic UFA can be assessed with {sup 1}H MRS. {sup 1}H MRS determined hepatic UFA correlate with clinical and metabolic parameters associated with NAFLD. Hepatic UFA are increased in patients with DM2. This study provides evidence for the use of non-invasive {sup 1}H MRS to assess hepatic UFA in vivo.

  12. Role of γ-glutamyl transferase levels in prediction of high cardiovascular risk among patients with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Benan Kasapoglu

    2016-01-01

    Full Text Available Background & objectives: Non-alcoholic fatty liver disease (NAFLD is an important cause of elevated liver functions. There is evidence showing an association between NAFLD and subclinical atherosclerosis independent of traditional risk factors. We undertook this retrospective study to determine the association of Framingham cardiovascular risk scoring system with liver function tests and inflammatory markers and to find the role of liver function tests in determination of CVD risk among non-obese and non-diabetic subjects with non-alcoholic fatty liver disease. Methods: A total of 2058 patients were included in the study. Framingham cardiovascular risk scoring was done of all patients according to the age, gender, systolic blood pressure, serum total cholesterol and HDL cholesterol levels, smoking and antihypertensive medication history. Liver function test, lipid profile, insulin, uric acid, ferritin levels, etc. were determined. Results: According to the ultrasonography findings, patients were grouped as without any fatty infiltration of the liver (control group (n=982, mild (n= 473, moderate (n=363 and severe fatty liver disease (n= 240 groups. In severe fatty liver disease group, the mean Framingham cardiovascular risk score was significantly higher than that of other groups. t0 here was a positive correlation between GGT, uric acid and ferritin levels with Framingham cardiovascular score. In multivariate analysis, high GGT levels were positively associated with high-risk disease presence (OR: 3.02, 95% CI: 2.62-3.42 compared to low GGT levels independent of the age and sex. Interpretation & conclusions: Cardiovascular disease risk increases with the presence and stage of fatty liver disease. Our findings showed a positive correlation between elevated GGT levels and Framingham cardiovascular risk scoring system among non-diabetic, non-obese adults which could be important in clinical practice. Though in normal limits, elevated GGT levels

  13. Histopathological aspects of liver under variable food restriction: has the intense one-week food restriction a protective effect on non-alcoholic-fatty-liver-disease (NAFLD) development?

    Science.gov (United States)

    Makovicky, Peter; Tumova, Eva; Volek, Zdenek; Makovicky, Pavol; Vodickova, Ludmila; Slyskova, Jana; Svoboda, Miroslav; Rejhova, Alexandra; Vodicka, Pavel; Samasca, Gabriel; Kralova, Alena; Nagy, Melinda; Mydlarova-Blascakova, Marta; Poracova, Jana

    2014-12-01

    Non-alcoholic-fatty-liver-disease (NAFLD) is a clinicopathologic entity characterized by a variety of hepatic injury patterns without significant alcohol use. It has a close association with obesity, so treatment includes weight loss, control of insulin sensitivity, interventions directed at inflammation and fibrosis. There is a certain relationship between the grade and duration of food restriction and hepatic function. The objective of this work was to describe the relationship between biochemistry, autoantibodies, insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and liver morphology in experimental rabbit groups with food restriction as compared to controls with ad libitum food (ADL) income. The experiment was performed on a total of 24 rabbits of a weaning age of 25-81 days. The first group (R1) was restricted between 32 and 39 days of age to 50 g of food per rabbit a day. The second group (R2) was also restricted between 32 and 39 days, but the rabbits received 65 g of food per rabbit a day. At the end of the experiment, the blood and liver samples were collected at necropsy. NAFLD has developed in all three groups. There was any autoantibody positivity in all three groups. IGF-I is moderately higher in R1 and R2 group, as compared to the control group (P > 0.05). IGFBP-3 is without statistical significance in all three groups. Alkaline phosphatase (ALP) is the only liver biochemical parameter that has significantly increased following food restriction (P > 0.039). Single one-week restriction has any protective effect on NAFLD development.

  14. Alcohol and liver, 2010

    Institute of Scientific and Technical Information of China (English)

    Natalia; A; Osna

    2010-01-01

    Liver is known as an organ that is primarily affected by alcohol. Alcoholic liver disease (ALD) is the cause of an increased morbidity and mortality worldwide. Progression of ALD is driven by "second hits". These second hits include the complex of nutritional, pharmacological, genetic and viral factors, which aggravate liver pathology. However, in addition to liver failure, ethanol causes damage to other organs and systems. These extrahepatic manifestations are regulated via the similar hepatitis mechanisms...

  15. Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation

    Science.gov (United States)

    Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...

  16. Fatty liver in children

    OpenAIRE

    Rafeey, Mandana; Mogaddasi,; Hasani, Alka; Ghaffari, Shamsi

    2009-01-01

    Mandana Rafeey1, Fakhrossadat Mortazavi2, Nafiseh Mogaddasi2, Ghergherehchi Robabeh2, Shamsi Ghaffari2, Alka Hasani31Liver and gastrointestinal Research Center; 2Tabriz University (Medical Science) Tabriz, Iran; 3Research Center of Infectious Diseases and Tropical MedicineAims: The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran.Methods: In this cross-section...

  17. The Efficacy of Silymarin in Decreasing Transaminase Activities in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Ali-Akbar Hajaghamohammadi

    2008-08-01

    Full Text Available Background and Aims: Non-alcoholic fatty liver disease (NAFLD is one of the most common causes of increased liver enzymes. According to statistical reports, 20%-40% of Western population and 5%-30% of the population of Pacific and Asian countries are afflicted with this disease. The prevalence of NAFLD is higher in hyperlipidemic, diabetic and obese people. Considering the high prevalence of NAFLD and its complications and lack of consensus on its treatment, we were motivated to study the efficacy of silymarin on this disease. Methods: In this randomized clinical trial, 50 patients including 32 men (64% and 18 women (36% were divided into case and control groups. The mean age of case group was 40.3 and for control group was 39.9 years. All patients had elevated liver enzymes and had increased liver echogenicity (lipid accumulation on sonography. The case group was treated with one tablet containing 140 mg silymarin per day for two months and the control group was treated in the same manner with placebo. Before and after the study, weight, body mass index (BMI and liver transaminases levels were measured for each patient.Results: The difference between the mean weight and BMI measured before and after the study was not statistically significant in both case and control groups. But the mean ALT and AST levels deceased from 103.1 to 41.4 and 53.7 to 29.1 IU/mL, respectively in case group which was statistically significant (P<0.001 & P<0.001. In the control group, the decrease in mean ALT and AST, with decrease of 7.8 and 2.2 IU/mL, respectively, was not statistically significant.Conclusions: Considering the significant drop in liver enzymes following administration of silymarin, it seems that after conducting similar studies in order to determine the appropriate doses and treatment periods, this cheap and easy to access drug can be prescribed for treatment of NAFLD.

  18. Nonalcoholic Fatty Liver Disease Treatment

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    M Sadeghian

    2014-04-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is increasing in pediatric age group parallel to the growing prevalence of obesity and overweight all around the world. So changing in life style and   interventions on obesogenic environment is cornerstone of NAFLD therapy in obese children. Some experts recommend that children and adolescents be encouraged to follow a low-fat, low-glycemic-index diet that includes eating a minimum of 5 servings of vegetables and fruits daily, engaging in physical activity for at least 1 hour daily, and minimizing television/computer time to 2 hours daily.  In spite of effectiveness of weight loss and exercise in improvement NAFLD, this goal is very difficult to be achieved and pharmacological approaches have become necessary. Pharmacologic therapies against one or more specific factors and/or molecules involved in the development of NAFLD (i.e., insulin resistance, free fatty acid lipid toxicity, and oxidative stress also might slow the progression of NAFLD to NASH or cirrhosis.  On this basis, insulin sensitizers, antioxidants, cytoprotective agents, and dietary supplementations have been evaluated in pediatric clinical trials but there is no approved pharmacologic therapy for NAFLD or NASH. Not all obese children affected by NAFLD. Diet modification and regular exercise beside to serial medical follow up highly suggested for this group of children. Normal weight and thin children with NAFLD or NASH should be investigated appropriately in a logical manner based on causes of primary liver steatosis in children and treatment of underlying disease can cause improvement fatty liver in these patients.   Keywords: Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Children; Steatosis; Treatment

  19. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Wang, Linlong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  20. Assessment of health utilities and quality of life in patients with non-alcoholic fatty liver disease

    Science.gov (United States)

    Sayiner, Mehmet; Stepanova, Maria; Pham, Huong; Noor, Bashir; Walters, Mercedes; Younossi, Zobair M

    2016-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease associated with increased liver-related mortality. Additionally, NAFLD could potentially impair health-related quality of life. Although an approved treatment for NAFLD does not exist, a number of new drugs for treatment of NAFLD are being developed. As the efficacy and safety of these regimens are being established, their cost-effectiveness, which requires the use of quality of life metrics and health utility scores to quality-adjusted outcomes, must also be assessed. The aim of this study was to report quality of life and health utilities in patients with NAFLD with and without cirrhosis for future use. Methods Patients with NAFLD were seen in an outpatient clinic setting. Each patient had extensive clinical data and completed the Short Form-36 (SF-36 V.1) questionnaire. The SF-6D health utility scores were calculated. Results There were 89 patients with the spectrum of NAFLD completed the SF-36 questionnaire: 59 with non-cirrhotic NAFLD and 30 with cirrhosis. Patients with NAFLD had significantly lower quality of life and health utility scores than the general population (all p<0.0001). Furthermore, patients with cirrhosis had lower quality of life and utility scores than non-cirrhotic NAFLD patients: SF-6D 0.660±0.107 in non-cirrhotic NAFLD vs 0.551±0.138 in cirrhotic NAFLD (p=0.0003). Conclusions Health utilities and quality of life scores are impaired in patients with cirrhotic NAFLD. These values should be used in cost-effectiveness analysis of the upcoming treatment regimens for advanced NAFLD. PMID:27648297

  1. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.

    Science.gov (United States)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming".

  2. Role of illness perception and self-efficacy in lifestyle modification among non-alcoholic fatty liver disease patients

    Science.gov (United States)

    Zelber-Sagi, Shira; Bord, Shiran; Dror-Lavi, Gali; Smith, Matthew Lee; Towne Jr, Samuel D; Buch, Assaf; Webb, Muriel; Yeshua, Hanny; Nimer, Assy; Shibolet, Oren

    2017-01-01

    AIM To describe the relationships between non-alcoholic fatty-liver disease (NAFLD) patient’s disease consequences and treatment perceptions, self-efficacy, and healthy lifestyle maintenance. METHODS A cross-sectional study among 146 ultrasound diagnosed NAFLD patients who visited the fatty liver clinic at the Tel-Aviv Medical Center. Eighty-seven of these individuals, participated in a clinical trial of physical activity and underwent fasting blood tests, analyzed at the same lab. Exclusion criteria included positivity for serum HBsAg or anti-HCV antibodies; fatty liver suspected to be secondary to hepatotoxic drugs; excessive alcohol consumption (≥ 30 g/d in men or ≥ 20 g/d in women) and positive markers of genetic or immune-mediated liver diseases. Patients were asked to complete a self-report structured questionnaire, assembled by the Israeli Center for Disease Control. Nutrition habits were measured using six yes/no questions (0 = no, 1 = yes) adopted from the national survey questionnaire. Participants in the clinical trial completed a detailed semi-quantitative food frequency questionnaire (FFQ) reporting their habitual nutritional intake during the past year. Self-efficacy was assessed by the Self-Efficacy Scale questionnaire, emotional representation, degree of illness understanding, timeline perception, treatment perception and symptoms were measured by the Brief Illness Perception questionnaire. Illness consequences were measured by the Personal Models of Diabetes Interview questionnaire. A path analysis was performed to describe the interrelationships between the patients’ illness perceptions, and assess the extent to which the data fit a prediction of nutritional habits. RESULTS The study sample included 54.1% men, with a mean age of 47.76 ± 11.68 years (range: 20-60) and mean body mass index of 31.56 ± 4.6. The average perceived nutrition habits score was 4.73 ± 1.45 on a scale between 0-6, where 6 represents the healthiest eating habits

  3. Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis?

    Science.gov (United States)

    Targher, Giovanni; Rossini, Maurizio; Lonardo, Amedeo

    2016-02-01

    Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are associated with obesity, insulin resistance, metabolic syndrome, cardiovascular disease, cirrhosis, and liver tumors. On these grounds, we have hypothesized that NAFLD and PCOS occur more frequently than expected by chance alone. We have tested this hypothesis by reviewing the clinical and biological evidence that supports a significant association between NAFLD and PCOS. PubMed was extensively searched for articles published through March 2015 using the keywords "nonalcoholic fatty liver disease" or "fatty liver" combined with "PCOS." Several cross-sectional and case-control studies have consistently demonstrated that the prevalence of NAFLD is remarkably increased in young women with PCOS, independent of overweight/obesity and other coexisting metabolic syndrome features, and that these women are more likely to have the more severe forms of NAFLD (non-alcoholic steatohepatitis, advanced fibrosis, and cirrhosis). Accumulating evidence suggests that NAFLD, especially its necro-inflammatory form, may exacerbate hepatic and systemic insulin resistance and releases multiple pro-inflammatory, pro-coagulant, and pro-fibrogenic mediators that may play important roles in the pathophysiology of PCOS. These findings call for more active and systematic search for NAFLD among women with PCOS. Conversely, gastroenterologists/hepatologists need to be aware of the presence of PCOS among female patients with NAFLD and compatible clinical features. Finally, all these patients should undergo regular follow-up not only for liver-related complications but also for cardio-metabolic diseases.

  4. Influence of Ala54Thr polymorphism of fatty acid-binding protein 2 on histological alterations and insulin resistance of non alcoholic fatty liver disease.

    Science.gov (United States)

    Aller, R; De Luis, D A; Fernandez, L; Calle, F; Velayos, B; Izaola, O; Gonzalez Sagrado, M; Conde, R; Gonzalez, J M

    2009-01-01

    A transition G to A at codon 54 of fatty acid binding protein type 2 (FABP2) produces an amino acid substitution (Ala 54 to Thr 54). This amino acid substitution was associated with modifications of insulin resistance, adipokines and insulin concentrations. The aim of this study was to evaluate the influence of Ala54Thr polymorphism in the FABP2 gene on the histological alterations of non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Thirty subjects with the presence of biopsy-proven NAFLD were enrolled for this study. Glucose, Insulin, Insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, resistin, leptin, adiponectin, interleukin-6 and TNF-alfa serum levels were measured at basal time. A tetrapolar bioimpedance, BMI, waist circumference, waist to hip ratio, blood pressure and a prospective serial assessment of nutritional intake with 3 days written food records were examined. Genotype of Ala54Thr FABP2 gene polymorphism was studied. The mean age was 41.6 +/- 11 years and the mean BMI 29.2 +/- 6.6 with 24 males (80%) and 6 females (20%). Fifteen patients (50%) had the genotype Ala54/Ala54 (wild type group) and 15 (50%) patients Ala54/Thr54 (13 patients) or Thr54/Thr54 (2 patients) (mutant type group). Both genotype groups have the similar anthropometric parameters. Serum aspartate aminotransferase and alcaline phosfatase were higher in wild type group than mutant type group, with an unclear explanation. Dietary intake was similar in both groups. A non-statistical significant low levels of adiponectin in mutant group was observed. No differences were detected among other adipokines. There were no differences between genotypes in histological results of inflammation (portal or lobular inflammation) or grade of steatosis or fibrosis. In conclusion, the present study demonstrates that the polymorphism Ala54Thr of FABP in patients with NAFLD doesn't predict liver histological changes, nor both insulin resistance

  5. Hepatic scavenger receptor BI is associated with type 2 diabetes but unrelated to human and murine non-alcoholic fatty liver disease.

    Science.gov (United States)

    Rein-Fischboeck, Lisa; Krautbauer, Sabrina; Eisinger, Kristina; Pohl, Rebekka; Meier, Elisabeth M; Weiss, Thomas S; Buechler, Christa

    2015-11-13

    Scavenger receptor, class B type I (SR-BI) is a physiologically relevant regulator of high density lipoprotein (HDL) metabolism. Low HDL is a common feature of patients with non-alcoholic fatty liver disease (NAFLD). Here, hepatic SR-BI expression was analyzed in human and murine NAFLD. In primary human hepatocytes NAFLD relevant factors like inflammatory cytokines, lipopolysaccharide and TGF-β did not affect SR-BI protein. Similarly, oleate and palmitate had no effect. The adipokines chemerin, adiponectin, leptin and omentin did not regulate SR-BI expression. Accordingly, hepatic SR-BI was not changed in human and murine fatty liver and non-alcoholic steatohepatits. SR-BI was higher in type 2 diabetes patients but not in those with hypercholesterolemia. The current study indicates a minor if any role of SR-BI in human and murine NAFLD.

  6. The effect of non-alcoholic fatty liver disease on virologic response in patients with hepatitis B e antigen-positive chronic hepatitis B treated with nucleoside analogues

    Institute of Scientific and Technical Information of China (English)

    陈梅琴

    2014-01-01

    Objective To investigate the effect of non-alcoholic fatty liver disease(NAFLD)on virologic response in chronic hepatitis B patients treated with nucleoside analogues.Methods Three hundred and thirty-two treatment-naive patients with hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB)who visited clinic or hospitalized in the First Affiliated Hospital of Wenzhou Medical College from January 2007 to December 2009

  7. Identification of individuals with non-alcoholic fatty liver disease by the diagnostic criteria for the metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    Masahide Hamaguchi; Noriyuki Takeda; Takao Kojima; Akihiro Ohbora; Takahiro Kato; Hiroshi Sarui; Michiaki Fukui

    2012-01-01

    AIM:To clarify the efficiency of the criterion of metabolic syndrome to detecting non-alcoholic fatty liver disease (NAFLD).METHODS:Authors performed a cross-sectional study involving participants of a medical health checkup program including abdominal ultrasonography.This study involved 11 714 apparently healthy Japanese men and women,18 to 83 years of age.NAFLD was defined by abdominal ultrasonography without an alcohol intake of more than 20 g/d,known liver disease,or current use of medication.The revised criteria of the National Cholesterol Education Program Adult Treatment Panel Ⅲ were used to characterize the metabolic syndrome.RESULTS:NAFLD was detected in 32.2% (95% CI:31.0%-33.5%) of men (n =1874 of 5811) and in 8.7%(95% CI:8.0%-9.5%) of women (n =514 of 5903).Among obese people,the prevalence of NAFLD was as high as 67.3% (95% CI:64.8%-69.7%) in men and 45.8% (95% CI:41.7%-50.0%) in women.Although NAFLD was thought of as being the liver phenotype of metabolic syndrome,the prevalence of the metabolic syndrome among subjects with NAFLD was low both in men and women.66.8% of men and 70.4% of women with NAFLD were not diagnosed with the metabolic syndrome.48.2% of men with NAFLD and 49.8% of women with NAFLD weren't overweight [body mass index (BMI) ≥ 25 kg/m2].In the same way,68.6% of men with NAFLD and 37.9% of women with NAFLD weren't satisfied with abdominal classification (≥ 90cm for men and ≥ 80 cm for women).Next,authors defined it as positive at screening for NAFLD when participants satisfied at least one criterion of metabolic syndrome.The sensitivity of the definition "at least 1 criterion" was as good as 84.8% in men and 86.6% in women.Separating subjects by BMI,the sensitivity was higher in obese men and women than in non-obese men and women (92.3% vs 76.8% in men,96.1% vs 77.0% in women,respectively).CONCLUSION:Authors could determine NAFLD effectively in epidemiological study by

  8. Co-existence of non-alcoholic fatty liver disease and inflammatory bowel disease: A review article

    Science.gov (United States)

    Chao, Che-Yung; Battat, Robert; Al Khoury, Alex; Restellini, Sophie; Sebastiani, Giada; Bessissow, Talat

    2016-01-01

    Emerging data have highlighted the co-existence of non-alcoholic 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. PMID:27678354

  9. Co-existence of non-alcoholic fatty liver disease and inflammatory bowel disease: A review article.

    Science.gov (United States)

    Chao, Che-Yung; Battat, Robert; Al Khoury, Alex; Restellini, Sophie; Sebastiani, Giada; Bessissow, Talat

    2016-09-14

    Emerging data have highlighted the co-existence of non-alcoholic 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.

  10. Glucose-induced glucagon-like Peptide 1 secretion is deficient in patients with non-alcoholic fatty liver disease.

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    Christine Bernsmeier

    Full Text Available BACKGROUND & AIMS: The incretins glucagon-like peptide-1 (GLP-1 and glucose-dependent insulinotropic polypeptide (GIP are gastrointestinal peptide hormones regulating postprandial insulin release from pancreatic β-cells. GLP-1 agonism is a treatment strategy in Type 2 diabetes and is evaluated in Non-alcoholic fatty liver disease (NAFLD. However, the role of incretins in its pathophysiology is insufficiently understood. Studies in mice suggest improvement of hepatic steatosis by GLP-1 agonism. We determined the secretion of incretins after oral glucose administration in non-diabetic NAFLD patients. METHODS: N=52 patients (n=16 NAFLD and n=36 Non-alcoholic steatohepatitis (NASH patients and n=50 matched healthy controls were included. Standardized oral glucose tolerance test was performed. Glucose, insulin, glucagon, GLP-1 and GIP plasma levels were measured sequentially for 120 minutes after glucose administration. RESULTS: Glucose induced GLP-1 secretion was significantly decreased in patients compared to controls (p<0.001. In contrast, GIP secretion was unchanged. There was no difference in GLP-1 and GIP secretion between NAFLD and NASH subgroups. All patients were insulin resistant, however HOMA2-IR was highest in the NASH subgroup. Fasting and glucose-induced insulin secretion was higher in NAFLD and NASH compared to controls, while the glucose lowering effect was diminished. Concomitantly, fasting glucagon secretion was significantly elevated in NAFLD and NASH. CONCLUSIONS: Glucose-induced GLP-1 secretion is deficient in patients with NAFLD and NASH. GIP secretion is contrarily preserved. Insulin resistance, with hyperinsulinemia and hyperglucagonemia, is present in all patients, and is more severe in NASH compared to NAFLD. These pathophysiologic findings endorse the current evaluation of GLP-1 agonism for the treatment of NAFLD.

