WorldWideScience

Sample records for mellitus non-alcoholic steatohepatitis

  1. Insulin resistance and neurodegeneration: Roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis

    OpenAIRE

    de la Monte, Suzanne M; Longato, Lisa; Tong, Ming; Wands, Jack R

    2009-01-01

    Recent studies have linked obesity, type 2 diabetes mellitus (T2DM) or non-alcoholic steatohepatitis (NASH) to insulin resistance in the brain, cognitive impairment and neurodegeneration. Insulin resistance compromises cell survival, metabolism and neuronal plasticity, and increases oxidative stress, cytokine activation and apoptosis. T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neu...

  2. Non-alcoholic steatohepatitis and liver transplantation.

    Science.gov (United States)

    Gitto, Stefano; Vukotic, Ranka; Vitale, Giovanni; Pirillo, Martina; Villa, Erica; Andreone, Pietro

    2016-06-01

    Non-alcoholic steatohepatitis is a growing liver-related health problem. In Europe, non-alcoholic fatty liver disease is the most usual reason of chronic liver illness while steatohepatitis, its progressive form, affects 1% of Europeans and North Americans. In the United States steatohepatitis-related cirrhosis is one of the main indications for liver transplant. A targeted stratification for patients waiting for transplant and affected by this disease is mandatory especially because of their increased cardiovascular and cancer risk. The adequate treatment of NAFLD is crucial for the reduction of the disease related morbidity and mortality. In post-transplant setting, the recurrent or de novo steatosis might seriously affect the allograft short- and long-term outcome. Many conditions can represent the basis of the post-transplant steatohepatitis: obesity, hyperlipidaemia, diabetes mellitus, arterial hypertension, immunosuppressant treatment, alcoholic habit and liver graft steatosis. Today, the only consolidated therapy is represented by a deep life-style intervention since the use of drug-based alternative strategies is still limited and a very few data are available for the post-transplant period. Targeted and personalized behaviour and pharmacological interventions have to be developed for both the pre- and post-transplant phase. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  3. Frequency Of Non-alcoholic Steatohepatitis On Histopathology In Patients Of Type 2 Diabetes Mellitus With Duration Of More Than 5 Years

    International Nuclear Information System (INIS)

    Seetlani, N.K.; Memon, A.R.; Tanveer, S.; Ali, A.; Ali, P.; Imran, K.; Haroon, H.

    2016-01-01

    Objective: To determine the frequency of non-alcoholic steatohepatitis (NASH) on histopathology in patients of type 2 diabetes mellitus with duration of more than 5 years. Study Design: Descriptive, cross-sectional study. Place and Duration of Study: Department of Medicine, Dow Medical College, Civil Hospital, Karachi, from November 2013 to April 2014. Methodology: Patients with type 2 diabetes mellitus of more than 5 years duration having raised alanine transaminases level and fatty liver on ultrasonography were selected. Informed consent was obtained and liver biopsy was performed in all patients by experienced physician of Civil Hospital Karachi. All samples of biopsy were sent for histopathology. Those patients with hepatitis B, C and D and steatosis like alcoholic and hypertriglyceridemia were excluded from the study. Descriptive statistics were calculated on SPSS version 17. Results: Out of the 262 cases, 56.49 percent (148/262) showed non-alcoholic steatohepatitis on the basis of histopathology. The mean age of the patients was 50.72 ±8.48 years. Median (interquartile) duration of diabetes mellitus of the cases was 9 years (15 - 4). Out of 148 NASH cases, 56.1 percent (83/148) were males and 43.9 percent (65/148) were females. Conclusion: Nonalcoholic steatohepatitis is an increasingly important and unrecognised spectrum of chronic liver disease associated with high prevalence of diabetes that is often overlooked and diagnosed with complications. So early recognition of these patients can prevent further complications. (author)

  4. Non-alcoholic steatohepatitis : Clinical significance and pathogenesis

    NARCIS (Netherlands)

    de Knegt, RJ

    2001-01-01

    Non-alcoholic steatohepatitis (NASH) is a form of liver disease resembling alcoholic liver disease in a patient who does not consume significant amounts of alcohol. Since its first description in 1980 it has been recognized with increasing frequency. The natural course is relatively benign, but

  5. [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.

  6. New therapeutic perspectives in non-alcoholic steatohepatitis.

    Science.gov (United States)

    Ampuero, Javier; Sánchez-Torrijos, Yolanda; Aguilera, Virginia; Bellido, Francisco; Romero-Gómez, Manuel

    2018-02-01

    Management of non-alcoholic steatohepatitis is focused on restitution of metabolic derangement, weight loss and drugs able to improve steatosis, ballooning and fibrosis. Life-style interventions based on Mediterranean diet and increasing physical activity are the first line therapy. In patients with unsuccessful life-style intervention several drugs are under development: agonist PPAR, agonist GLP-1R and agonist FXR together with drugs focussing on inflammation, ballooning, apoptosis and fibrosis. Bariatric surgery or advanced endoscopy are reserved for morbid obese without response to life-style intervention and weighting loss drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  7. Immunological Mechanisms in the Pathophysiology of Non-Alcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Sven Francque

    2013-10-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is characterized by the presence of steatosis, inflammation and hepatocyte injury and constitutes hepatic manifestation of the metabolic syndrome. The pathogenesis of NASH is complex and implicates cross-talk between different metabolically active sites, such as liver and adipose tissue. Obesity is considered a chronic low-grade inflammatory state and the liver has been recognized as being an “immunological organ”. The complex role of the immune system in the pathogenesis of NASH is currently raising great interest, also in view of the possible therapeutic potential of immunotherapy in NASH. This review focuses on the disturbances of the cells constituting the innate and adaptive immune system in the liver and in adipose tissue.

  8. A classification model for non-alcoholic steatohepatitis (NASH) using confocal Raman micro-spectroscopy

    Science.gov (United States)

    Yan, Jie; Yu, Yang; Kang, Jeon Woong; Tam, Zhi Yang; Xu, Shuoyu; Fong, Eliza Li Shan; Singh, Surya Pratap; Song, Ziwei; Tucker Kellogg, Lisa; So, Peter; Yu, Hanry

    2017-07-01

    We combined Raman micro-spectroscopy and machine learning techniques to develop a classification model based on a well-established non-alcoholic steatohepatitis (NASH) mouse model, using spectrum pre-processing, biochemical component analysis (BCA) and logistic regression.

  9. Lipotoxicity and steatohepatitis in an overfed mouse model for non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Gaemers, Ingrid C.; Stallen, Jan M.; Kunne, Cindy; Wallner, Christian; van Werven, Jochem; Nederveen, Aart; Lamers, Wouter H.

    2011-01-01

    The major risk factors for non-alcoholic fatty liver disease (NAFLD) are obesity, insulin resistance and dyslipidemia. The cause for progression from the steatosis stage to the inflammatory condition (non-alcoholic steatohepatitis (NASH)) remains elusive at present. Aim of this study was to test

  10. Methionine- and choline-deficient diet induces hepatic changes characteristic of non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Éder Marcolin

    2011-03-01

    Full Text Available CONTEXT: Non-alcoholic steatohepatitis is a disease with a high incidence, difficult diagnosis, and as yet no effective treatment. So, the use of experimental models for non-alcoholic steatohepatitis induction and the study of its routes of development have been studied. OBJECTIVES: This study was designed to develop an experimental model of non-alcoholic steatohepatitis based on a methionine- and choline-deficient diet that is manufactured in Brazil so as to evaluate the liver alterations resulting from the disorder. METHODS: Thirty male C57BL6 mice divided in two groups (n = 15 were used: the experimental group fed a methionine- and choline-deficient diet manufactured by Brazilian company PragSoluções®, and the control group fed a normal diet, for a period of 2 weeks. The animals were then killed by exsanguination to sample blood for systemic biochemical analyses, and subsequently submitted to laparotomy with total hepatectomy and preparation of the material for histological analysis. The statistical analysis was done using the Student's t-test for independent samples, with significance level of 5%. RESULTS: The mice that received the methionine- and choline-deficient diet showed weight loss and significant increase in hepatic damage enzymes, as well as decreased systemic levels of glycemia, triglycerides, total cholesterol, HDL and VLDL. The diagnosis of non-alcoholic steatohepatitis was performed in 100% of the mice that were fed the methionine- and choline-deficient diet. All non-alcoholic steatohepatitis animals showed some degree of macrovesicular steatosis, ballooning, and inflammatory process. None of the animals which were fed the control diet presented histological alterations. All non-alcoholic steatohepatitis animals showed significantly increased lipoperoxidation and antioxidant enzyme GSH activity. CONCLUSION: The low cost and easily accessible methionine- and choline-deficient diet explored in this study is highly effective in

  11. Low incidence of non-alcoholic steatohepatitis in a Danish liver unit

    DEFF Research Database (Denmark)

    Semb, Synne; Dam-Larsen, Sanne; Mogensen, Anne Mellon

    2012-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of histological lesions ranging from steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. Simple steatosis is generally benign, while NASH can progress to severe liver disease. The aim of the present study was to quantify the nu...... the number of patients with NASH and assess the prognosis associated with the condition in a large Danish referral centre for liver disease....

  12. Comparison of clinical, biochemical and histological features of alcoholic steatohepatitis and non-alcoholic steatohepatitis in Asian Indian patients

    Directory of Open Access Journals (Sweden)

    Singh Deepak

    2010-07-01

    Full Text Available Background: Alcoholic steatohepatitis (ASH and non-alcoholic steatohepatitis (NASH are significant forms of liver disease and may progress to end-stage liver disease, cirrhosis and potentially malignant complications. The most difficult aspect of establishing a diagnosis of NASH is distinguishing it from ASH. Laboratory markers such as AST, ALT and GGT lack sufficient sensitivity and specificity. Aim: To study the clinical, biochemical and histological differences between non-alcoholic steatohepatitis (NASH and alcoholic steatohepatitis (ASH. Materials and Methods: Sixty histologically confirmed cases of non-alcoholic steatohepatitis and 38 cases of alcoholic steatohepatitis were included in the study. A modified form of scoring system proposed by Yip and Burt was used to grade histological features of NASH and ASH. Results: Mean age was 42.85 ± 12.36 years in ASH group and 35.07 ± 8.06 years for NASH group. Male: Female ratio was 37:1 in ASH and 4:1 in NASH. The mean ALT (P = 0.012, SAP (P = 0.003, serum bilirubin (P = 0.001, AST/ALT ratio (P = 0.03, steatosis (P < 0.001, ballooning degeneration of hepatocytes (P < 0.001, portal inflammation (P < 0.001, Mallory hyaline (P = 0.001, ductular proliferation and fibrosis (P < 0.001 showed a significant difference between ASH and NASH cases. Discussion: Older age, male sex, larger derangement of serum biochemistry, high serum bilirubin, AST/ALT > 1, more ballooning degeneration, portal inflammation, Mallory′s hyaline, hepatocytic and ductular cholestasis, ductular proliferation and higher stage of fibrosis favors a diagnosis of ASH. Younger age, high ALT, AST/ALT < 1, higher grade of steatosis and absence of extensive neutrophilic portal inflammation favors a diagnosis of NASH.

  13. Beneficial effects of mineralocorticoid receptor blockade in experimental non-alcoholic steatohepatitis

    NARCIS (Netherlands)

    Pizarro, Margarita; Solis, Nancy; Quintero, Pablo; Barrera, Francisco; Cabrera, Daniel; Rojas-de Santiago, Pamela; Arab, Juan P.; Padilla, Oslando; Roa, Juan C.; Moshage, Han; Wree, Alexander; Inzaugarat, Eugenia; Feldstein, Ariel E.; Fardella, Carlos E.; Baudrand, Rene; Riquelme, Arnoldo; Arrese, Marco

    BackgroundTherapeutic options to treat Non-alcoholic steatohepatitis (NASH) are limited. Mineralocorticoid receptor (MR) activation could play a role in hepatic fibrogenesis and its modulation could be beneficial for NASH. AimTo investigate whether eplerenone, a specific MR antagonist, ameliorates

  14. Intrahepatic cholesterol influences progression, inhibition and reversal of non-alcoholic steatohepatitis in hyperlipidemic mice

    NARCIS (Netherlands)

    Wouters, Kristiaan; van Bilsen, Marc; van Gorp, Patrick J.; Bieghs, Veerle; Luetjohann, Dieter; Kerksiek, Anja; Staels, Bart; Hofker, Marten H.; Shiri-Sverdlov, Ronit

    2010-01-01

    Hepatic inflammation is the key factor in non-alcoholic steatohepatitis (NASH) and promotes progression to liver damage. We recently identified dietary cholesterol as the cause of hepatic inflammation in hyperlipidemic mice. We now show that hepatic transcriptome responses are strongly dependent on

  15. Rapid development of non-alcoholic steatohepatitis in Psammomys obesus (Israeli sand rat.

    Directory of Open Access Journals (Sweden)

    Briana Spolding

    Full Text Available BACKGROUND AND AIMS: A major impediment to establishing new treatments for non-alcoholic steatohepatitis is the lack of suitable animal models that accurately mimic the biochemical and metabolic characteristics of the disease. The aim of this study was to explore a unique polygenic animal model of metabolic disease as a model of non-alcoholic steatohepatitis by determining the effects of 2% dietary cholesterol supplementation on metabolic and liver endpoints in Psammomys obesus (Israeli sand rat. METHODS: P. obesus were provided ad libitum access to either a standard rodent diet (20% kcal/fat or a standard rodent diet supplemented with 2% cholesterol (w/w for 4 weeks. Histological sections of liver from animals on both diets were examined for key features of non-alcoholic steatohepatitis. The expression levels of key genes involved in hepatic lipid metabolism were measured by real-time PCR. RESULTS: P. obesus fed a cholesterol-supplemented diet exhibited profound hepatomegaly and steatosis, and higher plasma transaminase levels. Histological analysis identified extensive steatosis, inflammation, hepatocyte injury and fibrosis. Hepatic gene expression profiling revealed decreased expression of genes involved in delivery and uptake of lipids, and fatty acid and triglyceride synthesis, and increased expression of genes involved in very low density lipoprotein cholesterol synthesis, triglyceride and cholesterol export. CONCLUSIONS: P. obesus rapidly develop non-alcoholic steatohepatitis when fed a cholesterol-supplemented diet that appears to be histologically and mechanistically similar to patients.

  16. Individualized exercise prescription in non-alcoholic steatohepatitis: a case report

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Sánchez-Martos

    2015-03-01

    Full Text Available The effect of an individualized exercise programme on a non-alcoholic steatohepatitis case is presented. Before entering the programme the patient was treated with conventional recommendations on diet plus aerobic exercise during fourteen years, without major improvements of his analytical parameters. Two years after including him in a tailored exercise programme, aimed to fulfil the recommendations of the American College of Sports Medicine, his blood markers of liver dysfunction and cardio-metabolic risk tended to improve. Consequently, our data support the idea that in non-alcoholic steatohepatitis the exercise-based therapeutic interventions should be individualized taking into account the cardio-respiratory and muscular fitness of the patient, rather than using generic behavioural recommendations.

  17. 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.

  18. 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.

  19. An update on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Asia.

    Science.gov (United States)

    Hsu, Ching-Sheng; Kao, Jia-Horng

    2017-08-01

    Non-alcoholic fatty liver disease (NAFLD) has become the most overwhelming liver disease in Asia. In consideration of its increasing medical and economic impact on Asian people, it is time for us to review the update data in Asian countries and formulate strategies to cope with this emerging health problem in Asia. Moreover, growing data indicates that NAFLD may be a systemic disease, not just confined to liver-specific morbidity and mortality, but also associated with several extra-hepatic manifestations, such as cardiovascular diseases, chronic renal diseases, and malignancy. As the co-occurrence of NAFLD and viral hepatitis is common in Asia, issues related to the impact of NAFLD on the clinical outcomes and management of viral hepatitis remain to be elucidated. Areas covered: In this article, a narrative review was conducted, searching for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database till August 2016. Studies relevant to the emerging data of NAFLD in Asia, including the diagnosis, risk factors, the assessment and management of Asian NAFLD patients were examined and discussed. Expert commentary: Collaboration in Asian countries to develop an effective and practical measurement to assess the severity of NAFLD is urgently required.

  20. A disease-specific quality of life instrument for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: CLDQ-NAFLD.

    Science.gov (United States)

    Younossi, Zobair M; Stepanova, Maria; Henry, Linda; Racila, Andrei; Lam, Brian; Pham, Huong T; Hunt, Sharon

    2017-08-01

    Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are the most common causes of chronic liver disease with known negative impact on patients' health-related quality of life. Our aim was to validate a disease-specific health-related quality of life instrument useful for efficacy trials involving patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. From a long item selection questionnaire, we selected relevant items which, by factor analysis, were grouped into domains constituting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version. The developed instrument was subjected to internal validity, test-retest reliability and construct validity assessment using standard methods. For development of the Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument, a 75-item-long item selection questionnaire was administered to 25 patients with non-alcoholic fatty liver disease. After item reduction, factor analysis found that 98.7% of variance in the remaining items would be explained by six factors. Thus, the resulting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument had 36 items grouped into six domains: Abdominal Symptoms, Activity, Emotional, Fatigue, Systemic Symptoms, and Worry. The independent validation group included another 104 patients with non-alcoholic fatty liver disease. The Cronbach's alphas of 0.74-0.90 suggested good to excellent internal consistency of the domains. Furthermore, the presence of obesity and history of depression were discriminated best by Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version scores (P.15, intraclass correlations .76-.88). The Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version is a disease-specific health-related quality of life instrument developed and validated using an established methodology and useful for clinical trials of non-alcoholic

  1. Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis.

    Science.gov (United States)

    Koo, Bo Kyung; Kim, Donghee; Joo, Sae Kyung; Kim, Jung Ho; Chang, Mee Soo; Kim, Byeong Gwan; Lee, Kook Lae; Kim, Won

    2017-01-01

    We explored whether sarcopenia is associated with the histological severity of non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) and significant fibrosis. In a biopsy-proven NAFLD cohort, the appendicular skeletal muscle mass (ASM) was measured. Sarcopenia was defined as a ASM/body weight (ASM%) value beyond two standard deviations below the mean for healthy young adults. Among the entire set of 309 subjects, the prevalence of sarcopenia in subjects without NAFLD, with non-alcoholic fatty liver (NAFL), and with NASH were 8.7%, 17.9%, and 35.0%, respectively (psarcopenia than in those without (45.7% vs. 24.7%; psarcopenia was associated with NAFLD (odds ratio [OR], 3.82; 95% confidence interval [CI], 1.58-9.25), which became insignificant after adjustment for body mass index (BMI), diabetes, and hypertension. Among NAFLD subjects, subjects with sarcopenia were more likely to have NASH than those without sarcopenia through a multivariate analysis adjusted for age, gender, BMI, hypertension, diabetes, and smoking status (OR, 2.28; 95% CI, 1.21-4.30), and this finding was obtained even after adjustment for insulin resistance (OR, 2.30; 95% CI, 1.08-4.93). Sarcopenia was also associated with significant fibrosis independent of BMI and insulin resistance (OR, 2.05; 95% CI, 1.01-4.16). In this large biopsy-proven NAFLD cohort, sarcopenia was significantly associated with NASH and significant fibrosis. Low muscle mass was found to be associated with histological severity in non-alcoholic fatty liver disease, and sarcopenia was significantly associated with non-alcoholic steatohepatitis and significant fibrosis, independent of obesity, inflammation, and insulin resistance. Clinical trial number: NCT 02206841. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  2. Differences in innate immune signaling between alcoholic and non-alcoholic steatohepatitis.

    Science.gov (United States)

    Petrasek, Jan; Csak, Timea; Ganz, Michal; Szabo, Gyongyi

    2013-08-01

    The similar histopathological characteristics of alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH), and the crucial role of the innate immune response in both conditions may lead to the assumption that ASH and NASH represent the same pathophysiological entities caused by different risk factors. In this review paper, we elaborate on the pathophysiological differences between these two entities and highlight the disease-specific involvement of signaling molecules downstream of the Toll-like receptor 4, and the differential mechanism by which the inflammasome contributes to ASH versus NASH. Our findings emphasize that ASH and NASH have disease-specific mechanisms and therefore represent distinct biological entities. Further studies are needed to dissect the emerging differences in pathogenesis of these two conditions. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  3. Hepatocellular carcinoma and non-alcoholic steatohepatitis: The state of play.

    Science.gov (United States)

    Charrez, Bérénice; Qiao, Liang; Hebbard, Lionel

    2016-02-28

    Hepatocellular carcinoma (HCC) is now the fifth cancer of greatest frequency and the second leading cause of cancer related deaths worldwide. Chief amongst the risks of HCC are hepatitis B and C infection, aflatoxin B1 ingestion, alcoholism and obesity. The latter can promote non-alcoholic fatty liver disease (NAFLD), that can lead to the inflammatory form non-alcoholic steatohepatitis (NASH), and can in turn promote HCC. The mechanisms by which NASH promotes HCC are only beginning to be characterized. Here in this review, we give a summary of the recent findings that describe and associate NAFLD and NASH with the subsequent HCC progression. We will focus our discussion on clinical and genomic associations that describe new risks for NAFLD and NASH promoted HCC. In addition, we will consider novel murine models that clarify some of the mechanisms that drive NASH HCC formation.