  11. [Non-alcoholic fatty liver disease (NAFLD) in patients with metabolic syndrome and type 2 diabetes mellitus. Pathomechanism, new diagnostic markers].

    Science.gov (United States)

    Kieć-Wilk, Beata; Klupa, Tomasz; Dembińska-Kieć, Aldona

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a complex of a wide spectrum of liver pathology--from steatosis alone, to cirrhosis and liver cancer. The pathogenic concept of NAFLD covers overnutrition with fatty acids, underactivity. Insulin resistance is believed to play the main role in this process. NAFLD is mostly related to visceral adiposity, metabolic syndrome and type 2 diabetes melitus. The presented work is a review of in vitro and in vivo modern studies, as well as clinical observations on molecular mechanisms leading to development and progress of NAFLD. Up till today their is no treatment od NAFLD, and this pathology is not benign--it may lead to patients' death in 10 years. The clinical approach to NAFLD is prevention of it's development. The manuscript is a review of new biochemical markers allowing for early detection of metabolic disorders leading to NAFLD development, thus to sufficient prevention of this pathology in patients.

  12. Evaluation of flaxseed effects on non-alcoholic fatty liver disease (NAFLD in rabbits submitted to a hypercholesterolemic diet

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    Caroline Tatim Saad

    2014-10-01

    Full Text Available Background: The aim of the present study is to evaluate the role of flaxseed in non-alcoholic fatty liver disease, as well as on the lipid profile in rabbits submitted to hypercholesterolemic diet. Subject and Methods: 32 male rabbits, weighing approximately 1.5kg and averaging four months of age, were distributed into three groups. Group 1 received standard food plus 0.5% of cholesterol from dried egg, during 8 weeks. Group 2 obtained the same diet in the first 4 weeks, and 8mg/kg of ground flaxseed was added in the remaining weeks. Lastly, group 3 was fed with the previous group’s increased diet throughout the entire period. In the follow-up, the animals were euthanized, and liver blades were prepared to evaluate the histopathologic study. The evaluation score of NAFLD (ESN, as well as plasma levels of total cholesterol, LDLcholesterol, HDL-cholesterol, triglycerides and body weight, were all determined. Results: Increased levels of total cholesterol were obtained in both groups, with the smallest variation found in G3 (p=0.002. This variation was also found when the levels of LDLcholesterol were assessed (p=0.001. There was a reduction of triglyceride levels at the end of the study in G3 (p=0.008. A variation was noticed between the ESN groups, but the induced reduction was not statistically significant. Conclusion: Further studies are necessary, in order to elucidate the effects of flaxseed in NAFLD as well as in diseases that have risk factors for the development of the disease

  13. Independent effects of diet and exercise training on fat oxidation in non-alcoholic fatty liver disease

    Science.gov (United States)

    Croci, Ilaria; Byrne, Nuala M; Chachay, Veronique S; Hills, Andrew P; Clouston, Andrew D; O’Moore-Sullivan, Trisha M; Prins, Johannes B; Macdonald, Graeme A; Hickman, Ingrid J

    2016-01-01

    AIM To investigate the independent effects of 6-mo of dietary energy restriction or exercise training on whole-body and hepatic fat oxidation of patients with non-alcoholic fatty liver disease (NAFLD). METHODS Participants were randomised into either circuit exercise training (EX; n = 13; 3 h/wk without changes in dietary habits), or dietary energy restriction (ER) without changes in structured physical activity (ER; n = 8). Respiratory quotient (RQ) and whole-body fat oxidation rates (Fatox) were determined by indirect calorimetry under basal, insulin-stimulated and exercise conditions. Severity of disease and steatosis was determined by liver histology; hepatic Fatox was estimated from plasma β-hydroxybutyrate concentrations; cardiorespiratory fitness was expressed as VO2peak. Complete-case analysis was performed (EX: n = 10; ER: n = 6). RESULTS Hepatic steatosis and NAFLD activity score decreased with ER but not with EX. β-hydroxybutyrate concentrations increased significantly in response to ER (0.08 ± 0.02 mmol/L vs 0.12 ± 0.04 mmol/L, P = 0.03) but remained unchanged in response to EX (0.10 ± 0.03 mmol/L vs 0.11 ± 0.07 mmol/L, P = 0.39). Basal RQ decreased (P = 0.05) in response to EX, while this change was not significant after ER (P = 0.38). VO2peak (P 0.05). The increase in β-hydroxybutyrate concentrations was correlated with the reduction in hepatic steatosis (r = -0.56, P = 0.04). CONCLUSION ER and EX lead to specific benefits on fat metabolism of patients with NAFLD. Increased hepatic Fatox in response to ER could be one mechanism through which the ER group achieved reduction in steatosis.

  14. Non-Alcoholic Fatty Liver Disease Is not Related to the Incidence of Diabetic Nephropathy in Type 2 Diabetes

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    Chun-Shan Bi

    2012-11-01

    Full Text Available To analyze the association between non-alcoholic fatty liver disease (NAFLD and the incidence of diabetic nephropathy in patients with type 2 diabetes, the incidence of diabetic nephropathy was assessed in 413 type 2 diabetic patients, by testing the 24 h urinary albumin excretion rate (UAER. The NAFLD was diagnosed based on patient’s medical history and liver ultrasound. The difference in diabetic nephropathy incidence between patients with and without NAFLD was tested by χ2. Multivariate logistic regression analysis was used to assess the factors associated with diabetic nephropathy among type 2 diabetic patients. Total 363 out of 413 type 2 diabetic patients were enrolled in this study. The incidences of NAFLD and diabetic nephropathy in participants were approximately 56% (202/363 and 38% (137/363 respectively, and there was no significant difference in the prevalence of diabetic nephropathy between patients with and without NAFLD (37.1% vs. 38.5%, p = 0.787. The duration of diabetes (odds ratio [OR] 1.065, 95% confidence interval [CI] 1.014–1.120, p = 0.012, waist circumference (OR 1.077, 95% CI 1.040–1.116, p = 0.000, and fasting blood glucose (FBG; OR 1.136, 95% CI 1.023–1.1262, p = 0.017 were significantly associated with diabetic nephropathy, whereas sex, high blood pressure, total cholesterol (TC, triglyceride (TG, and ankle brachial pressure index (ABI were not significantly associated with the disorder. The present results suggest that NAFLD is not related to the incidence of diabetic nephropathy in type 2 diabetes, but the duration of diabetes, waist circumference, and FBG are important factors for diabetic nephropathy in type 2 diabetes.

  15. Doppler Tissue Evaluation of Atrial Conduction Properties in Patients With Non-alcoholic Fatty-liver Disease.

    Science.gov (United States)

    Ozveren, Olcay; Izgi, Cemil; Eroglu, Elif; Simsek, Mustafa Aytek; Turer, Ayca; Kucukdurmaz, Zekeriya; Cinar, Veysel; Degertekin, Muzaffer

    2016-05-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in clinical practice, and there is an increasing trend in its prevalence in the general population. Recent studies have demonstrated increased risk of atrial fibrillation (AF) in NAFLD. However, information on the mechanism of increased risk of AF in NAFLD is lacking. Impaired atrial conduction is an important factor in the pathophysiology of AF. We aimed to investigate atrial conduction properties in patients with NAFLD by tissue Doppler echocardiography. Fifty-nine ultrasound diagnosed NAFLD patients without clinical diagnosis of hypertension, diabetes mellitus, or cardiac disease and 22 normal subjects as controls were included in this study. Atrial conduction properties were assessed by electromechanical delay (EMD) derived from Doppler tissue echocardiography examination and P-wave dispersion (PWD) calculated from the 12-lead electrocardiogram. Inter-atrial and intra-atrial EMD intervals were significantly longer in NAFLD patients than in controls (inter-atrial EMD, 31.9 ± 8.5 ms vs. 23.4 ± 4.6 ms,p= 0.0001, and intra-atrial EMD, 14.3 ± 5.2 vs. 10.2 ± 4.0 ms,p= 0.001). Similarly, PWD was significantly higher in NAFLD patients compared with controls (49.2 ± 6.3 ms vs. 43.3 ± 4.2 ms,p= 0.0001). Maximum left atrial volume was also significantly higher in the NAFLD group than in controls (51 ± 11 mL vs. 34 ± 9 mL,pNAFLD. Also, in a patient population of NAFLD without any clinical diagnosis of cardiac disease, diabetes, or hypertension, left atrial volume was increased compared with controls. These findings suggest impaired atrial conduction as a factor in increased risk of AF in NAFLD.

  16. Risk factors associated with non-alcoholic fatty liver disease in subjects from primary care units. A case-control study

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    Bernad Jesús

    2008-10-01

    Full Text Available Abstract Background Non alcoholic fatty liver disease (NAFL consists in the accumulation of fat vacuoles in the cytoplasm of hepatocytes. Many etiologic factors are associated with NAFL, such as, the metabolic syndrome factors, medications, bariatric surgery, nutritional disorders. However, very little information is available on the clinical relevance of this disorder as a health problem in the general population. Methods and design The aim of the study is establish the risk factors most frequently associated with NAFL in a general adult population assigned to the primary care units and to investigate the relationship between each component of the metabolic syndrome and the risk of having a NAFL. A population based case-control, observational and multicenter study will be carried out in 18 primary care units from the "Area de Gestión del Barcelonés Nord y Maresme" (Barcelona attending a population of 360,000 inhabitants and will include 326 cases and 370 controls. Cases are defined as all subjects fulfilling the inclusion criteria and with evidence of fatty liver in an abdominal ultrasonography performed for any reason. One control will be randomly selected for each case from the population, matched for age, gender and primary care center. Controls with fatty liver or other liver diseases will be excluded. All cases and controls will be asked about previous hepatic diseases, consumption of alcohol, smoking and drugs, and a physical examination, biochemical analyses including liver function tests, the different components of the metabolic syndrome and the HAIR score will also be performed. Paired controls will also undergo an abdominal ultrasonography. Discussion This study will attempt to determine the factors most frequently associated with the presence of NAFL investigate the relationship between the metabolic syndrome and the risk of fatty liver and study the influence of the different primary care professionals in avoiding the evolution

  17. Effect and the probable mechanisms of silibinin in regulating insulin resistance in the liver of rats with non-alcoholic fatty liver

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Jiayin; Zhi, Min; Gao, Xiang; Hu, Pinjin; Li, Chujun; Yang, Xiaobo [Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province (China)

    2013-03-15

    Our previous study has shown that reduced insulin resistance (IR) was one of the possible mechanisms for the therapeutic effect of silibinin on non-alcoholic fatty liver disease (NAFLD) in rats. In the present study, we investigated the pathways of silibinin in regulating hepatic glucose production and IR amelioration. Forty-five 4- to 6-week-old male Sprague Dawley rats were divided into a control group, an HFD group (high-fat diet for 6 weeks) and an HFD + silibinin group (high-fat diet + 0.5 mg kg{sup -1}·day{sup -1} silibinin, starting at the beginning of the protocol). Both subcutaneous and visceral fat was measured. Homeostasis model assessment-IR index (HOMA-IR), intraperitoneal glucose tolerance test and insulin tolerance test (ITT) were performed. The expression of adipose triglyceride lipase (ATGL) and of genes associated with hepatic gluconeogenesis was evaluated. Silibinin intervention significantly protected liver function, down-regulated serum fat, and improved IR, as shown by decreased HOMA-IR and increased ITT slope. Silibinin markedly prevented visceral obesity by reducing visceral fat, enhanced lipolysis by up-regulating ATGL expression and inhibited gluconeogenesis by down-regulating associated genes such as Forkhead box O1, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Silibinin was effective in ameliorating IR in NAFLD rats. Reduction of visceral obesity, enhancement of lipolysis and inhibition of gluconeogenesis might be the underlying mechanisms.

  18. Betulinic acid alleviates non-alcoholic fatty liver by inhibiting SREBP1 activity via the AMPK-mTOR-SREBP signaling pathway.

    Science.gov (United States)

    Quan, Hai Yan; Kim, Do Yeon; Kim, Soo Jung; Jo, Hee Kyung; Kim, Go Woon; Chung, Sung Hyun

    2013-05-01

    Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. The discovery of food components that can ameliorate NAFLD is therefore of interest. Betulinic acid (BA) is a triterpenoid with many pharmacological activities, but the effect of BA on fatty liver is as yet unknown. To explore the possible anti-fatty liver effects and their underlying mechanisms, we used insulin-resistant HepG2 cells, primary rat hepatocytes and liver tissue from ICR mice fed a high-fat diet (HFD). Oil Red O staining revealed that BA significantly suppressed excessive triglyceride accumulation in HepG2 cells and in the livers of mice fed a HFD. Ca(+2)-calmodulin dependent protein kinase kinase (CAMKK) and AMP-activated protein kinase (AMPK) were both activated by BA treatment. In contrast, the protein levels of sterol regulatory element-binding protein 1 (SREBP1), mammalian target of rapamycin (mTOR) and S6 kinase (S6K) were all reduced when hepatocytes were treated with BA for up to 24h. We found that BA activates AMPK via phosphorylation, suppresses SREBP1 mRNA expression, nuclear translocation and repressed SREBP1 target gene expression in HepG2 cells and primary hepatocytes, leading to reduced lipogenesis and lipid accumulation. These effects were completely abolished in the presence of STO-609 (a CAMKK inhibitor) or compound C (an AMPK inhibitor), indicating that the BA-induced reduction in hepatic steatosis was mediated via the CAMKK-AMPK-SREBP1 signaling pathway. Taken together, our results suggest that BA effectively ameliorates intracellular lipid accumulation in liver cells and thus is a potential therapeutic agent for the prevention of fatty liver disease.

  19. Fatty liver in childhood

    Institute of Scientific and Technical Information of China (English)

    Yesim; Ozturk; Ozlem; Bekem; Soylu

    2014-01-01

    Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is reported. Nonalcoholic fatty liver disease(NAFLD) has no specific symptoms or signs but should be considered in obese children. NAFLD does not have a proven treatment. Weight loss with family based treatments is the most acceptable management. Exercise and an applicable diet with low glycemic index and appropriate calorie intake are preferred. Drugs are promising but not sufficient in children for today.

  20. Fatty liver in childhood

    OpenAIRE

    Ozturk,Yesim; Soylu, Ozlem Bekem

    2014-01-01

    Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is repor...

  1. Nonalcoholic Fatty Liver Disease

    OpenAIRE

    You, Jie; Huang, Sha; Huang, Gui-Qian; Zhu, Gui-Qi; Ma, Rui-Min; Liu, Wen-yue; Shi, Ke-Qing; Guo, Gui-Long; Chen, Yong-Ping; Braddock, Martin; Zheng, Ming-Hua

    2015-01-01

    Abstract Nonalcoholic fatty liver disease (NAFLD) is known to be associated with an increased risk of colorectal cancer (CRC). However, the relationship between NAFLD and the prognosis of CRC remains unclear. The primary objective of this study was to evaluate the overall survival (OS) and disease-free survival (DFS) rates in patients with CRC and the secondary objective was to compare clinicopathologic variables which were stratified by NAFLD. We performed a large cohort study of 1314 patien...

  2. Non alcoholic fatty liver disease and its relationship with hsCRP in type 2 diabetes mellitus

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    Naina Bhuyan

    2014-08-01

    Conclusions: High hsCRP is a cheap, easily available laboratory marker to suspect fatty liver and possibly steatohepatitis in T2 Diabetics in our region. It can identify a subgroup of diabetic patients in whom liver biopsy may be advisable to confirm steatohepatitis which is important for prognosis and therefore need aggressive intervention. [Int J Res Med Sci 2014; 2(4.000: 1586-1590

  3. Clinicopathological characteristics and metabolic profiles of non-alcoholic fatty liver disease in Indian patients with normal body mass index: Do they differ from obese or overweight non-alcoholic fatty liver disease?

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    Ramesh Kumar

    2013-01-01

    Full Text Available Background: Obesity is an important risk factor for non-alcoholic fatty liver disease (NAFLD; however, NAFLD does occur in lean subjects. This study was aimed to evaluate the magnitude, clinical, pathological, and metabolic profiles of NAFLD in normal body mass index (BMI subjects (defined as lean NAFLD in comparison to overweight or obese NAFLD and lean healthy control. Materials and Methods: 336 subjects (205 consecutive NAFLD, and 131 healthy controls were studied. Results: Among 205 NAFLD patients, 27 (13.2% were lean, while 141 (68.8% and 37 (18% patients were obese and overweight, respectively. The lean NAFLD compared to obese NAFLD had significantly lesser degree of fasting hyperinsulinemia ( P < 0.001, homeostasis model assessment insulin resistance (HOMA-IR, P < 0.001, and lower prevalence of diabetes mellitus ( P = 0.01 and metabolic syndrome ( P < 0.001. The profiles of serum lipids were similar between all 3 BMI categories, and 89% of lean NAFLD were dyslipidemic. Compared to obese subjects, patients with lean NAFLD had less hepatic necro-inflammation ( P = 0.05 and fibrosis ( P < 0.001. However, the proportion of steatohepatitis and advanced fibrosis were similar between all BMI categories. The profiles of overweight NAFLD were similar to those of lean NAFLD, except for higher HOMA-IR, uric acids and male gender in overweight group. Despite being lean, the mean BMI of lean NAFLD were still higher than unselected lean healthy controls ( P = 0.02. Conclusions: Lean NAFLD patients have less severe disease, minor, or no insulin resistance, but are frequently dyslipidemic and have BMI higher than lean healthy control.

  4. Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver.

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    Lu Mei

    Full Text Available Non-alcoholic fatty liver disease (NAFLD has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC together with cholesterol-lowering probiotics (P to improve high-fat diet (HFD-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague-Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7α-hydroxylase (CYP7A1, low density lipoprotein receptor (LDL-R and farnesoid X receptor (FXR were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR was reduced. The expression of peroxisome proliferator activated receptor (PPAR-α protein was significantly increased while the expression of PPAR-γ and sterol regulatory element binding protein-1c (SREBP-1c was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1 were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-α protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-γ and SREBP-1c, and through normalizing the

  5. Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver.

    Science.gov (United States)

    Mei, Lu; Tang, Youcai; Li, Ming; Yang, Pingchang; Liu, Zhiqiang; Yuan, Jieli; Zheng, Pengyuan

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC) together with cholesterol-lowering probiotics (P) to improve high-fat diet (HFD)-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague-Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7α-hydroxylase (CYP7A1), low density lipoprotein receptor (LDL-R) and farnesoid X receptor (FXR) were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) was reduced. The expression of peroxisome proliferator activated receptor (PPAR)-α protein was significantly increased while the expression of PPAR-γ and sterol regulatory element binding protein-1c (SREBP-1c) was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1) were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-α protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-γ and SREBP-1c, and through normalizing the intestinal

  6. Long term prognosis of fatty liver: risk of chronic liver disease and death

    DEFF Research Database (Denmark)

    Dam-Larsen, S; Franzmann, M; Andersen, I B

    2004-01-01

    and the risk of death in a cohort diagnosed with pure fatty liver without inflammation. METHODS: A total of 215 patients who had a liver biopsy performed during the period 1976-1987 were included in the study. The population consisted of 109 non-alcoholic and 106 alcoholic fatty liver patients. Median follow...... of Patients and the nationwide Registry of Causes of Death, and all admissions, discharge diagnoses, and causes of death were obtained. RESULTS: In the non-alcoholic fatty liver group, one patient developed cirrhosis during the follow up period compared with 22 patients in the alcoholic group. Survival...... estimates were significantly (palcoholic fatty liver group. Survival estimates in the non-alcoholic fatty liver group were not different from the Danish population. CONCLUSIONS: This study revealed...

  7. Genetic polymorphisms in non-alcoholic fatty liver disease in obese Egyptian children

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    Nehal M El-Koofy

    2011-01-01

    Full Text Available Background/Aim : Polymorphisms in the promoter of microsomal triglyceride transfer protein (MTP lead to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. Therefore, functional polymorphisms in MTP may be involved in determining susceptibility to nonalcoholic steatohepatitis (NASH. The aim of this study is to examine the effect of some genetic influences among a group of obese Egyptian children. Patients and Methods: A cross-sectional study was conducted on 76 overweight and obese children presenting to the Pediatric Endocrinology Unit, Cairo University Children′s Hospital, Egypt, as well as on 20 healthy controls. Anthropometric measurements were taken for all the patients and they underwent clinical examination, ultrasonographic examination of the liver, and liver biopsy when appropriate. Liver functions, blood glucose, serum insulin, C-peptide, and lipid profile were assessed and HOMA-IR calculated. Blood samples from biopsy-proven NASH patients and controls were analyzed by polymerase chain reaction (PCR and restriction fragment length polymorphism for the −493 G/T polymorphism in the promoter of MTP and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD. Results : Eight had biopsy-proven simple steatosis and 7 had NASH. NASH patients had a much higher incidence of the MTP G/G genotype (P = 0.002, CI: 2.9-392 compared with the controls. NASH patients also had a 100% prevalence of the MnSOD T/T genotype. Conclusion: Certain genotypes in MTP and MnSOD are significantly more prevalent among obese children with NASH and may be responsible for such a phenotype.

  8. Influence of gut bacteria on development and progressionof non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The intestine of the human contains a dynamic populationof microbes that have a symbiotic relationship withthe host. In addition, there is an effect of the intestinalmicrobiota on metabolism and digestion. Non-alcoholicfatty liver disease (NAFLD) is a common cause worldwideof hepatic pathology and is thought to be the hepaticmanifestation of the metabolic syndrome. In this reviewwe examine the effect of the human microbiome onthe components and pathogenesis of the metabolicsyndrome. We are now on the threshold of therapeuticinterventions on the human microbiome in order to effecthuman disease including NAFLD.

  9. The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Emma L Anderson

    Full Text Available Narrative reviews of paediatric NAFLD quote prevalences in the general population that range from 9% to 37%; however, no systematic review of the prevalence of NAFLD in children/adolescents has been conducted. We aimed to estimate prevalence of non-alcoholic fatty liver disease (NAFLD in young people and to determine whether this varies by BMI category, gender, age, diagnostic method, geographical region and study sample size.We conducted a systematic review and meta-analysis of all studies reporting a prevalence of NAFLD based on any diagnostic method in participants 1-19 years old, regardless of whether assessing NAFLD prevalence was the main aim of the study.The pooled mean prevalence of NAFLD in children from general population studies was 7.6% (95%CI: 5.5% to 10.3% and 34.2% (95% CI: 27.8% to 41.2% in studies based on child obesity clinics. In both populations there was marked heterogeneity between studies (I2 = 98%. There was evidence that prevalence was generally higher in males compared with females and increased incrementally with greater BMI. There was evidence for differences between regions in clinical population studies, with estimated prevalence being highest in Asia. There was no evidence that prevalence changed over time. Prevalence estimates in studies of children/adolescents attending obesity clinics and in obese children/adolescents from the general population were substantially lower when elevated alanine aminotransferase (ALT was used to assess NAFLD compared with biopsies, ultrasound scan (USS or magnetic resonance imaging (MRI.Our review suggests the prevalence of NAFLD in young people is high, particularly in those who are obese and in males.

  10. Visceral obesity and the risk of Barrett's esophagus in Japanese patients with non-alcoholic fatty liver disease

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    Kirikoshi Hiroyuki

    2009-07-01

    Full Text Available Abstract Background The association between obesity and the risk of Barrett's esophagus (BE is unclear. Furthermore, the association between visceral obesity and the risk of BE is entirely unknown. Methods We conducted a retrospective study in 163 patients with non-alcoholic fatty liver disease (NAFLD who underwent both endoscopy and abdominal CT at an interval of less than a year at our institution. BE was endoscopically diagnosed based on the Prague C & M Criteria. The surface areas of visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT were calculated from CT images at the level of the umbilicus. The correlations between the BMI, VAT, and SAT and the risk of BE were examined by univariate and multivariate analyses. Results Sixty-nine of the 163 study participants (42.3% were diagnosed to have endoscopic BE, which was classified as short-segment BE (SSBE in almost all of the cases. There were no significant differences in the age or gender distribution between the groups with and without BE. According to the results of the univariate analysis, VAT was significantly associated with the risk of BE; the BMI tended to be higher in the group with BE than in the group without BE, but this relation did not reach statistical significance. VAT was independently associated with the risk of BE even after adjustment for the BMI. Conclusion In Japanese patients with NAFLD, obesity tended to be associated with the risk of BE, and this risk appeared to be mediated for the most part by abdominal visceral adiposity.

  11. Association of non-alcoholic fatty liver disease with major adverse cardiovascular events: A systematic review and meta-analysis

    Science.gov (United States)

    Wu, Shunquan; Wu, Fuquan; Ding, Yingying; Hou, Jun; Bi, Jingfeng; Zhang, Zheng

    2016-01-01

    Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to cardiovascular disease (CVD). The aim of this study is to assess whether and to what extent the excess risk of CVD is conferred by NAFLD in a meta-analysis. We systematically searched PubMed, EmBase, Web of Science, and Cochrane Library for reports published between 1965 and July 3, 2015. Studies that reported data on association between NAFLD and adverse cardiovascular events or mortality were included. Thirty-four studies (164,494 participants, 21 cross-sectional studies, and 13 cohort studies) were included. NAFLD was not associated with overall mortality (HR = 1.14, 95% CI: 0.99–1.32) and CVD mortality (HR = 1.10, 95% CI: 0.86–1.41). However, NAFLD was associated with an increased risk of prevalent (OR = 1.81, 95% CI: 1.23–2.66) and incident (HR = 1.37, 95% CI: 1.10–1.72) CVD. For some specific CVDs, NAFLD was associated with an increased risk of prevalent (OR = 1.87, 95% CI: 1.47–2.37) and incident (HR = 2.31, 95% CI: 1.46–3.65) coronary artery disease (CAD), prevalent (OR = 1.24, 95% CI: 1.14–1.36) and incident (HR = 1.16, 95% CI: 1.06–1.27) hypertension, and prevalent (OR = 1.32, 95% CI: 1.07–1.62) atherosclerosis. In conclusion, the presence of NAFLD is associated with an increased risk of major adverse cardiovascular events, although it is not related to mortality from all causes or CVD. PMID:27633274

  12. Associations between sitting time and non-alcoholic fatty liver diseases in Chinese male workers: a cross-sectional study

    Science.gov (United States)

    Wei, Huili; Qu, Hua; Wang, Hang; Deng, Huacong

    2016-01-01

    Objectives Various studies have revealed a close association between sedentary behaviour and metabolic diseases, yet the association between sedentary time and non-alcoholic fatty liver disease (NAFLD) remains unclear. In this study, we investigated the association between sitting time and NAFLD in a Chinese male population and explored its underlying mechanism. Study design A cross-sectional study. Setting Chongqing, China. Participants Our study included 2054 male participants; all of the participants were of Han nationality. Primary outcome measures Sitting time was assessed using a self-reported questionnaire concerning the time devoted to sitting behaviour. Various clinical and demographic biomarkers were measured. Logistic regression analyses were used to investigate the ORs and the 95% CIs between sitting time and NAFLD. Results We found a higher proportion of NAFLD across the tertiles of sitting time (p trend=0.003). Multivariate linear regression analyses showed sitting time independently correlated with homoeostasis model assessment for insulin resistance (HOMA-IR), alanine aminotransferase, γ-glutamyl transpeptidase, body mass index, triglyceride and the high-sensitive C reactive protein (hsCRP) (all p7.1 hours/day) was associated with a higher prevalence of NAFLD (OR 1.09; 95% CI (1.04 to 1.67)) after adjusting for confounders. However, this association was insignificant after further adjusting for hsCRP (OR 1.03; 95% CI (0.92 to 1.84)). Conclusions Sitting time was positively associated with the prevalence of NAFLD, and this association might be affected by inflammation. PMID:27609847

  13. High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway

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    Napolitano Mariarosaria

    2011-04-01

    Full Text Available Abstract Background Hyperhomocysteinemia (HHcy causes increased oxidative stress and is an independent risk factor for cardiovascular disease. Oxidative stress is now believed to be a major contributory factor in the development of non alcoholic fatty liver disease, the most common liver disorder worldwide. In this study, the changes which occur in homocysteine (Hcy metabolism in high fat-diet induced non alcoholic fatty liver disease (NAFLD in rats were investigated. Methods and results After feeding rats a standard low fat diet (control or a high fat diet (57% metabolisable energy as fat for 18 weeks, the concentration of homocysteine in the plasma was significantly raised while that of cysteine was lowered in the high fat as compared to the control diet fed animals. The hepatic activities of cystathionine β-synthase (CBS and cystathionine γ-lyase (CGS, the enzymes responsible for the breakdown of homocysteine to cysteine via the transsulphuration pathway in the liver, were also significantly reduced in the high fat-fed group. Conclusions These results indicate that high fat diet-induced NAFLD in rats is associated with increased plasma Hcy levels caused by down-regulation of hepatic CBS and CGL activity. Thus, HHcy occurs at an early stage in high fat diet-induced NAFLD and is likely to contribute to the increased risk of cardiovascular disease associated with the condition.

  14. Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease.

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    Hong-Mei Yan

    Full Text Available A randomized, parallel controlled, open-label clinical trial was conducted to evaluate the effect of a botanic compound berberine (BBR on NAFLD.A randomized, parallel controlled, open-label clinical trial was conducted in three medical centers (NIH Registration number: NCT00633282. A total of 184 eligible patients with NAFLD were enrolled and randomly received (i lifestyle intervention (LSI, (ii LSI plus pioglitazone (PGZ 15mg qd, and (iii LSI plus BBR 0.5g tid, respectively, for 16 weeks. Hepatic fat content (HFC, serum glucose and lipid profiles, liver enzymes and serum and urine BBR concentrations were assessed before and after treatment. We also analyzed hepatic BBR content and expression of genes related to glucose and lipid metabolism in an animal model of NAFLD treated with BBR.As compared with LSI, BBR treatment plus LSI resulted in a significant reduction of HFC (52.7% vs 36.4%, p = 0.008, paralleled with better improvement in body weight, HOMA-IR, and serum lipid profiles (all p<0.05. BBR was more effective than PGZ 15mg qd in reducing body weight and improving lipid profile. BBR-related adverse events were mild and mainly occurred in digestive system. Serum and urine BBR concentrations were 6.99ng/ml and 79.2ng/ml, respectively, in the BBR-treated subjects. Animal experiments showed that BBR located favorably in the liver and altered hepatic metabolism-related gene expression.BBR ameliorates NAFLD and related metabolic disorders. The therapeutic effect of BBR on NAFLD may involve a direct regulation of hepatic lipid metabolism.ClinicalTrials.gov NCT00633282.

  15. Gut-liver axis and non-alcoholic fatty liver disease%肠-肝轴与非酒精性脂肪性肝病

    Institute of Scientific and Technical Information of China (English)

    丁佳; 吴健

    2014-01-01

    Changes in phylotypes and composition of intestinal bacterial community affect host metabolism , inflammatory and immunogenic responses .In non-alcoholic fatty liver disease (NAFLD) ,small intestinal bacterial overgrowth , changes in colony composition and quantity , and increased intestinal permeability promote the development of liver inflammation and fibrogenesis through enhancing hepatic lipogenesis , causing insulin resistance and stimulating innate immune response .Identification of specific bacterial species and their products that alter metabolic status and cause sustained but low-grade inflammatory and immune responses will advance our understanding of the critical role of “gut-liver axis” in promoting the initiation and progression of non-alcoholic steatohepatitis (NASH ) ,and explore novel therapeutic strategies for its prevention and treatment .%肠道菌群组成和数量的改变影响宿主的能量代谢、免疫应答和炎症反应状态。非酒精性脂肪性肝病患者常伴有小肠细菌过度生长或某些菌群种类和数量的改变,以及肠道黏膜通透性增加。肠道细菌通过增强肝脏脂肪合成、诱导机体胰岛素抵抗、激活天然免疫系统相关分子模式等机制,诱发肝脏炎症反应,启动纤维化进程,促进单纯性脂肪变向脂肪性肝炎发展。鉴定影响机体能量代谢和炎症反应的肠道菌群及其产物将为阐明肠-肝轴对肝脏炎症发生、发展所起的作用奠定基础,为揭示非酒精性脂肪性肝病发生、发展的机制开辟新思路,为该病的防治探索新策略。

  16. Reversible fatty infiltration of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Bostel, F.; Hauger, W.

    1987-11-01

    Case studies show that acute pancreatitis occurring independently or combined with a preceding abuse of alcohol may be the cause of fatty infiltration of the liver. These fat areas can evolve in a very short time and provoke in the case of focal incidence diagnostic problems of differentiation against abscesses of metastases. Due to this fact and because of the rapid reversibility of the fatty infiltration under therapy, the safest method to clarify the situation consists of short-term CT controls.

  17. Different Effects of Eicosapentaenoic and Docosahexaenoic Acids on Atherogenic High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice

    Science.gov (United States)

    Suzuki-Kemuriyama, Noriko; Matsuzaka, Takashi; Kuba, Motoko; Ohno, Hiroshi; Han, Song-iee; Takeuchi, Yoshinori; Isaka, Masaaki; Kobayashi, Kazuto; Iwasaki, Hitoshi; Yatoh, Shigeru; Suzuki, Hiroaki; Miyajima, Katsuhiro; Nakae, Dai; Yahagi, Naoya; Nakagawa, Yoshimi; Sone, Hirohito; Yamada, Nobuhiro; Shimano, Hitoshi

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, can progress to steatohepatitis (NASH) and advanced liver damage, such as that from liver cirrhosis and cancer. Recent studies have shown the benefits of consuming n-3 polyunsaturated fatty acids (PUFAs) for the treatment of NAFLD. In the present study, we investigated and compared the effects of the major n-3 PUFAs—eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6)—in preventing atherogenic high-fat (AHF) diet-induced NAFLD. Mice were fed the AHF diet supplemented with or without EPA or DHA for four weeks. Both EPA and DHA reduced the pathological features of AHF diet-induced NASH pathologies such as hepatic lobular inflammation and elevated serum transaminase activity. Intriguingly, EPA had a greater hepatic triacylglycerol (TG)-reducing effect than DHA. In contrast, DHA had a greater suppressive effect than EPA on AHF diet-induced hepatic inflammation and ROS generation, but no difference in fibrosis. Both EPA and DHA could be effective for treatment of NAFLD and NASH. Meanwhile, the two major n-3 polyunsaturated fatty acids might differ in a relative contribution to pathological intermediate steps towards liver fibrosis. PMID:27333187

  18. Long term prognosis of fatty liver: risk of chronic liver disease and death

    DEFF Research Database (Denmark)

    Dam-Larsen, S; Franzmann, M; Andersen, I B;

    2004-01-01

    BACKGROUND AND AIMS: Fatty liver is a common histological finding in human liver biopsy specimens. It affects 10-24% of the general population and is believed to be a marker of risk of later chronic liver disease. The present study examined the risk of development of cirrhotic liver disease...... and the risk of death in a cohort diagnosed with pure fatty liver without inflammation. METHODS: A total of 215 patients who had a liver biopsy performed during the period 1976-1987 were included in the study. The population consisted of 109 non-alcoholic and 106 alcoholic fatty liver patients. Median follow...... of Patients and the nationwide Registry of Causes of Death, and all admissions, discharge diagnoses, and causes of death were obtained. RESULTS: In the non-alcoholic fatty liver group, one patient developed cirrhosis during the follow up period compared with 22 patients in the alcoholic group. Survival...

  19. Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Petta, Salvatore; Marrone, Oreste; Torres, Daniele; Buttacavoli, Maria; Cammà, Calogero; Di Marco, Vito; Licata, Anna; Lo Bue, Anna; Parrinello, Gaspare; Pinto, Antonio; Salvaggio, Adriana; Tuttolomondo, Antonino; Craxì, Antonio; Bonsignore, Maria Rosaria

    2015-01-01

    Background/Aims We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes. Methods Consecutive patients (n = 126) with chronically elevated ALT and NAFLD underwent STOP-BANG questionnaire to estimate OSA risk and ultrasonographic carotid assessment. In patients accepting to perform cardiorespiratory polygraphy (PG, n = 50), OSA was defined as an apnea/hypopnea index ≥5. A carotid atherosclerotic plaque was defined as a focal thickening >1.3 mm. Results Prevalence of high OSA risk was similar in patients refusing or accepting PG (76% vs 68%, p = 0.17). Among those accepting PG, overall OSA prevalence was significantly higher in patients with F2-F4 fibrosis compared to those without (72% vs 44%; p = 0.04). Significant fibrosis was independently associated with mean nocturnal oxygen saturation (SaO2)1 (OR 6.30, 95%C.I. 1.02–12.3; p = 0.01). Conclusions In NAFLD patients with chronically elevated ALT at low prevalence of morbid obesity, OSA was highly prevalent and indexes of SaO2 resulted independently associated with severity of liver fibrosis and carotid atherosclerosis. These data suggest to consider sleep disordered breathing as a potential additional therapeutic target in severe NAFLD patients. PMID:26672595

  20. Imaging biomarkers for steatohepatitis and fibrosis detection in non-alcoholic fatty liver disease

    Science.gov (United States)

    Gallego-Durán, Rocío; Cerro-Salido, Pablo; Gomez-Gonzalez, Emilio; Pareja, María Jesús; Ampuero, Javier; Rico, María Carmen; Aznar, Rafael; Vilar-Gomez, Eduardo; Bugianesi, Elisabetta; Crespo, Javier; González-Sánchez, Francisco José; Aparcero, Reyes; Moreno, Inmaculada; Soto, Susana; Arias-Loste, María Teresa; Abad, Javier; Ranchal, Isidora; Andrade, Raúl Jesús; Calleja, Jose Luis; Pastrana, Miguel; Iacono, Oreste Lo; Romero-Gómez, Manuel

    2016-01-01

    There is a need, in NAFLD management, to develop non-invasive methods to detect steatohepatitis (NASH) and to predict advanced fibrosis stages. We evaluated a tool based on optical analysis of liver magnetic resonance images (MRI) as biomarkers for NASH and fibrosis detection by investigating patients with biopsy-proven NAFLD who underwent magnetic resonance (MR) protocols using 1.5T General Electric (GE) or Philips devices. Two imaging biomarkers (NASHMRI and FibroMRI) were developed, standardised and validated using area under the receiver operating characteristic curve (AUROC) analysis. The results indicated NASHMRI diagnostic accuracy for steatohepatitis detection was 0.83 (95% CI: 0.73–0.93) and FibroMRI diagnostic accuracy for significant fibrosis determination was 0.85 (95% CI: 0.77–0.94). These findings were independent of the MR system used. We conclude that optical analysis of MRI has high potential to define non-invasive imaging biomarkers for the detection of steatohepatitis (NASHMRI) and the prediction of significant fibrosis (FibroMRI) in NAFLD patients. PMID:27514671

  1. Low-ω3 Fatty Acid and Soy Protein Attenuate Alcohol-Induced Fatty Liver and Injury by Regulating the Opposing Lipid Oxidation and Lipogenic Signaling Pathways

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    Karina Reyes-Gordillo

    2016-01-01

    Full Text Available Chronic ethanol-induced downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1β affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-ω3 fatty acid (Low-ω3FA that primarily regulates PGC1α and soy protein (SP that seems to have its major regulatory effect on PGC1β were evaluated for their protective effects against ethanol-induced hepatosteatosis in rats fed with Lieber-deCarli control or ethanol liquid diets with high or low ω3FA fish oil and soy protein. Low-ω3FA and SP opposed the actions of chronic ethanol by reducing serum and liver lipids with concomitant decreased fatty liver. They also prevented the downregulation of hepatic Sirtuin 1 (SIRT1 and PGC1α and their target fatty acid oxidation pathway genes and attenuated the upregulation of hepatic PGC1β and sterol regulatory element-binding protein 1c (SREBP1c and their target lipogenic pathway genes via the phosphorylation of 5′ adenosine monophosphate-activated protein kinase (AMPK. Thus, these two novel modulators attenuate ethanol-induced hepatosteatosis and consequent liver injury potentially by regulating the two opposing lipid oxidation and lipogenic pathways.

  2. AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease

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    Trerotoli Paolo

    2008-07-01

    Full Text Available Abstract Background The incidence and mortality of hepatocellular cancer (HCC complicating alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD is rising in western societies. Despite knowing the at risk populations for HCC development, the lack of sensitive and specific means of surveillance hampers disease detection at curable stages. The most widely used serum HCC marker is alpha-fetoprotein (AFP, while PIVKA-II, glypican-3 (GP3 and Squamous Cell Carcinoma Antigen -1 (SCCA-1 have been proposed as new biomarkers. Assessment of these HCC biomarkers has largely been performed in patients with viral hepatitis. We conducted a cross sectional study assessing the value of these serum proteins, as well a novel candidate biomarker -follistatin – in patients with HCC arising on a background of ALD or NAFLD. Methods Pre-treatment serum samples from 50 patients with HCC arising on a background of ALD (n = 31 or NAFLD (n = 19 were assessed by specific ELISA assay for PIVKAII, Glypican-3, SCCA-1 and Follistatin. Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n = 41. The diagnostic accuracy of each of the candidate biomarkers was evaluated using receiver operating characteristic (ROC curve analysis, reporting the area under the curve (AUC and its 95% confidence interval (CI. Performance was compared to that of the established biomarker, AFP. Results Serum levels of all proteins were assessed by specific ELISA assays. GP3, SCCA-1 and follistatin had no HCC surveillance benefit in these patients. AFP and PIVKAII were superior to the other markers, particularly in combination. Conclusion We conclude that while novel means of surveillance are urgently required, the combination of AFP and PIVKAII for HCC is an improvement on AFP alone in ALD/NAFLD patients. Furthermore, our data in this homogenous subset of patients- particularly that confirming no role for SCCA-1 – suggests

  3. Effect of insulin-sensitizing agents in combination with ezetimibe, and valsartan in rats with non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Nimer Assy; Masha Grozovski; Ilana Bersudsky; Sergio Szvalb; Osamah Hussein

    2006-01-01

    AIM: To assess whether treatment with insulinsensitizing agents (ISAs) in combination with ezetimibe and valsartan have greater effect on hepatic fat content and lipid peroxidation compared to monotherapy in the methionine choline-deficient diet (MCDD) rat model of non-alcoholic fatty liver disease (NAFLD).METHODS: Rats (n = 6 per group) were treated with different drugs, including MCDD only, MCDD diet with either metformin (200 mg/kg), rosiglitazone (3 mg/kg),metformin plus rosiglitazone (M+R), ezetimibe (2 mg/kg), valsartan (2 mg/kg), or combination of all drugs for a total of 15 wk. Liver histology, lipids, parameters of oxidative stress and TNF-alpha were measured.RESULTS: Fatty liver (FL) rats demonstrated severe hepatic fatty infiltration (> 91% fat), with an increase in hepatic TG (+1263%, P < 0.001), hepatic cholesterol (+245%, P < 0.03), hepatic MDA levels (+225%, P <0.001), serum TNF-alpha (17.8 ± 10 vs 7.8 ± 0.0, P < 0.001), but a decrease in hepatic alpha tocopherol (-74%, P < 0.001) as compared to the control rats.Combination therapy with all drugs produced a significant decrease in liver steatosis (-54%), hepatic TG (-64%), hepatic cholesterol (-31%) and hepatic MDA (-70%), but increased hepatic alpha tocopherol (+443%)as compared to FL rats. Combination therapy with ISA alone produced a smaller decrease in liver steatosis (-32% vs -54%, P < 0.001) and in hepatic MDA levels (-55% vs -70%, P < 0.01), but a similar decrease in hepatic lipids when compared with the all drugs combination.TNF-alpha levels decreased significantly in all treatment groups except in ISA group.CONCLUSION: Combination therapies have a greater effect on liver fat content as compared to monotherapy.Rosiglitazone appears to improve hepatic steatosis to a greater extent than metformin.