  4. Prevalence of Non-alcoholic Fatty Liver Disease and Steatohepatitis Risk Factors in Patients Undergoing Bariatric Surgery.

    Science.gov (United States)

    Morita, Shinhiti; Neto, Dalísio De Santi; Morita, Flávio Hiroshi Ananias; Morita, Nina Kimie; Lobo, Suzana Margareth Ajeje

    2015-12-01

    Non-alcoholic fatty liver disease (NAFLD) associated with obesity comprises pathological changes ranging from steatosis to steatohepatitis; these can evolve to cirrhosis and hepatocellular carcinoma. The objectives of this study are to assess the prevalence of and predictive markers for steatohepatitis in obese patients undergoing bariatric surgery. A prospective study of 184 morbidly obese patients undergoing bariatric surgery formed the study cohort. Patients taking potentially hepatotoxic medications and those with viral diseases and a history of excessive alcohol consumption were excluded. Liver biopsies were performed during surgery with a "Trucut" needle. Patients were classified into the following groups according to the histopathological findings: normal, steatosis, mild steatohepatitis, and moderate-severe steatohepatitis. Factors associated with steatohepatitis were evaluated using logistic regression. p values non-invasive predictive markers for the diagnosis and management of steatohepatitis in morbidly obese patients.

  5. Molecular Mechanisms and New Treatment Strategies for Non-Alcoholic Steatohepatitis (NASH

    Directory of Open Access Journals (Sweden)

    Akinobu Takaki

    2014-04-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of non-alcoholic fatty liver disease (NAFLD, in which most patients exhibit non-progressive, non-alcoholic fatty liver (NAFL attributable to simple steatosis. Multiple hits, including genetic differences, fat accumulation, insulin resistance and intestinal microbiota changes, account for the progression of NASH. NAFLD is strongly associated with obesity, which induces adipokine secretion, endoplasmic reticulum (ER and oxidative stress at the cellular level, which in turn induces hepatic steatosis, inflammation and fibrosis. Among these factors, gut microbiota are acknowledged as having an important role in initiating this multifactorial disease. Oxidative stress is considered to be a key contributor in the progression from NAFL to NASH. Macrophage infiltration is apparent in NAFL and NASH, while T-cell infiltration is apparent in NASH. Although several clinical trials have shown that antioxidative therapy with vitamin E can effectively control hepatitis pathology in the short term, the long-term effects remain obscure and have often proved to be ineffective in many other diseases. Several long-term antioxidant protocols have failed to reduce mortality. New treatment modalities that incorporate current understanding of NAFLD molecular pathogenesis must be considered.

  6. Rapid Recovery from Acute Liver Failure Secondary to Pancreatoduodenectomy-Related Non-Alcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Kazushige Nirei

    2013-01-01

    Full Text Available This report describes a case of liver failure secondary to pancreatoduodenectomy and rapid recovery following treatment. A 68-year-old woman with cancer on the ampulla of Vater underwent surgery for pancreatoduodenectomy. The patient developed liver failure 3 months postsurgically. She was hospitalized after presenting with jaundice, hypoalbuminemia and decreased serum zinc. Computed tomography (CT of the abdomen showed a reduction in CT attenuation values postoperatively. We suspected fatty liver due to impaired absorption caused by pancreatoduodenectomy. We initiated treatment with branched-chain amino acids and a zinc formulation orally. Trace elements were administered intravenously. Two months after treatment, there was a noticeable improvement in CT findings. The patient’s jaundice and hypoalbuminemia prompted a liver biopsy, which led to a diagnosis of non-alcoholic steatohepatitis.

  7. Early diet-induced non-alcoholic steatohepatitis in APOE2 knock-in mice and its prevention by fibrates

    NARCIS (Netherlands)

    Shiri-Sverdlov, Ronit; Wouters, Kristiaan; van Gorp, Patrick J.; Gijbels, Marion J.; Noel, Benoit; Buffat, Laurent; Staels, Bart; Maeda, Nobuyo; van Bilsen, Marc; Hofker, Marten H.

    2006-01-01

    The molecular mechanisms leading to Non-Alcoholic Steatohepatitis (NASH) are not fully understood. In mice, NASH can be inhibited by fenofibrate, a synthetic agonist for the nuclear receptor peroxisome proliferator activated receptor alpha, which regulates hepatic triglyceride metabolism. This study

  8. Special features of bile acids spectral composition in patients with hyperuricemia in combination with obesity and non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Олена Володимирівна Барабанчик

    2015-10-01

    Full Text Available Aim. To study changes of the bile acids spectral composition in patients with hyperuricemia combined with obesity and non-alcoholic steatohepatitis using thin-layer chromatography.Materials and methods. We examined 146 patients separated in two groups. The main group included 84 patients with hyperurecimia combined with obesity and non-alcoholic steatohepatitis. 62 patients with non-alcoholic steatohepatitis without additional factors of metabolic syndrome formed the control group. The non-alcoholic steatohepatitis (NASH was diagnosed on the base of criteria of exclusion of the chronic diffuse disease of liver of viral, autoimmune, inherited and medicamental genesis as a cause of cytolytic syndrome and also increase of exogeneity and decrease of sound conductivity of the liver according to the results of ultrasound examination.Results. Examined patients with hyperurecemia combined with NASH and obesity demonstrated the reliable increase of cholic acid level in cystic bile in 2,9 times (р<0,001 and deoxycholic acid level in 2,6 times (р<0,001. We observed decrease of taurocholic acid in cystic bile in 1,4 times (р<0,001 and decrease of glycocholic acid in 2,1 times (р<0,01. We noticed an increase of index of taurohenodeoxycholic and taurodeoxycholic acids mixture in 1,5 times (р<0,05 and also glycohenodeoxycholic and glycodeoxycholic ones in 1,3 times (р<0,01.Conclusions. So during the research there were demonstrated changes of spectral composition of bile acids in patients with hyperuricemia combined with obesity and non-alcoholic steatohepatitis. There was demonstrated an importance of defining the bile acids spectrum with the method of thin-layer chromatography for further prevention of cholelithiasis development

  9. Novel Molecular Mechanisms in the Development of Non-Alcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Davide Povero

    2016-02-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is one of the most common causes of chronic liver disease in adults and children worldwide. NAFLD has become a severe health issue and it can progress towards a more severe form of the disease, the non-alcoholic steatohepatitis (NASH. A combination of environmental factors, host genetics, and gut microbiota leads to excessive accumulation of lipids in the liver (steatosis, which may result in lipotoxicity and trigger hepatocyte cell death, liver inflammation, fibrosis, and pathological angiogenesis. NASH can further progress towards liver cirrhosis and cancer. Over the last few years, cell-derived extracellular vesicles (EVs have been identified as effective cell-to-cell messengers that transfer several bioactive molecules in target cells, modulating the pathogenesis and progression of NASH. In this review, we focused on recently highlighted aspects of molecular pathogenesis of NASH, mediated by EVs via their bioactive components. The studies included in this review summarize the state of art regarding the role of EVs during the progression of NASH and bring novel insight about the potential use of EVs for diagnosis and therapeutic strategies for patients with this disease.

  10. Toll-like receptor-2 deficiency enhances non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Brady Kristen

    2010-05-01

    Full Text Available Abstract Background Previously we reported that mice deficient in toll-like receptor 4 (TLR-4 signalling were protected from diet-induced non-alcoholic steatohepatitis (NASH. Another member of the toll-like receptor family, TLR-2, has been shown to play a role in lipid trafficking via uptake of diacylated lipoproteins. However, a role for TLR-2 in NASH has not been elucidated. The objectives of the current study were to examine the influence of dietary fat quality and TLR-2 on NASH pathogenesis. Methods Steatohepatitis was induced in male Db, C57BL/6 and TLR-2-/- mice by feeding an L-amino acid-defined diet that was deficient in methionine and choline (MCDD. Mice fed the base diet supplemented with methionine and choline (control diet; CD were used as controls. To determine the role of fat quality, MCDD was enriched with polyunsaturated corn oil (PUFA or coconut oil that is comprised mostly of saturated fat (SAFA; the total amount of each fat was 112.9 g/kg of diet. After 8 weeks of feeding CD or MCDD, hepatic steatosis, inflammation and necrosis were evaluated in histological sections. Total RNA was extracted from frozen liver samples and mRNA expression of TNFα, collagen α1, IL-10, peroxisome proliferator-activated receptor-γ (PPAR-γ, TLR-4, and CD14, was analyzed via real-time PCR. Protein levels of TLR-2 were analyzed by western blot. Results Panlobular macrovessicular steatosis and diffuse leukocyte infiltration were noted in PUFA-fed Db mice. Histological scores demonstrated significantly less steatosis, inflammation and necrosis in SAFA-fed mice of all mouse strains. However, compared to wild type mice, hepatocellular damage was notably more severe in TLR-2-/- mice. Consistent with histological findings, mRNA expression of TNFα was elevated by approximately 3-fold in TLR-2-/- mice; PPAR-γ expression was blunted in this strain compared to wild type. Expression of the matrix protein collagen αI was also significantly higher in TLR-2

  11. Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma: Implications for Lycopene Intervention

    Directory of Open Access Journals (Sweden)

    Blanche C. Ip

    2013-12-01

    Full Text Available Increased prevalence of non-alcoholic fatty liver disease (NAFLD is one of the consequences of the current obesity epidemic. NAFLD is a major form of chronic liver disease that is highly prevalent in obese and overweight adults and children. Nonalcoholic steatohepatitis (NASH is the severe form of NAFLD, and uncontrolled inflammation as displayed in NASH has been identified as one of the key events in enhancing hepatic carcinogenesis. Lycopene is a non-provitamin A carotenoid and the pigment principally responsible for the characteristic deep-red color of ripe tomato and tomato products, as well as some fruits and vegetables. Lycopene’s innate antioxidant and anti-inflammatory properties have generated research interests on its capacity to protect against human diseases that are associated with oxidative stress and inflammation. In addition, differential mechanisms of lycopene metabolism including endogenous cleavage by carotenoid cleavage oxygenases (BCOs, generate lycopene metabolites that may also have significant impact on human disease development. However, it remains to be elucidated as to whether lycopene or its metabolites apolycopenoids have protective effects against obesity-related complications including inflammation and tumorigenesis. This article summarizes the in vivo experiments that elucidated molecular mechanisms associated with obesity-related hepatic inflammation and carcinogenesis. This review also provides an overview of lycopene metabolism, and the molecular pathways involved in the potential beneficial properties of lycopene and apolycopenoids. More research is clearly needed to fully unravel the importance of BCOs in tomato carotenoid metabolism and the consequence on human health and diseases.

  12. 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.

  13. Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model

    Energy Technology Data Exchange (ETDEWEB)

    Stefano, J.T.; Pereira, I.V.A.; Torres, M.M.; Bida, P.M. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Coelho, A.M.M. [Disciplina de Transplante de Órgãos do Aparelho Digestivo (LIM-37), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Xerfan, M.P. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Cogliati, B. [Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); Barbeiro, D.F. [Disciplina de Emergências Clínicas (LIM-51), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mazo, D.F.C. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Kubrusly, M.S.; D' Albuquerque, L.A.C. [Disciplina de Transplante de Órgãos do Aparelho Digestivo (LIM-37), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Souza, H.P. [Disciplina de Emergências Clínicas (LIM-51), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Carrilho, F.J.; Oliveira, C.P. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-02-24

    Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg{sup -1}·day{sup -1} by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.

  14. Usefulness of Cytokeratin-18M65 in Diagnosing Non-Alcoholic Steatohepatitis in Japanese Population.

    Science.gov (United States)

    Hasegawa, Yutaka; Kim, Soo Ryang; Hatae, Takashi; Ohta, Mitsuhiro; Fujinami, Aya; Sugimoto, Kayo; Kim, Ke Ih; Imoto, Susumu; Tohyama, Madoka; Kim, Soo Ki; Ikura, Yoshihiro; Kudo, Masatoshi

    2015-10-01

    The aim of this study was to evaluate cytokeratin-18M65 (CK-18M65) for distinguishing between simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) against healthy individuals (HIs) in Japanese population. The serum from 24 HIs, 21 patients with SS and 20 patients with NASH were examined. Serum CK-18M65 was measured by enzyme-linked immunosorbent assay. Aspartate aminotransferase was significantly different between NASH patients and HIs with p fashion in HIs and also in SS and NASH patients. Multivariate logistic regression analysis revealed that NASH could be diagnosed with the use of CK-18M65 alone (p = 0.0285, OR 1.0038, 95% CI 1.0004-1.0073). At the optimal cut-off level of 548 U/l, CK-18M65 had an AUC value of 0.7369, 60.00% sensitivity and 85.70% specificity. In patients with NASH, no significant difference was observed between low fibrosis (Stage 0-1, 794.30 ± 454.41, n = 10) and high fibrosis (Stage 2-3, 809.70 ± 641.43, n = 10; p = 0.5967) and between slight steatosis (Japanese population. © 2015 S. Karger AG, Basel.

  15. Fatty Acid Elongation in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Sonja M. Kessler

    2014-04-01

    Full Text Available Non-alcoholic steatohepatitis (NASH represents a risk factor for the development of hepatocellular carcinoma (HCC and is characterized by quantitative and qualitative changes in hepatic lipids. Since elongation of fatty acids from C16 to C18 has recently been reported to promote both hepatic lipid accumulation and inflammation we aimed to investigate whether a frequently used mouse NASH model reflects this clinically relevant feature and whether C16 to C18 elongation can be observed in HCC development. Feeding mice a methionine and choline deficient diet to model NASH not only increased total hepatic fatty acids and cholesterol, but also distinctly elevated the C18/C16 ratio, which was not changed in a model of simple steatosis (ob/ob mice. Depletion of Kupffer cells abrogated both quantitative and qualitative methionine-and-choline deficient (MCD-induced alterations in hepatic lipids. Interestingly, mimicking inflammatory events in early hepatocarcinogenesis by diethylnitrosamine-induced carcinogenesis (48 h increased hepatic lipids and the C18/C16 ratio. Analyses of human liver samples from patients with NASH or NASH-related HCC showed an elevated expression of the elongase ELOVL6, which is responsible for the elongation of C16 fatty acids. Taken together, our findings suggest a detrimental role of an altered fatty acid pattern in the progression of NASH-related liver disease.

  16. Diabetes mellitus and non-alcoholic fatty liver disease: the thread of Ariadne.

    Science.gov (United States)

    Kosmidou, Maria; Milionis, Haralampos

    2017-06-01

    Non alcoholic fatty liver disease (NAFLD, the hepatic fat accumulation) and non alcoholic steatohepatitis (NASH, the aggressive form of liver steatosis plus inflammation and hepatocyte necrosis) are reaching epidemic dimensions in subjects with diabetes mellitus (DM). Taking into account that the incidence of DM increases worldwide, these entities represent major health problems. There is accumulating evidence that diabetic subjects with NASH are at increased risk not only for cardiovascular disease compications but also for cirrhosis and hepatocellular cancer. On the other hand, the presence of NAFLD correlates with an increased risk for the development of DM. The most-widely accepted pathophysiological mechanisms relating DM and NAFLD include central obesity and insulin resistanc, but new insights are under scrutiny. Therapeutic modalities used for the management of diabetes have been studied for their impact on NAFLD/NASH and both neutral and beneficial effects have been reported. In this review, we discuss issues regarding the epidemiology, the pathophysiological pathways relating NAFLD with DM and consider strategies that may be useful in the management of NAFLD in the diabetic population.

  17. The effect of 12 weeks vitamin E supplemention and aerobic training on liver enzymes of non-alcoholic steatohepatitis patients

    Directory of Open Access Journals (Sweden)

    M Aghah

    2017-01-01

    Full Text Available Background and aim: Non-alcoholic steatohepatitis is a part of broad spectrum of chronic non-alcoholic fatty liver disease. The aim of present study was to evaluate the effect of 12 weeks vitamin E supplementation and aerobic training on liver enzymes level of non-alcoholic steatohepatitis patients (NASH.   Methods: In the present quasi-experimental study, 30 NASH patients, aged 25-50 years were participated, and divided into three groups of vitamin E (n=10, aerobic training (n=10 and combination (aerobic training plus vitamin E, n=10 randomly. Vitamin E Supplementation and aerobic training combination groups consumed 400 IU per day of Vitamin E Supplementation. Also in the group of aerobic exercise and combined, exercise program including the increasing activity of anaerobic (running on a treadmill with increasing intensity every two weeks 5% was carried out three times a week for 12 weeks. Data evaluation were analyzed using t-test, ANOVA and Scheffe. Results: A significant differences was observed  ALT (intra-group of vitamin E (0001/0 = p aerobic exercise (0001/0 = p and combination (001/0 = p, respectively.There was a significant difference was seen among pre – post training in AST in supplementation(P=0.001, aerobic training(P=0.001 and combination (P=0.002 groups. But no significant difference in ALP level observed(P>0.05. In comparison among the groups, a significant differences was observed between groups ALP vitamin E, combination aerobic exercise but no significant difference was observed among the groups at the levels of ALT and AST. Conclusion: The results of this study showed that vitamin E supplementation and aerobic training can improve non-alcoholic steatohepatitis Patients (NASH.  

  18. Non-Alcoholic Steatohepatitis (NASH): Risk Factors in Morbidly Obese Patients

    Science.gov (United States)

    Losekann, Alexandre; Weston, Antonio C.; de Mattos, Angelo A.; Tovo, Cristiane V.; de Carli, Luis A.; Espindola, Marilia B.; Pioner, Sergio R.; Coral, Gabriela P.

    2015-01-01

    The aim was to investigate the prevalence of non-alcoholic steatohepatitis (NASH) and risk factors for hepatic fibrosis in morbidly obese patients submitted to bariatric surgery. This retrospective study recruited all patients submitted to bariatric surgery from January 2007 to December 2012 at a reference attendance center of Southern Brazil. Clinical and biochemical data were studied as a function of the histological findings of liver biopsies done during the surgery. Steatosis was present in 226 (90.4%) and NASH in 176 (70.4%) cases. The diagnosis of cirrhosis was established in four cases (1.6%) and fibrosis in 108 (43.2%). Risk factors associated with NASH at multivariate analysis were alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN); glucose ≥ 126 mg/dL and triglycerides ≥ 150 mg/dL. All patients with ALT ≥1.5 times the ULN had NASH. When the presence of fibrosis was analyzed, ALT > 1.5 times the ULN and triglycerides ≥ 150 mg/dL were risk factors, furthermore, there was an increase of 1% in the prevalence of fibrosis for each year of age increase. Not only steatosis, but NASH is a frequent finding in MO patients. In the present study, ALT ≥ 1.5 times the ULN identifies all patients with NASH, this finding needs to be further validated in other studies. Moreover, the presence of fibrosis was associated with ALT, triglycerides and age, identifying a subset of patients with more severe disease. PMID:26512661

  19. Non-Alcoholic Steatohepatitis (NASH: Risk Factors in Morbidly Obese Patients

    Directory of Open Access Journals (Sweden)

    Alexandre Losekann

    2015-10-01

    Full Text Available The aim was to investigate the prevalence of non-alcoholic steatohepatitis (NASH and risk factors for hepatic fibrosis in morbidly obese patients submitted to bariatric surgery. This retrospective study recruited all patients submitted to bariatric surgery from January 2007 to December 2012 at a reference attendance center of Southern Brazil. Clinical and biochemical data were studied as a function of the histological findings of liver biopsies done during the surgery. Steatosis was present in 226 (90.4% and NASH in 176 (70.4% cases. The diagnosis of cirrhosis was established in four cases (1.6% and fibrosis in 108 (43.2%. Risk factors associated with NASH at multivariate analysis were alanine aminotransferase (ALT >1.5 times the upper limit of normal (ULN; glucose ≥ 126 mg/dL and triglycerides ≥ 150 mg/dL. All patients with ALT ≥1.5 times the ULN had NASH. When the presence of fibrosis was analyzed, ALT > 1.5 times the ULN and triglycerides ≥ 150 mg/dL were risk factors, furthermore, there was an increase of 1% in the prevalence of fibrosis for each year of age increase. Not only steatosis, but NASH is a frequent finding in MO patients. In the present study, ALT ≥ 1.5 times the ULN identifies all patients with NASH, this finding needs to be further validated in other studies. Moreover, the presence of fibrosis was associated with ALT, triglycerides and age, identifying a subset of patients with more severe disease.