  4. Associations between Methylenetetrahydrofolate Reductase (MTHFR Polymorphisms and Non-Alcoholic Fatty Liver Disease (NAFLD Risk: A Meta-Analysis.

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    Man-Yi Sun

    Full Text Available C677T and A1298C are the most common allelic variants of Methylenetetrahydrofolate Reductase (MTHFR gene. The association between MTHFR polymorphisms and the occurrence of non-alcoholic fatty liver disease (NAFLD remains controversial. This study was thus performed to examine whether MTHFR mutations are associated with the susceptibility to NAFLD.A first meta-analysis on the association between the MTHFR polymorphisms and NAFLD risks was carried out via Review Manager 5.0 and Stata/SE 12.0 software. The on-line databases, such as PubMed, EMBASE, CENTRAL, WOS, Scopus and EBSCOhost (updated to April 1st, 2016, were searched for eligible case-control studies. The odd radio (OR, 95% confidence interval (CI and P value were calculated through Mantel-Haenszel statistics under random- or fixed-effect model.Eight articles (785 cases and 1188 controls contributed data to the current meta-analysis. For C677T, increased NAFLD risks were observed in case group under homozygote model (T/T vs C/C, OR = 1.49, 95% CI = 1.03~2.15, P = 0.04 and recessive model (T/T vs C/C+C/T, OR = 1.42, 95% CI = 1.07~1.88, P = 0.02, but not the other genetics models, compared with control group. For A1298C, significantly increased NAFLD risks were detected in allele model (C vs A, OR = 1.53, 95% CI = 1.13~2.07, P = 0.006, homozygote model (C/C vs A/A, OR = 2.81, 95% CI = 1.63~4.85, P = 0.0002, dominant model (A/C+C/C vs A/A, OR = 1.60, 95% CI = 1.06~2.41, P = 0.03 and recessive model (C/C vs A/A+A/C, OR = 2.08, 95% CI = 1.45~3.00, P<0.0001, but not heterozygote model.T/T genotype of MTHFR C677T polymorphism and C/C genotype of MTHFR A1298C are more likely to be associated with the susceptibility to NAFLD.

  5. miR-21 regulates triglyceride and cholesterol metabolism in non-alcoholic fatty liver disease by targeting HMGCR.

    Science.gov (United States)

    Sun, Chuanzheng; Huang, Feizhou; Liu, Xunyang; Xiao, Xuefei; Yang, Mingshi; Hu, Gui; Liu, Huaizheng; Liao, Liangkan

    2015-03-01

    Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health issue with a prevalence of 15-30% in Western populations and 6-25% in Asian populations. Certain studies have revealed the alteration of microRNA (miRNA or miR) profiles in NAFLD and it has been suggested that miR-21 is associated with NAFLD. In the present study, we measured the serum levels of miR-21 in patients with NAFLD and also performed in vitro experiments using a cellular model of NAFLD to further investigate the effects of miR-21 on triglyceride and cholesterol metabolism. Furthermore, a novel target through which miR-21 exerts its effects on NAFLD was identified. The results revealed that the serum levels of miR-21 were lower in patients with NAFLD compared with the healthy controls. In addition, 3-hydroxy-3-methylglutaryl-co-enzyme A reductase (HMGCR) expression was increased in the serum of patients with NAFLD both at the mRNA and protein level. To mimic the NAFLD condition in vitro, HepG2 cells were treated with palmitic acid (PA) and oleic acid (OA). Consistent with the results obtained in the in vivo experiments, the expression levels of miR-21 were decreased and those of HMGCR were increased in the in vitro model of NAFLD. Luciferase reporter assay revealed that HMGCR was a direct target of miR-21 and that miR-21 exerted an effect on both HMGCR transcript degradation and protein translation. Furthermore, the results from the in vitro experiments revealed that miR-21 decreased the levels of triglycerides (TG), free cholesterol (FC) and total cholesterol (TC) in the PA/OA-treated HepG2 cells and that this effect was attenuated by HMGCR overexpression. Taken together, to the best of our knowledge, the present study is the first to report that miR-21 regulates triglyceride and cholesterol metabolism in an in vitro model of NAFLD, and that this effect is achieved by the inhibition of HMGCR expression. We speculate that miR-21 may be a useful biomarker for the diagnosis and

  6. PREVALENCE OF NON-ALCOHOLIC FATTY LIVER DISEASE IN WOMEN WITH POLYCYSTIC OVARY SYNDROME AND ITS CORRELATION WITH METABOLIC SYNDROME

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    Mariana Drechmer ROMANOWSKI

    2015-06-01

    Full Text Available Background The polycystic ovary syndrome (PCOS is one of the most common endocrine disorders in women at childbearing age. Metabolic syndrome is present from 28% to 46% of patients with PCOS. Non-alcoholic fatty liver disease (NAFLD is considered the hepatic expression of metabolic syndrome. There are few published studies that correlate PCOS and NAFLD. Objective To determine the prevalence of NAFLD and metabolic syndrome in patients with PCOS, and to verify if there is a correlation between NAFLD and metabolic syndrome in this population. Methods Study developed at Gynecology Department of Clinical Hospital of Federal University of Parana (UFPR. The sessions were conducted from April 2008 to January 2009. One hundred and thirty-one patients joined the analysis; 101 were diagnosed with PCOS and 30 formed the control group. We subdivided the PCOS patients into two subgroups: PCOS+NAFLD and PCOS. All the patients were submitted to hepatic sonography. For hepatoestheatosis screening, hepatic ecotexture was compared do spleen’s. For diagnosis of metabolic syndrome, we adopted the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III criteria, as well as the criteria proposed by International Diabetes Federation. Statistical analysis were performed with t of student and U of Mann-Whitney test for means and chi square for proportions. Results At PCOS group, NAFLD was present in 23.8% of the population. At control group, it represented 3.3%, with statistical significance (P=0.01. Metabolic syndrome, by NCEP/ATP III criteria, was diagnosed in 32.7% of the women with PCOS and in 26.6% of the women at control group (no statistical difference, P=0.5. At PCOS+DHGNA subgroup, age, weight, BMI, abdominal circumference and glucose tolerance test results were higher when compared to PCOS group (P<0.01. Metabolic syndrome by NCEP/ATPIII criteria was present in 75% and by International Diabetes Federation criteria in 95.8% of women with

  7. Circulating miRNA in patients with non-alcoholic fatty liver disease and coronary artery disease

    Science.gov (United States)

    Mehta, Rohini; Otgonsuren, Munkzhul; Younoszai, Zahra; Allawi, Hussain; Raybuck, Bryan; Younossi, Zobair

    2016-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and coronary artery disease (CAD) is the cardiac manifestation of metabolic syndrome. NAFLD is strongly linked to CAD and hepatic steatosis is an independent risk factor for CAD and cardiac mortality. The pathogenic mechanism underlying this association remains poorly understood. In this study, we explored expression of circulating microRNAs (miRNAs) in patients with NAFLD and associated CAD. Results When compared to patients with NAFLD without CAD, patients with NAFLD and CAD had lower circulating levels of miR-132 (0.24±0.16 vs 0.30±0.11, p=0.03), while the circulating levels of miR-143 were higher (0.96±0.90 vs 0.64±0.77, p=0.02). The levels in circulation demonstrated trends opposite to previously observed intracellular levels in patients with CAD. In obese patients with NAFLD, lower circulating levels of miR-145 (1.42±1.00 vs 2.41±1.80), miR-211 (41.26±20.40 vs 57.56±25.45), miR-146a (2.13±1.40 vs 2.90±1.36) and miR-30c (6.92±4.99 vs 11.0±6.92) were detected when compared to lean patients with NAFLD. For miR-161 (0.59±1.19 vs 0.15±0.14) and miR-241 (0.28±0.29 vs 0.16±0.13), higher circulatory levels were detected in the obese patients with NAFLD. These observations suggest altered circulating levels of miRNAs that may serve to balance intracellular levels of miRNA in target tissues. Additional studies examining paired samples of target and producing tissues as well as respective plasma samples will help delineate the regulatory circuits governing the secretion and the uptake of miRNA in multitissue diseases. PMID:27493762

  8. Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Sulin Cheng

    Full Text Available Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49 and women (n = 52 with and without NAFLD.Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS. Serum samples were analyzed using a nuclear magnetic resonance (NMR metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot.Increased branched-chain amino acid (BCAA, aromatic amino acid (AAA and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all. Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all, whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all.Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.

  9. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2005-01-01

    Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease.......Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease....

  10. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Fede, Giuseppe; Germani, Giacomo; Gluud, Christian;

    2011-01-01

    Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease.......Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease....

  11. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2002-01-01

    Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease.......Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease....

  12. Serum dipeptidyl peptidase-4 activity in insulin resistant patients with non-alcoholic fatty liver disease: a novel liver disease biomarker.

    Directory of Open Access Journals (Sweden)

    Gábor Firneisz

    Full Text Available BACKGROUND: In a cross-sectional study we studied the fasting serum DPP-4 enzymatic activity (sDPP-4 and the insulin resistance index (HOMA2-IR in gliptin naïve patients with type 2 diabetes and in non-alcoholic fatty liver disease (NAFLD and in healthy controls (CNTRL. METHODS AND FINDINGS: sDPP-4 was measured by kinetic assay in 39 NAFLD (F/M:19/20, mean age: 47.42 yrs and 82 type 2 diabetes (F/M:48/34, 62.8 yrs patients and 26 (F/M:14/12, 35.3 yrs controls. Definition of T2D group as patients with type 2 diabetes but without clinically obvious liver disease created non-overlapping study groups. Diagnosis of NAFLD was based on ultrasonography and the exclusion of other etiololgy. Patients in T2D and NAFLD groups were similarly obese. 75 g CH OGTT in 39 NAFLD patients: 24-NGT, 4-IGT or IFG ("prediabetes", 11-type 2 diabetes. HOMA2-IR: CNTRL: 1.44; T2D-group: 2.62 (p = 0.046 vs CNTRL, parametric tests; NAFLD(NGTonly: 3.23 (p = 0.0013 vs CNTRL; NAFLD(IFG/IGT/type 2 diabetes: 3.82 (p<0.001 vs CNTRL, p = 0.049 vs 2TD group. sDPP-4 activity was higher in NAFLD both with NGT (mean:33.08U/L and abnormal glucose metabolism (30.38U/L than in CNTRL (25.89U/L, p<0.001 and p = 0.013 or in T2D groups (23.97U/L, p<0.001 and p = 0.004. Correlations in NAFLD among sDPP-4 and ALT: r = 0.4637,p = 0.0038 and gammaGT: r = 0.4991,p = 0.0017 and HOMA2-IR: r = 0.5295,p = 0.0026 and among HOMA2-IR and ALT: r = 0.4340,p = 0.0147 and gammaGT: r = 0.4128,p = 0.0210. CONCLUSIONS: The fasting serum DPP-4 activity was not increased in T2D provided that patients with liver disease were intentionally excluded. The high serum DPP-4 activities in NAFLD were correlated with liver tests but not with the fasting plasma glucose or HbA1C supporting that the excess is of hepatic origin and it might contribute to the speedup of metabolic deterioration. The correlation among gammaGT, ALT and serum DPP-4 activity and also between serum DPP-4 activity and HOMA2-IR in NAFLD strongly

  13. Acute fatty liver in pregnancy.

    NARCIS (Netherlands)

    Tan, A.; Krieken, J.H.J.M. van; Peters, W.H.M.; Steegers, E.A.P.

    2002-01-01

    When confronted with liver abnormalities during the third trimester of pregnancy, one should consider acute fatty liver of pregnancy. The differential diagnosis with (pre-)eclampsia and HELLP syndrome is sometimes difficult. In these cases a liver biopsy is helpful though rarely performed during pre

  14. The metabolism of fatty alcohols in lipid nanoparticles by alcohol dehydrogenase.

    Science.gov (United States)

    Dong, X; Mumper, R J

    2006-09-01

    Fatty alcohols are commonly used in lipid-based drug delivery systems including parenteral emulsions and solid lipid nanoparticles (NPs). The purpose of these studies was to determine whether horse liver alcohol dehydrogenase (HLADH), a NAD-dependent enzyme, could metabolize the fatty alcohols within the NPs and thus serve as a mechanism to degrade these NPs in the body. Solid nanoparticles (endogenous alcohol dehydrogenase enzyme systems.

  15. Non-alcoholic fatty liver disease: From insulin resistance to mitochondrial dysfunction Enfermedad grasa del hígado no alcohólica: Desde la resistencia a la insulina a la disfunción mitocondrial

    Directory of Open Access Journals (Sweden)

    J. A. Solís Herruzo

    2006-11-01

    Full Text Available Non-alcoholic fatty liver disease represents a set of liver lesions similar to those induced by alcohol that develop in individuals with no alcohol abuse. When lesions consist of fatty and hydropic degeneration, inflammation, and eventually fibrosis, the condition is designated non-alcoholic steatohepatitis (NASH. The pathogenesis of these lesions is not clearly understood, but they are associated with insulin resistance in most cases. As a result, abdominal fat tissue lipolysis and excessive fatty acid uptake by the liver occur. This, together with a disturbance of triglyceride export as VLDL, results in fatty liver development. Both the inflammatory and hepatocellular degenerative components of NASH are attributed to oxidative stress. Mitochondrial respiratory chain loss of activity plays a critical role in the genesis of latter stress. This may be initiated by an increase in the hepatic TNFa, iNOS induction, peroxynitrite formation, tyrosine nitration and inactivation of enzymes making up this chain. Consequences of oxidative stress include: lipid peroxidation in cell membranes, stellate cell activation in the liver, liver fibrosis, chronic inflammation, and apoptosis.

  16. The epidemiology, pathogenesis and histopathology of fatty liver disease.

    Science.gov (United States)

    Levene, Adam P; Goldin, Robert D

    2012-08-01

    Fatty liver disease includes non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), each of which is increasing in prevalence. Each represents a histological spectrum that extends from isolated steatosis to steatohepatitis and cirrhosis. NAFLD is associated with obesity, diabetes, and insulin resistance, and is considered to be the liver manifestation of the metabolic syndrome. The pathogenesis of NAFLD and ALD involves cytokines, adipokines, oxidative stress, and apoptosis. Histopathology is the gold standard for assessing the severity of liver damage in NAFLD and ALD. We have reviewed the literature, and described and compared the epidemiology, natural disease history, pathogenesis and histopathology of NAFLD and ALD.

  17. [State of intestinal microbiota in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease].

    Science.gov (United States)

    Lytvynenko, K O; Bodnar, P M; Lysiana, T O; Ponomar'ova, I H; Koval'chuk, O A

    2014-01-01

    High prevalence of type 2 diabetes mellitus (DM) and nonalcoholic fatty liver disease (NAFLD) contributes to the intensification of scientific research the aim of which is to improve existing treatment. It is given the data about the state of intestinal microbiota in 64 patients with type 2 DM and NAFLD, 26 patients with type 2 DM and 28--with NAFLD. The research revealed significant changes in microbiota composition in patients with type 2 DM combined with NAFLD. Decompensated dysbiosis was registered in 71.9% of patients in this group which manifested in increased quantitative indicators of transient microflora crop with pathogenic characteristics and lack of microflora with protective characteristics.

  18. A study on the relationship between alcohol drinking and fatty liver%饮酒与脂肪肝的关系研究

    Institute of Scientific and Technical Information of China (English)

    朱方超; 黄春伟; 潘达

    2015-01-01

    目的:探讨不同酒精摄入量对脂肪肝发生率及其危险因素高血糖、高血脂等代谢紊乱的影响。方法选取2013年10—12月期间温州市中心医院体检中心394名体检人员进行问卷调查,并进行人体学和实验室指标测量作分析。结果经 LSD -t 检验,甘油三酯随着饮酒量增加而升高(P <0.05);高甘油三酯、高尿酸、高胆固醇在不同饮酒量组间的检出率差异有统计学意义(P 均<0.05),经卡方线性趋势检验显示,高甘油三酯及高尿酸患病率随着酒精摄入量增加而升高(P 均<0.05)。饮酒量在脂肪肝和非脂肪肝的分布差异无统计学意义(P >0.05)。二项分类变量 Logistic 回归分析显示,腰臀比超标、高血压、超重肥胖、高甘油三酯血症为脂肪肝的独立危险因素,但未见“日均饮酒量”是脂肪肝的独立危险因素。结论腰臀比超标、高血压、超重肥胖、高甘油三酯血症是脂肪肝的危险因素,饮酒虽可导致高甘油三酯、高尿酸患病率升高,但未发现饮酒对脂肪肝患病率的直接影响。%Objective To explore the relationship between alcohol drinking and fatty liver disease and its influencing factors.Methods From October to December,2013,a total of 394 people who underwent a physical examination in the medical examination center of Wenzhou central hospital were selected for this study.Anthroposomatology measurement and biochemical tests were conducted.Results There were significantly statistical differences of triglyceride,uric acid and cholesterol in different drinking groups (P <0.05).The prevalence of high triglyceride and uric acid were increased with alcohol consumption (P <0.05).There was no significant difference of alcohol consumption between fatty liver and non -fatty liver group (P =0.42).Logistic regression showed that waist -hip ratio,hypertension,overweight,obesity and hypertriglyceridemia were risk

  19. Diagnostic value of serum prolidase enzyme activity to predict the liver histological lesions in non-alcoholic fatty liver disease: a surrogate marker to distinguish steatohepatitis from simple steatosis.

    Science.gov (United States)

    Kayadibi, Huseyin; Gültepe, Mustafa; Yasar, Bulent; Ince, Ali T; Ozcan, Omer; Ipcioglu, Osman M; Kurdas, Oya O; Bolat, Burhanettin; Benek, Yusuf Z; Guveli, Hakan; Atalay, Sacide; Ozkara, Selvinaz; Keskin, Ozcan

    2009-08-01

    Determination of the liver histological lesions with noninvasive tests is an important part of the diagnostic work-up of patients with non-alcoholic fatty liver disease (NAFLD). We aimed to determine the predictive value of noninvasive biochemical markers, serum prolidase enzyme activity (SPEA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and AST/ALT ratio for the liver histological lesions. Fifty-four liver biopsy-proven patients with NAFLD and 37 healthy controls were enrolled to the study. The diagnostic accuracies of biochemical markers were evaluated by receiver operating characteristic (ROC) curves and multiple linear regression analysis to predict the degree of fatty infiltration, lobular inflammation, NAFLD activity score, and stage of fibrosis. The SPEA of patients with steatohepatitis is significantly increased compared with the patients with simple steatosis and controls (1,338 [1,138-1,624] U/l; 974 [768-1,160] U/l; 972 [862-1,122] U/l, shown as median [25th-75th interquartile range], respectively, P steatohepatitis from simple steatosis according to the ROC analysis (area under the curve [AUC]: 0.85). Multivariate analysis revealed that the most useful single test for predicting lobular inflammation, NAFLD activity score, and fibrosis was SPEA, and for predicting the fatty infiltration, it was ALT (P steatohepatitis from simple steatosis and reducing the need for liver biopsy in the majority of patients with NAFLD.

  20. Reduction of obesity-associated white adipose tissue inflammation by rosiglitazone is associated with reduced non-alcoholic fatty liver disease in LDLr-deficient mice

    Science.gov (United States)

    Mulder, Petra; Morrison, Martine C.; Verschuren, Lars; Liang, Wen; van Bockel, J. Hajo; Kooistra, Teake; Wielinga, Peter Y.; Kleemann, Robert

    2016-01-01

    Obesity is associated with chronic low-grade inflammation that drives the development of metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). We recently showed that white adipose tissue (WAT) constitutes an important source of inflammatory factors. Hence, interventions that attenuate WAT inflammation may reduce NAFLD development. Male LDLr−/− mice were fed a high-fat diet (HFD) for 9 weeks followed by 7 weeks of HFD with or without rosiglitazone. Effects on WAT inflammation and NAFLD development were analyzed using biochemical and (immuno)histochemical techniques, combined with gene expression analyses. Nine weeks of HFD feeding induced obesity and WAT inflammation, which progressed gradually until the end of the study. Rosiglitazone fully blocked progression of WAT inflammation and activated PPARγ significantly in WAT. Rosiglitazone intervention did not activate PPARγ in liver, but improved liver histology and counteracted the expression of genes associated with severe NAFLD in humans. Rosiglitazone reduced expression of pro-inflammatory factors in WAT (TNF-α, leptin) and increased expression of adiponectin, which was reflected in plasma. Furthermore, rosiglitazone lowered circulating levels of pro-inflammatory saturated fatty acids. Together, these observations provide a rationale for the observed indirect hepatoprotective effects and suggest that WAT represents a promising therapeutic target for the treatment of obesity-associated NAFLD. PMID:27545964

  1. Nutritional Strategies for the Individualized Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) Based on the Nutrient-Induced Insulin Output Ratio (NIOR)

    Science.gov (United States)

    Stachowska, Ewa; Ryterska, Karina; Maciejewska, Dominika; Banaszczak, Marcin; Milkiewicz, Piotr; Milkiewicz, Małgorzata; Gutowska, Izabela; Ossowski, Piotr; Kaczorowska, Małgorzata; Jamioł-Milc, Dominika; Sabinicz, Anna; Napierała, Małgorzata; Wądołowska, Lidia; Raszeja-Wyszomirska, Joanna

    2016-01-01

    Nutrients play a fundamental role as regulators of the activity of enzymes involved in liver metabolism. In the general population, the action of nutrients may be affected by gene polymorphisms. Therefore, individualization of a diet for individuals with fatty liver seems to be a fundamental step in nutritional strategies. In this study, we tested the nutrient-induced insulin output ratio (NIOR), which is used to identify the correlation between the variants of genes and insulin resistance. We enrolled 171 patients, Caucasian men (n = 104) and women (n = 67), diagnosed with non-alcoholic fatty liver disease (NAFLD). From the pool of genes sensitive to nutrient content, we selected genes characterized by a strong response to the NIOR. The polymorphisms included Adrenergic receptor (b3AR), Tumor necrosis factor (TNFα), Apolipoprotein C (Apo C III). Uncoupling Protein type I (UCP-1), Peroxisome proliferator activated receptor γ2 (PPAR-2) and Apolipoprotein E (APOEs). We performed three dietary interventions: a diet consistent with the results of genotyping (NIOR (+)); typical dietary recommendations for NAFLD (Cust (+)), and a diet opposite to the genotyping results (NIOR (−) and Cust (−)). We administered the diet for six months. The most beneficial changes were observed among fat-sensitive patients who were treated with the NIOR (+) diet. These changes included improvements in body mass and insulin sensitivity and normalization of blood lipids. In people sensitive to fat, the NIOR seems to be a useful tool for determining specific strategies for the treatment of NAFLD. PMID:27455252

  2. Oral administration of S-nitroso-N-acetylcysteine prevents the onset of non alcoholic fatty liver disease in rats

    Institute of Scientific and Technical Information of China (English)

    Claudia PMS de Oliveira; Marcelo G de Oliveira; Fernanda I Simplicio; Vicência MR de Lima; Katia Yuahasi; Fabio P Lopasso; Ven(a)ncio AF Alves; Dulcinéia SP Abdalla; Flair J Carrilho; Francisco RM Laurindo

    2006-01-01

    AIM: To evaluate the potential of S-nitroso-N-acetylcysteine (SNAC) in inhibition of lipid peroxidation and the effect of oral SNAC administration in the prevention of nonalcoholic fatty liver disease (NAFLD) in an animal model.METHODS: NAFLD was induced in Wistar male rats by choline-deficient diet for 4 wk. SNAC-treated animals (n=6) (1.4 mg/kg/day of SNAC, orally) were compared to 2 control groups: one (n=6) received PBS solution and the other (n=6) received NAC solution (7 mg/kg/d).Histological variables were semiquantitated with respect to macro and microvacuolar fat changes, its zonal distribution, foci of necrosis, portal and perivenular fibrosis, and inflammatory infiltrate with zonal distribution.LOOHs from samples of liver homogenates were quantified by HPLC. Nitrate levels in plasma of portal vein were assessed by chemiluminescence. Aqueous low-density lipoprotein (LDL) suspensions (200 μg protein/mL) were incubated with CuCl2 (300 μmol/L) in the absence and presence of SNAC (300 μmol/L) for 15 h at 37 ℃. Extent of LDL oxidation was assessed by fluorimetry. Linoleic acid (LA) (18.8 μmol/L) oxidation was induced by soybean lipoxygenase (SLO) (0.056 μmol/L) at 37 ℃ in the presence and absence of N-acetylcysteine (NAC) and SNAC (56 and 560 μmol/L) and monitored at 234 nm.RESULTS: Animals in the control group developed moderate macro and microvesicular fatty changes in periportal area. SNAC-treated animals displayed only discrete histological alterations with absence of fatty changes and did not develop liver steatosis. The absence of NAFLD in the SNAC-treated group was positively correlated with a decrease in the concentration of LOOH in liver homogenate, compared to the control group (0.7±0.2 nmol/mg vs 3.2±0.4 nmol/mg protein, respectively, P<0.05), while serum levels of aminotransferases were unaltered. The ability of SNAC in preventing lipid peroxidation was confirmed in in vitro experiments using LA and LDL as model substrates

  3. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008310 Expression of αVβ3 integrin and platelet-endothelial cell adhesion molecule-1 in progressive liver fibrosis: experiment with rats. SONG Zhengji(宋正已), et al. Dept Gastroenterol, Zhongshan Hosp, Fudan Univ, Shanghai 200032. Natl Med J China 2008;88(16):1121-1125.Objective To investigate the expression ofαVβ3 integrin and platelet endothelial cell adhesion molecule-1(CD31)in progressive liver fibrosis of rats.Methods Sixty-four SD rats were randomly divided into 4 equal groups:TAA group,undergoing peritoneal injection of

  4. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970345 An experimental and clinical study on α1-adrenergic receptor of liver plasma membranes in cir-rhosis with portal hypertension. ZHANG Youcheng(张有成), et al. Dept Surg, People’s Hosp, Beijing MedUniv, Beijing, 100044 Chin J Dig 1996; 16(6): 332-335.

  5. Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice.

    Science.gov (United States)

    Rodríguez, Amaia; Moreno, Natalia R; Balaguer, Inmaculada; Méndez-Giménez, Leire; Becerril, Sara; Catalán, Victoria; Gómez-Ambrosi, Javier; Portincasa, Piero; Calamita, Giuseppe; Soveral, Graça; Malagón, María M; Frühbeck, Gema

    2015-07-10

    Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4-weeks) was associated with improved body weight, whole-body adiposity, and hepatosteatosis of ob/ob mice and to a down-regulation of AQP3, AQP7 in WAT and an up-regulation of hepatic AQP9. Acute leptin stimulation in vitro (4-h) induced the mobilization of aquaglyceroporins towards lipid droplets (AQP3) and the plasma membrane (AQP7) in murine adipocytes. Our results show that leptin restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, a step which might prevent lipid overaccumulation in WAT and liver in obesity.

  6. Evaluation of tissue metal and trace element content in a rat model of non-alcoholic fatty liver disease using ICP-DRC-MS.

    Science.gov (United States)

    Gatiatulina, Eugenia R; Popova, Elizaveta V; Polyakova, Valentina S; Skalnaya, Anastasia A; Agletdinov, Eduard F; Nikonorov, Alexandr A; Skalny, Anatoly V; Tinkov, Alexey A

    2017-01-01

    The primary objective of the study was to assess the level of metals and trace elements in liver, serum, and hair of rats with diet-induced non-alcoholic fatty liver disease (NAFLD) using inductively coupled plasma dynamic reaction cell mass spectrometer (ICP-DRC-MS). 56 female 3-months-old Wistar rats divided into two equal groups were fed either standard (10% calories from fat) or high-fat high-carbohydrate diet (60% calories from fat in chow and 10% sucrose solution) for 6 weeks. Serum was examined for insulin resistance markers, lipid profile, and alanine aminotransferase (ALT) activity. Liver histology was assessed after hematoxylin and eosin staining. Metal and trace element concentrations were assessed by means of ICP-DRC-MS. Overfed animals were characterized by higher values of morphometric parameters. Liver examination revealed large and small droplet steatosis, hepatocyte ballooning and necrosis, being characteristic for NAFLD. Animals with NAFLD were characterized by insulin resistance, atherogenic changes of lipid profile and increased ALT activity. Significantly decreased hepatic Co, Cu, I, Li, Mn, Se, Zn levels were observed in rats with NAFLD. At the same time, only hepatic Mn and Se levels remained decreased after adjustment for total protein. Overfed animals were characterized by significantly lower I, Li, and Mn levels in blood serum, whereas concentration of Co, Se, V, and Sr exceeded the control values. In general, the results of the study demonstrate that NAFLD significantly affects metal and trace element status in experimental animals.

  7. Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    E Louise Thomas; Audrey E Brynes; Gavin Hamilton; Nayna Patel; Adam Spong; Robert D Goldin; Gary Frost; Jimmy D Bell; Simon D Taylor-Robinson

    2006-01-01

    AIM: To assess the effectiveness of the current UK clinical practice in reducing hepatic fat (IHCL).METHODS: Whole body MRI and 1H MRS were obtained, before and after 6 mo nutritional counselling,from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease (NAFLD).RESULTS: A 500 Kcal-restricted diet resulted in an average weight loss of 4% (-3.4 kg,) accompanied by significant reductions in most adipose tissue (AT)depots, including subcutaneous (-9.9%), abdominal subcutaneous (-10.2%) and intra-abdominalAT (-11.4%). Intramyocellular lipids (IMCL) were significantly reduced in the tibialis muscle (-28.2%).Decreases in both IHCL (-39.9%) and soleus IMCL (-12.2%) content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests: serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT,but not with changes in IHCL.CONCLUSION: This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LFTs.

  8. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930137 Effects of selective and non-selectiveβ-adrenoreceptor blockers on portal hemody-namics in patients with liver cirrhosis.HUANGTianwei(黄天卫),et al.1st Affili Hosp,DalianMed Coll.Chin J Digest 1992;12(3):145-147.Effects of selective(atenolol)and non-selec-tive(propranolol)β-adrenoreceptor blockerson portal hemodynamics in patients with livercirrhosis were measured by pulsed Doppler du-

  9. Alcoholic liver disease: the gut microbiome and liver cross talk.

    Science.gov (United States)

    Hartmann, Phillipp; Seebauer, Caroline T; Schnabl, Bernd

    2015-05-01

    Alcoholic liver disease (ALD) is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with ALD have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier, or preventing cellular responses to microbial products protect from experimental ALD. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of ALD. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship, and consequences for ALD. We also discuss how the liver affects the intestinal microbiota.

  10. miR-212 downregulation contributes to the protective effect of exercise against non-alcoholic fatty liver via targeting FGF-21.

    Science.gov (United States)

    Xiao, Junjie; Bei, Yihua; Liu, Jingqi; Dimitrova-Shumkovska, Jasmina; Kuang, Dapeng; Zhou, Qiulian; Li, Jin; Yang, Yanning; Xiang, Yang; Wang, Fei; Yang, Changqing; Yang, Wenzhuo

    2016-02-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and lifestyle, while exercise is beneficial for NAFLD. Dysregulated microRNAs (miRs) control the pathogenesis of NAFLD. However, whether exercise could prevent NAFLD via targeting microRNA is unknown. In this study, normal or high-fat diet (HF) mice were either subjected to a 16-week running program or kept sedentary. Exercise attenuated liver steatosis in HF mice. MicroRNA array and qRT-PCR demonstrated that miR-212 was overexpressed in HF liver, while reduced by exercise. Next, we investigated the role of miR-212 in lipogenesis using HepG2 cells with/without long-chain fatty acid treatment (± FFA). FFA increased miR-212 in HepG2 cells. Moreover, miR-212 promoted lipogenesis in HepG2 cells (± FFA). Fibroblast growth factor (FGF)-21, a key regulator for lipid metabolism, was negatively regulated by miR-212 at protein level in HepG2 cells. Meanwhile, FFA downregulated FGF-21 both at mRNA and protein levels in HepG2 cells. Also, FGF-21 protein level was reduced in HF liver, while reversed by exercise in vivo. Furthermore, siRNA-FGF-21 abolished the lipogenesis-reducing effect of miR-212 inhibitor in HepG2 cells (± FFA), validating FGF-21 as a target gene of miR-212. These data link the benefit of exercise and miR-212 downregulation in preventing NAFLD via targeting FGF-21.

  11. (S)YS-51, a novel isoquinoline alkaloid, attenuates obesity-associated non-alcoholic fatty liver disease in mice by suppressing lipogenesis, inflammation and coagulation.

    Science.gov (United States)

    Park, Eun Jung; Kim, Young Min; Kim, Hye Jung; Jang, Se-Yun; Oh, Moo Hyun; Lee, Duck-Hyung; Chang, Ki Churl

    2016-10-01

    Obesity-associated non-alcoholic fatty liver disease (NAFLD) increases coagulation and inflammation. We hypothesized that (S)YS-51, an agent found to be beneficial in animal models of sepsis, may reduce NAFLD in high-fat diet (HFD) mice by reducing coagulation and inflammation. C57BL/6 mice were fed either a chow diet or HFD and each was supplemented with or without (S)YS-51 (10mg/kg, daily, i.p.) for 16 weeks. The results showed that HFD caused significant increases in lipogenesis [CD36, fatty acid synthase (FAS) and sterol response element binding protein (SREBP)-1c mRNA and protein], inflammation [monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-α, intercellular cell adhesion molecule-1 (ICAM-1), TGF-β, and procollagen type 1 mRNA, macrophage infiltration] and coagulation [tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) mRNA and thrombin antithrombin complex (TAT)] in the liver, adipose tissue and serum, which were significantly reduced by (S)YS-51. These results of (S)YS-51 were accompanied by significant reduction of weight gain, liver size, hepatic steatosis and fibrosis, blood cholesterol, hepatic triglyceride, and macrophage infiltration and inflammatory cytokines in adipose tissue without affecting food intake in HFD mice. Interestingly, (S)YS-51 increased SIRT1 mRNA and protein and AMPK expression in the liver of HFD mice by increasing both NAD(+)/NADH ratio and LKB1 phosphorylation. In HepG2 cells, (S)YS-51 activated SIRT1 followed by AMPK. Finally, (S)YS-51 improved glucose tolerance and insulin resistance in HFD mice. We concluded that (S)YS-51 attenuates NAFLD and insulin resistance in HFD mice by, at least, activation of SIRT1/AMPK signals. Thus, (S)YS-51 may be beneficial in NAFLD treatment.

  12. Non-alcoholic Fatty Liver Disease and Metabolic Syndrome-Position Paper of the Indian National Association for the Study of the Liver, Endocrine Society of India, Indian College of Cardiology and Indian Society of Gastroenterology.

    Science.gov (United States)

    Duseja, Ajay; Singh, Shivaram P; Saraswat, Vivek A; Acharya, Subrat K; Chawla, Yogesh K; Chowdhury, Subhankar; Dhiman, Radha K; Jayakumar, Rohinivilasam V; Madan, Kaushal; Misra, Sri P; Mishra, Hrudananda; Modi, Sunil K; Muruganathan, Arumugam; Saboo, Banshi; Sahay, Rakesh; Upadhyay, Rajesh

    2015-03-01

    Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic syndrome. Prevalence of metabolic risk factors including diabetes mellitus, obesity, etc. is rapidly increasing in India putting this population at risk for NAFLD. Patients with NAFLD are at increased risk for liver-related morbidity and mortality and also cardiovascular disease risk and increased incidence of diabetes mellitus on long-term follow-up. Management of patients with NAFLD may require a multi-disciplinary approach involving not only the hepatologists but also the internists, cardiologists, and endocrinologists. This position paper which is a combined effort of the Indian National Association for Study of the Liver (INASL), Endocrine Society of India (ESI), Indian College of Cardiology (ICC) and the Indian Society of Gastroenterology (ISG) defines the spectrum of NAFLD and the association of NAFLD with insulin resistance and metabolic syndrome besides suggesting preferred approaches for the diagnosis and management of patients with NAFLD in the Indian context.

  13. Comparison of Predicted Energy Expenditure in Japanese Patients with Non-Alcoholic Fatty Liver Disease to Establish a Suitable Nutrition Intervention.

    Science.gov (United States)

    Endo, Kei; Kakisaka, Keisuke; Oikawa, Kanta; Endo, Ryujin; Takikawa, Yasuhiro

    2016-01-01

    The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing in Western and Asian countries, including Japan. NAFLD includes the condition of non-alcoholic steatohepatitis, which can progress to end-stage liver disease. Weight reduction based on basal energy expenditure (BEE) is considered to be the only established treatment for patients with NAFLD. However, a formula that is suitable for predicting BEE in Japanese patients with NAFLD remains to be determined. We enrolled 77 Japanese patients who were diagnosed with NAFLD according to histological findings. Their BEE was measured (mBEE) by indirect calorimetry. Physical findings, laboratory data and their predicted BEE (pBEE) values were compared with the mBEE values. All pBEE values were evaluated as a root mean squared error (RMSE) and an accurate estimation. The mBEE values correlated with the patient's weight, skeletal muscle mass, and age. Most of predictive formulae overestimated BEE in NAFLD patients in the present study. In contrast, the Kyoto equation provided an accurate prediction. Most prediction formulae included body weight as a reference of the skeletal muscle mass and were established using data from a healthy study population. However, differences in muscle mass exist among different races, and body composition differs between healthy individuals and those with high BMIs. The improved accuracy of the Kyoto equation is likely due to the similar backgrounds of the patients in the present study. The Kyoto equation is the most suitable formula for estimating BEE in Japanese patients with NAFLD.

  14. Effects of Berberine on Hepatic Sirtuin 1-uncoupling Protein 2 Pathway in Non-alcoholic Fatty Liver Disease Rats Induced by High-fat Diet

    Institute of Scientific and Technical Information of China (English)

    Yuan-jun Deng; Yu-pei Zhang; Qin-he Yang; Li Han; Yin-ji Liang; Yi-fang He; Yuan-yuan Li

    2016-01-01

    Objective To investigate the involvement of sirtuin 1 (SIRT1)-uncoupling protein 2 (UCP2) pathway in the development of non-alcoholic fatty liver disease and whether berberine exerts its effects by regulating this pathway.Methods Male SD rats were divided into three groups:normal control group,high-fat diet group,and berberine supplement group.The rats in the normal control group were given normal diet while the rats in the other two groups were fed with high-fat diet.Rats in the berberine supplement group were concurrently given berberine (100 mg/kg body weight) once daily.After 1 6 weeks,the levels of serum,liver lipids,and serum aminotransferase were measured using an automatic biochemical analyzer.Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the liver were measured using commercial kits.Histopathological changes of liver tissues were observed by hematoxylin and eosin (HE) staining and Oil Red O staining.The hepatic mRNA and protein levels of SIRT1 and UCP2 were assayed by reverse transcription polymerase chain reaction (RT-PCR) or Western blotting.Results Berberine supplement could significantly decrease the serum and liver lipid contents in rats fed with high-fat diet.Meanwhile,SOD level was significantly elevated,but MDA level was reduced in the liver.The results of HE and Oil Red O staining showed that the hepatic steatosis was alleviated in berberine supplement group.Furthermore,berberine induced an increase in SlRT1 expression but a decrease in UCP2 expression.Conclusion The regulation of hepatic SIRT1-UCP2 pathway may be an important mechanism by which berberine exerts the beneficial effects in NAFLD rats.

  15. Effects of the new thiazolidine derivative LPSF/GQ-02 on hepatic lipid metabolism pathways in non-alcoholic fatty liver disease (NAFLD).

    Science.gov (United States)

    Araújo, Shyrlene; Soares E Silva, Amanda; Gomes, Fabiana; Ribeiro, Edlene; Oliveira, Wilma; Oliveira, Amanda; Lima, Ingrid; Lima, Maria do Carmo; Pitta, Ivan; Peixoto, Christina

    2016-10-01

    Non-alcoholic fatty liver disease (NAFLD) is considered the most common manifestation of metabolic syndrome. One of its most important features is the accumulation of triglycerides in the hepatocyte cells. Thiazolidinediones (TZDs) act as insulin sensitizers and are used to treat patients with type 2 diabetes and other conditions that are resistant to insulin, such as hepatic steatosis. Controversially, TZDs are also associated with the development of cardiovascular events and liver problems. For this reason, new therapeutic strategies are necessary to improve liver function in patients with chronic liver diseases. The aim of the present study was to evaluate the effects of LPSF/GQ-02 on the liver lipid metabolism in a murine model of NAFLD. Eighty male LDLR-/- mice were divided into 3 groups: 1-fed with a high-fat diet (HFD); 2-HFD+Pioglitazone (20mg/kg/day); 3-HFD+LPSF/GQ-02 (30mg/kg/day). The experiments lasted 12 weeks and drugs were administered daily by gavage in the final four weeks. The liver was processed for optical microscopy, Oil Red O, immunohistochemistry, immunofluorescence and western blot analysis. LPSF/GQ-02 effectively decreased fat accumulation, increased the hepatic levels of p-AMPK, FoxO1, ATGL, p-ACC and PPARα, and reduced the expression of LXRα, SREBP-1c and ACC. These results suggest that LPSF/GQ-02 acts directly on the hepatic lipid metabolism through the activation of the PPAR-α/AMPK/FoxO1/ATGL lipolytic pathway, and the inhibition of the AMPK/LXR/SREBP-1c/ACC/FAS lipogenic pathway.