  20. Fatty acid metabolism is altered in non-alcoholic steatohepatitis independent of obesity.

    Science.gov (United States)

    Walle, Paula; Takkunen, Markus; Männistö, Ville; Vaittinen, Maija; Lankinen, Maria; Kärjä, Vesa; Käkelä, Pirjo; Ågren, Jyrki; Tiainen, Mika; Schwab, Ursula; Kuusisto, Johanna; Laakso, Markku; Pihlajamäki, Jussi

    2016-05-01

    Non-alcoholic steatohepatitis (NASH) is associated with changes in fatty acid (FA) metabolism. However, specific changes in metabolism and hepatic mRNA expression related to NASH independent of simple steatosis, obesity and diet are unknown. Liver histology, serum and liver FA composition and estimated enzyme activities based on the FA ratios in cholesteryl esters and triglycerides were assessed in 92 obese participants of the Kuopio Obesity Surgery Study (KOBS) divided to those with normal liver, steatosis or NASH (30 men and 62 women, age 46.8±9.5years (mean±SD), BMI 44.2±6.2kg/m(2)). Plasma FA composition was also investigated in the Metabolic Syndrome in Men (METSIM) Study (n=769), in which serum alanine aminotransferase (ALT) was used as a marker of liver disease. Obese individuals with NASH had higher activity of estimated activities of delta-6 desaturase (D6D, pliver. Estimated activities of D5D, D6D and SCD1 correlated positively between liver and serum indicating that serum estimates reflected liver metabolism. Accordingly, NASH was associated with higher hepatic mRNA expression of corresponding genes FADS1, FADS2 and SCD. Finally, differences in FA metabolism that associated with NASH in obese individuals were also associated with high ALT in the METSIM Study. We demonstrated alterations in FA metabolism and endogenous desaturase activities that associate with NASH, independent of obesity and diet. This suggests that changes in endogenous FA metabolism are related to NASH and that they may contribute to the progression of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model

    International Nuclear Information System (INIS)

    Winkler, Sandra; Borkham-Kamphorst, Erawan; Stock, Peggy; Brückner, Sandra; Dollinger, Matthias; Weiskirchen, Ralf; Christ, Bruno

    2014-01-01

    Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. The aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver. - Highlights: • First time to show NASH in an immune-deficient mouse model. • Human MSC attenuate NASH and improve lipid homeostasis. • MSC act anti-fibrotic and augment liver regeneration by stimulation of proliferation. • Pre-clinical assessment of human MSC for stem cell-based therapy of NASH

  2. Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, Sandra, E-mail: sandra.pelz@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Borkham-Kamphorst, Erawan, E-mail: ekamphorst@ukaachen.de [Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen (Germany); Stock, Peggy, E-mail: peggy.stock@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Brückner, Sandra, E-mail: sandra.brueckner@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Dollinger, Matthias, E-mail: matthias.dollinger@uniklinik-ulm.de [Department for Internal Medicine I, University Hospital Ulm, Albert-Einstein-Allee 23, D-89081 Ulm (Germany); Weiskirchen, Ralf, E-mail: rweiskirchen@ukaachen.de [Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen (Germany); Christ, Bruno, E-mail: bruno.christ@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig (Germany)

    2014-08-15

    Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. The aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver. - Highlights: • First time to show NASH in an immune-deficient mouse model. • Human MSC attenuate NASH and improve lipid homeostasis. • MSC act anti-fibrotic and augment liver regeneration by stimulation of proliferation. • Pre-clinical assessment of human MSC for stem cell-based therapy of NASH.

  3. Placental extract ameliorates non-alcoholic steatohepatitis (NASH by exerting protective effects on endothelial cells

    Directory of Open Access Journals (Sweden)

    Akihiro Yamauchi

    2017-09-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma. Treatment with human placental extract (HPE reportedly ameliorates the hepatic injury. We evaluated the effect of HPE treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD diet-induced liver injury model, fibrosis started from regions adjacent to the sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the drinking water to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE. In both the HPE and control groups, fibrosis was seen in regions adjacent to the sinusoids, but the fibrosis was less pronounced in the HPE-treated mice. Levels of TNF-α and MMP9 expression were also significantly reduced in HPE-treated mice, and oxidative stress was suppressed in the perivascular region. In addition, HPE dose-dependently increased survival of cultured endothelial cells exposed to 100 μM H2O2, and it upregulated expression of eNOS and the anti-apoptotic factors bcl-2 and bcl-xL. From these observations, we conclude that HPE ameliorates NASH-associated pathologies by suppressing inflammation, oxidative stress and fibrosis. These beneficially effects of HPE are in part attributable to its protective effects on liver sinusoidal endothelial cells. HPE could thus be an attractive therapeutic candidate with which to suppress progression from simple fatty liver to NASH.

  4. Nonalcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Childhood: Endocrine-Metabolic “Mal-Programming”

    Science.gov (United States)

    Manti, Sara; Romano, Claudio; Chirico, Valeria; Filippelli, Martina; Cuppari, Caterina; Loddo, Italia; Salpietro, Carmelo; Arrigo, Teresa

    2014-01-01

    Context: Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased. Evidence Acquisition: A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver". Results: NAFLD/NASH is probably promoted by “multiple parallel hits”: environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown. Conclusions: Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH. PMID:24829591

  5. Effects of dark chocolate on endothelial function in patients with non-alcoholic steatohepatitis.

    Science.gov (United States)

    Loffredo, L; Baratta, F; Ludovica, P; Battaglia, S; Carnevale, R; Nocella, C; Novo, M; Pannitteri, G; Ceci, F; Angelico, F; Violi, F; Del Ben, M

    2018-02-01

    Oxidative stress plays a pivotal role in inducing endothelial dysfunction and progression from simple fatty liver steatosis (FLD) to non-alcoholic steatohepatitis (NASH). Polyphenols could reduce oxidative stress and restore endothelial function by inhibiting the nicotinamide-adenine-dinucleotide-phosphate (NADPH) oxidase isoform Nox2. The aim of this study was to assess endothelial function and oxidative stress in a population affected by simple FLD and NASH. Furthermore, we analysed the effect of high vs low content of cocoa polyphenols on endothelial function and oxidative stress in patients with NASH. In a cross-sectional study we analysed endothelial function, as assessed by flow-mediated dilation (FMD), and oxidative stress, as assessed by Nox2 activation, serum isoprostanes and nitric oxide bioavailability (NOx), in patients with NASH (n = 19), FLD (n = 19) and controls (n = 19). Then, we performed a randomized, cross-over study in 19 subjects with NASH comparing the effect of 14-days administration of 40 g of chocolate at high (dark chocolate, cocoa >85%) versus low content (milk chocolate, cocoa stress. Compared to controls, NASH and FLD patients had higher Nox2 activity and isoprostanes levels and lower FMD and NOx, with a significant gradient between FLD and NASH. The interventional study showed that, compared to baseline, FMD and NOx increased (from 2.9 ± 2.4 to 7.2 ± 3.0% p chocolate. A simple linear regression analysis showed that Δ (expressed by difference of values between before and after 14 days of chocolate assumption) of FMD was associated with Δ of Nox2 activity (Rs = -0.323; p = 0.04), serum isoprostanes (Rs: -0.553; p < 0.001) and NOx (Rs: 0.557; p < 0.001). Cocoa polyphenols improve endothelial function via Nox2 down-regulation in NASH patients. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of

  6. Lipid-lowering agents inhibit hepatic steatosis in a non-alcoholic steatohepatitis-derived hepatocellular carcinoma mouse model.

    Science.gov (United States)

    Orime, Kazuki; Shirakawa, Jun; Togashi, Yu; Tajima, Kazuki; Inoue, Hideaki; Nagashima, Yoji; Terauchi, Yasuo

    2016-02-05

    Non-alcoholic fatty liver disease (NAFLD) is associated with various metabolic disorders, and the therapeutic strategies for treating NAFLD and non-alcoholic steatohepatitis (NASH) have not been fully established. In the present study, we examined whether lipid-lowering agents inhibited the progression of NAFLD and tumorigenesis in a non-alcoholic steatohepatitis-derived hepatocellular carcinoma model mouse (STAM mice) generated by streptozotocin injection and a high-fat diet. Seven-week-old STAM mice were divided into groups fed a high-fat diet (Ctl) or a high-fat diet supplemented with ezetimibe (Ez), fenofibrate (Ff), rosuvastatin (Rs), ezetimibe plus fenofibrate (EF), or ezetimibe plus rosuvastatin (ER) for 4 weeks. At the end of the experiments, an oral glucose tolerance test, an insulin tolerance test, biochemical analyses using serum and liver, and a histological analysis of liver were performed in 11-week-old STAM mice. The lipid-lowering agents did not affect the body weight or the casual blood glucose levels in any of the groups. The serum triglyceride level was significantly decreased by Ff, Rs, and EF. Glucose tolerance was improved by Ez and Ff, but none of these agents improved insulin sensitivity. A histochemical analysis revealed that the lipid-lowering agents, with the exception of Rs, significantly inhibited the progression of hepatic steatosis. Nonetheless, no significant changes in the incidence of hepatic tumors were observed in any of the groups. Lipid-lowering agents inhibited the progression of hepatic steatosis without suppressing tumorigenesis in STAM mice. Our data has implications for the mechanism underlying steatosis-independent hepatic tumorigenesis in mice. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model with upregulation of mitochondrial pathway.

    Directory of Open Access Journals (Sweden)

    Hisashi Ishikawa

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of non-alcoholic fatty liver disease characterized by lobular inflammation, hepatocellular ballooning, and fibrosis with an inherent risk for progression to cirrhosis and hepatocellular carcinoma (HCC. Mitochondrial dysfunction appears to play a role in the progression from simple steatosis to NASH. L-carnitine (L-b-hydroxy-g-N-trimethylaminobutyric acid, an essential nutrient that converts fat into energy in mitochondria, has been shown to ameliorate liver damage. The aim of the present study was to explore the preventive and therapeutic effect of L-carnitine in NASH model mice. Eight-week-old male STAM mice, a NASH-cirrhosis-hepatocarcinogenic model, were divided into 3 experimental groups and fed as follows: 1 high-fat diet (HFD (control group; 2 HFD mixed with 0.28% L-carnitine (L-carnitine group; and 3 HFD mixed with 0.01% α-tocopherol (α-tocopherol group. After 4 or 8 weeks, mice were sacrificed. Blood samples and livers were collected, and hepatic tumors were counted and measured. Livers were subjected to histological study, immunohistochemical staining of 4-hydroxynonenal and ferritin, determination of 8-OHdG levels, mRNA and protein expressions for multiple genes, and metabolomic analysis. The intestinal microbiome was also analyzed. L-carnitine increased hepatic expression of genes related to long-chain fatty acid transport, mitochondrial β-oxidation, and antioxidant enzymes following suppression of hepatic oxidative stress markers and inflammatory cytokines in NASH, and mice treated with L-carnitine developed fewer liver tumors. Although α-tocopherol resulted in NASH improvement in the same manner as L-carnitine, it increased periodontitis-related microbiotic changes and hepatic iron transport-related gene expression and led to less effective for anti-hepatocarcinogenesis. Conclusion: L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model by

  8. Predictive value of ALT levels for non-alcoholic steatohepatitis (NASH) and advanced fibrosis in non-alcoholic fatty liver disease (NAFLD).

    Science.gov (United States)

    Verma, Siddharth; Jensen, Donald; Hart, John; Mohanty, Smruti R

    2013-10-01

    Non-alcoholic fatty liver disease (NAFLD) patients with elevated serum alanine aminotransferase (ALT) generally undergo a liver biopsy to evaluate for possible non-alcoholic steatohepatitis (NASH) or advanced fibrosis. However, patients with normal ALT could also have advanced stages of NAFLD. To determine ALT value that will accurately predict NASH and advanced fibrosis using area under the receiver operating characteristics curve (AUROC) analysis. Demographic, clinical and laboratory data of an ethnically diverse cohort of biopsy proven NAFLD patients were retrospectively analysed under univariate and multivariate analyses. Liver biopsies were scored using NASH clinical research network (NASH CRN) system. AUROC were performed for NAFLD Activity Score ≥5 (NASH) and fibrosis score ≥2 (advanced fibrosis). Two hundred and twenty-two patients were analysed. Fifty six (23%) had normal ALT. There was no difference in the rate of advanced fibrosis between normal and elevated ALT (26.8% vs. 18.1%, P = 0.19). However, significantly lower percentage of normal ALT group had NASH compared with elevated ALT group (10.7% vs. 28.9%, P ALT group had NASH or advanced fibrosis, whereas 53% of elevated ALT had no NASH or advanced fibrosis. Higher ALT values correlated with higher specificity, but lower sensitivity for both NASH and advanced fibrosis. AUROC for ALT level correlating NASH and advanced fibrosis were 0.62 and 0.46 respectively. There is no optimal ALT level to predict NASH and advanced fibrosis. Metabolic risk factors should be evaluated to select patients for a liver biopsy to confirm NASH and advanced fibrosis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Polychlorinated Biphenyl-Xenobiotic Nuclear Receptor Interactions Regulate Energy Metabolism, Behavior, and Inflammation in Non-alcoholic-Steatohepatitis.

    Science.gov (United States)

    Wahlang, Banrida; Prough, Russell A; Falkner, K Cameron; Hardesty, Josiah E; Song, Ming; Clair, Heather B; Clark, Barbara J; States, J Christopher; Arteel, Gavin E; Cave, Matthew C

    2016-02-01

    Polychlorinated biphenyls (PCBs) are environmental pollutants associated with non-alcoholic-steatohepatitis (NASH), diabetes, and obesity. We previously demonstrated that the PCB mixture, Aroclor 1260, induced steatohepatitis and activated nuclear receptors in a diet-induced obesity mouse model. This study aims to evaluate PCB interactions with the pregnane-xenobiotic receptor (Pxr: Nr1i2) and constitutive androstane receptor (Car: Nr1i3) in NASH. Wild type C57Bl/6 (WT), Pxr(-/-) and Car(-/-) mice were fed the high fat diet (42% milk fat) and exposed to a single dose of Aroclor 1260 (20 mg/kg) in this 12-week study. Metabolic phenotyping and analysis of serum, liver, and adipose was performed. Steatohepatitis was pathologically similar in all Aroclor-exposed groups, while Pxr(-/-) mice displayed higher basal pro-inflammatory cytokine levels. Pxr repressed Car expression as evident by increased basal Car/Cyp2b10 expression in Pxr(-/-) mice. Both Pxr(-/-) and Car(-/-) mice showed decreased basal respiratory exchange rate (RER) consistent with preferential lipid metabolism. Aroclor increased RER and carbohydrate metabolism, associated with increased light cycle activity in both knockouts, and decreased food consumption in the Car(-/-) mice. Aroclor exposure improved insulin sensitivity in WT mice but not glucose tolerance. The Aroclor-exposed, Pxr(-/-) mice displayed increased gluconeogenic gene expression. Lipid-oxidative gene expression was higher in WT and Pxr(-/-) mice although RER was not changed, suggesting PCB-mediated mitochondrial dysfunction. Therefore, Pxr and Car regulated inflammation, behavior, and energy metabolism in PCB-mediated NASH. Future studies should address the 'off-target' effects of PCBs in steatohepatitis. Published by Oxford University Press on behalf of the Society of Toxicology 2015. This work is written by US Government employees and is in the public domain in the US.

  10. Empagliflozin (an SGLT2 inhibitor), alone or in combination with linagliptin (a DPP-4 inhibitor), prevents steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis and diabetes

    OpenAIRE

    Jojima, Teruo; Tomotsune, Takanori; Iijima, Toshie; Akimoto, Kazumi; Suzuki, Kunihiro; Aso, Yoshimasa

    2016-01-01

    Background Sodium-glucose co-transporter-2 (SGLT2) inhibitors are new oral antidiabetic drugs that reduce hyperglycemia by promoting urinary glucose excretion. Glycosuria produced by SGLT2 inhibitors is associated with weight loss, mainly due to reduced fat volume. We investigated the effects of empagliflozin (selective SGLT2 inhibitor) and linagliptin (DPP-4 inhibitor) on steatohepatitis and fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH) with diabetes. Methods A novel NASH...

  11. Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

    NARCIS (Netherlands)

    Cabrera, Daniel; Wree, Alexander; Povero, Davide; Solís, Nancy; Hernandez, Alejandra; Pizarro, Margarita; Moshage, Han; Torres, Javiera; Feldstein, Ariel E; Cabello-Verrugio, Claudio; Brandan, Enrique; Barrera, Francisco; Arab, Juan Pablo; Arrese, Marco

    2017-01-01

    Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-kB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the

  12. Mirtoselect, an anthocyanin-rich bilberry extract, attenuates non-alcoholic steatohepatitis and associated fibrosis in ApoE∗3Leiden mice

    NARCIS (Netherlands)

    Morrison, M.C.; Liang, W.; Mulder, P.; Verschuren, L.; Pieterman, E.; Toet, K.; Heeringa, P.; Wielinga, P.Y.; Kooistra, T.; Kleemann, R.

    2015-01-01

    Background & Aims Anthocyanins may have beneficial effects on lipid metabolism and inflammation and are demonstrated to have hepatoprotective properties in models of restraint-stress- and chemically-induced liver damage. However, their potential to protect against non-alcoholic steatohepatitis

  13. Mirtoselect, an anthocyanin-rich bilberry extract, attenuates non-alcoholic steatohepatitis and associated fibrosis in ApoE*3Leiden mice

    NARCIS (Netherlands)

    Morrison, Martine C.; Liang, Wen; Mulder, Petra; Verschuren, Lars; Pieterman, Elsbet; Toet, Karin; Heeringa, Peter; Wielinga, Peter Y.; Kooistra, Teake; Kleemann, Robert

    Background & Aims: Anthocyanins may have beneficial effects on lipid metabolism and inflammation and are demonstrated to have hepatoprotective properties in models of restraint-stressand chemically-induced liver damage. However, their potential to protect against non-alcoholic steatohepatitis (NASH)

  14. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?

    Science.gov (United States)

    Firneisz, Gábor

    2014-07-21

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

  15. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age?

    Science.gov (United States)

    Firneisz, Gábor

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients. PMID:25083080

  16. Hepatic crown-like structure: a unique histological feature in non-alcoholic steatohepatitis in mice and humans.

    Directory of Open Access Journals (Sweden)

    Michiko Itoh

    Full Text Available Although macrophages are thought to be crucial for the pathogenesis of chronic inflammatory diseases, how they are involved in disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH is poorly understood. Here we report the unique histological structure termed "hepatic crown-like structures (hCLS" in the mouse model of human NASH; melanocortin-4 receptor deficient mice fed a Western diet. In hCLS, CD11c-positive macrophages aggregate to surround hepatocytes with large lipid droplets, which is similar to those described in obese adipose tissue. Histological analysis revealed that hCLS is closely associated with activated fibroblasts and collagen deposition. When treatment with clodronate liposomes effectively depletes macrophages scattered in the liver, with those in hCLS intact, hepatic expression of inflammatory and fibrogenic genes is unaffected, suggesting that hCLS is an important source of inflammation and fibrosis during the progression of NASH. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. We also observed increased number of hCLS in the liver of non-alcoholic fatty liver disease/NASH patients. Collectively, our data provide evidence that hCLS is involved in the development of hepatic inflammation and fibrosis, thereby suggesting its pathophysiologic role in disease progression from simple steatosis to NASH.

  17. The adaptor protein alpha-syntrophin is reduced in human non-alcoholic steatohepatitis but is unchanged in hepatocellular carcinoma.