  16. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930537 Preliminary report on portal hyperten-tion in liver cirrhosis treated by transjugular in-trahepatic portosystemic stent shunt(analysis of8 cases).XU Ke(徐克),et al.Dept Radiol,lst Hosp,China Med Univ,Shenyang,110001.Chin J Radiol 1993;25(5):294—297.Transjugular intrahepatic portosystemic stentshunt(TIPPS)was performed in 8 cases of livercirrhosis with portal hypertention.Moderate orsevere hemorrhage from gastroesophageal variceshad happened in all patients for 2~5 times beforTIPSS.The average pressure of portal veindropped from 3.80±0.50kPa to 2.58±0.26kPa.The diameter of the shunt established be-tween portal and hepatic veins was 10~12mm.Gastrointestinal bleeding and ascites were effec-

  17. LPSF/GQ-02 inhibits the development of hepatic steatosis and inflammation in a mouse model of non-alcoholic fatty liver disease (NAFLD).

    Science.gov (United States)

    Soares e Silva, Amanda Karolina; de Oliveira Cipriano Torres, Dilênia; dos Santos Gomes, Fabiana Oliveira; dos Santos Silva, Bruna; Lima Ribeiro, Edlene; Costa Oliveira, Amanda; dos Santos, Laise Aline Martins; de Lima, Maria do Carmo Alves; Pitta, Ivan da Rocha; Peixoto, Christina Alves

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) defines a wide spectrum of liver diseases that extends from simple steatosis to non-alcoholic steatohepatitis. Although the pathogenesis of NAFLD remains undefined, it is recognized that insulin resistance is present in almost all patients who develop this disease. Thiazolidinediones (TZDs) act as an insulin sensitizer and have been used in the treatment of patients with type 2 diabetes and other insulin-resistant conditions, including NAFLD. Hence, therapy of NAFLD with insulin-sensitizing drugs should ideally improve the key hepatic histological changes, while also reducing cardiometabolic and cancer risks. Controversially, TZDs are associated with the development of cardiovascular events and liver problems. Therefore, there is a need for the development of new therapeutic strategies to improve liver function in patients with chronic liver diseases. The aim of the present study was to assess the therapeutic effects of LPSF/GQ-02 on the liver of LDLR-/- mice after a high-fat diet. Eighty male mice were divided into 4 groups and two different experiments: 1-received a standard diet; 2-fed with a high-fat diet (HFD); 3-HFD+pioglitazone; 4-HFD+LPSF/GQ-02. The experiments were conducted for 10 or 12 weeks and in the last two or four weeks respectively, the drugs were administered daily by gavage. The results obtained with an NAFLD murine model indicated that LPSF/GQ-02 was effective in improving the hepatic architecture, decreasing fat accumulation, reducing the amount of collagen, decreasing inflammation by reducing IL-6, iNOS, COX-2 and F4 / 80, and increasing the protein expression of IκBα, cytoplasmic NFκB-65, eNOS and IRS-1 in mice LDLR -/-. These results suggest a direct action by LPSF/GQ-02 on the factors that affect inflammation, insulin resistance and fat accumulation in the liver of these animals. Further studies are being conducted in our laboratory to investigate the possible mechanism of action of LPSF/GQ-02 on

  18. Fucoidan ameliorates steatohepatitis and insulin resistance by suppressing oxidative stress and inflammatory cytokines in experimental non-alcoholic fatty liver disease.

    Science.gov (United States)

    Heeba, Gehan H; Morsy, Mohamed A

    2015-11-01

    Fucoidan, a sulfated polysaccharide derived from brown seaweeds, possesses a wide range of pharmacological properties. In the present study, we investigated the therapeutic effect of fucoidan on non-alcoholic fatty liver disease (NAFLD) in rats. Rats were fed a high-fat diet (HFD) for 12 weeks to induce NAFLD. Oral administrations of fucoidan (100mg/kg, orally), metformin (200mg/kg, orally) or the vehicle were started in the last four weeks. Results showed that administration of fucoidan for 4 weeks attenuated the development of NAFLD as evidenced by the significant decrease in liver index, serum liver enzymes activities, serum total cholesterol and triglycerides, fasting serum glucose, insulin, insulin resistance, and body composition index. Further, fucoidan decreased hepatic malondialdehyde as well as nitric oxide concentrations, and concomitantly increased hepatic reduced glutathione level. In addition, the effect of fucoidan was accompanied with significant decrease in hepatic mRNA expressions of tumor necrosis factor-α, interleukins-1β and matrix metalloproteinase-2. Furthermore, histopathological examination confirmed the effect of fucoidan. In conclusion, fucoidan ameliorated the development of HFD-induced NAFLD in rats that may be, at least partly, related to its hypolipidemic, insulin sensitizing, antioxidant and anti-inflammatory mechanisms.

  19. Structural changes of gut microbiota in a rat non-alcoholic fatty liver disease model treated with a Chinese herbal formula.

    Science.gov (United States)

    Yin, Xiaochen; Peng, Jinghua; Zhao, Liping; Yu, Yunpeng; Zhang, Xu; Liu, Ping; Feng, Qin; Hu, Yiyang; Pang, Xiaoyan

    2013-05-01

    Accumulating evidence indicates that disruption of the gut microbiota by a high-fat diet (HFD) may play a pivotal role in the progression of metabolic disorders such as non-alcoholic fatty liver disease (NAFLD). In this study, the structural changes of gut microbiota were analyzed in an HFD-induced NAFLD rat model during treatment with an ancient Chinese herbal formula (CHF) used in clinical practice -Qushi Huayu Fang. CHF treatment significantly reduced body weight, alleviated hepatic steatosis, and decreased the content of triglycerides and free fatty acids in the livers of the rats. Gut microbiota of treated and control rats were profiled with polymerase chain reaction-denaturing gradient gel electrophoresis and bar-coded pyrosequencing of the V3 region of 16S rRNA genes. Both analyses indicated that the CHF-treated group harbored significantly different gut microbiota from that of model rats. Partial least squares discriminant analysis and taxonomy-based analysis were further employed to identify key phylotypes responding to HFD and CHF treatment. Most notably, the genera Escherichia/Shigella, containing opportunistic pathogens, were significantly enriched in HFD-fed rats compared to controls fed normal chow (P<0.05) but they decreased to control levels after CHF treatment. Collinsella, a genus with short chain fatty acid producers, was significantly elevated in CHF-treated rats compared to HFD-fed rats (P<0.05). The results revealed that the bacterial profiles of HFD-induced rats could be modulated by the CHF. Elucidation of these differences in microbiota composition provided a basis for further understanding the pharmacological mechanism of the CHF.

  20. SU-E-I-64: Transverse Relaxation Time in Methylene Protons of Non-Alcoholic Fatty Liver Disease Rats

    Energy Technology Data Exchange (ETDEWEB)

    Song, K-H; Lee, D-W; Choe, B-Y [Department of Biomedical Engineering, Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Seoul (Korea, Republic of)

    2015-06-15

    Purpose: The aim of this study was to evaluate transverse relaxation time of methylene resonance compared to other lipid resonances. Methods: The examinations were performed using a 3.0 T scanner with a point — resolved spectroscopy (PRESS) sequence. Lipid relaxation time in a lipid phantom filled with canola oil was estimated considering repetition time (TR) as 6000 msec and echo time (TE) as 40 — 550 msec. For in vivo proton magnetic resonance spectroscopy ({sup 1}H — MRS), eight male Sprague — Dawley rats were given free access to a normal - chow (NC) and eight other male Sprague-Dawley rats were given free access to a high — fat (HF) diet. Both groups drank water ad libitum. T{sub 2} measurements in the rats’ livers were conducted at a fixed TR of 6000 msec and TE of 40 – 220 msec. Exponential curve fitting quality was calculated through the coefficients of determination (R{sup 2}). Results: A chemical analysis of phantom and liver was not performed but a T{sub 2} decay curve was acquired. The T{sub 2} relaxation time of methylene resonance was estimated as follows: NC rats, 37.07 ± 4.32 msec; HF rats, 31.43 ± 1.81 msec (p < 0.05). The extrapolated M0 values were higher in HF rats than in NC rats (p < 0.005). Conclusion: This study of {sup 1}H-MRS led to sufficient spectral resolution and signal — to — noise ratio differences to characterize all observable resonances for yielding T{sub 2} relaxation times of methylene resonance. {sup 1}H — MRS relaxation times may be useful for quantitative characterization of various liver diseases, including fatty liver disease. This study was supported by grant (2012-007883 and 2014R1A2A1A10050270) from the Mid-career Researcher Program through the NRF funded by Ministry of Science. In addition, this study was supported by the Industrial R&D of MOTIE/KEIT (10048997, Development of the core technology for integrated therapy devices based on real-time MRI-guided tumor tracking)

  1. Decreased MiR-155 Level in the Peripheral Blood of Non-Alcoholic Fatty Liver Disease Patients may Serve as a Biomarker and may Influence LXR Activity

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2016-11-01

    Full Text Available Background: Obesity is now a common risk factor for non-alcoholic fatty liver disease (NAFLD. Thus, it is important to explore its underlying mechanisms. Methods: Total RNA was extracted from peripheral whole blood samples from 50 NAFLD patients and 50 healthy controls. In addition, human liver specimens were obtained through liver biopsies from NAFLD patients and healthy controls. The level of miRNA was studied using real-time PCR. The expression of lipogenic genes was analyzed using western blot, and a dual luciferase reporter assay was conducted to identify the possible target gene. Adenovirus vectors were injected into the tail vein of the high fat diet (HFD-fed mice to study the role of miR-155 on lipid accumulation in vivo. Results: The level of miR-155 was markedly reduced in the livers and peripheral blood of NAFLD patients compared with healthy controls. Upregulation of miR-155 decreased intracellular lipid content and the SREBP1 and FAS protein levels, while inhibition of miR-155 enhanced the intracellular lipid content. The dual luciferase reporter assay showed that Liver X receptor (LXRα was the target gene of miR-155, and silencing miR-155 reduced the expression of SREBP1 and FAS. An in vivo study showed that upregulation of miR-155 decreased the hepatic lipid accumulation mainly by suppressing the LXRα-dependent lipogenic signaling pathway. Conclusions: In summary, decreased expression of miR-155 in the peripheral blood may be utilized as a potential novel biomarker for NAFLD screening mainly by targeting LXRα.

  2. Acute fatty liver of pregnancy

    OpenAIRE

    Ko, Hin Hin; Yoshida, Eric

    2006-01-01

    Acute fatty liver of pregnancy (AFLP) is a rare, potentially fatal complication that occurs in the third trimester or early postpartum period. Although the exact pathogenesis is unknown, this disease has been linked to an abnormality in fetal fatty acid metabolism. Early diagnosis of AFLP sometimes can be difficult because it shares features with other common conditions such as pre-eclampsia, viral hepatitis and cholestasis of pregnancy. However, a careful history and physical examination, in...

  3. Alcohol Dependence and Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Karl Mann

    2015-01-01

    Full Text Available Alcohol dependence is a disabling condition that has a high prevalence, but in Europe only a small fraction of the people diagnosed with alcohol abuse and dependence are treated, representing the widest treatment gap, as compared with other mental disorders. Early diagnosis and monitoring of alcoholic liver disease (ALD is still insufficiently solved. Although ALD is the most common cause for liver disease in the Western world, it largely remains underestimated and underdiagnosed for many reasons. The recent introduction of non-invasive elastographic techniques such as transient elastography (TE has significantly improved the early diagnosis of alcoholic liver cirrhosis (ALC. As demonstrated in the literature, inflammation-associated liver stiffness (LS rapidly decreases during alcohol detoxification, and is also directly correlated to change in LS in both abstinent and relapsing patients. Newly published data show that LS could be used to monitor and validate hepatoprotective effects during nalmefene usage. Nalmefene is an opioid system modulator that diminishes the reinforcing effects of alcohol, helping the patient to reduce drinking. Three randomised, multicentre, double-blind, placebo-controlled, parallelgroup Phase III studies were designed to assess the efficacy and safety of nalmefene in reducing alcohol consumption. Patients with a high or very high drinking risk level (DRL at baseline and randomisation show a clinically significant effect from nalmefene treatment, which is generally well tolerated. Moreover, reduced alcohol consumption supported by nalmefene in combination with psychosocial support may indeed help to reduce the alcohol-related burden and the large treatment gap.

  4. Does vitamin C deficiency promote fatty liver disease development?

    DEFF Research Database (Denmark)

    Ipsen, David Højland; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-01-01

    Obesity and the subsequent reprogramming of the white adipose tissue are linked to human disease-complexes including metabolic syndrome and concurrent non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The dietary imposed dyslipidemia promotes redox imbalance...

  5. Alcohol-induced steatosis in liver cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Alcohol-induced fatty liver (steatosis) was believed to result from excessive generation of reducing equivalents from ethanol metabolism, thereby enhancing fat accumulation. Recent findings have revealed a more complex picture in which ethanol oxidation is still required,but specific transcription as well as humoral factors also have important roles. Transcription factors involved include the sterol regulatory element binding protein 1 (SREBP-1)which is activated to induce genes that regulate lipid biosynthesis. Conversely, ethanol consumption causes a general down-regulation of lipid (fatty acid) oxidation, a reflection of inactivation of the peroxisome proliferatoractivated receptor-alpha (PPAR-α) that regulates genes involved in fatty acid oxidation. A third transcription factor is the early growth response-1 (Egr-1), which is strongly induced prior to the onset of steatosis. The activities of all these factors are governed by that of the principal regulatory enzyme, AMP kinase. Important humoral factors, including adiponectin, and tumor necrosis factor-α(TNF-α), also regulate alcohol-induced steatosis. Their levels are affected by alcohol consumption and by each other. This review will summarize the actions of these proteins in ethanol-elicited fatty liver. Because steatosis is now regarded as a significant risk factor for advanced liver pathology, an understanding of the molecular mechanisms in its etiology is essential for development of effective therapies.

  6. The Effect of Symbiotic Supplementation on Liver Enzymes, C-reactive Protein and Ultrasound Findings in Patients with Non-alcoholic Fatty Liver Disease: A Clinical Trial

    Science.gov (United States)

    Asgharian, Atefe; Askari, Gholamreza; Esmailzade, Ahmad; Feizi, Awat; Mohammadi, Vida

    2016-01-01

    Background: Regarding to the growing prevalence of nonalcoholic fatty liver disease (NAFLD), concentrating on various strategies to its prevention and management seems necessary. The aim of this study was to determine the effects of symbiotic on C-reactive protein (CRP), liver enzymes, and ultrasound findings in patients with NAFLD. Methods: Eighty NAFLD patients were enrolled in this randomized, double-blind, placebo-controlled clinical trial. Participants received symbiotic in form of a 500 mg capsule (containing seven species of probiotic bacteria and fructooligosaccharides) or a placebo capsule daily for 8 weeks. Ultrasound grading, CRP, and liver enzymes were evaluated at the baseline and the end of the study. Results: In the symbiotic group, ultrasound grade decreased significantly compared to baseline (P < 0.005) but symbiotic supplementation was not associated with changes in alanine aminotransferase (ALT) and aspartate transaminase (AST) levels. In the placebo group, there was no significant change in steatosis grade whereas ALT and AST levels were significantly increased (P = 0.002, P = 0.02, respectively). CRP values remained static in either group. Conclusions: Symbiotic supplementation improved steatosis in NAFLD patients and might be useful in the management of NAFLD or protective against its progression. PMID:27076897

  7. Hepatic Macrosteatosis Is Partially Converted to Microsteatosis by Melatonin Supplementation in ob/ob Mice Non-Alcoholic Fatty Liver Disease.

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    Alessandra Stacchiotti

    Full Text Available Obesity is a common risk factor for non-alcoholic fatty liver disease (NAFLD. Currently, there are no specific treatments against NAFLD. Thus, examining any molecule with potential benefits against this condition emerged melatonin as a molecule that influences metabolic dysfunctions. The aim of this study was to determine whether melatonin would function against NAFDL, studying morphological, ultrastuctural and metabolic markers that characterize the liver of ob/ob mice.Lean and ob/ob mice were supplemented with melatonin in the drinking water for 8 weeks. Histology and stereology were performed to assess hepatic steatosis and glycogen deposition. Ultrastructural features of mitochondria, endoplasmic reticulum (ER and their juxtapositions were evaluated in livers of all experimental groups. Furthermore, hepatic distribution and expression of markers of ER and mitochondria (calnexin, ATP sintase β, GRP78 and CHOP and metabolic dysfunction (RPB4, β-catenin and cellular longevity (SIRT1 were analyzed.Melatonin significantly reduced glycemia, identified also by a decrease of hepatic RBP4 expression, reversed macrosteatosis in microsteatosis at the hepatic pericentral zone, enlarged ER-mitochondrial distance and ameliorated the morphology and organization of these organelles in ob/ob mouse liver. Furthermore, in ob/ob mice, calnexin and ATP synthase β were partially restored, GRP78 and CHOP decreased in periportal and midzonal hepatocytes and β-catenin expression was, in part, restored in peripheral membranes of hepatocytes. Melatonin supplementation to ob/ob mice improves hepatic morphological, ultrastructural and metabolic damage that occurs as a result of NAFLD.Melatonin may be a potential adjuvant treatment to limit NAFLD and its progression into irreversible complications.

  8. Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Jiang, Weiwei; Wu, Na; Wang, Xuemei; Chi, Yujing; Zhang, Yuanyuan; Qiu, Xinyun; Hu, Ying; Li, Jing; Liu, Yulan

    2015-02-03

    Non-alcoholic fatty liver disease (NAFLD) has recently been considered to be under the influence of the gut microbiota, which might exert toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein. In this study, the composition of the gut microbiota in NAFLD patients and healthy subjects was determined via 16S ribosomal RNA Illumina next-generation sequencing. Among those taxa displaying greater than 0.1% average abundance in all samples, five genera, including Alistipes and Prevotella, were significantly more abundant in the gut microbiota of healthy subjects compared to NAFLD patients. Alternatively, Escherichia, Anaerobacter, Lactobacillus and Streptococcus were increased in the gut microbiota of NAFLD patients compared to healthy subjects. In addition, decreased numbers of CD4+ and CD8+ T lymphocytes and increased levels of TNF-α, IL-6 and IFN-γ were detected in the NAFLD group compared to the healthy group. Furthermore, irregularly arranged microvilli and widened tight junctions were observed in the gut mucosa of the NAFLD patients via transmission electron microscopy. We postulate that aside from dysbiosis of the gut microbiota, gut microbiota-mediated inflammation of the intestinal mucosa and the related impairment in mucosal immune function play an important role in the pathogenesis of NAFLD.

  9. Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials.

    Science.gov (United States)

    Sáez-Lara, Maria Jose; Robles-Sanchez, Candido; Ruiz-Ojeda, Francisco Javier; Plaza-Diaz, Julio; Gil, Angel

    2016-06-13

    The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS), type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders.

  10. Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials

    Directory of Open Access Journals (Sweden)

    Maria Jose Sáez-Lara

    2016-06-01

    Full Text Available The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS, type 2 diabetes (T2D and non-alcoholic fatty liver disease (NAFLD in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders.

  11. Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials

    Science.gov (United States)

    Sáez-Lara, Maria Jose; Robles-Sanchez, Candido; Ruiz-Ojeda, Francisco Javier; Plaza-Diaz, Julio; Gil, Angel

    2016-01-01

    The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS), type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders. PMID:27304953

  12. Efficacy of Resveratrol Supplementation against Non-Alcoholic Fatty Liver Disease: A Meta-Analysis of Placebo-Controlled Clinical Trials

    Science.gov (United States)

    Fang, Jianguo; Wang, Wenqing; He, Pei; Lei, Jiahui; Wang, Chunxu

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with rising prevalence. Increasing evidence has demonstrated that resveratrol, a dietary phytochemical, is capable of attenuating NAFLD development and progression; however, results from clinical studies are inconsistent and inconclusive. Here, we conducted a meta-analysis to evaluate the efficacy of resveratrol on NAFLD, using several parameters to provide new insights for clinical application. We systematically searched EMBASE, PubMed, Science Citation Index, Elsevier, and Cochrane Library databases for studies published up to date (July 2016), in English, to identify and screen eligible, relevant studies. Either a fixed-effect model or random model was used to estimate mean difference (MD) and 95% confidence intervals (CIs) for the effect of resveratrol on NAFLD. Four randomized, double-blinded, placebo-controlled trials involving 156 patients were included in the meta-analysis. Levels of low-density lipoprotein (MD = 0.47, 95% CI: 0.21, 0.74, P < 0.05) and total cholesterol (MD = 0.49, 95% CI: 0.18, 0.80, P < 0.05) were higher in the resveratrol treatment groups than in placebo control groups, whereas other parameters were not altered. Overall, this study indicates that resveratrol treatment has negligible effects on attenuating NAFLD, given the small improvement in NAFLD features. More high-quality clinical trials of resveratrol for NAFLD are required to confirm these results. PMID:27560482

  13. 酒精合并高脂饮食建立大鼠脂肪肝模型%Establishing alcoholic fatty liver model with alcohol and fat emulsion in rats

    Institute of Scientific and Technical Information of China (English)

    邹丽宜; 吴铁; 崔燎; 尤婷婷; 许碧连; 张新乐; 刘钰瑜

    2011-01-01

    目的 探讨建立大鼠脂肪肝动物模型的方法.方法 60只雄性SD大鼠随机分成3组:正常对照(NS)组每日灌胃生理盐水和普通饲料喂养,高剂量模型(HM)组和低剂量模型(LM)组每天按照5 g/kg体重对大鼠灌胃浓度为 60%(V/V)和30%(V/V)的乙醇和按照5 ml/kg灌胃脂肪乳剂的方法,连续3 w,分别在第2周末和第3周末随机选取各组大鼠10只,观察其肝脏病理改变及血液生化指标的变化.结果 造模2 w可见轻度的肝脂肪变.造模3 w后,模型组大鼠肝脏重量明显升高,与正常组比较有显著性差异;病理表现为广泛的脂肪变性,血清三酰甘油(TG)、丙氨酸氨基转移酶 (ALT)、天冬氨酸氨基转氨酶(AST)、总胆固醇(TC)升高,高密度脂蛋白胆固醇(HDL-C)显著降低,与正常组比较差异有显著意义(P0.05).结论 本造模方法与人类脂肪肝病变类似,方法简单易行,实验周期短,模型稳定可靠.%Objective To establish alcoholic fatty liver model with alcohol and fat emulsion in rats. Methods Sixty SD male rats were randomly divided into NS (intragastric infusion of saline, 5 ml/kg, fed with common diet), HM and LM groups (intragastric infusion of alcohol by 60% V/V or 30% V/V ,5 ml/kg , fed with intralipid, 5 ml/kg). Half of rats were sacrificed after 2 w to evaluate the process of alcoholic fatty liver formation. All rats were sacrificed at the end of the third week. The pathologic of the liver and the biochemistry index of plasma were observed. Results Slight fatty deposition was observed at the end of the 2nd week after experiment, and 3 weeks later, severe fatty deposition appeared. The levels of serum TG, CH, ALT and AST of HM and LM groups were higher than those of NS group(P< 0. 05 ). Conclusions The lesion of the alcoholic fatty liver model in rats is similar to that in humans. The experimant is very simple and the experiment cycle is short and the conclusion is clear.

  14. Usefulness of T1 mapping on Gd-EOB-DTPA-enhanced MR imaging in assessment of non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Ying; Rao, Sheng-Xiang; Meng, Tao; Chen, Caizhong; Li, Renchen; Zeng, Meng-Su [Zhongshan/Hospital of Fudan University, Department of Radiology, Shanghai (China)

    2014-04-15

    This study evaluates the value of Gd-EOB-DTPA-enhanced MRI for diagnosis and staging of non-alcoholic fatty liver disease (NAFLD) in an animal model by T{sub 1} relaxation time measurement. Thirty-four rabbits were divided into the control group (n = 10) and NAFLD group, which was split into four groups (n = 6) with a high-fat diet for an interval of 3 weeks. A dual flip angle was performed before and at the hepatobiliary phase (HBP). T{sub 1} relaxation times of the liver parenchyma and the decrease rate (∇%) were calculated. Histological findings according to semi-quantitative scoring of steatosis, activity and fibrosis were the standard of reference. HBP and ∇% T{sub 1} relaxation time measurement showed significant differences between normal and NAFLD groups, between non-alcoholic steatohepatitis (NASH) and NAFLD without NASH (p = 0.000-0.049), between fibrosis groups (p = 0.000-0.019), but no difference between F1 and F2 (p = 0.834). The areas under the receiver operating characteristic curves (AUCs) of T{sub 1} relaxation time for HBP and ∇% were 0.86-0.93 for the selection of NASH and activity score ≥2, and 0.86-0.95 for the selection of F ≥ 1, 2, 3. No significant difference was found for diagnostic performance between HBP and ∇% T{sub 1} relaxation time. HBP T{sub 1} relaxation time measurement of Gd-EOB-DTPA-enhanced MRI was useful to evaluate NAFLD according to the SAF score. HBP T{sub 1} relaxation time measurement was as accurate as ∇% T{sub 1} relaxation time. (orig.)

  15. Association of Circulating Serum miR-34a and miR-122 with Dyslipidemia among Patients with Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Salvoza, Noel C; Klinzing, David C; Gopez-Cervantes, Juliet; Baclig, Michael O

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of diseases from simple steatosis to non-alcoholic steatohepatitis, with approximately 20% risk of progressing to fibrosis and cirrhosis. The aim of this study was to compare the relative expression levels of circulating miR-21, miR-34a, miR-122, miR-125b and miR-375 between healthy controls and NAFLD patients, and to assess the feasibility of microRNAs as potential biomarkers for NAFLD. A cross-sectional study was conducted to evaluate circulating serum miRNAs as potential diagnostic markers for NAFLD. Twenty-eight clinically diagnosed and histologically-confirmed NAFLD patients, as well as 36 healthy controls were enrolled in this study. The relative expression of serum microRNAs were calculated using the comparative cycle threshold with spiked-in C. elegans miR-39 as exogenous internal control. Serum levels of miR-34a and miR-122 were significantly higher in NAFLD patients than in healthy controls (P = NAFLD. Interestingly, receiver operating characteristic (ROC) curve analysis revealed that miR-34a and miR-122 are potential markers for discriminating NAFLD patients from healthy controls with an area under the curve (AUC) values of 0.781 and 0.858, respectively. Serum levels of miR-34a and miR-122 were found to be significantly higher among NAFLD patients, and were positively correlated with VLDL-C and triglyceride levels. Thus, circulating miR-34a and miR-122 can be used as potential biomarkers for discriminating NAFLD patients from healthy controls. Larger cohorts are required to validate the utility of miR-34a and miR-122 in monitoring liver injury.

  16. Relationships between variable time, percentage of food restriction and liver histology: which alternative is the best for non-alcoholic fatty liver disease (NAFLD) prevention?

    Science.gov (United States)

    Makovicky, Peter; Tumova, Eva; Volek, Zdenek; Makovicky, Pavol; Sedlacek, Radislav

    2016-10-01

    The objective of this study was to analyse the hepatic effects of food restriction in an experimental rabbit model. The study comprised 105 rabbits divided into 6 groups. The two control groups were fed ad libitum (ADL) during the entire experiment (C1 and C2). The experimental groups were restricted between 42-49 days of age, where the rabbits received 50g (R1) or 65g (R2) of food per rabbit per day. Others were restricted between 35-42 days of age, where the rabbits received 50g (R3) or 65g (R4) of food per rabbit per day. For liver analysis, 5 rabbits per group were slaughtered at the ages of 49, 56, 63, 70 days from the R1, R2 groups and at 42, 49, 70 days from the R3, R4 groups. All animals from the C1 and C2 groups developed steatosis with inflammation. Animals from the R1 and R2 groups developed steatosis without inflammation while in the R3 and R4 groups steatosis was not visible. In C1 and C2 groups we observed mostly fatty deposit accumulations while in the R1, R2, R3 and R4 groups, more PAS-positive material accumulations were visible. Liver steatosis correlated with inflammation development and interstitial tissue growth. These results can be used in clinical praxis as signs of NAFLD progression. Early food restriction had intense effects on liver morphology and it seems promising that similar approaches could be applied as preventive treatment for NAFLD development.

  17. Nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Patrick-Melin, A J; Kalinski, M I; Kelly, K R

    2009-01-01

    that features steatosis plus inflammation, termed nonalcoholic steatohepatitis (NASH), which may in turn progress to hepatic fibrosis, cirrhosis, and sub-acute liver failure. Thus, NAFLD and its subsequent complications create a significant health burden, and currently there is no effective treatment strategy...

  18. Assessment of Diet and Physical Activity in Paediatric Non-Alcoholic Fatty Liver Disease Patients: A United Kingdom Case Control Study.

    Science.gov (United States)

    Gibson, Philippa S; Lang, Sarah; Gilbert, Marianne; Kamat, Deepa; Bansal, Sanjay; Ford-Adams, Martha E; Desai, Ashish P; Dhawan, Anil; Fitzpatrick, Emer; Moore, J Bernadette; Hart, Kathryn H

    2015-11-26

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children, with prevalence rising alongside childhood obesity rates. This study aimed to characterise the habitual diet and activity behaviours of children with NAFLD compared to obese children without liver disease in the United Kingdom (UK). Twenty-four biopsy-proven paediatric NAFLD cases and eight obese controls without biochemical or radiological evidence of NAFLD completed a 24-h dietary recall, a Physical Activity Questionnaire (PAQ), a Dutch Eating Behavior Questionnaire (DEBQ) and a 7-day food and activity diary (FAD), in conjunction with wearing a pedometer. Groups were well matched for age and gender. Obese children had higher BMI z-scores (p = 0.006) and BMI centiles (p = 0.002) than participants with NAFLD. After adjusting for multiple hypotheses testing and controlling for differences in BMI, no differences in macro- or micronutrient intake were observed as assessed using either 24-h recall or 7-day FAD (p > 0.001). Under-reporting was prevalent (NAFLD 75%, Obese Control 87%: p = 0.15). Restrained eating behaviours were significantly higher in the NAFLD group (p = 0.005), who also recorded more steps per day than the obese controls (p = 0.01). In conclusion, this is the first study to assess dietary and activity patterns in a UK paediatric NAFLD population. Only a minority of cases and controls were meeting current dietary and physical activity recommendations. Our findings do not support development of specific dietary/ physical activity guidelines for children with NAFLD; promoting adherence with current general paediatric recommendations for health should remain the focus of clinical management.

  19. Dietary Oleate Has Beneficial Effects on Every Step of Non-Alcoholic Fatty Liver Disease Progression in a Methionine- and Choline-Deficient Diet-Fed Animal Model

    Directory of Open Access Journals (Sweden)

    Ji Young Lee

    2011-10-01

    Full Text Available BackgroundNon-alcoholic fatty liver disease (NAFLD is increasingly recognized as a major cause of liver-related morbidity and mortality. The underlying mechanisms of disease progression remain poorly understood, and primary therapy of NAFLD is not yet established. We investigated the effects of dietary oleate on the development and progression of NAFLD in a methionine- and choline-deficient (MCD diet-fed animal model.MethodsA total of 30 C57BL/6J mice were randomly divided into three groups (n=10 in each group and fed various experimental diets for four weeks: chow, MCD diet, or OMCD (MCD diet with oleate, 0.5 mg/g/day. Liver samples were examined for steatohepatitis and fibrosis parameters and associated genes.ResultsAdditional dietary oleate dramatically reduced MCD diet-induced hepatic steatosis. Hepatic carbohydrate responsive element-binding protein was overexpressed in MCD diet-fed mice, and dietary oleate prevented this overexpression (P<0.001. Dietary oleate partially prevented MCD diet-induced serum level increases in aspartate aminotransferase and alanine aminotransferase (P<0.001, respectively. The mRNA expressions of hepatic monocyte chemoattractant protein 1, tumor necrosis factor-α and matrix metalloproteinase-9 were increased in MCD diet-fed mice, and this overexpression of inflammatory molecules was prevented by dietary oleate (P<0.001. Hepatic pericellular fibrosis was observed in MCD diet-fed mice, and dietary oleate prevented this fibrosis. Altogether, dietary oleate prevented MCD diet-induced hepatic steatosis, inflammation and fibrosis.ConclusionDietary oleate has beneficial effects in every step of NAFLD development and progression and could be a nutritional option for NAFLD prevention and treatment.

  20. Assessment of Diet and Physical Activity in Paediatric Non-Alcoholic Fatty Liver Disease Patients: A United Kingdom Case Control Study

    Directory of Open Access Journals (Sweden)

    Philippa S. Gibson

    2015-11-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most common cause of chronic liver disease in children, with prevalence rising alongside childhood obesity rates. This study aimed to characterise the habitual diet and activity behaviours of children with NAFLD compared to obese children without liver disease in the United Kingdom (UK. Twenty-four biopsy-proven paediatric NAFLD cases and eight obese controls without biochemical or radiological evidence of NAFLD completed a 24-h dietary recall, a Physical Activity Questionnaire (PAQ, a Dutch Eating Behavior Questionnaire (DEBQ and a 7-day food and activity diary (FAD, in conjunction with wearing a pedometer. Groups were well matched for age and gender. Obese children had higher BMI z-scores (p = 0.006 and BMI centiles (p = 0.002 than participants with NAFLD. After adjusting for multiple hypotheses testing and controlling for differences in BMI, no differences in macro- or micronutrient intake were observed as assessed using either 24-h recall or 7-day FAD (p > 0.001. Under-reporting was prevalent (NAFLD 75%, Obese Control 87%: p = 0.15. Restrained eating behaviours were significantly higher in the NAFLD group (p = 0.005, who also recorded more steps per day than the obese controls (p = 0.01. In conclusion, this is the first study to assess dietary and activity patterns in a UK paediatric NAFLD population. Only a minority of cases and controls were meeting current dietary and physical activity recommendations. Our findings do not support development of specific dietary/ physical activity guidelines for children with NAFLD; promoting adherence with current general paediatric recommendations for health should remain the focus of clinical management.

  1. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease: is universal screening appropriate?

    Science.gov (United States)

    Byrne, Christopher D; Targher, Giovanni

    2016-06-01

    Non-alcoholic fatty liver disease (NAFLD) is very common in people with type 2 diabetes and although estimates for the prevalence NAFLD vary according to age, obesity and ethnicity, some studies have indicated that up to 75% of patients with type 2 diabetes may be affected. During the last 15 years there has been a vast amount of research into understanding the natural history, aetiology and pathogenesis of NAFLD; and now there is a better understanding of the strengths and limitations of diagnostic tests for NAFLD, the influence of lifestyle changes and the effects of potential treatments. With this advance in knowledge, it is apposite that a number of organisations have started to develop guidelines for the diagnosis and management of NAFLD. Given the high proportion of patients with type 2 diabetes who are affected by this liver condition, it is now important to consider how any guideline will affect the care, diagnosis and treatment of patients with type 2 diabetes. It is to the credit of the European Association for the Study of the Liver (EASL), the European Association for the Study of Diabetes (EASD) and the European Association for the Study of Obesity (EASO) that guidelines for NAFLD have been produced (Diabetologia DOI: 10.1007/s00125-016-3902-y ) and a consensus achieved between these three organisations. The purpose of this commentary is to discuss briefly the EASL-EASD-EASO clinical practice guidelines with a focus on their relevance for clinicians caring for patients with type 2 diabetes.

  2. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    OpenAIRE

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH ...

  3. Liver proteomics in progressive alcoholic steatosis

    Energy Technology Data Exchange (ETDEWEB)

    Fernando, Harshica [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Wiktorowicz, John E.; Soman, Kizhake V. [Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Kaphalia, Bhupendra S.; Khan, M. Firoze [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Shakeel Ansari, G.A., E-mail: sansari@utmb.edu [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2013-02-01

    Fatty liver is an early stage of alcoholic and nonalcoholic liver disease (ALD and NALD) that progresses to steatohepatitis and other irreversible conditions. In this study, we identified proteins that were differentially expressed in the livers of rats fed 5% ethanol in a Lieber–DeCarli diet daily for 1 and 3 months by discovery proteomics (two-dimensional gel electrophoresis and mass spectrometry) and non-parametric modeling (Multivariate Adaptive Regression Splines). Hepatic fatty infiltration was significantly higher in ethanol-fed animals as compared to controls, and more pronounced at 3 months of ethanol feeding. Discovery proteomics identified changes in the expression of proteins involved in alcohol, lipid, and amino acid metabolism after ethanol feeding. At 1 and 3 months, 12 and 15 different proteins were differentially expressed. Of the identified proteins, down regulation of alcohol dehydrogenase (− 1.6) at 1 month and up regulation of aldehyde dehydrogenase (2.1) at 3 months could be a protective/adaptive mechanism against ethanol toxicity. In addition, betaine-homocysteine S-methyltransferase 2 a protein responsible for methionine metabolism and previously implicated in fatty liver development was significantly up regulated (1.4) at ethanol-induced fatty liver stage (1 month) while peroxiredoxin-1 was down regulated (− 1.5) at late fatty liver stage (3 months). Nonparametric analysis of the protein spots yielded fewer proteins and narrowed the list of possible markers and identified D-dopachrome tautomerase (− 1.7, at 3 months) as a possible marker for ethanol-induced early steatohepatitis. The observed differential regulation of proteins have potential to serve as biomarker signature for the detection of steatosis and its progression to steatohepatitis once validated in plasma/serum. -- Graphical abstract: The figure shows the Hierarchial cluster analysis of differentially expressed protein spots obtained after ethanol feeding for 1 (1–3

  4. Low skeletal muscle mass is associated with non-alcoholic fatty liver disease in Korean adults:the Fifth Korea National Health and Nutrition Examination Survey

    Institute of Scientific and Technical Information of China (English)

    Hee Yeon Kim; Chang Wook Kim; Chung-Hwa Park; Jong Young Choi; Kyungdo Han; Anwar T Merchant; Yong-Moon Park

    2016-01-01

    BACKGROUND: Sarcopenia and non-alcoholic fatty liver dis-ease (NAFLD) share similar pathophysiological mechanisms, and the relationship between sarcopenia and NAFLD has been recently investigated. The study investigated whether low skel-etal muscle mass is differentially associated with NAFLD by gender in Korean adults. METHODS: We conducted a cross-sectional analysis of the data from the Fifth Korea National Health and Nutrition Examination Survey. The skeletal muscle index (SMI) was obtained by the appendicular skeletal muscle mass divided by the weight. NAFLD was defined as a fatty liver index (FLI) ≥60 in the absence of other chronic liver disease. RESULTS: Among the included subjects, 18.3% (SE: 1.4%) in men and 7.0% (SE: 0.7%) in women were classified as having FLI-defined NAFLD. Most of the risk factors for FLI-defined NAFLD showed a significant negative correlation with the SMI in both genders. Multiple logistic regression analysis showed that low SMI was associated with FLI-defined NAFLD, inde-pendent of other metabolic and lifestyle parameters in both genders [males: odds ratio (OR)=1.35; 95% confidence inter-val (CI): 1.17-1.54; females: OR=1.36; 95% CI: 1.18-1.55]. The magnitude of the association between FLI-defined NAFLD and low SMI was higher in middle aged to elderly males (OR=1.50; 95% CI: 1.22-1.84) than in males less than 45 years of age (OR=1.25; 95% CI: 1.02-1.52) and in premenopausal females (OR=1.50; 95% CI: 1.12-2.03) than in postmenopausal females (OR=1.36; 95% CI: 1.20-1.54). CONCLUSIONS: Low SMI is associated with the risk of FLI-defined NAFLD independent of other well-known metabolic risk factors in both genders. This association may differ ac-cording to age group or menopausal status. Further studies are warranted to confirm this relationship.

  5. 4Ps medicine of the fatty liver: the research model of predictive, preventive, personalized and participatory medicine—recommendations for facing obesity, fatty liver and fibrosis epidemics

    OpenAIRE

    Trovato, Francesca Maria; Catalano, Daniela; Musumeci, Giuseppe; Trovato, Guglielmo M

    2014-01-01

    Relationship between adipose tissue and fatty liver, and its possible evolution in fibrosis, is supported by clinical and research experience. Given the multifactorial pathogenesis of non-alcoholic fatty liver disease (NAFLD), treatments for various contributory risk factors have been proposed; however, there is no single validated therapy or drug association recommended for all cases which can stand alone. Mechanisms, diagnostics, prevention and treatment of obesity, fatty liver and insulin ...

  6. Effect of probiotics on non-alcoholic fatty liver disease%益生菌作用治疗非酒精性脂肪肝

    Institute of Scientific and Technical Information of China (English)

    姚晓敏; 曲均革; 林爱斌; 李宏伟

    2014-01-01

    非酒精性脂肪肝(NAFLD)是一种比较常见的慢性肝病,其涵盖范围包括脂肪肝、脂肪性肝炎以及肝硬化。其发病率的增加与肥胖、2型糖尿病等密切相关。越来越多人体试验表明,肠道微生物菌群过度生长与 NAFLD 和非酒精性脂肪肝炎(NASH)有关。最近,已有很多研究表明益生菌在改善 NAFLD 方面有效,已被视为一种治疗 NAFLD 的新方式,但仍需大样本试验和较长周期的临床随访进行深入研究。鉴于此,本文主要对 NAFLD 以及益生菌治疗 NAFLD 的动物实验和临床试验研究进展情况进行综述,从而进一步为益生菌用于 NAFLD 的治疗提供借鉴。%Non-alcoholic fatty liver disease (NAFLD)is a common chronic liver disease. It covers a spectrum of liver diseases that range from hepatic steatosis to steatohepatitis and cirrhosis. The increase in its prevalence is linked to obesity and type 2 diabetes. More evidence shows a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). Recently,many studies indicate that probiotics have very good effcts on improving NAFLD. Probiotics have been seen as a new way of treating NAFLD. But probiotics as treatment of NAFLD still need substantiation through more trials with a larger sample size and with longer-term clinical follow-up. Therefore,the research progress in probiotics treatment on animal experiments and clinical trials in NAFLD is reviewed in order to further understand the role of probiotics treatment,and provide the basis for the treatment of NAFLD.