    Science.gov (United States)

    Rein-Fischboeck, Lisa; Pohl, Rebekka; Haberl, Elisabeth M; Weiss, Thomas S; Buechler, Christa

    2017-10-01

    The adaptor protein alpha-syntrophin (SNTA) is differentially expressed in varying types of cancer and affects triglyceride levels, inflammatory response and cell proliferation. However, little is known about the expression of SNTA in liver diseases. Non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis, inflammation and eventually fibrosis, and may progress to hepatocellular carcinoma (HCC). Here, SNTA mRNA was analyzed in liver tissues from 71 non-alcoholic fatty liver disease patients and 32 controls to assess associations with disease characteristics. SNTA mRNA expression was reduced in NASH liver and negatively correlated with steatosis, inflammation, fibrosis and NASH scores. In the NASH patients, those with type 2 diabetes had a higher fibrosis score, reduced inflammation and increased hepatic SNTA mRNA levels demonstrating a strong association of SNTA mRNA levels with inflammation. Recently, we have shown diminished expression of the high-density lipoprotein scavenger receptor BI (SR-BI) in the liver of syntrophin-deficient mice. Indeed, hepatic SNTA and SR-BI mRNA were positively correlated. SNTA protein was further determined in tumor and non-tumorous tissues of 21 HCC patients. Protein expression was unchanged in the tumor and not related to staging and grading. Present study identified associations of hepatic SNTA mRNA levels with SR-BI and features of NASH assuming a function of this protein in chronic liver disease and cholesterol metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Heme oxygenase-1 prevents non-alcoholic steatohepatitis through suppressing hepatocyte apoptosis in mice

    Directory of Open Access Journals (Sweden)

    Fu Na

    2010-10-01

    Full Text Available Abstract Objective Heme oxygenase-1 (HO-1, the rate-limiting enzyme in heme catabolism, has been reported to have potential antioxidant properties. However, the role of HO-1 on hepatocyte apoptosis remains unclear. We aim to elucidate the effects of HO-1 on oxidative stress related hepatocellular apoptosis in nutritional steatohepatitis in mice. Methods C57BL/6J mice were fed with methionine-choline deficient (MCD diet for four weeks to induce hepatic steatohepatitis. HO-1 chemical inducer (hemin, HO-1 chemical inhibitor zinc protoporphyrin IX (ZnPP-IX and/or adenovirus carrying HO-1 gene (Ad-HO-1 were administered to mice, respectively. Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay, the mRNA and protein expression of apoptosis related genes were assayed by quantitative real-time PCR and Western blot. Results Hepatocyte signs of oxidative related apoptotic injury were presented in mice fed with MCD diet for 4 weeks. Induction of HO-1 by hemin or Ad-HO-1 significantly attenuated the severity of liver histology, which was associated with decreased hepatic lipid peroxidation content, reduced number of apoptotic cells by TUNEL staining, down-regulated expression of pro-apoptosis related genes including Fas/FasL, Bax, caspase-3 and caspase-9, reduced expression of cytochrome p4502E1 (CYP2E1, inhibited cytochrome c (Cyt-c release, and up-regulated expression of anti-apoptosis gene Bcl-2. Whereas, inhibition of HO-1 by ZnPP-IX caused oxidative stress related hepatic injury, which concomitant with increased number of TUNEL positive cells and up-regulated expression of pro-apoptosis related genes. Conclusions The present study provided evidences for the protective role of HO-1 in preventing nutritional steatohepatitis through suppressing hepatocyte apoptosis in mice.

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

    Directory of Open Access Journals (Sweden)

    Han-Sol Park

    2016-04-01

    Full Text Available BackgroundNon-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.MethodsSeven-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.ResultsStatin 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.ConclusionStatins 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.

  20. Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population

    Science.gov (United States)

    Liu, Xiao-Lin; Pan, Qin; Zhang, Rui-Nan; Shen, Feng; Yan, Shi-Yan; Sun, Chao; Xu, Zheng-Jie; Chen, Yuan-Wen; Fan, Jian-Gao

    2016-01-01

    AIM To assess disease-specific circulating microRNAs (miRNAs) in non-alcoholic steatohepatitis (NASH) patients. METHODS A total of 111 biopsy-proven non-alcoholic fatty liver disease (NAFLD) or chronic hepatitis B (CHB) patients and healthy controls from mainland China were enrolled to measure their serum levels of miR-122, -125b, -146b, -16, -21, -192, -27b and -34a. The correlations between serum miRNAs and histological features of NAFLD were determined. The diagnostic value of miRNA in NASH and significant fibrosis was analyzed and compared with that of cytokeratin-18 (CK-18), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI), respectively. RESULTS Circulating miR-122, -16, -192 and -34a showed differential expression levels between NAFLD and CHB patients, and miR-34a had an approximately 2-fold increase in NAFLD samples compared with that of CHB samples (P steatosis (R = 0.302, 0.323 and 0.470, respectively, P < 0.05) and inflammatory activity (R = 0.445, 0.447 and 0.517, respectively, P < 0.01); only serum miR-16 levels were associated with fibrosis (R = 0.350, P < 0.05) in patients with NAFLD. The diagnostic value of miR-34a for NASH (area under the receiver operating characteristic, 0.811, 95%CI: 0.670-0.953) was superior to that of alanine aminotransferase, CK-18, FIB-4 and APRI in NAFLD, but miR-16 showed a limited performance in the diagnosis of significant fibrosis in NASH. CONCLUSION Circulating miR-34a may serve as a disease-specific noninvasive biomarker for the diagnosis of NASH. PMID:27956809

  1. Deleterious effect of n-3 polyunsaturated fatty acids in non-alcoholic steatohepatitis in the fat-1 mouse model

    Directory of Open Access Journals (Sweden)

    Diana Shefer-Weinberg

    2017-04-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD represents a spectrum of pathologies, ranging from hepatocellular steatosis to non-alcoholic steatohepatitis (NASH, fibrosis and cirrhosis. It has been suggested that fish oil containing n-3 polyunsaturated fatty acids (n-3 PUFA induce beneficial effects in NAFLD. However, n-3 PUFA are sensitive to peroxidation that generate free radicals and reactive aldehydes. We aimed at determining whether changing the tissue ratio of n-3 to n-6 PUFA may be beneficial or alternatively harmful to the etiology of NAFLD. The transgenic Fat-1 mouse model was used to determine whether n-3 PUFA positively or negatively affect the development of NAFLD. fat-1mice express the fat-1 gene of Caenorhabditis elegans, which encodes an n-3 fatty-acid desaturase that converts n-6 to n-3 fatty acids. Wild-type C57BL/6 mice served as the control group. Both groups of mice were fed methionine and choline deficient (MCD diet, which induces NASH within 4 weeks. The study shows that NASH developed faster and was more severe in mice from the fat-1 group when compared to control C57BL/6 mice. This was due to enhanced lipid peroxidation of PUFA in the liver of the fat-1 mice as compared to the control group. Results of our mice study suggest that supplementing the diet of individuals who develop or have fatty livers with n-3 PUFA should be carefully considered and if recommended adequate antioxidants should be added to the diet in order to reduce such risk.

  2. β-glycosphingolipids ameliorated non-alcoholic steatohepatitis in the Psammomys obesus model

    Directory of Open Access Journals (Sweden)

    Zigmond E

    2014-10-01

    Full Text Available Ehud Zigmond,1,* Oshrat Tayer-Shifman,1,* Gadi Lalazar,1 Ami Ben Ya'acov,1 Sarah Weksler-Zangen,2 David Shasha,1 Miriam Sklair-Levy,3 Lidya Zolotarov,1 Zvi Shalev,1 Rony Kalman,2 Ehud Ziv,2 Itamar Raz,2 Yaron Ilan1 1Liver Unit, 2Diabetes Unit, 3Department of Radiology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel *These authors contributed equally to this workAbstract: Liver steatosis is a common characteristic of obesity and type 2 diabetes, and fatty liver disease is increasingly recognized as a major health burden. Accumulating evidence suggests that β-glycosphingolipids play an important role in insulin sensitivity and thus could affect hepatic steatosis. To determine the effect associated with β-glycosphingolipid-mediated amelioration of liver injury, seven groups of Psammomys obesus on a high-energy diet were studied. Animals were treated with daily injections of β-glucosylceramide, β-lactosylceramide, or a combination of both. β-glycosphingolipids ameliorated the hepatic injury manifested by decreased liver enzymes, liver weight, and hepatic fat, and improved liver histology. Administration of both β-glucosylceramide and β-lactosylceramide also decreased interferon (IFN-γ serum levels. These effects were associated with improved serum cholesterol and triglyceride levels. These data suggest that β-glycosphingolipids ameliorate liver injury in an animal model of nonalcoholic steatohepatitis.Keywords: NAFLD, glycolipids, STAT, NASH, insulin resistance, diabetes

  3. Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas

    Directory of Open Access Journals (Sweden)

    Anna Kakehashi

    2017-02-01

    Full Text Available To uncover mechanisms of nonalcoholic steatohepatitis (NASH associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs and HCCs of HCV+ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed. Similar changes in the proteome spectrum such as overexpression of enzymes involved in lipid, cholesterol and bile acid biosynthesis and examples associated with suppression of fatty acid oxidation and catabolism, alcohol metabolism, mitochondrial function as well as low expression levels of cytokeratins 8 and 18 were observed in both human NASH biopsies and NASH HCCs, but not HCV+ HCCs. Alterations in downstream protein expression pointed to significant activation of transforming growth factor β, SMAD family member 3, β-catenin, Nrf2, SREBP-LXRα and nuclear receptor-interacting protein 1 (NRIP1, and inhibition of PPARs and p53 in human NASH biopsies and/or HCCs, suggesting their involvement in accumulation of lipids, development of fibrosis, oxidative stress, cell proliferation and suppression of apoptosis in NASH hepatocarcinogenesis. In STAM mice, PPARs inhibition was not obvious, while expression of cytokeratins 8 and 18 was elevated, indicative of essential differences between human and mouse NASH pathogenesis.

  4. The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement.

    Science.gov (United States)

    Athyros, Vasilios G; Alexandrides, Theodore K; Bilianou, Helen; Cholongitas, Evangelos; Doumas, Michael; Ganotakis, Emmanuel S; Goudevenos, John; Elisaf, Moses S; Germanidis, Georgios; Giouleme, Olga; Karagiannis, Asterios; Karvounis, Charalambos; Katsiki, Niki; Kotsis, Vasilios; Kountouras, Jannis; Liberopoulos, Evangelos; Pitsavos, Christos; Polyzos, Stergios; Rallidis, Loukianos S; Richter, Dimitrios; Tsapas, Apostolos G; Tselepis, Alexandros D; Tsioufis, Konstantinos; Tziomalos, Konstantinos; Tzotzas, Themistoklis; Vasiliadis, Themistoklis G; Vlachopoulos, Charalambos; Mikhailidis, Dimitri P; Mantzoros, Christos

    2017-06-01

    Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (>5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients. Current guidelines suggest the use of pioglitazone both in patients with T2DM and in those without. The use of statins, though considered safe by the guidelines, have very limited use; only 10% in high CVD risk patients are on statins by tertiary centers in the US. There are data from several animal studies, 5 post hoc analyses of prospective long-term survival studies, and 5 rather small biopsy proven NASH studies, one at baseline and on at the end of the study. All these studies provide data for biochemical and histological improvement of NAFLD/NASH with statins and in the clinical studies large reductions in CVD events in comparison with those also on statins and normal liver. Ezetimibe was also reported to improve NAFLD. Drugs currently in clinical trials seem to have potential for slowing down the evolution of NAFLD and for reducing liver- and CVD-related morbidity and mortality, but it will take time before they are ready to be used in everyday clinical practice. The suggestion of this Expert Panel is that, pending forthcoming randomized clinical trials, physicians should consider using a PPARgamma agonist, such as pioglitazone, or, statin use in those with NAFLD/NASH at high CVD or HCC risk, alone and/or preferably in combination with each other or with ezetimibe, for the primary or secondary prevention of CVD, and the avoidance of cirrhosis, liver transplantation or HCC, bearing in mind that CVD is the main cause

  5. Effects of dark chocolate on NOX-2-generated oxidative stress in patients with non-alcoholic steatohepatitis.

    Science.gov (United States)

    Loffredo, L; Del Ben, M; Perri, L; Carnevale, R; Nocella, C; Catasca, E; Baratta, F; Ceci, F; Polimeni, L; Gozzo, P; Violi, F; Angelico, F

    2016-08-01

    Activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is considered a pathogenetic mechanism determining fibrosis and disease progression in non-alcoholic steatohepatitis (NASH). Polyphenols exert antioxidant action and inhibit NADPH oxidase in humans. To analyse the effect of cocoa polyphenols on NADPH oxidase isoform 2 (NOX2) activation, oxidative stress and hepatocyte apoptosis in a population affected by NASH. In a cross-sectional study comparing 19 NASH and 19 controls, oxidative stress, as assessed by serum NOX2 activity and F2-isoprostanes, and hepatocyte apoptosis, as assessed by serum cytokeratin-18 (CK-18) levels, were measured. Furthermore, the 19 NASH patients were randomly allocated in a crossover design to 40 g/day of dark chocolate (>85% cocoa) or 40 g/day of milk chocolate (chocolate intake. Compared to controls, NASH patients had higher sNOX2-dp, serum isoprostanes and CK-18 levels. A significant difference for treatments was found in subjects with respect to sNOX2-dp, serum isoprostanes and serum CK-18. The pairwise comparisons showed that, compared to baseline, after 14 days of dark chocolate intake, a significant reduction in sNOX2-dp serum isoprostanes and CK-18 M30 was found. No change was observed after milk chocolate ingestion. A simple linear regression analysis showed that ∆ of sNOX2-dp was associated with ∆ of serum isoprostanes. Cocoa polyphenols exert an antioxidant activity via NOX2 down-regulation in NASH patients. © 2016 John Wiley & Sons Ltd.

  6. Metabolomic profiling to identify predictors of response to vitamin E for non-alcoholic steatohepatitis (NASH.

    Directory of Open Access Journals (Sweden)

    Jianfeng Cheng

    Full Text Available Vitamin E was recently shown to improve hepatic histology in a randomized controlled trial of pioglitazone or vitamin E for nonalcoholic steatohepatitis (PIVENS. The current study utilized samples collected in the PIVENS trial to identify: (1 baseline metabolomic profiles that could identify who would respond to vitamin E treatment and (2 end of treatment metabolomic profiles reflective of histologic improvement. A comprehensive analysis of metabolomics profiles (n = 547 quantified by mass spectrometry was performed in vitamin E responders (n = 16, vitamin E non-responders (n = 15, and placebo responders (n = 15. At baseline, phenyl-propionic acid (Odds ratio: 29.4, p<0.01, indole-propionic acid levels (Odds ratio: 16.2, p<0.01 were directly associated with a subsequent histologic response to vitamin E treatment whereas γ-carboxyethylhydroxychroman (CEHC levels were inversely related to histologic response. Adjusting for baseline values by analysis of covariance, the end of treatment levels of gamma-glutamyl leucine (Fold change: 0.82, p<0.02 and gamma-glutamyl valine (Fold change: 0.8, p<0.03 were significantly lower in vitamin E responders compared to non-responders. The levels of gamma-glutamyl transpeptidase were not significantly different across the two groups. Subjects receiving placebo who demonstrated a histologic improvement also demonstrated lower levels of gamma-glutamylated amino acids (leucine, valine and isoleucine compared to vitamin E non-responders. These data provide exploratory proof that there are measurable differences in the metabolic profile of subjects who are likely (vs unlikely to respond to vitamin E treatment for NASH and in those experiencing histologic improvement (vs no improvement on treatment and support further studies to validate these biomarkers.

  7. Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis.

    Science.gov (United States)

    Cotler, Scott J; Kanji, Kiran; Keshavarzian, Ali; Jensen, Donald M; Jakate, Shriram

    2004-10-01

    The aim of this study is to evaluate the prevalence and the clinical and histologic correlates of autoantibodies in patients with nonalcoholic steatohepatitis (NASH). Antinuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) have been identified in patients with NASH. The significance of autoantibodies in NASH is uncertain. Clinical data from patients with a histologic diagnosis of NASH at a university hospital in Chicago, Illinois between January 1999 and April 2003 were reviewed retrospectively. Seventy-four patients who were tested for autoantibodies and had no history of alcohol abuse or a systemic autoimmune disease were included. Demographic information and laboratory data were collected. Autoantibody titers > or = 1:40 were considered positive. A single pathologist reviewed all liver biopsies and scored features of NASH and identified characteristics of autoimmune hepatitis. Thirty-four percent of patients with NASH had positive ANA titers and 6% were ASMA positive. Demographic and laboratory parameters did not differ by ANA status, except that women were more frequently ANA positive then men (P = 0.01). The severity of steatosis, inflammation, and fibrosis on liver biopsy were similar in the ANA positive and negative groups. Only 15% of ANA positive patients with NASH had a plasma cell infiltrate on liver biopsy and there was no difference in the frequency of histologic features of autoimmune hepatitis between ANA positive and negative patients. Antinuclear antibodies are common in patients with NASH and most frequently represent a nonspecific antibody response that is not associated with the pattern or severity of injury on liver biopsy.

  8. Caspase-1 as a central regulator of high fat diet-induced non-alcoholic steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Laura J Dixon

    Full Text Available Nonalcoholic steatohepatitis (NASH is associated with caspase activation. However, a role for pro-inflammatory caspases or inflammasomes has not been explored in diet-induced liver injury. Our aims were to examine the role of caspase-1 in high fat-induced NASH. C57BL/6 wild-type and caspase 1-knockout (Casp1(-/- mice were placed on a 12-week high fat diet. Wild-type mice on the high fat diet increased hepatic expression of pro-caspase-1 and IL-1β. Both wild-type and Casp1(-/- mice on the high fat diet gained more weight than mice on a control diet. Hepatic steatosis and TG levels were increased in wild-type mice on high fat diet, but were attenuated in the absence of caspase-1. Plasma cholesterol and free fatty acids were elevated in wild-type, but not Casp1(-/- mice, on high fat diet. ALT levels were elevated in both wild-type and Casp1(-/- mice on high fat diet compared to control. Hepatic mRNA expression for genes associated with lipogenesis was lower in Casp1(-/- mice on high fat diet compared to wild-type mice on high fat diet, while genes associated with fatty acid oxidation were not affected by diet or genotype. Hepatic Tnfα and Mcp-1 mRNA expression was increased in wild-type mice on high fat diet, but not in Casp1(-/- mice on high fat diet. αSMA positive cells, Sirius red staining, and Col1α1 mRNA were increased in wild-type mice on high fat diet compared to control. Deficiency of caspase-1 prevented those increases. In summary, the absence of caspase-1 ameliorates the injurious effects of high fat diet-induced obesity on the liver. Specifically, mice deficient in caspase-1 are protected from high fat-induced hepatic steatosis, inflammation and early fibrogenesis. These data point to the inflammasome as an important therapeutic target for NASH.

  9. Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid.

    Directory of Open Access Journals (Sweden)

    Wonbeak Yoo

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most common form of liver disease and ranges from isolated steatosis to NASH. To determine whether circulating fatty acids could serve as diagnostic markers of NAFLD severity and whether specific fatty acids could contribute to the pathogenesis of NASH, we analyzed two independent NAFLD patient cohorts and used the methionine- and choline-deficient diet (MCD NASH mouse model. We identified six fatty acids that could serve as non-invasive markers of NASH in patients with NAFLD. Serum levels of 15:0, 17:0 and 16:1n7t negatively correlated with NAFLD activity scores and hepatocyte ballooning scores, while 18:1n7c serum levels strongly correlated with fibrosis stage and liver inflammation. Serum levels of 15:0 and 17:0 also negatively correlated with fasting glucose and AST, while 16:1n7c and 18:1n7c levels positively correlated with AST and ferritin, respectively. Inclusion of demographic and clinical parameters improved the performance of the fatty acid panels in detecting NASH in NAFLD patients. The panel [15:0, 16:1n7t, 18:1n7c, 22:5n3, age, ferritin and APRI] predicted intermediate or advanced fibrosis in NAFLD patients, with 82% sensitivity at 90% specificity [AUROC = 0.92]. 15:0 and 18:1n7c were further selected for functional studies in vivo. Mice treated with 15:0-supplemented MCD diet showed reduced AST levels and hepatic infiltration of ceroid-laden macrophages compared to MCD-treated mice, suggesting that 15:0 deficiency contributes to liver injury in NASH. In contrast, 18:1n7c-supplemented MCD diet didn't affect liver pathology. In conclusion, 15:0 may serve as a promising biomarker or therapeutic target in NASH, opening avenues for the integration of diagnosis and treatment.

  10. Camel milk ameliorates steatohepatitis, insulin resistance and lipid peroxidation in experimental non-alcoholic fatty liver disease.