  7. Effect of modulation of PPAR-γ activity on Kupffer cells M1/M2 polarization in the development of non-alcoholic fatty liver disease

    Science.gov (United States)

    Luo, Wenjing; Xu, Qinyu; Wang, Qi; Wu, Huimin; Hua, Jing

    2017-01-01

    Abnormal lipid-mediated hepatic inflammatory-immune dysfunction and chronic low grade inflammation play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Macrophage polarization is an important mechanism for the regulation of inflammatory response. Since PPAR-γ has emerged as a master regulator of macrophage polarization, we aimed to investigate the lipid-induced macrophage/Kupffer cell polarization in vivo and in vitro, and explore the association between PPAR-γ activity and macrophages M1/M2 polarization shifting. Here we showed that long-term high-fat diet increased Kupffer cells content with M1-predominant phenotype and increasing production of pro-inflammatory cytokines. Saturated fatty acids polarized Kupffer cells/macrophages to an M1-predominant phenotype while n-3 PUFA polarized Kupffer cells/macrophages to an M2 phenotype, which was associated with activation of NF-κB signal pathway and PPAR-γ respectively. Furthermore, up-regulation of PPAR-γ shifted lipid-induced macrophages polarization from M1-predominant phenotype to M2 phenotype. Macrophages polarization switch was associated with the interaction between PPAR-γ and NF-κBp65 signal pathway. Rosiglitazone restored high-fat diet-induced imblance of Kupffer cells M1/M2 polarization and alleviated hepatic steatosis as well as local pro-inflammatory response. These findings suggest that manipulation of PPAR-γ activity has the potential to balance lipid-induced M1/M2 macrophage/Kupffer cell polarization, and leading to prevent the development of NAFLD. PMID:28300213

  8. Role of bioactive fatty acids in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Juárez-Hernández, Eva; Chávez-Tapia, Norberto C; Uribe, Misael; Barbero-Becerra, Varenka J

    2016-08-02

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat deposition in hepatocytes, and a strong association with nutritional factors. Dietary fatty acids are classified according to their biochemical properties, which confer their bioactive roles. Monounsaturated fatty acids have a dual role in various human and murine models. In contrast, polyunsaturated fatty acids exhibit antiobesity, anti steatosic and anti-inflammatory effects. The combination of these forms of fatty acids-according to dietary type, daily intake and the proportion of n-6 to n-3 fats-can compromise hepatic lipid metabolism. A chemosensory rather than a nutritional role makes bioactive fatty acids possible biomarkers for NAFLD. Bioactive fatty acids provide health benefits through modification of fatty acid composition and modulating the activity of liver cells during liver fibrosis. More and better evidence is necessary to elucidate the role of bioactive fatty acids in nutritional and clinical treatment strategies for patients with NAFLD.

  9. Application of localized {sup 31}P MRS saturation transfer at 7 T for measurement of ATP metabolism in the liver: reproducibility and initial clinical application in patients with non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Valkovic, Ladislav [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Slovak Academy of Sciences, Department of Imaging Methods, Institute of Measurement Science, Bratislava (Slovakia); Gajdosik, Martin; Chmelik, Marek; Trattnig, Siegfried [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Traussnigg, Stefan; Kienbacher, Christian; Trauner, Michael [Medical University of Vienna, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Vienna (Austria); Wolf, Peter; Krebs, Michael [Medical University of Vienna, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Vienna (Austria); Bogner, Wolfgang [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA (United States); Krssak, Martin [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Medical University of Vienna, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Vienna (Austria)

    2014-07-15

    Saturation transfer (ST) phosphorus MR spectroscopy ({sup 31}P MRS) enables in vivo insight into energy metabolism and thus could identify liver conditions currently diagnosed only by biopsy. This study assesses the reproducibility of the localized {sup 31}P MRS ST in liver at 7 T and tests its potential for noninvasive differentiation of non-alcoholic fatty liver (NAFL) and steatohepatitis (NASH). After the ethics committee approval, reproducibility of the localized {sup 31}P MRS ST at 7 T and the biological variation of acquired hepato-metabolic parameters were assessed in healthy volunteers. Subsequently, 16 suspected NAFL/NASH patients underwent MRS measurements and diagnostic liver biopsy. The Pi-to-ATP exchange parameters were compared between the groups by a Mann-Whitney U test and related to the liver fat content estimated by a single-voxel proton ({sup 1}H) MRS, measured at 3 T. The mean exchange rate constant (k) in healthy volunteers was 0.31 ± 0.03 s{sup -1} with a coefficient of variation of 9.0 %. Significantly lower exchange rates (p < 0.01) were found in NASH patients (k = 0.17 ± 0.04 s{sup -1}) when compared to healthy volunteers, and NAFL patients (k = 0.30 ± 0.05 s{sup -1}). Significant correlation was found between the k value and the liver fat content (r = 0.824, p < 0.01). Our data suggest that the {sup 31}P MRS ST technique provides a tool for gaining insight into hepatic ATP metabolism and could contribute to the differentiation of NAFL and NASH. (orig.)

  10. Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6 Is a Novel Nutritional Therapeutic Target for Hyperlipidemia, Non-Alcoholic Fatty Liver Disease, and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Gwang-woong Go

    2015-06-01

    Full Text Available Low-density lipoprotein receptor-related protein 6 (LRP6 is a member of the low-density lipoprotein receptor family and has a unique structure, which facilitates its multiple functions as a co-receptor for Wnt/β-catenin signaling and as a ligand receptor for endocytosis. The role LRP6 plays in metabolic regulation, specifically in the nutrient-sensing pathway, has recently garnered considerable interest. Patients carrying an LRP6 mutation exhibit elevated levels of LDL cholesterol, triglycerides, and fasting glucose, which cooperatively constitute the risk factors of metabolic syndrome and atherosclerosis. Since the discovery of this mutation, the general role of LRP6 in lipid homeostasis, glucose metabolism, and atherosclerosis has been thoroughly researched. These studies have demonstrated that LRP6 plays a role in LDL receptor-mediated LDL uptake. In addition, when the LRP6 mutant impaired Wnt-LRP6 signaling, hyperlipidemia, non-alcoholic fatty liver disease, and atherosclerosis developed. LRP6 regulates lipid homeostasis and body fat mass via the nutrient-sensing mechanistic target of the rapamycin (mTOR pathway. Furthermore, the mutant LRP6 triggers atherosclerosis by activating platelet-derived growth factor (PDGF-dependent vascular smooth muscle cell differentiation. This review highlights the exceptional opportunities to study the pathophysiologic contributions of LRP6 to metabolic syndrome and cardiovascular diseases, which implicate LRP6 as a latent regulator of lipid metabolism and a novel therapeutic target for nutritional intervention.

  11. Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults.

    Science.gov (United States)

    Chen, Yu-ming; Liu, Yan; Zhou, Rui-fen; Chen, Xiao-ling; Wang, Cheng; Tan, Xu-ying; Wang, Li-jun; Zheng, Rui-dan; Zhang, Hong-wei; Ling, Wen-hua; Zhu, Hui-lian

    2016-01-08

    Many studies suggest that trimethylamine-N-oxide (TMAO), a gut-flora-dependent metabolite of choline, contributes to the risk of cardiovascular diseases, but little is known for non-alcoholic fatty liver disease (NAFLD). We examined the association of circulating TMAO, choline and betaine with the presence and severity of NAFLD in Chinese adults. We performed a hospital-based case-control study (CCS) and a cross-sectional study (CSS). In the CCS, we recruited 60 biopsy-proven NAFLD cases and 35 controls (18-60 years) and determined serum concentrations of TMAO, choline and betaine by HPLC-MS/MS. For the CSS, 1,628 community-based adults (40-75 years) completed the blood tests and ultrasonographic NAFLD evaluation. In the CCS, analyses of covariance showed adverse associations of ln-transformed serum levels of TMAO, choline and betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P-trend betaine and betaine/choline ratio (all P-trend betaine-NAFLD relationship in the community-based participants.

  12. 非酒精性脂肪肝的健康管理效果评价%Influence of Health Management on Non-alcoholic Fatty Liver Disease

    Institute of Scientific and Technical Information of China (English)

    孙蓉; 盛国滨; 高琛; 邹雨佳

    2012-01-01

    目的 观察通过健康教育提高人们对于非酒精性脂肪肝(non-alcoholic fatty liver disease,NAFLD)的知识、态度和行为水平.方法 选择来我院健康体检的且被检出患有非酒精性脂肪肝的患者196例,对其实施一系列的健康管理措施.结果 对于实施健康管理的196例非酒精性脂肪肝患者进行为期1年的体检结果 追踪,其中:治愈95例,好转45例.结论 实施一系列健康管理措施,对治愈非酒精性脂肪肝患者的有效率达到了70%以上,这对于提高患者的健康水平具有切实有效的意义.

  13. Non-alcoholic fatty liver disease (NAFLD) fibrosis score predicts 6.6-year overall mortality of Chinese patients with NAFLD.

    Science.gov (United States)

    Xun, Yun-Hao; Guo, Jian-Chun; Lou, Guo-Qiang; Jiang, Yan-Ming; Zhuang, Zhen-Jie; Zhu, Meng-Fei; Luo, Yan; Ma, Xiao-Jie; Liu, Jing; Bian, Dong-Xue; Shi, Jun-Ping

    2014-09-01

    The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has emerged as a useful predictor of long-term outcome in NAFLD patients. We evaluated the predictive performance of the NFS for overall mortality in a Chinese population with NAFLD. All NAFLD patients diagnosed ultrasonographically at Xixi Hospital of Hangzhou between 1996 and 2011 were retrospectively recruited to the study. Outcome was determined by interview and causes of death were confirmed by medical records. The area under the receiver operating characteristic curve (AUCROC ) was used to determine the predictive accuracy of the NFS, BARD (body mass index, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, diabetes) score, FIB-4 index and the AST/platelet ratio index (APRI) for mortality. Data from a total of 180 eligible patients (median age 39 years; 96 men) were analysed, with 12 deaths over a median follow-up period of 6.6 years (range 0.5-14.8 years). Using Cox model analysis, the NFS as a continuous variable was identified as the only predictor for all-cause mortality (hazard ratio 2.743, 95% confidence interval (CI) 1.670-4.504). The NFS yielded the highest AUCROC of 0.828 (95% CI 0.728-0.928, P NAFLD.

  14. Lack of association between SREBF-1c gene polymorphisms and risk of non-alcoholic fatty liver disease in a Chinese Han population

    Science.gov (United States)

    Peng, Xian-E.; Chen, Feng-Lin; Liu, Wenjuan; Hu, ZhiJian; Lin, Xu

    2016-01-01

    The transcription factor sterol regulatory element-binding protein-1c (SREBP-1c) is a key regulator of lipogenesis and insulin sensitivity, and is associated with non-alcoholic fatty liver disease (NAFLD). Here, we assessed the impact of common single nucleotide polymorphisms (SNPs) in SREBF-1c on NAFLD susceptibility and associated metabolic phenotypes in a Han Chinese population. Four common SNPs (rs62064119, rs2297508, rs11868035 and rs13306741) in the SREBP-1c gene were selected and genotyped in 593 patients with NAFLD and 593 healthy controls. Unconditional logistic regression was performed to assess the risk of NAFLD by determining odds ratios and 95% confidence intervals (CIs). No significant differences in genotype and allele frequencies of these four SNPs were found between the NAFLD population and the controls (all P > 0.05). In addition, we did not find any association between the SREBF-1c SNPs and the clinical and biochemical parameters, such as body mass index, total cholesterol, high density lipoprotein-and low density lipoprotein-cholesterol or systolic and diastolic blood pressure, except that the rs2297508 C-allele or rs11868035 G-allele showed significant associations with lower triglyceride levels in control subjects (P < 0.01). Our findings suggested that the four polymorphisms in SREBF-1c gene are not associated with risk of NAFLD in the Chinese Han population. PMID:27572914

  15. Comparison between a pediatric health promotion center and a pediatric obesity clinic in detecting metabolic syndrome and non-alcoholic fatty liver disease in children.

    Science.gov (United States)

    Yang, Hye Ran; Yi, Dae Yong; Choi, Hyoung Soo

    2014-12-01

    This study was done to evaluate the efficacy of health check-ups in children in detecting metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) by comparing the pediatric health promotion center with the pediatric obesity clinic. Children who visited a pediatric health promotion center (n=218) or a pediatric obesity clinic (n=178) were included. Anthropometric data, blood pressure, laboratory tests, and abdominal ultrasonography were evaluated. Two different criteria were applied to diagnose metabolic syndrome. The prevalence of metabolic syndrome in the 2 units was 3.2%-3.7% in a pediatric health promotion center and 23%-33.2% in a pediatric obesity clinic. Significant differences were observed in the prevalence of each component of metabolic syndrome between the 2 units including abdominal adiposity, blood pressure, serum triglycerides, and fasting blood glucose (Pobesity clinic targeting obese children than that among patients visiting the health promotion center offering routine check-ups. An obesity-oriented approach is required to prevent obesity-related health problems in children.

  16. Co-administration of metformin and N-acetylcysteine with dietary control improves the biochemical and histological manifestations in rats with non-alcoholic fatty liver

    Directory of Open Access Journals (Sweden)

    Naglaa Mohamed El-Lakkany

    2016-01-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF and N-acetylcysteine (NAC with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I, NAFLD-induced by feeding high-fat diet (HFD; II for 12 weeks, NAFLD switched to regular diet (RD; III, NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V, NAC in a dose of 500 mg/kg (VI, VII or MTF+NAC (VIII, IX respectively for 8 weeks. After 20 weeks, the rats in group II showed notable steatosis, lobular inflammation, fibrosis accompanied with elevated (P < 0.05 serum alanine transaminase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, gamma glutamyl transferase (g-GT, cholesterol, triglycerides, LDL, VLDL, leptin, tumor necrosis factor (TNF-α, transforming growth factor (TGF-β1 and hepatic malondialdehyde (MDA compared with group I. Meanwhile, hepatic superoxide dismutase (SOD, glutathione GSH with serum HDL, adiponectin were significantly decreased (P < 0.05. These changes were to a less extent in group III. MTF or NAC individually resulted in improvement of most of these biochemical and histological parameters. These improvements were more pronounced in the combined groups VIII and IX versus each drug alone. NAC supplementation concomitant with MTF could be beneficial for the treatment of NAFLD and prevention of nonalcoholic steatohepatitis (NASH.

  17. Co-administration of metformin and N-acetylcysteine with dietary control improves the biochemical and histological manifestations in rats with non-alcoholic fatty liver.

    Science.gov (United States)

    El-Lakkany, Naglaa Mohamed; Seif El-Din, Sayed Hassan; Sabra, Abdel-Nasser Abdel-Aal; Hammam, Olfat Ali; Ebeid, Fatma Abdel-Latif

    2016-10-01

    Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF) and N-acetylcysteine (NAC) with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I), NAFLD-induced by feeding high-fat diet (HFD; II) for 12 weeks, NAFLD switched to regular diet (RD; III), NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V), NAC in a dose of 500 mg/kg (VI, VII) or MTF+NAC (VIII, IX) respectively for 8 weeks. After 20 weeks, the rats in group II showed notable steatosis, lobular inflammation, fibrosis accompanied with elevated (P < 0.05) serum alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (γ-GT), cholesterol, triglycerides, LDL, VLDL, leptin, tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1) and hepatic malondialdehyde (MDA) compared with group I. Meanwhile, hepatic superoxide dismutase (SOD), glutathione GSH with serum HDL, adiponectin were significantly decreased (P < 0.05). These changes were to a less extent in group III. MTF or NAC individually resulted in improvement of most of these biochemical and histological parameters. These improvements were more pronounced in the combined groups VIII and IX versus each drug alone. NAC supplementation concomitant with MTF could be beneficial for the treatment of NAFLD and prevention of nonalcoholic steatohepatitis (NASH).

  18. Inhibition of HMGB1 release via salvianolic acid B-mediated SIRT1 up-regulation protects rats against non-alcoholic fatty liver disease.

    Science.gov (United States)

    Zeng, Wenjing; Shan, Wen; Gao, Lili; Gao, Dongyan; Hu, Yan; Wang, Guangzhi; Zhang, Ning; Li, Zhenlu; Tian, Xiaofeng; Xu, Wei; Peng, Jinyong; Ma, Xiaochi; Yao, Jihong

    2015-11-03

    The inflammatory mediator high-mobility group box 1 (HMGB1) plays a critical role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the regulation of HMGB1 in NAFLD, particularly through sirtuin 1 (SIRT1), remains unclear. In this study, we investigated the role of SIRT1-mediated inhibition of HMGB1 release in NAFLD and the effect of salvianolic acid B (SalB), which is a water-soluble phenolic acid extracted from Radix Salvia miltiorrhiza, on NAFLD through SIRT1/HMGB1 signaling. In vivo, SalB treatment significantly attenuated high-fat diet (HFD)-induced liver damage, hepatic steatosis, and inflammation. Importantly, SalB significantly inhibited HMGB1 nuclear translocation and release, accompanied by SIRT1 elevation. In HepG2 cells, palmitic acid (PA)-induced pro-inflammatory cytokines release were blocked by HMGB1 small interfering RNA (siRNA) transfection. Moreover, pharmacological SIRT1 inhibition by Ex527 induced HMGB1 translocation and release, whereas SIRT1 activation by resveratrol or SalB reversed this trend. SIRT1 siRNA abrogated the SalB-mediated inhibition of HMGB1 acetylation and release, suggesting that SalB-mediated protection occurs by SIRT1 targeting HMGB1 for deacetylation. We are the first to demonstrate that the SIRT1/HMGB1 pathway is a key therapeutic target for controlling NAFLD inflammation and that SalB confers protection against HFD- and PA-induced hepatic steatosis and inflammation through SIRT1-mediated HMGB1 deacetylation.

  19. Effects of insulin resistance and hepatic lipid accumulation on hepatic mRNA expression levels of apoB, MTP and L-FABP in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Higuchi, Nobito; Kato, Masaki; Tanaka, Masatake; Miyazaki, Masayuki; Takao, Shinichiro; Kohjima, Motoyuki; Kotoh, Kazuhiro; Enjoji, Munechika; Nakamuta, Makoto; Takayanagi, Ryoichi

    2011-11-01

    Non-alcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome, which is known to be associated with insulin resistance (IR). NAFLD occurs when the rate of hepatic fatty acid uptake from plasma and de novo fatty acid synthesis is greater than the rate of fatty acid oxidation and excretion as very low-density lipoprotein (VLDL). To estimate the effects of IR on hepatic lipid excretion, mRNA expression levels of genes involved in VLDL assembly were analyzed in NAFLD liver. Twenty-two histologically proven NAFLD patients and 10 healthy control subjects were enrolled in this study. mRNA was extracted from liver biopsy samples and real-time PCR was performed to quantify the expression levels of apolipoprotein B (apoB), microsomal triglyceride transfer protein (MTP) and liver fatty-acid binding protein (L-FABP). Hepatic expression levels of the genes were compared between NAFLD patients and control subjects. In NAFLD patients, we also examined correlations between expression levels of the genes and metabolic factors, including IR, and the extent of obesity and hepatic lipid accumulation. Hepatic expression levels of apoB, MTP and L-FABP were significantly up-regulated in NAFLD patients compared to control subjects. The expression levels of MTP were correlated with those of apoB, but not with those of L-FABP. In the NAFLD liver, the expression levels of MTP were significantly reduced in patients with HOMA-IR >2.5. In addition, a significant reduction in MTP expression was observed in livers with advanced steatosis. Enhanced expression of genes involved in VLDL assembly may be promoted to release excess lipid from NAFLD livers. However, the progression of IR and hepatic steatosis may attenuate this compensatory process.

  20. Role of liver biopsy in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Nalbantoglu, I L Ke; Brunt, Elizabeth M

    2014-07-21

    Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the "gold standard" for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease.

  1. Higher hepatic gene expression and serum levels of matrix metalloproteinase-2 are associated with steatohepatitis in non-alcoholic fatty liver diseases.

    Science.gov (United States)

    Toyoda, Hidenori; Kumada, Takashi; Kiriyama, Seiki; Tanikawa, Makoto; Hisanaga, Yasuhiro; Kanamori, Akira; Tada, Toshifumi; Murakami, Yoshiki

    2013-02-01

    We investigated the gene expression of tissue inhibitor metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) and serum levels of TIMPs, MMPs, and hyaluronic acid that are associated with liver fibrosis in 64 patients with nonalcoholic fatty liver diseases (NAFLD). Whereas, no differences were found between patients with and without nonalcoholic steatohepatitis (NASH) in serum levels of hyaluronic acid when excluding NASH patients with advanced fibrosis, the quantity of MMP2 mRNA in liver tissue and serum MMP2 levels were significantly higher in patients with NASH than those without, even focusing on patients with less advanced fibrosis, indicating the initiation of liver fibrosis.

  2. Herbal medicines and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Yao, Hong; Qiao, Yu-Jie; Zhao, Ya-Li; Tao, Xu-Feng; Xu, Li-Na; Yin, Lian-Hong; Qi, Yan; Peng, Jin-Yong

    2016-08-14

    Nonalcoholic fatty liver disease (NAFLD), which is characterized by excessive fat accumulation in the liver of patients who consume little or no alcohol, becomes increasingly common with rapid economic development. Long-term excess fat accumulation leads to NAFLD and represents a global health problem with no effective therapeutic approach. NAFLD is considered to be a series of complex, multifaceted pathological processes involving oxidative stress, inflammation, apoptosis, and metabolism. Over the past decades, herbal medicines have garnered growing attention as potential therapeutic agents to prevent and treat NAFLD, due to their high efficacy and low risk of side effects. In this review, we evaluate the use of herbal medicines (including traditional Chinese herbal formulas, crude extracts from medicinal plants, and pure natural products) to treat NAFLD. These herbal medicines are natural resources that can inform innovative drug research and the development of treatments for NAFLD in the future.