    Science.gov (United States)

    Korish, Aida A; Arafah, Maha M

    2013-10-13

    Camel milk (CM) is gaining increasing recognition due to its beneficial effects in the control and prevention of multiple health problems. The current study aimed to investigate the effects of CM on the hepatic biochemical and cellular alterations induced by a high-fat, cholesterol-rich diet (HCD), specifically, non-alcoholic fatty liver disease (NAFLD). Seventy male Wistar rats were divided into four groups: the Control (C) Group fed a standard diet; the Control + camel milk (CCM) Group fed a standard diet and CM, the Cholesterol (Ch) Group fed a HCD with no CM, and the Cholesterol + camel milk (ChM) Group fed a HCD and CM. The following parameters were investigated in the studied groups; basal, weekly random and final fasting blood glucose levels, intraperitoneal glucose tolerance test (GTT) and insulin tolerance test (ITT), serum insulin, serum lipids, liver functions, lipid peroxidation products, the antioxidant activity of catalase (CAT) and the levels of reduced glutathione (GSH). In addition, HOMA-IR as an index of insulin resistance (IR) and the histopathology of the hepatic tissue were assessed. The Ch Group developed features similar to those of non-alcoholic steatohepatitis (NASH), characterized by hepatic steatosis; inflammatory cellular infiltration in liver tissue; altered liver functions; and increased total cholesterol, triglycerides, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, atherogenic index (AI), blood glucose, IR, and malondialdehyde (MDA) levels. Additionally, feeding the HCD to animals in the Ch Group decreased CAT activity and the GSH and high-density lipoprotein (HDL) cholesterol levels. Camel milk intake for eight weeks decreased hepatic fat accumulation and inflammatory cellular infiltration, preserved liver function, increased the GSH levels and CAT activity, decreased the MDA levels, and ameliorated the changes in the lipid profile, AI, and IR in animals from the ChM Group. CM has a unique composition

  11. Detection of carcinogenic etheno-DNA adducts in children and adolescents with non-alcoholic steatohepatitis (NASH).

    Science.gov (United States)

    Teufel, Ulrike; Peccerella, Teresa; Engelmann, Guido; Bruckner, Thomas; Flechtenmacher, Christa; Millonig, Gunda; Stickel, Felix; Hoffmann, Georg F; Schirmacher, Peter; Mueller, Sebastian; Bartsch, Helmut; Seitz, Helmut K

    2015-12-01

    Carcinogenic exocyclic-DNA adducts like 1,N(6)-etheno-2'-deoxyadenosine (εdA) are formed through reactive intermediates of 4-hydroxynonenal (4-HNE) or other lipid peroxidation (LPO) products with the DNA bases A, C, methyl-C and G. High levels of hepatic etheno-DNA adducts have been detected in cancer prone liver diseases including alcoholic liver disease (ALD). In ALD εdA levels correlated significantly with cytochrome P-450 2E1 (CYP2E1) expression which is also induced in non-alcoholic steatohepatitis (NASH). We investigated the occurrence of εdA adducts in children with NASH as a DNA damage marker. Liver biopsies from 21 children/adolescents with histologically proven NASH were analysed for hepatic fat content, inflammation, and fibrosis. εdA levels in DNA, CYP2E1-expression and protein bound 4-hydroxynonenal (HNE) were semi-quantitatively evaluated by immunohistochemistry. Among 21 NASH children, εdA levels in the liver were high in 3, moderate in 5, weak in 9 and not elevated in 4 patients. There was a positive correlation between CYP2E1 and protein-bound 4-HNE (r=0.60; P=0.008) and a trend for a positive relationship for CYP2E1 vs. staining intensity of εdA (r=0.45; P=0.06). Inflammatory activity and fibrosis correlated significantly (r=0.49, P=0.023). Our results demonstrate for the first time the presence of elevated carcinogenic etheno-DNA lesions (εdA) in the majority (17/21) of liver biopsies from young NASH patients. Our data suggest that LPO-derived etheno-adducts are implicated in NASH. Whether these adducts may serve as predictive risk markers in NASH children to develop hepatocellular cancer later in life remains to be investigated.

  12. Eicosapentaenoic acid ameliorates non-alcoholic steatohepatitis in a novel mouse model using melanocortin 4 receptor-deficient mice.

    Science.gov (United States)

    Konuma, Kuniha; Itoh, Michiko; Suganami, Takayoshi; Kanai, Sayaka; Nakagawa, Nobutaka; Sakai, Takeru; Kawano, Hiroyuki; Hara, Mitsuko; Kojima, Soichi; Izumi, Yuichi; Ogawa, Yoshihiro

    2015-01-01

    Many attempts have been made to find novel therapeutic strategies for non-alcoholic steatohepatitis (NASH), while their clinical efficacy is unclear. We have recently reported a novel rodent model of NASH using melanocortin 4 receptor-deficient (MC4R-KO) mice, which exhibit the sequence of events that comprise hepatic steatosis, liver fibrosis, and hepatocellular carcinoma with obesity-related phenotypes. In the liver of MC4R-KO mice, there is a unique histological feature termed hepatic crown-like structures (hCLS), where macrophages interact with dead hepatocytes and fibrogenic cells, thereby accelerating inflammation and fibrosis. In this study, we employed MC4R-KO mice to examine the effect of highly purified eicosapentaenoic acid (EPA), a clinically available n-3 polyunsaturated fatty acid, on the development of NASH. EPA treatment markedly prevented the development of hepatocyte injury, hCLS formation and liver fibrosis along with lipid accumulation. EPA treatment was also effective even after MC4R-KO mice developed NASH. Intriguingly, improvement of liver fibrosis was accompanied by the reduction of hCLS formation and plasma kallikrein-mediated transforming growth factor-β activation. Moreover, EPA treatment increased the otherwise reduced serum concentrations of adiponectin, an adipocytokine with anti-inflammatory and anti-fibrotic properties. Collectively, EPA treatment effectively prevents the development and progression of NASH in MC4R-KO mice along with amelioration of hepatic steatosis. This study unravels a novel anti-fibrotic mechanism of EPA, thereby suggesting a clinical implication for the treatment of NASH.

  13. Eicosapentaenoic acid ameliorates non-alcoholic steatohepatitis in a novel mouse model using melanocortin 4 receptor-deficient mice.

    Directory of Open Access Journals (Sweden)

    Kuniha Konuma

    Full Text Available Many attempts have been made to find novel therapeutic strategies for non-alcoholic steatohepatitis (NASH, while their clinical efficacy is unclear. We have recently reported a novel rodent model of NASH using melanocortin 4 receptor-deficient (MC4R-KO mice, which exhibit the sequence of events that comprise hepatic steatosis, liver fibrosis, and hepatocellular carcinoma with obesity-related phenotypes. In the liver of MC4R-KO mice, there is a unique histological feature termed hepatic crown-like structures (hCLS, where macrophages interact with dead hepatocytes and fibrogenic cells, thereby accelerating inflammation and fibrosis. In this study, we employed MC4R-KO mice to examine the effect of highly purified eicosapentaenoic acid (EPA, a clinically available n-3 polyunsaturated fatty acid, on the development of NASH. EPA treatment markedly prevented the development of hepatocyte injury, hCLS formation and liver fibrosis along with lipid accumulation. EPA treatment was also effective even after MC4R-KO mice developed NASH. Intriguingly, improvement of liver fibrosis was accompanied by the reduction of hCLS formation and plasma kallikrein-mediated transforming growth factor-β activation. Moreover, EPA treatment increased the otherwise reduced serum concentrations of adiponectin, an adipocytokine with anti-inflammatory and anti-fibrotic properties. Collectively, EPA treatment effectively prevents the development and progression of NASH in MC4R-KO mice along with amelioration of hepatic steatosis. This study unravels a novel anti-fibrotic mechanism of EPA, thereby suggesting a clinical implication for the treatment of NASH.

  14. Candidate proteomic biomarkers for non-alcoholic fatty liver disease (steatosis and non-alcoholic steatohepatitis) discovered with mass-spectrometry: a systematic review.

    Science.gov (United States)

    Lădaru, Anca; Bălănescu, Paul; Stan, Mihaela; Codreanu, Ioana; Anca, Ioana Alina

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver which is accompanied by a series of metabolic deregulations. There are sustained research efforts focusing upon biomarker discovery for NAFLD diagnosis and its prognosis in order investigate and follow-up patients as minimally invasive as possible. The objective of this study is to critically review proteomic studies that used mass spectrometry techniques and summarize relevant proteomic NAFLD candidate biomarkers. Medline and Embase databases were searched from inception to December 2014. A final number of 22 records were included that identified 251 candidate proteomic biomarkers. Thirty-three biomarkers were confirmed - 14 were found in liver samples, 21 in serum samples, and two from both serum and liver samples. Some of the biomarkers identified have already been extensively studied regarding their diagnostic and prognostic capacity. However, there are also more potential biomarkers that still need to be addressed in future studies.

  15. Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH).

    Science.gov (United States)

    Cortez-Pinto, Helena; Borralho, Paula; Machado, Jorge; Lopes, Maria T; Gato, Inês V; Santos, António M; Guerreiro, António S

    2016-01-01

    Gut microbiota may play a role in non-alcoholic steatohepatitis (NASH). Previous studies showed that prebiotics and probiotics might halt the progression of steatohepatitis. To clarify the potential effect of Synbiotic 2000 ® Forte (Synb) in preventing or ameliorating diet induced steatohepatitis, particularly in fibrosis progression and how this intervention correlates with gut microbiota composition and endotoxinemia. Twenty-seven C57BL/6 mice were divided into three groups: chow diet (CD, n = 7); high-fat choline deficient diet (HFCD, n = 10) and HFCD diet supplemented with Synbiotic 2000 ® Forte (four probiotic strains and four prebiotics mixture) (HFCD + Synb, n = 10). At 6 and 18 weeks, blood samples (lipopolysaccharides assay - LPS), cecal feaces (gut microbiota) and liver tissue (histology) were collected for analysis. Both HCFD diet mice developed steatohepatitis with ballooning at 6 and 18 weeks, opposite to CD. Comparison of histological scores in HFCD and HFCD + Synb, at 6 and 18 weeks showed no significant difference regarding steatosis, inflammation, or ballooning. Evaluating fibrosis with Sirius Red, and degree of smooth-muscle cell activation, HFCD mice had significantly more fibrosis; addition of Synb significantly reduced fibrosis at 6 weeks and 18 weeks. Serum endotoxin levels were similarly increased in HFCD and HFCD + Synb at week 6; however at week 18 HFCD + Synb had significantly lower endotoxin levels than HFCD. Gut microbiota of HFCD vs CD, showed no significant differences regarding the phyla Firmicutes and Bacteroidetes , either at 6 or 18 weeks; Proteobacteria increased at 6 week (3.3) and 18 week (7.5), while the addition of Synb resulted in a decrease at week 18 (-3.90). Fusobacteria markedly increase at week 18 (10.0), but less so with the addition of Synb (5.2). Synbiotic 2000 ® Forte is able to modulate the mouse gut microbiota reducing the degree of fibrosis while simultaneously decreasing endotoxemia.

  16. Losartan, an angiotensin-II type 1 receptor blocker, attenuates the liver fibrosis development of non-alcoholic steatohepatitis in the rat

    Directory of Open Access Journals (Sweden)

    Kawaratani Hideto

    2009-05-01

    Full Text Available Abstract Background Apart from simple steatosis, the non-alcoholic steatohepatitis (NASH can progress into liver fibrosis and cirrhosis. To date, however, no widely accepted therapeutic modalities have been established against NASH in the clinical practice. To find out promising new therapeutic agents, it is important to employ an appropriate experimental model of NASH, such as association with insulin resistance. Findings In the current study, we found that losartan, a clinically used angiotensin-II type 1 receptor blocker, significantly attenuated a choline-deficient L-amino acid-defined (CDAA diet-induced steatohepatitis in obese diabetic- and insulin resistance-associated Otsuka Long-Evans Tokushima Fatty (OLETF rats. The transforming growth factor-beta, a well-known major fibrogenic cytokine, was also suppressed in a similar magnitude to that of the fibrosis area. Noteworthy was the finding that these inhibitory effects were achieved even at a clinically comparable low dose. Conclusion Since losartan is widely used without serious side effects in the clinical practice, this agent may be an effective new therapeutic strategy against NASH.

  17. Relationship between liver tissue stiffness and histopathological findings analyzed by shear wave elastography and compression testing in rats with non-alcoholic steatohepatitis.

    Science.gov (United States)

    Ogawa, Saori; Moriyasu, Fuminori; Yoshida, Keiko; Oshiro, Hisashi; Kojima, Mayumi; Sano, Takatomo; Furuichi, Yoshihiro; Kobayashi, Yoshiyuki; Nakamura, Ikuo; Sugimoto, Katsutoshi

    2016-07-01

    The aim of the present study was to investigate two methods of determining liver stiffness in rats with various degrees of non-alcoholic steatohepatitis induced by a methionine- and choline-deficient (MCD) diet by comparing each finding with reference to histopathological liver findings. Twenty male Wister rats were fed an MCD diet for up to 32 weeks, and four were fed a normal diet. Ultrasound-based shear wave elastography (SWE) and mechanical compression testing using an Instron Universal Testing machine were performed on each rat at designated time points. After each examination, liver histopathology was analyzed to evaluate the degrees of steatosis, inflammation, and fibrosis based on non-alcoholic fatty liver disease (NAFLD) activity score, and each finding was compared with reference to liver histopathologic findings. Median liver stiffness values measured using SWE showed a stepwise increase with increasing histological inflammation score (P = 0.002), hepatic fibrosis stage (P = 0.029), ballooning score (P = 0.012), and steatosis grade (P = 0.030). Median liver stiffness measured using an Instron machine showed a stepwise increase only with increasing histological fibrosis stage (P = 0.033). Degree of liver stiffness measured by SWE and the Instron machine differed. SWE reflected mainly inflammation, whereas Instron machine-derived values primarily reflected fibrosis. This is the main source of discrepancies between measurements made with these two modalities.

  18. Chemokine-Like Receptor 1 mRNA Weakly Correlates with Non-Alcoholic Steatohepatitis Score in Male but Not Female Individuals

    Directory of Open Access Journals (Sweden)

    Maximilian Neumann

    2016-08-01

    Full Text Available The chemokine-like receptor 1 (CMKLR1 ligands resolvin E1 and chemerin are known to modulate inflammatory response. The progression of non-alcoholic fatty liver disease (NAFLD to non-alcoholic steatohepatitis (NASH is associated with inflammation. Here it was analyzed whether hepatic CMKLR1 expression is related to histological features of NASH. Therefore, CMKLR1 mRNA was quantified in liver tissue of 33 patients without NAFLD, 47 patients with borderline NASH and 38 patients with NASH. Hepatic CMKLR1 mRNA was not associated with gender and body mass index (BMI in the controls and the whole study group. CMKLR1 expression was similar in controls and in patients with borderline NASH and NASH. In male patients weak positive correlations with inflammation, fibrosis and NASH score were identified. In females CMKLR1 was not associated with features of NAFLD. Liver CMKLR1 mRNA tended to be higher in type 2 diabetes patients of both genders and in hypercholesterolemic women. In summary, this study shows that hepatic CMKLR1 mRNA is weakly associated with features of NASH in male patients only.

  19. Detection of non-alcoholic steatohepatitis in patients with morbid obesity before bariatric surgery: preliminary evaluation with acoustic radiation force impulse imaging

    International Nuclear Information System (INIS)

    Guzman-Aroca, F.; Reus, M.; Dios Berna-Serna, Juan de; Frutos-Bernal, M.D.; Lujan-Mompean, J.A.; Parrilla, P.; Bas, A.

    2012-01-01

    To investigate the utility of acoustic radiation force impulse (ARFI) imaging, with the determination of shear wave velocity (SWV), to differentiate non-alcoholic fatty liver disease (NAFLD) from non-alcoholic steatohepatitis (NASH) in patients with morbid obesity before bariatric surgery. Thirty-two patients with morbid obesity were evaluated with ARFI and conventional ultrasound before bariatric surgery. The ARFI and ultrasound results were compared with liver biopsy findings, which is the reference standard. The patients were classed according to their histological findings into three groups: group A, simple steatosis; group B, inflammation; and group C, fibrosis. The median SWV was 1.57 ± 0.79 m/s. Hepatic alterations were observed in the histopathological findings for all the patients in the study (100 %), with the results of the laboratory tests proving normal. Differences in SWV were also observed between groups A, B and C: 1.34 ± 0.90 m/s, 1.55 ± 0.79 m/s and 1.86 ± 0.75 m/s (P < 0.001), respectively. The Az for differentiating NAFLD from NASH or fibrosis was 0.899 (optimal cut-off value 1.3 m/s; sensitivity 85 %; specificity 83.3 %). The ARFI technique is a useful diagnostic tool for differentiating NAFLD from NASH in asymptomatic patients with morbid obesity. (orig.)

  20. Detection of non-alcoholic steatohepatitis in patients with morbid obesity before bariatric surgery: preliminary evaluation with acoustic radiation force impulse imaging

    Energy Technology Data Exchange (ETDEWEB)

    Guzman-Aroca, F.; Reus, M.; Dios Berna-Serna, Juan de [Virgen de la Arrixaca University Hospital, Department of of Radiology, El Palmar, Murcia (Spain); Frutos-Bernal, M.D.; Lujan-Mompean, J.A.; Parrilla, P. [Virgen de la Arrixaca University Hospital, Department of Surgery, El Palmar, Murcia (Spain); Bas, A. [Virgen de la Arrixaca University Hospital, Department of Pathology, El Palmar, Murcia (Spain)

    2012-11-15

    To investigate the utility of acoustic radiation force impulse (ARFI) imaging, with the determination of shear wave velocity (SWV), to differentiate non-alcoholic fatty liver disease (NAFLD) from non-alcoholic steatohepatitis (NASH) in patients with morbid obesity before bariatric surgery. Thirty-two patients with morbid obesity were evaluated with ARFI and conventional ultrasound before bariatric surgery. The ARFI and ultrasound results were compared with liver biopsy findings, which is the reference standard. The patients were classed according to their histological findings into three groups: group A, simple steatosis; group B, inflammation; and group C, fibrosis. The median SWV was 1.57 {+-} 0.79 m/s. Hepatic alterations were observed in the histopathological findings for all the patients in the study (100 %), with the results of the laboratory tests proving normal. Differences in SWV were also observed between groups A, B and C: 1.34 {+-} 0.90 m/s, 1.55 {+-} 0.79 m/s and 1.86 {+-} 0.75 m/s (P < 0.001), respectively. The Az for differentiating NAFLD from NASH or fibrosis was 0.899 (optimal cut-off value 1.3 m/s; sensitivity 85 %; specificity 83.3 %). The ARFI technique is a useful diagnostic tool for differentiating NAFLD from NASH in asymptomatic patients with morbid obesity. (orig.)

  1. Proteomic analysis of serum in patients with non-alcoholic steatohepatitis using matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

    Science.gov (United States)

    Ulukaya, Engin; Yilmaz, Yusuf; Moshkovskii, Sergei; Karpova, Maria; Pyatnitskiy, Mikhail; Atug, Ozlen; Dolar, Enver

    2009-01-01

    We sought to investigate whether serum proteomic pattern analysis obtained using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF-MS) may help to diagnose non-alcoholic steatohepatitis (NASH) in the setting of non-alcoholic fatty liver disease (NAFLD). We enrolled 80 patients with biopsy-proven NAFLD and 19 healthy comparison subjects. Patients with NAFLD were classified according to their liver histology as having definite NASH (n = 48), borderline NASH (n = 22) or simple steatosis (n = 10). Liver ultrasound scanning was performed to assess the degree of steatosis. Mass spectra of serum samples were obtained using a Ultraflex II mass spectrometer. The highest accuracy for NASH diagnostics was reached using 15 peaks. Corresponding sensitivity and specificity values were 73.95% +/- 3.38% and 88.71% +/- 1.39%, respectively. However, mass spectra did not allow us to distinguish NASH from simple steatosis. We conclude that proteomic analyses of serum samples from NAFLD patients by MALDI TOF-MS do not seem to have a major clinical value for diagnosing NASH. However, the identification of 15 peaks in our study may help to further elucidate the pathophysiology of NASH and merits further investigation.

  2. Hepatic artery resistive index (HARI) and non-alcoholic fatty liver disease (NAFLD) fibrosis score in NAFLD patients: cut-off suggestive of non-alcoholic steatohepatitis (NASH) evolution.

    Science.gov (United States)

    Tana, Claudio; Tana, Marco; Rossi, Stefano; Silingardi, Mauro; Schiavone, Cosima

    2016-09-01

    Conventional ultrasound (US) is reliable to reveal the presence of non-alcoholic fatty liver disease (NAFLD), but it is neither sensitive nor specific to reveal fibrosis clues, except in advanced stages where signs of cirrhosis are evident. NALFD fibrosis score is a non-invasive parameter that predicts well the presence of significant fibrosis, but correlations with US parameters are lacking. The aim of this study was, therefore, to compare resistive index of hepatic artery (HARI) of NAFLD patients with different severity degrees of diffuse fatty liver disease vs HARI of controls, and to compare HARI of NAFLD patients with different NAFLD fibrosis scores vs HARI of controls. This was a spontaneous, no-profit observational study conducted in our US department between December 2013 and July 2014. Patients with NAFLD with different severity of disease and healthy controls were included. Echogenicity and size of liver and spleen, maximum portal vein velocity, RI, peak systolic velocity (PSV), and end diastolic velocity (EDV) of splenic artery, PSV, EDV, and RI of hepatic artery, and NAFLD fibrosis score were acquired and compared between groups. HARI was significantly lower in NAFLD patients than controls (p steatosis, might suggest the execution of biopsy to predict the risk of progression to steatohepatitis and fibrous tissue accumulation. Low values of HARI may be expression of lower risk, which does not necessitate any biopsy.

  3. Ultra-high-field magnetic resonance spectroscopy in non-alcoholic fatty liver disease: Novel mechanistic and diagnostic insights of energy metabolism in non-alcoholic steatohepatitis and advanced fibrosis.

    Science.gov (United States)

    Traussnigg, Stefan; Kienbacher, Christian; Gajdošík, Martin; Valkovič, Ladislav; Halilbasic, Emina; Stift, Judith; Rechling, Christian; Hofer, Harald; Steindl-Munda, Petra; Ferenci, Peter; Wrba, Fritz; Trattnig, Siegfried; Krššák, Martin; Trauner, Michael

    2017-10-01

    With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) non-invasive tools obtaining pathomechanistic insights to improve risk stratification are urgently needed. We therefore explored high- and ultra-high-field magnetic resonance spectroscopy (MRS) to obtain novel mechanistic and diagnostic insights into alterations of hepatic lipid, cell membrane and energy metabolism across the spectrum of NAFLD. MRS and liver biopsy were performed in 30 NAFLD patients with NAFL (n=8) or NASH (n=22). Hepatic lipid content and composition were measured using 3-Tesla proton ( 1 H)-MRS. 7-Tesla phosphorus ( 31 P)-MRS was applied to determine phosphomonoester (PME) including phosphoethanolamine (PE), phosphodiester (PDE) including glycerophosphocholine (GPC), phosphocreatine (PCr), nicotinamide adenine dinucleotide phosphate (NADPH), inorganic phosphate (Pi), γ-ATP and total phosphorus (TP). Saturation transfer technique was used to quantify hepatic ATP flux. Hepatic steatosis in 1 H-MRS highly correlated with histology (Penergy metabolism including dynamic ATP flux in inflammation and fibrosis in NASH. Non-invasive profiling by MRS appears feasible and may assist further mechanistic and therapeutic studies in NAFLD/NASH. © 2017 The Authors Liver International Published by John Wiley & Sons Ltd.

  4. Spirulina improves non-alcoholic steatohepatitis, visceral fat macrophage aggregation, and serum leptin in a mouse model of metabolic syndrome.

    Science.gov (United States)

    Fujimoto, Makoto; Tsuneyama, Koichi; Fujimoto, Takako; Selmi, Carlo; Gershwin, M Eric; Shimada, Yutaka

    2012-09-01

    Nutritional approaches are sought to overcome the limits of pioglitazone in metabolic syndrome and non-alcoholic fatty liver disease. Spirulina, a filamentous unicellular alga, reduces serum lipids and blood pressure while exerting antioxidant effects. To determine whether Spirulina may impact macrophages infiltrating the visceral fat in obesity characterizing our metabolic syndrome mouse model induced by the subcutaneous injection treatment of monosodium glutamate. Mice were randomized to receive standard food added with 5% Spirulina, 0.02% pioglitazone, or neither. We tested multiple biochemistry and histology (both liver and visceral fat) readouts at 24 weeks of age. Data demonstrate that both the Spirulina and the pioglitazone groups had significantly lower serum cholesterol and triglyceride levels and liver non-esterified fatty acid compared to untreated mice. Spirulina and pioglitazone were associated with significantly lower leptin and higher levels, respectively, compared to the control group. At liver histology, non-alcoholic fatty liver disease activity score and lipid peroxide were significantly lower in mice treated with Spirulina. Spirulina reduces dyslipidaemia in our metabolic syndrome model while ameliorating visceral adipose tissue macrophages. Human studies are needed to determine whether this safe supplement could prove beneficial in patients with metabolic syndrome. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  5. Anti-oxidative and anti-inflammatory effects of spirulina on rat model of non-alcoholic steatohepatitis

    Science.gov (United States)

    Pak, Wing; Takayama, Fusako; Mine, Manaka; Nakamoto, Kazuo; Kodo, Yasumasa; Mankura, Mitsumasa; Egashira, Toru; Kawasaki, Hiromu; Mori, Akitane

    2012-01-01

    The pathogenesis of nonalcoholic steatohepatitis (NASH) remains unclear, but accumulating data suggest oxidative stress and the relationship between inflammation and immunity plays a crucial role. The aim of this study is to investigate the spirulina, which is a blue-green algae rich in proteins and other nutritional elements, and its component-phycocyanin effect on a rat model of NASH. NASH model rats were established by feeding male Wistar rats with choline-deficient high-fat diet (CDHF) and intermittent hypoxemia by sodium nitrite challenge after 5 weeks of CDHF. After experimental period of 10 weeks, blood and liver were collected to determine oxidative stress injuries and efficacies of spirulina or phycocyanin on NASH model rats. In the NASH model rats, increase in plasma liver enzymes and liver fibrosis, increases in productions of reactive oxygen species from liver mitochondria and from leukocytes, the activation of nuclear factor-kappa B, and the change in the lymphocyte surface antigen ratio (CD4+/CD8+) were observed. The spirulina and phycocyanin administration significantly abated these changes. The spirulina or phycocyanin administration to model rats of NASH might lessen the inflammatory response through anti-oxidative and anti-inflammatory mechanisms, breaking the crosstalk between oxidative stress and inflammation, and effectively inhibit NASH progression. PMID:23170052

  6. Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance, hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C.

    Science.gov (United States)

    Miquilena-Colina, María Eugenia; Lima-Cabello, Elena; Sánchez-Campos, Sonia; García-Mediavilla, María Victoria; Fernández-Bermejo, Miguel; Lozano-Rodríguez, Tamara; Vargas-Castrillón, Javier; Buqué, Xabier; Ochoa, Begoña; Aspichueta, Patricia; González-Gallego, Javier; García-Monzón, Carmelo

    2011-10-01

    Fatty acid translocase CD36 (FAT/CD36) mediates uptake and intracellular transport of long-chain fatty acids in diverse cell types. While the pathogenic role of FAT/CD36 in hepatic steatosis in rodents is well-defined, little is known about its significance in human liver diseases. To examine the expression of FAT/CD36 and its cellular and subcellular distribution within the liver of patients with non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection. 34 patients with non-alcoholic steatosis (NAS), 30 with non-alcoholic steatohepatitis (NASH), 66 with HCV genotype 1 (HCV G1) and 32 with non-diseased liver (NL). Real-time PCR and western blot analysis were used to assess hepatic FAT/CD36 expression. Computational image analysis of immunostained liver biopsy sections was performed to determine subcellular distribution and FAT/CD36 expression index. Compared with NL, hepatic mRNA and protein levels of FAT/CD36 were significantly higher in patients with NAS (median fold increase 0.84 (range 0.15-1.61) and 0.66 (range 0.33-1.06), respectively); NASH (0.91 (0.22-1.81) and 0.81 (0.38-0.92), respectively); HCV G1 without steatosis (0.30 (0.17-1.59) and 0.33 (0.29-0.52), respectively); and HCV G1 with steatosis (0.85 (0.15-1.98) and 0.87 (0.52-1.26), respectively). In contrast to NL, FAT/CD36 was predominantly located at the plasma membrane of hepatocytes in patients with NAFLD and HCV G1 with steatosis. A significant correlation was observed between hepatic FAT/CD36 expression index and plasma insulin levels, insulin resistance (HOMA-IR) and histological grade of steatosis in patients with NASH (r=0.663, r=0.735 and r=0.711, respectively) and those with HCV G1 with steatosis (r=0.723, r=0.769 and r=0.648, respectively). Hepatic FAT/CD36 upregulation is significantly associated with insulin resistance, hyperinsulinaemia and increased steatosis in patients with NASH and HCV G1 with fatty liver. Translocation of this fatty acid transporter to

  7. Aristolochia manshuriensis Kom ethyl acetate extract protects against high-fat diet-induced non-alcoholic steatohepatitis by regulating kinase phosphorylation in mouse.

    Science.gov (United States)

    Kwak, Dong Hoon; Kim, Ji-Su; Chang, Kyu-Tae; Choo, Young-Kug

    2016-09-30

    Aristolochia manshuriensis Kom (AMK) is an herb used as a traditional medicine; however, it causes side effects such as nephrotoxicity and carcinogenicity. Nevertheless, AMK can be applied in specific ways medicinally, including via ingestion of low doses for short periods of time. Non-alcoholic steatohepatitis (NASH) induced the hepatocyte injury and inflammation. The protective effects of AMK against NASH are unclear; therefore, in this study, the protective effects of AMK ethyl acetate extract were investigated in a high-fat diet (HFD)-induced NASH model. We found decreased hepatic steatosis and inflammation, as well as increased levels of lipoproteins during AMK extract treatment. We also observed decreased hepatic lipid peroxidation and triglycerides, as well as suppressed hepatic expression of lipogenic genes in extract-treated livers. Treatment with extract decreased the activation of c-jun N-terminal kinase 1/2 (JNK1/2) and increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). These results demonstrate that the protective effect of the extract against HFD-induced NASH occurred via reductions in reactive oxygen species production, inflammation suppression, and apoptosis related to the suppression of JNK1/2 activation and increased ERK1/2 phosphorylation. Taken together, these results indicate that that ethyl acetate extract of AMK has potential therapeutic effects in the HFD-induced NASH mouse model.

  8. Over-expressing the soluble gp130-Fc does not ameliorate methionine and choline deficient diet-induced non alcoholic steatohepatitis in mice.

    Directory of Open Access Journals (Sweden)

    Helene L Kammoun

    Full Text Available Non-alcoholic steatohepatitis (NASH is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6 has been implicated in the pathogenesis of NASH, with the so-called IL-6 'trans-signaling' cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 'trans-signaling', using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet and hypothesized that markers of NASH would be ameliorated in such mice. Sgp130Fc Tg and littermate control mice were fed a MCD or control diet for 4 weeks. The MCD diet induced many hallmarks of NASH including hepatomegaly, steatosis, and liver inflammation. However, in contrast with other mouse models and, indeed, human NASH, the MCD diet model did not increase the mRNA or protein expression of IL-6. Not surprisingly, therefore, markers of MCD diet-induced NASH were unaffected by sgp130Fc transgenic expression. While the MCD diet model induces many pathophysiological markers of NASH, it does not induce increased IL-6 expression in the liver, a key hallmark of human NASH. We, therefore, caution the use of the MCD diet as a viable mouse model of NASH.

  9. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

    OpenAIRE

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is k...

  10. Bile acids override steatosis in farnesoid X receptor deficient mice in a model of non-alcoholic steatohepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Weibin; Liu, Xijun; Peng, Xiaomin [Gene Research Center, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Xue, Ruyi [Department of Gastroenterology and Hepatology, Zhongshan Hospital, Shanghai Institute of Liver Disease, Fudan University, Shanghai 200032 (China); Ji, Lingling [Gene Research Center, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Shen, Xizhong [Department of Gastroenterology and Hepatology, Zhongshan Hospital, Shanghai Institute of Liver Disease, Fudan University, Shanghai 200032 (China); Chen, She, E-mail: shechen@fudan.edu.cn [Gene Research Center, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Gene Research Center, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhang, Si, E-mail: zhangsi@fudan.edu.cn [Gene Research Center, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China)

    2014-05-23

    Highlights: • FXR deficiency enhanced MCD diet-induced hepatic fibrosis. • FXR deficiency attenuated MCD diet-induced hepatic steatosis. • FXR deficiency repressed genes involved in fatty acid uptake and triglyceride accumulation. - Abstract: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, and the pathogenesis is still not well known. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily and plays an essential role in maintaining bile acid and lipid homeostasis. In this study, we study the role of FXR in the pathogenesis of NFALD. We found that FXR deficient (FXR{sup −/−}) mice fed methionine- and choline-deficient (MCD) diet had higher serum ALT and AST activities and lower hepatic triglyceride levels than wild-type (WT) mice fed MCD diet. Expression of genes involved in inflammation (VCAM-1) and fibrosis (α-SMA) was increased in FXR{sup −/−} mice fed MCD diet (FXR{sup −/−}/MCD) compared to WT mice fed MCD diet (WT/MCD). Although MCD diet significantly induced hepatic fibrosis in terms of liver histology, FXR{sup −/−}/MCD mice showed less degree of hepatic steatosis than WT/MCD mice. Moreover, FXR deficiency synergistically potentiated the elevation effects of MCD diet on serum and hepatic bile acids levels. The super-physiological concentrations of hepatic bile acids in FXR{sup −/−}/MCD mice inhibited the expression of genes involved in fatty acid uptake and triglyceride accumulation, which may be an explanation for less steatosis in FXR{sup −/−}/MCD mice in contrast to WT/MCD mice. These results suggest that hepatic bile acids accumulation could override simple steatosis in hepatic injury during the progression of NAFLD and further emphasize the role of FXR in maintaining hepatic bile acid homeostasis in liver disorders and in hepatic protection.

  11. Bile acids override steatosis in farnesoid X receptor deficient mice in a model of non-alcoholic steatohepatitis

    International Nuclear Information System (INIS)

    Wu, Weibin; Liu, Xijun; Peng, Xiaomin; Xue, Ruyi; Ji, Lingling; Shen, Xizhong; Chen, She; Gu, Jianxin; Zhang, Si

    2014-01-01

    Highlights: • FXR deficiency enhanced MCD diet-induced hepatic fibrosis. • FXR deficiency attenuated MCD diet-induced hepatic steatosis. • FXR deficiency repressed genes involved in fatty acid uptake and triglyceride accumulation. - Abstract: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, and the pathogenesis is still not well known. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily and plays an essential role in maintaining bile acid and lipid homeostasis. In this study, we study the role of FXR in the pathogenesis of NFALD. We found that FXR deficient (FXR −/− ) mice fed methionine- and choline-deficient (MCD) diet had higher serum ALT and AST activities and lower hepatic triglyceride levels than wild-type (WT) mice fed MCD diet. Expression of genes involved in inflammation (VCAM-1) and fibrosis (α-SMA) was increased in FXR −/− mice fed MCD diet (FXR −/− /MCD) compared to WT mice fed MCD diet (WT/MCD). Although MCD diet significantly induced hepatic fibrosis in terms of liver histology, FXR −/− /MCD mice showed less degree of hepatic steatosis than WT/MCD mice. Moreover, FXR deficiency synergistically potentiated the elevation effects of MCD diet on serum and hepatic bile acids levels. The super-physiological concentrations of hepatic bile acids in FXR −/− /MCD mice inhibited the expression of genes involved in fatty acid uptake and triglyceride accumulation, which may be an explanation for less steatosis in FXR −/− /MCD mice in contrast to WT/MCD mice. These results suggest that hepatic bile acids accumulation could override simple steatosis in hepatic injury during the progression of NAFLD and further emphasize the role of FXR in maintaining hepatic bile acid homeostasis in liver disorders and in hepatic protection

  12. Hepatic energy metabolism in human diabetes mellitus, obesity and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Koliaki, Chrysi; Roden, Michael

    2013-10-15

    Alterations of hepatic mitochondrial function have been observed in states of insulin resistance and non-alcoholic fatty liver disease (NAFLD). Patients with overt type 2 diabetes mellitus (T2DM) can exhibit reduction in hepatic adenosine triphosphate (ATP) synthesis and impaired repletion of their hepatic ATP stores upon ATP depletion by fructose. Obesity and NAFLD may also associate with impaired ATP recovery after ATP-depleting challenges and augmented oxidative stress in the liver. On the other hand, patients with obesity or NAFLD can present with upregulated hepatic anaplerotic and oxidative fluxes, including β-oxidation and tricarboxylic cycle activity. The present review focuses on the methods and data on hepatic energy metabolism in various states of human insulin resistance. We propose that the liver can adapt to increased lipid exposition by greater lipid storing and oxidative capacity, resulting in increased oxidative stress, which in turn could deteriorate hepatic mitochondrial function in chronic insulin resistance and NAFLD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Trypanosoma cruzi infection is a potent risk factor for non-alcoholic steatohepatitis enhancing local and systemic inflammation associated with strong oxidative stress and metabolic disorders.

    Directory of Open Access Journals (Sweden)

    Luisina I Onofrio

    2015-02-01

    Full Text Available The immune mechanisms underlying experimental non-alcoholic steatohepatitis (NASH, and more interestingly, the effect of T. cruzi chronic infection on the pathogenesis of this metabolic disorder are not completely understood.We evaluated immunological parameters in male C57BL/6 wild type and TLR4 deficient mice fed with a standard, low fat diet, LFD (3% fat as control group, or a medium fat diet, MFD (14% fat in order to induce NASH, or mice infected intraperitoneally with 100 blood-derived trypomastigotes of Tulahuen strain and also fed with LFD (I+LFD or MFD (I+MFD for 24 weeks. We demonstrated that MFD by itself was able to induce NASH in WT mice and that parasitic infection induced marked metabolic changes with reduction of body weight and steatosis revealed by histological studies. The I+MFD group also improved insulin resistance, demonstrated by homeostasis model assessment of insulin resistance (HOMA-IR analysis; although parasitic infection increased the triglycerides and cholesterol plasma levels. In addition, hepatic M1 inflammatory macrophages and cytotoxic T cells showed intracellular inflammatory cytokines which were associated with high levels of IL6, IFNγ and IL17 plasmatic cytokines and CCL2 chemokine. These findings correlated with an increase in hepatic parasite load in I+MFD group demonstrated by qPCR assays. The recruitment of hepatic B lymphocytes, NK and dendritic cells was enhanced by MFD, and it was intensified by parasitic infection. These results were TLR4 signaling dependent. Flow cytometry and confocal microscopy analysis demonstrated that the reactive oxygen species and peroxinitrites produced by liver inflammatory leukocytes of MFD group were also exacerbated by parasitic infection in our NASH model.We highlight that a medium fat diet by itself is able to induce steatohepatitis. Our results also suggest a synergic effect between damage associated with molecular patterns generated during NASH and parasitic infection

  14. Role of physical exercise on hepatic insulin, glucocorticoid and inflammatory signaling pathways in an animal model of non-alcoholic steatohepatitis.

    Science.gov (United States)

    Passos, E; Pereira, C D; Gonçalves, I O; Rocha-Rodrigues, S; Silva, N; Guimarães, J T; Neves, D; Ascensão, A; Magalhães, J; Martins, M J

    2015-02-15

    Pro-inflammatory mediators, glucocorticoids and transforming growth factor (TGF)-β are implicated in the pathogenesis of non-alcoholic steatohepatitis (NASH)-related insulin resistance. As physical activity is beneficial against NASH, we analyzed the voluntary physical activity (VPA) and endurance training (ET) (preventive and therapeutic strategies) effects on hepatic insulin, pro-inflammatory and glucocorticoid signaling regulators/mediators in high-fat (Lieber-DeCarli) diet (HFD)-induced NASH. Adult male Sprague-Dawley rats were divided in standard diet (SD) or HFD, with sedentary, VPA and ET animals in both diet regimens. Plasma glucose and insulin concentrations were analyzed; plasma insulin sensitivity index (ISI) was calculated. Hepatic insulin, pro-inflammatory and glucocorticoid signaling regulators/mediators were evaluated by Western blot or reverse transcriptase-PCR. ET improved ISI in both diet regimens. HFD-feeding increased interleukin-1β and induced a similar pattern on interleukin-6 and TGF-β, which were globally reduced by physical exercise. ET decreased HFD leukemia inhibitory factor level, SD+VPA animals presenting higher values than HFD+VPA animals. HFD increased the ratio of IRS-1(Ser307)/total IRS-1, which was completely mitigated by physical exercise. Physical exercise reduced total ERK and JNK (total and activated) expression in HFD. In SD vs. HFD, VPA presented higher activated JNK and ET presented higher total JNK. Generally, in HFD, the ratio (activated/total) of AKT, and each separately, decreased with exercise and also for activated AKT in SD. Overall, in both diets, exercise reduced 11β-hydroxysteroid dehydrogenase type 1. ET increased glucocorticoid receptor and reduced PTP1B in HFD. Physical exercise mitigates the expression of pro-inflammatory mediators and positively modulates insulin and glucocorticoid signaling in NASH. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Intervention with a caspase-1 inhibitor reduces obesity-associated hyperinsulinemia, non-alcoholic steatohepatitis and hepatic fibrosis in LDLR-/-.Leiden mice.

    Science.gov (United States)

    Morrison, M C; Mulder, P; Salic, K; Verheij, J; Liang, W; van Duyvenvoorde, W; Menke, A; Kooistra, T; Kleemann, R; Wielinga, P Y

    2016-09-01

    Non-alcoholic steatohepatitis (NASH) is a serious liver condition, closely associated with obesity and insulin resistance. Recent studies have suggested an important role for inflammasome/caspase-1 in the development of NASH, but the potential therapeutic value of caspase-1 inhibition remains unclear. Therefore, we aimed to investigate the effects of caspase-1 inhibition in the ongoing disease process, to mimic the clinical setting. To investigate effects of caspase-1 inhibition under therapeutic conditions, male LDLR-/-.Leiden mice were fed a high-fat diet (HFD) for 9 weeks to induce a pre-diabetic state before start of treatment. Mice were then continued on HFD for another 12 weeks, without (HFD) or with (HFD-YVAD) treatment with the caspase-1 inhibitor Ac-YVAD-cmk (40 mg kg(-1) per day). Nine weeks of HFD feeding resulted in an obese phenotype, with obesity-associated hypertriglyceridemia, hypercholesterolemia, hyperglycemia and hyperinsulinemia. Treatment with Ac-YVAD-cmk did not affect further body weight gain or dyslipidemia, but did attenuate further progression of insulin resistance. Histopathological analysis of livers clearly demonstrated prevention of NASH development in HFD-YVAD mice: livers were less steatotic and neutrophil infiltration was strongly reduced. In addition, caspase-1 inhibition had a profound effect on hepatic fibrosis, as assessed by histological quantification of collagen staining and gene expression analysis of fibrosis-associated genes Col1a1, Acta2 and Tnfa. Intervention with a caspase-1 inhibitor attenuated the development of NASH, liver fibrosis and insulin resistance. Our data support the importance of inflammasome/caspase-1 in the development of NASH and demonstrate that therapeutic intervention in the already ongoing disease process is feasible.

  16. Acetylcholine induces fibrogenic effects via M2/M3 acetylcholine receptors in non-alcoholic steatohepatitis and in primary human hepatic stellate cells.

    Science.gov (United States)

    Morgan, Maelle L; Sigala, Barbara; Soeda, Junpei; Cordero, Paul; Nguyen, Vi; McKee, Chad; Mouraliderane, Angelina; Vinciguerra, Manlio; Oben, Jude A

    2016-02-01

    The parasympathetic nervous system (PNS), via neurotransmitter acetylcholine (ACh), modulates fibrogenesis in animal models. However, the role of ACh in human hepatic fibrogenesis is unclear. We aimed to determine the fibrogenic responses of human hepatic stellate cells (hHSC) to ACh and the relevance of the PNS in hepatic fibrosis in patients with non-alcoholic steatohepatitis (NASH). Primary hHSC were analyzed for synthesis of endogenous ACh and acetylcholinesterase and gene expression of choline acetyltransferase and muscarinic ACh receptors (mAChR). Cell proliferation and fibrogenic markers were analyzed in hHSC exposed to ACh, atropine, mecamylamine, methoctramine, and 4-diphenylacetoxy-N-methylpiperidine methiodide. mAChR expression was analyzed in human NASH scored for fibrosis. We observed that hHSC synthesize ACh and acetylcholinesterase and express choline acetyltransferase and M1-M5 mAChR. We also show that M2 was increased during NASH progression, while both M2 and M3 were found upregulated in activated hHSC. Furthermore, endogenous ACh is required for hHSC basal growth. Exogenous ACh resulted in hHSC hyperproliferation via mAChR and phosphoinositide 3-kinase and Mitogen-activated protein kinase kinase (MEK) signaling pathways, as well as increased fibrogenic markers. We show that ACh regulates hHSC activation via M2 and M3 mAChR involving the phosphoinositide 3-kinase and MEK pathways in vitro. Finally, we provide evidence that the PNS may be involved in human NASH fibrosis. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  17. Usefulness of the index of NASH - ION for the diagnosis of steatohepatitis in patients with non-alcoholic fatty liver: An external validation study.

    Science.gov (United States)

    Younes, Ramy; Rosso, Chiara; Petta, Salvatore; Cucco, Monica; Marietti, Milena; Caviglia, Gian Paolo; Ciancio, Alessia; Abate, Maria Lorena; Cammà, Carlo; Smedile, Antonina; Craxì, Antonio; Saracco, Giorgio Maria; Bugianesi, Elisabetta

    2017-10-13

    The non-invasive identification of steatohepatitis (NASH) in patients with Non-Alcoholic Fatty Liver Disease is an unmet need in clinical practice. Index of NASH (ION) is a new tool for the prediction of NASH. We aimed to externally validate ION and to compare it with CK-18. Since necroinflammation precedes fibrosis, we also tested ION in combination with non-invasive tools for fibrosis. We analysed data from 292 Italian patients (169 Southern cohort, and 123 Northern cohort) with an histological diagnosis of NAFLD. The ION, FIB-4 and NFS scores were calculated according to published algorithms. Serum cytokeratin18-Aspartate396 levels and liver stiffness (LS) by Fibroscan were assessed within three months from liver biopsy. The diagnostic accuracy of ION for the identification of NASH was not as satisfactory as reported (area under the ROC curve, AUROC = 0.687 [95% CI = 0.62-0.75]). The proposed cut-off value ≥50 showed a poor sensitivity (Se) (28%) and a good specificity (Sp) (92%), with a positive predictive value (PPV) of 91% and a negative predictive value (NPV) of 30%. A new cut-off value >26 improved Se (73%) but decreased Sp (60%) (PPV of 84% and a NPV of 43%). ION performed slightly better in obese NAFLD (AUROC = 0.700). The combination of ION and markers of fibrosis did not improve the identification of advanced liver disease. ION is not feasible for the non-invasive diagnosis of NASH across different populations of NAFLD patients, mainly because its limited reproducibility in non-obese subjects. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Liver microRNA-21 is overexpressed in non-alcoholic steatohepatitis and contributes to the disease in experimental models by inhibiting PPARα expression

    Science.gov (United States)

    Loyer, Xavier; Paradis, Valérie; Hénique, Carole; Vion, Anne-Clémence; Colnot, Nathalie; Guerin, Coralie L; Devue, Cécile; On, Sissi; Scetbun, Jérémy; Romain, Mélissa; Paul, Jean-Louis; Rothenberg, Marc E; Marcellin, Patrick; Durand, François; Bedossa, Pierre; Prip-Buus, Carina; Baugé, Eric; Staels, Bart; Boulanger, Chantal M; Tedgui, Alain; Rautou, Pierre-Emmanuel

    2016-01-01

    Objective Previous studies suggested that microRNA-21 may be upregulated in the liver in non-alcoholic steatohepatitis (NASH), but its role in the development of this disease remains unknown. This study aimed to determine the role of microRNA-21 in NASH. Design We inhibited or suppressed microRNA-21 in different mouse models of NASH: (a) low-density lipoprotein receptor-deficient (Ldlr−/−) mice fed a high-fat diet and treated with antagomir-21 or antagomir control; (b) microRNA-21-deficient and wild-type mice fed a methionine-choline-deficient (MCD) diet; (c) peroxisome proliferation-activator receptor α (PPARα)-deficient mice fed an MCD diet and treated with antagomir-21 or antagomir control. We assessed features of NASH and determined liver microRNA-21 levels and cell localisation. MicroRNA-21 levels were also quantified in the liver of patients with NASH, bland steatosis or normal liver and localisation was determined. Results Inhibiting or suppressing liver microRNA-21 expression reduced liver cell injury, inflammation and fibrogenesis without affecting liver lipid accumulation in Ldlr−/− fed a high-fat diet and in wild-type mice fed an MCD diet. Liver microRNA-21 was overexpressed, primarily in biliary and inflammatory cells, in mouse models as well as in patients with NASH, but not in patients with bland steatosis. PPARα, a known microRNA-21 target, implicated in NASH, was decreased in the liver of mice with NASH and restored following microRNA-21 inhibition or suppression. The effect of antagomir-21 was lost in PPARα-deficient mice. Conclusions MicroRNA-21 inhibition or suppression decreases liver injury, inflammation and fibrosis, by restoring PPARα expression. Antagomir-21 might be a future therapeutic strategy for NASH. PMID:26338827

  19. Evaluation of Methionine Content in a High-Fat and Choline-Deficient Diet on Body Weight Gain and the Development of Non-Alcoholic Steatohepatitis in Mice.

    Science.gov (United States)

    Chiba, Tsuyoshi; Suzuki, Sachina; Sato, Yoko; Itoh, Tatsuki; Umegaki, Keizo

    2016-01-01

    Non-alcoholic steatohepatitis (NASH) is a globally recognized liver disease. A methionine- and choline-deficient diet is used to induce NASH in mice; however, this diet also causes severe body weight loss. To resolve this issue, we examined the effects of methionine content in a high-fat and choline-deficient (HFCD) diet on body weight and the development of NASH in mice. C57BL/6J mice (male, 10 weeks of age) were fed an L-amino acid rodent (control) diet, high-fat (HF) diet, or HFCD diet containing various amounts of methionine (0.1-0.6% (w/w)) for 12 weeks. Plasma lipid levels, hepatic lipid content and inflammatory marker gene expression were measured, and a pathological analysis was conducted to evaluate NASH. The 0.1% methionine in HFCD diet suppressed body weight gain, which was lower than that with control diet. On the other hand, the 0.2% methionine in HFCD diet yielded similar body weight gains as the control diet, while more than 0.4% methionine showed the same body weight gains as the HF diet. Liver weights and hepatic lipid contents were the greatest with 0.1% methionine and decreased in a methionine dose-dependent manner. Pathological analysis, NAFLD activity scores and gene expression levels in the liver revealed that 0.1% and 0.2% methionine for 12 weeks induced NASH, whereas 0.4% and 0.6% methionine attenuated the induction of NASH by HFCD diet. However, the 0.2% methionine in HFCD diet did not induce insulin resistance, despite the body weight gain. The 0.2% methionine in HFCD diet for 12 weeks was able to induce NASH without weight loss.

  20. Liraglutide efficacy and action in non-alcoholic steatohepatitis (LEAN): study protocol for a phase II multicentre, double-blinded, randomised, controlled trial.

    Science.gov (United States)

    Armstrong, Matthew J; Barton, Darren; Gaunt, Piers; Hull, Diana; Guo, Kathy; Stocken, Deborah; Gough, Stephen C L; Tomlinson, Jeremy W; Brown, Rachel M; Hübscher, Stefan G; Newsome, Philip N

    2013-11-04

    Non-alcoholic steatohepatitis (NASH) is now the commonest cause of chronic liver disease. Despite this, there are no universally accepted pharmacological therapies for NASH. Liraglutide (Victoza), a human glucagon-like peptide-1 (GLP-1) analogue, has been shown to improve weight loss, glycaemic control and liver enzymes in type 2 diabetes. There is currently a lack of prospective-controlled studies investigating the efficacy of GLP-1 analogues in patients with NASH. Liraglutide efficacy and action in NASH (LEAN) is a phase II, multicentre, double-blinded, placebo-controlled, randomised clinical trial designed to investigate whether a 48-week treatment with 1.8 mg liraglutide will result in improvements in liver histology in patients with NASH. Adult, overweight (body mass index ≥25 kg/m(2)) patients with biopsy-confirmed NASH were assessed for eligibility at five recruitment centres in the UK. Patients who satisfied the eligibility criteria were randomly assigned (1:1) to receive once-daily subcutaneous injections of either 1.8 mg liraglutide or liraglutide-placebo (control). Using A'Hern's single stage phase II methodology (significance level 0.05; power 0.90) and accounting for an estimated 20% withdrawal rate, a minimum of 25 patients were randomised to each treatment group. The primary outcome measure will be centrally assessed using an intention-to-treat analysis of the proportion of evaluable patients achieving an improvement in liver histology between liver biopsies at baseline and after 48 weeks of treatment. Histological improvement will be defined as a combination of the disappearance of active NASH and no worsening in fibrosis. The protocol was approved by the National Research Ethics Service (East Midlands-Northampton committee; 10/H0402/32) and the Medicines and Healthcare products Regulatory Agency. Recruitment into the LEAN started in August 2010 and ended in May 2013, with 52 patients randomised. The treatment follow-up of LEAN participants is

  1. Elevation of liver endoplasmic reticulum stress in a modified choline-deficient l-amino acid-defined diet-fed non-alcoholic steatohepatitis mouse model.

    Science.gov (United States)

    Muraki, Yo; Makita, Yukimasa; Yamasaki, Midori; Amano, Yuichiro; Matsuo, Takanori

    2017-05-06

    Endoplasmic reticulum (ER) stress caused by accumulation of misfolded proteins is observed in several kinds of diseases. Since ER stress is reported to be involved in the progression of non-alcoholic steatohepatitis (NASH), highly sensitive and simple measurement methods are required for research into developing novel therapy for NASH. To investigate the involvement of ER stress in NASH pathogenesis in a mouse model, an assay for liver ER stress was developed using ER stress activated indicator-luciferase (ERAI-Luc) mice. To establish the assay method for detection of ER stress in the liver, tunicamycin (TM) (0.3 mg/kg i. p.) was administered to ERAI-Luc mice, and the luciferase activity was measured in ex vivo and in vivo. To evaluate ER stress in the NASH model, ERAI-Luc mice were fed a modified choline-deficient l-amino acid-defined (mCDAA) diet for 14 weeks. After measurement of ER stress by luminescence imaging, levels of liver lipids and pro-fibrotic and pro-inflammatory gene expression were measured as NASH-related indexes. In non-invasive whole-body imaging, TM elevated luciferase activity in the liver, induced by activation of ER stress. The highest luminescence in the liver was confirmed by ex vivo imaging of isolated tissues. In parallel with progression of NASH, elevated luminescence induced by ER stress in liver was observed in mCDAA diet-fed ERAI-Luc mice. Luciferase activity was significantly and positively correlated to levels of triglyceride and free cholesterol in the liver, as well as to the mRNA expression of type 1 collagen α1 chain and tumor necrosis factor α. These data indicated that the use of ERAI-Luc mice was effective in the detection of ER stress in the liver. Moreover, the NASH model using ERAI-Luc mice can be a useful tool to clarify the role of ER stress in pathogenesis of NASH and to evaluate effects of drugs targeted against ER stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. A preliminary investigation and feature analysis of non-alcoholic fatty liver and nonalcoholic steatohepatitis in employees in an IT company

    Directory of Open Access Journals (Sweden)

    LI Xiuchi

    2017-07-01

    Full Text Available ObjectiveTo investigate the incidence rates and features of non-alcoholic fatty liver (NAFL and nonalcoholic steatohepatitis (NASH, and to provide a theoretical basis for health management and development of intervention and preventive measures in the health management department. MethodsPhysical examination reports in 2016 were obtained from a large IT company to analyze the incidence rates of NAFL and NASH in different age and sex groups, as well as the correlation with the indices including overweight (or obesity, triglyceride, fasting blood glucose, blood uric acid, and blood pressure. The chi-square test was used for comparison of rates. Results In all employees, the incidence rates of NAFL and NASH were 4.51% and 17.64%, respectively, and the overall incidence rate of these two diseases was 22.15%. The NAFL-NASH group had significantly higher incidence rates of overweight (or obesity (91.20% vs 12.68%, χ2=7571.9, P<0.001, hyperlipidemia (95.06% vs 9.27%, χ2=9373.8, P<0.001, and hyperuricemia (40.02% vs 10.51%, χ2=1591.90, P<0.001 than the non-NAFL-NASH group. Compared with female employees, male employees had significantly higher incidence rates of NAFL (6.78% vs 1.81%, χ2=190.35, P<0.001 and NASH (25.04% vs 5.06%, χ2=991.90, P<0.001, as well as significantly higher incidence rates of overweight (or obesity (40.90% vs 12.97%, χ2=1319.10, P<0.001, hyperlipidemia (36.00% vs 16.07%, χ2=696.22, P<0.001, hyperglycemia (2.17% vs 0.64%, χ2=53.82, P<0.01, hyperuricemia (2676% vs 1.69%, χ2=1581.10, P<0.001, and hypertension (6.21% vs 1.22%, χ2=170.94, P<0.001. Compared with those aged <35 years, the employees aged ≥35 years had significantly higher incidence rates of NAFL (8.13% vs 4.47%, χ2=41.56, P<0.001 and NASH (21.73% vs 16.76%, χ2=24.72, P<0.001, as well as significantly higher incidence rates of hyperglycemia (2.79% vs 143%, χ2=17.26, P<0.001 and hypertension (6.33% vs 4.03%, χ2=18.56, P<0

  3. COMPARISON OF CLINICAL PROFILE OF DIABETES MELLITUS PATIENTS WITH OR WITHOUT NON-ALCOHOLIC FATTY LIVER DISEASES

    Directory of Open Access Journals (Sweden)

    Satish Kumar

    2017-11-01

    Full Text Available BACKGROUND Non-alcoholic fatty liver disease represents a spectrum of conditions, which is characterised histologically by significant macrovesicular hepatic steatosis that occurs in those who do not consume alcohol in amounts considered to be harmful to liver and in the absence of known toxins, drugs, viral disease, etc. This disease is quite frequently seen in diabetes especially type 2 diabetes mellitus, which is probably related to altered glucose metabolism. The spectrum of non-alcoholic fatty liver disease is quite variable from mild alteration of transaminases, which is a benign disease to one with high morbidity and mortality. Type 2 diabetes mellitus is a risk factor for NAFLD and the prevalence of NAFLD in diabetic patients have been shown to be between 30-80%. MATERIALS AND METHODS In this study, normative survey technique was selected. Duration of the study was one year. The sample comprised of 100 diabetic patients age ranged 31-70 years. The sample was selected on the basis of inclusion and exclusion criteria. The tools such as clinical profile and checklist were administered. RESULTS The study found out that NAFLD is very common in diabetes mellitus. Diabetic patients with NAFLD has a longer duration of diabetes compared to that of diabetic patients without NAFLD diabetic patients with NAFLD had higher BMI, waist circumference and systolic blood pressure than that of patients without NAFLD. CONCLUSION All the patients within the spectrum of NAFLD should be considered potentially affected not only by a liver disease, but by a multisystem disease. Clinicians should be aware of the importance of a complete clinical evaluation for early diagnosis and treatment of liver disease as well as the different manifestations. All type 2 diabetic patients should be monitored for the development of NAFLD. Early diagnosis of NAFLD can prevent the progression to NASH and its complications.

  4. Steatosis and Steatohepatitis: Complex Disorders

    Directory of Open Access Journals (Sweden)

    Kira Bettermann

    2014-06-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD which includes steatosis and steatohepatitis, in particular non-alcoholic steatohepatitis (NASH, is a rising health problem world-wide and should be separated from alcoholic steatohepatitis (ASH. NAFLD is regarded as hepatic manifestation of the metabolic syndrome (MetSy, being tightly linked to obesity and type 2 diabetes mellitus (T2DM. Development of steatosis, liver fibrosis and cirrhosis often progresses towards hepatocellular carcinogenesis and frequently results in the indication for liver transplantation, underlining the clinical significance of this disease complex. Work on different murine models and several human patients studies led to the identification of different molecular key players as well as epigenetic factors like miRNAs and SNPs, which have a promoting or protecting function in AFLD/ASH or NAFLD/NASH. To which extent they might be translated into human biology and pathogenesis is still questionable and needs further investigation regarding diagnostic parameters, drug development and a better understanding of the genetic impact. In this review we give an overview about the currently available knowledge and recent findings regarding the development and progression of this disease.

  5. Steatosis and Steatohepatitis: Complex Disorders

    Science.gov (United States)

    Bettermann, Kira; Hohensee, Tabea; Haybaeck, Johannes

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) which includes steatosis and steatohepatitis, in particular non-alcoholic steatohepatitis (NASH), is a rising health problem world-wide and should be separated from alcoholic steatohepatitis (ASH). NAFLD is regarded as hepatic manifestation of the metabolic syndrome (MetSy), being tightly linked to obesity and type 2 diabetes mellitus (T2DM). Development of steatosis, liver fibrosis and cirrhosis often progresses towards hepatocellular carcinogenesis and frequently results in the indication for liver transplantation, underlining the clinical significance of this disease complex. Work on different murine models and several human patients studies led to the identification of different molecular key players as well as epigenetic factors like miRNAs and SNPs, which have a promoting or protecting function in AFLD/ASH or NAFLD/NASH. To which extent they might be translated into human biology and pathogenesis is still questionable and needs further investigation regarding diagnostic parameters, drug development and a better understanding of the genetic impact. In this review we give an overview about the currently available knowledge and recent findings regarding the development and progression of this disease. PMID:24897026

  6. Tobacco carcinogen (NNK) induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation

    Science.gov (United States)

    Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carc...

  7. Modulating the gut microbiota by dietary guar gum protects against diet-induced obesity but promotes non-alcoholic steatohepatitis in mice

    NARCIS (Netherlands)

    Janssen, Aafke; Houben, Tom; Katiraei, Saeed; Boutens, Lily; Bolt, van der Nieke; Wang, Zeneng; Brown, Jonathan M.; Hazen, Stanley L.; Shiri-Sverdlov, Ronit; Willems van Dijk, Ko; Vervoort, Jacques; Stienstra, Rinke; Hooiveld, Guido; Kersten, Sander

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary

  8. The non-invasive 13C-methionine breath test detects hepatic mitochondrial dysfunction as a marker of disease activity in non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Banasch M

    2012-06-01

    Full Text Available Abstract Introduction Mitochondrial dysfunction plays a central role in the general pathogenesis of non-alcoholic fatty liver disease (NAFLD, increasing the risk of developing steatosis and subsequent hepatocellular inflammation. We aimed to assess hepatic mitochondrial function by a non-invasive 13C-methionine breath test (MeBT in patients with histologically proven NAFLD. Methods 118 NAFLD-patients and 18 healthy controls were examined by MeBT. Liver biopsy specimens were evaluated according to the NASH scoring system. Results Higher grades of NASH activity and fibrosis were independently associated with a significant decrease in cumulative 13C-exhalation (expressed as cPDR(%. cPDR1.5h was markedly declined in patients with NASH and NASH cirrhosis compared to patients with simple steatosis or borderline diagnosis (cPDR1.5h: 3.24 ± 1.12% and 1.32 ± 0.94% vs. 6.36 ± 0.56% and 4.80 ± 0.88% respectively; p 13C-exhalation further declined in the presence of advanced fibrosis which was correlated with NASH activity (r = 0.36. The area under the ROC curve (AUROC for NASH diagnosis was estimated to be 0.87 in the total cohort and 0.83 in patients with no or mild fibrosis (F0-1. Conclusion The 13C-methionine breath test indicates mitochondrial dysfunction in non-alcoholic fatty liver disease and predicts higher stages of disease activity. It may, therefore, be a valuable diagnostic addition for longitudinal monitoring of hepatic (mitochondrial function in non-alcoholic fatty liver disease.

  9. First-Degree Relatives of Patients with Type 2 Diabetes Mellitus and Risk of Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Adibi, Atoosa; Janghorbani, Mohsen; Shayganfar, Sanaz; Amini, Masoud

    2007-01-01

    AIMS: The aim of this study was to determine whether first-degree relatives (FDR) of patients with type 2 diabetes mellitus (T2DM) are at higher risk of non-alcoholic fatty liver disease (NAFLD) than healthy controls. METHODS: A total of 222 FDR of consecutive patients with T2DM aged between 35 and 55 years and 202 healthy individuals with no family history of diabetes were investigated for NAFLD. Fatty liver was diagnosed by ultrasonography using standard criteria. Height, weight, fasting glucose, alanine aminotransferase (ALT), total cholesterol and triglyceride were determined by routine laboratory methods. RESULTS: Compared to subjects with no family history of diabetes, the age and sex adjusted odds ratio (OR) of NAFLD was 1.83 (95% CI: 1.11-3.03) for FDR of patients with T2DM. After further adjusting for BMI, fasting glucose, ALT, asparate aminotransferase (AST), triglyceride and cholesterol, the multivariate OR of prevalent NAFLD in FDR of patients with T2DM compared with individuals with no family history of diabetes was 1.56 (95% CI: 0.85-2.86). CONCLUSIONS: The present study suggests that the relation between FDR of patients with T2DM and NAFLD is affected by the other covariates, in particular obesity, which points to a more complex relationship between the diseases. It appears that obesity and diabetes may independently predispose to NAFLD. PMID:18338077

  10. A randomised, double-blind, placebo-controlled phase 1 study of the safety, tolerability and pharmacodynamics of volixibat in overweight and obese but otherwise healthy adults: implications for treatment of non-alcoholic steatohepatitis.

    Science.gov (United States)

    Palmer, Melissa; Jennings, Lee; Silberg, Debra G; Bliss, Caleb; Martin, Patrick

    2018-03-16

    Accumulation of toxic free cholesterol in hepatocytes may cause hepatic inflammation and fibrosis. Volixibat inhibits bile acid reuptake via the apical sodium bile acid transporter located on the luminal surface of the ileum. The resulting increase in bile acid synthesis from cholesterol could be beneficial in patients with non-alcoholic steatohepatitis. This adaptive dose-finding study investigated the safety, tolerability, pharmacodynamics, and pharmacokinetics of volixibat. Overweight and obese adults were randomised 3:1 to double-blind volixibat or placebo, respectively, for 12 days. Volixibat was initiated at a once-daily dose of 20 mg, 40 mg or 80 mg. Based on the assessment of predefined safety events, volixibat dosing was either escalated or reduced. Other dose regimens (titrations and twice-daily dosing) were also evaluated. Assessments included safety, tolerability, stool hardness, faecal bile acid (FBA) excretion, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and lipids. All 84 randomised participants (volixibat, 63; placebo, 21) completed the study, with no serious adverse events at doses of up to 80 mg per day (maximum assessed dose). The median number of daily bowel evacuations increased from 1 (range 0-4) to 2 (0-8) during volixibat treatment, and stool was looser with volixibat than placebo. Volixibat was minimally absorbed; serum levels were rarely quantifiable at any dose or sampling time point, thereby precluding pharmacokinetic analyses. Mean daily FBA excretion was 930.61 μmol (standard deviation [SD] 468.965) with volixibat and 224.75 μmol (195.403) with placebo; effects were maximal at volixibat doses ≥20 mg/day. Mean serum C4 concentrations at day 12 were 98.767 ng/mL (standard deviation, 61.5841) with volixibat and 16.497 ng/mL (12.9150) with placebo. Total and low-density lipoprotein cholesterol levels decreased in the volixibat group, with median changes of - 0.70 mmol/L (range - 2.8 to 0.4) and - 0.6990

  11. High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs

    DEFF Research Database (Denmark)

    Ipsen, David Højland; Tveden-Nyborg, Pernille; Rolin, Bidda

    2016-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are closely related. Diet plays an important role in the progression of these diseases, but the role of specific dietary components is not completely understood. Therefore, we investigated the role of dietary sucrose and fat....../cholesterol on the development of dyslipidemia and NAFLD. Methods Seventy female guinea pigs were block-randomized (based on weight) into five groups and fed a normal chow diet (control: 4 % fat), a very high-sucrose diet (vHS: 4 % fat, 25 % sucrose), a high-fat diet (HF: 20 % fat, 0.35 % cholesterol), a high......-fat/high-sucrose diet (HFHS: 20 % fat, 15 % sucrose, 0.35 % cholesterol) or a high-fat/very high-sucrose diet (HFvHS: 20 % fat, 25 % sucrose, 0.35 % cholesterol) for 16 and 25 weeks. Results All three high-fat diets induced dyslipidemia with increased concentrations of plasma cholesterol (p 

  12. Comparison of effects of obesity and non-alcoholic fatty liver disease on incidence of type 2 diabetes mellitus.

    Science.gov (United States)

    Li, Wei-Dong; Fu, Kun-Fa; Li, Gui-Mei; Lian, Yan-Shu; Ren, Ai-Min; Chen, Yun-Jue; Xia, Jin-Rong

    2015-08-28

    To compare and analyze the effects of obesity and non-alcoholic fatty liver disease (NAFLD) on the incidence of type 2 diabetes mellitus (T2DM) in Chinese subjects. In 2008, a population of 4847 subjects was randomly sampled from 17 medical units for enrollment in this cohort study. Baseline information was obtained via a questionnaire on general information, physical examination (height, weight, and blood pressure), laboratory tests (triglycerides, total cholesterol, fasting blood glucose, alanine aminotransferase (ALT), uric acid, and creatinine), B-mode ultrasound, and ECG screening. The incidence of T2DM after four years of follow-up was calculated. Numeric variable data was tested for normality, with the data expressed as mean ± SD. Kaplan-Meier analysis was performed to calculate the cumulative incidence. The Cox proportional hazards model was used to analyze the relative risk (RR) of different body mass index (BMI) levels and NAFLD on T2DM, as well as analyzing the RR adjusted for age, sex, blood pressure, lipids, transaminases, uric acid, and creatinine. A total of 4736 (97.71%) subjects completed 4-year follow-up, with a median follow-up time of 3.85 years, totaling 17223 person-years. 380 subjects were diagnosed with T2DM, with a cumulative incidence of 8.0%. The cumulative incidence of T2DM in the NAFLD and control groups was 17.4% vs 4.1% (P obese subjects was 11.0% vs 15.8% (P obese subjects after adjustment for age, sex, BMI, blood pressure, lipids and other factors was 1.274 (0.997-1.629) and 1.554 (1.140-2.091), respectively. Stratification of three BMI levels (BMI obesity.

  13. The impact of non-alcoholic fatty liver disease on incident type 2 diabetes mellitus in non-overweight individuals.

    Science.gov (United States)

    Fukuda, Takuya; Hamaguchi, Masahide; Kojima, Takao; Hashimoto, Yoshitaka; Ohbora, Akihiro; Kato, Takahiro; Nakamura, Naoto; Fukui, Michiaki

    2016-02-01

    The aim of this study was to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on incident type 2 diabetes mellitus (T2DM) in non-overweight individuals with NAFLD. A population-based retrospective cohort study of 4629 participants who were enrolled in a health check-up programme for more than 10 years. A standardized questionnaire and abdominal ultrasonography were used to diagnose NAFLD. A cut-off point of BMI 23 kg/m(2) was used to define overweight (≥23.0 kg/m(2)) or non-overweight (overweight without NAFLD group, 14.4% in the non-overweight with NAFLD group, 8.0% in the overweight without NAFLD group and 26.4% in the overweight with NAFLD group. The adjusted hazard ratios for incident T2DM compared with the non-overweight without NAFLD group were as follows: 3.59 (95% CI: 2.14-5.76) in the non-overweight with NAFLD group, 1.99 (95% CI: 1.47-2.69) in the overweight without NAFLD group and 6.77 (95% CI: 5.17-8.91) in the overweight with NAFLD group. The adjusted hazard ratio in the non-overweight with NAFLD group was significantly higher than that in the overweight without NAFLD group or that in the non-overweight without NAFLD group. Non-overweight individuals with NAFLD had a high risk of incident T2DM. Diagnosis of NAFLD is important in non-overweight individuals, and therefore it might be necessary to follow their health conditions on a long-term basis after detection of NAFLD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α

    Science.gov (United States)

    Ren, Tingting; Zhu, Juanjuan; Zhu, Lili; Cheng, Mingliang

    2017-01-01

    Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets (p < 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models (p < 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) (p < 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3 pathway

  15. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research.

    Science.gov (United States)

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Crespo Yanguas, Sara; Colle, Isabelle; Van Den Bossche, Bert; Da Silva, Tereza Cristina; de Oliveira, Cláudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini; Cogliati, Bruno; Vinken, Mathieu

    2015-07-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and '-omics'-based read-outs are still in their infancy, but show great promise. In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

    Science.gov (United States)

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

  17. Deoxyribonucleic acid telomere length shortening can predict the incidence of non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Ping, Fan; Li, Zeng-Yi; Lv, Ke; Zhou, Mei-Cen; Dong, Ya-Xiu; Sun, Qi; Li, Yu-Xiu

    2017-03-01

    To investigate the effect of telomere shortening and other predictive factors of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus patients in a 6-year prospective cohort study. A total of 70 type 2 diabetes mellitus (mean age 57.8 ± 6.7 years) patients without NAFLD were included in the study, and 64 of them were successfully followed up 6 years later, excluding four cases with significant alcohol consumption. NAFLD was diagnosed by the hepatorenal ratio obtained by a quantitative ultrasound method using NIH image analysis software. The 39 individuals that developed NAFLD were allocated to group A, and the 21 individuals that did not develop NAFLD were allocated to group B. Fluorescent real-time quantitative polymerase chain reaction was used to measure telomere length. There was no significant difference between the two groups in baseline telomere length; however, at the end of the 6th year, telomere length had become shorter in group A compared with group B. There were significant differences between these two groups in baseline body mass index, waistline, systolic blood pressure, glycated hemoglobin and fasting C-peptide level. In addition, the estimated indices of baseline insulin resistance increased in group A. Fasting insulin level, body mass index, systolic blood pressure at baseline and the shortening of telomere length were independent risk factors of NAFLD in type 2 diabetes mellitus patients. Telomere length became shorter in type 2 diabetes mellitus patients who developed NAFLD over the course of 6 years. Type 2 diabetes mellitus patients who developed NAFLD had more serious insulin resistance compared with those who did not develop NAFLD a long time ago. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  18. Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases

    Directory of Open Access Journals (Sweden)

    Eugene Han

    2017-11-01

    Full Text Available As the number of individuals with non-alcoholic fatty liver disease (NAFLD has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged.

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

    Science.gov (United States)

    Calzadilla Bertot, Luis; Adams, Leon Anton

    2016-05-20

    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.

  20. Non-Alcoholic Fatty Liver Disease in HIV Infection.

    Science.gov (United States)

    Macías, Juan; Pineda, Juan A; Real, Luis M

    2017-01-01

    Non-alcoholic fatty liver disease is one of the most frequent chronic hepatic conditions worldwide. The spectrum of non-alcoholic fatty liver disease goes from hepatic steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Risk factors for non-alcoholic fatty liver disease are metabolic, mainly obesity and the accompanying consequences. Treatment and prevention of non-alcoholic fatty liver disease should target those metabolic abnormalities. The frequency of and the factors associated with hepatic steatosis in HIV infection seem to be similar to those reported in the general population, though direct comparisons are lacking. Hepatic steatosis in HIV infection may also be secondary to antiretroviral drugs or HCV-related factors in HCV-coinfected subjects. However, more recent data suggest that hepatic steatosis in HIV infection represents true non-alcoholic fatty liver disease. As such, management of non-alcoholic fatty liver disease in HIV infection should follow the same principles as in the general population.

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

    Directory of Open Access Journals (Sweden)

    Stefano Gitto

    2016-04-01

    Full Text Available 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.

  2. 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.

  3. Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity.

    Science.gov (United States)

    Pavlides, Michael; Banerjee, Rajarshi; Tunnicliffe, Elizabeth M; Kelly, Catherine; Collier, Jane; Wang, Lai Mun; Fleming, Kenneth A; Cobbold, Jeremy F; Robson, Matthew D; Neubauer, Stefan; Barnes, Eleanor

    2017-07-01

    The diagnosis of non-alcoholic steatohepatitis and fibrosis staging are central to non-alcoholic fatty liver disease assessment. We evaluated multiparametric magnetic resonance in the assessment of non-alcoholic steatohepatitis and fibrosis using histology as standard in non-alcoholic fatty liver disease. Seventy-one patients with suspected non-alcoholic fatty liver disease were recruited within 1 month of liver biopsy. Magnetic resonance data were used to define the liver inflammation and fibrosis score (LIF 0-4). Biopsies were assessed for steatosis, lobular inflammation, ballooning and fibrosis and classified as non-alcoholic steatohepatitis or simple steatosis, and mild or significant (Activity ≥2 and/or Fibrosis ≥2 as defined by the Fatty Liver Inhibition of Progression consortium) non-alcoholic fatty liver disease. Transient elastography was also performed. Magnetic resonance success rate was 95% vs 59% for transient elastography (Pliver inflammation and fibrosis (r s =.51, Pliver inflammation and fibrosis for the diagnosis of cirrhosis was 0.85. Liver inflammation and fibrosis score for ballooning grades 0, 1 and 2 was 1.2, 2.7 and 3.5 respectively (Pliver inflammation and fibrosis (1.3) compared to patients with non-alcoholic steatohepatitis (3.0) (PLiver inflammation and fibrosis scores for patients with mild and significant non-alcoholic fatty liver disease were 1.2 and 2.9 respectively (Pliver inflammation and fibrosis for the diagnosis of significant non-alcoholic fatty liver disease was 0.89. Multiparametric magnetic resonance is a promising technique with good diagnostic accuracy for non-alcoholic fatty liver disease histological parameters, and can potentially identify patients with non-alcoholic steatohepatitis and cirrhosis. © 2017 The Authors Liver International Published by John Wiley & Sons Ltd.

  4. The Cholesterol Derivative 27-Hydroxycholesterol Reduces Steatohepatitis in Mice

    NARCIS (Netherlands)

    Bieghs, Veerle; Hendrikx, Tim; van Gorp, Patrick J.; Verheyen, Fons; Guichot, Yasmin Dias; Walenbergh, Sofie M. A.; Jeurissen, Mike L. J.; Gijbels, Marion; Rensen, Sander S.; Bast, Aalt; Plat, Jogchum; Kalhan, Satish C.; Koek, Ger H.; Leitersdorf, Eran; Hofker, Marten H.; Luetjohann, Dieter; Shiri-Sverdlov, Ronit

    BACKGROUND & AIMS: Non-alcoholic steatohepatitis is characterized by hepatic steatosis with inflammation. Although steatosis is benign and reversible, inflammation can increase liver damage. Hepatic inflammation has been associated with accumulation of cholesterol in lysosomes of Kupffer cells.

  5. The cholesterol derivative 27-hydroxycholesterol reduces steatohepatitis in mice

    NARCIS (Netherlands)

    Bieghs, Veerle; Hendrikx, Tim; van Gorp, Patrick J.; Verheyen, Fons; Guichot, Yasmin Dias; Walenbergh, Sofie M. A.; Jeurissen, Mike L. J.; Gijbels, Marion; Rensen, Sander S.; Bast, Aalt; Plat, Jogchum; Kalhan, Satish C.; Koek, Ger H.; Leitersdorf, Eran; Hofker, Marten H.; Lütjohann, Dieter; Shiri-Sverdlov, Ronit

    2013-01-01

    Non-alcoholic steatohepatitis is characterized by hepatic steatosis with inflammation. Although steatosis is benign and reversible, inflammation can increase liver damage. Hepatic inflammation has been associated with accumulation of cholesterol in lysosomes of Kupffer cells. 27-Hydroxycholesterol

  6. A preliminary study of inflammatory markers in non-alcoholic ...

    African Journals Online (AJOL)

    2010-03-19

    Mar 19, 2010 ... (AMG), alpha-1 anti-trypsin (AAT) and lipoprotein a [Lp(a)] were measured in coronary artery disease patients (CAD) and CAD patients with ... artery disease; non-alcoholic steatohepatitis. Received: 1 November 2009; Accepted in ..... Al Arab Medical University. PO Box 18251, Hawari Road. Benghazi ...

  7. Combined Non-alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Sleeve Gastrectomy or Gastric Bypass?-a Controlled Matched Pair Study of 34 Patients.

    Science.gov (United States)

    Billeter, Adrian T; Senft, Jonas; Gotthardt, Daniel; Knefeli, Philipp; Nickel, Felix; Schulte, Thilo; Fischer, Lars; Nawroth, Peter P; Büchler, Markus W; Müller-Stich, Beat P

    2016-08-01

    Although all bariatric procedures improve non-alcoholic fatty liver disease (NAFLD) in metabolically sick obese patients, it remains unclear whether different procedures achieve similar effects. Sleeve gastrectomy (SG) and Roux-Y-gastric bypass (RYGB) were compared for their effects on liver function tests (LFT) and glycemic control in a highly selected group of metabolically sick obese patients with both elevated alanine aminotransferase (ALT), a common marker for NAFLD and type 2 diabetes mellitus (T2DM). Thirty-four obese patients with a body mass index (BMI) >35 kg/m(2), ALT > 35 U/L, and T2DM were well-matched from a prospective database and retrospectively analyzed. Seventeen patients each underwent RYGB and SG, respectively. The effects on LFT and glycemic control were evaluated over 12 months. Both procedures significantly lowered ALT and aspartate aminotransferase (AST) after 12 months, but SG improved both LFT significantly better than RYGB (ALT 17.8 ± 8.8 vs. 31.1 ± 11.2 U/L, p = 0.003; AST 17.0 ± 8.8 vs. 24.3 ± 7.5 U/L, p = 0.004). In contrast to RYGB, SG normalized elevated ALT levels completely (41 vs. 0 %, p = 0.007). Both SG and RYGB improved insulin resistance, glycemic control, and reduced the need of insulin significantly without any difference between the procedures. SG appears to improve LFT better than RYGB in well-matched obese patients with both elevated ALT and T2DM. This suggests that SG may have a better effect on NAFLD than RYGB with similar effects on glycemic control. The present findings should be verified in randomized controlled trials to obtain further evidence for the decision-making on the most appropriate bariatric procedure for metabolically sick patients.

  8. Pathogenesis of hepatic steatosis: The link between hypercortisolism and non-alcoholic fatty liver disease

    OpenAIRE

    Tarantino, Giovanni; Finelli, Carmine

    2013-01-01

    Based on the available literature, non alcoholic fatty liver disease or generally speaking, hepatic steatosis, is more frequent among people with diabetes and obesity, and is almost universally present amongst morbidly obese diabetic patients. Non alcoholic fatty liver disease is being increasingly recognized as a common liver condition in the developed world, with non alcoholic steatohepatitis projected to be the leading cause of liver transplantation. Previous data report that only 20% of p...

  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. Molecular pathways in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Berlanga, Alba; Guiu-Jurado, Esther; Porras, José Antonio; Auguet, Teresa

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the "double-hit" hypothesis. The primary insult or the "first hit" includes lipid accumulation in the liver, followed by a "second hit" in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs) and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA synthesis is increased, but FAs are also taken up from the serum. Furthermore, a decrease in mitochondrial FA oxidation and secretion of very-low-density lipoproteins has been reported. This review discusses the molecular mechanisms that underlie the pathophysiological changes of hepatic lipid metabolism that contribute to NAFLD.

  11. Molecular pathways in non-alcoholic fatty liver disease

    Science.gov (United States)

    Berlanga, Alba; Guiu-Jurado, Esther; Porras, José Antonio; Auguet, Teresa

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the “double-hit” hypothesis. The primary insult or the “first hit” includes lipid accumulation in the liver, followed by a “second hit” in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs) and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA synthesis is increased, but FAs are also taken up from the serum. Furthermore, a decrease in mitochondrial FA oxidation and secretion of very-low-density lipoproteins has been reported. This review discusses the molecular mechanisms that underlie the pathophysiological changes of hepatic lipid metabolism that contribute to NAFLD. PMID:25045276

  12. Non-alcoholic fatty liver disease: The diagnosis and management

    Science.gov (United States)

    Abd El-Kader, Shehab M; El-Den Ashmawy, Eman M Salah

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease that occurs across all age groups and is recognized to occur in 14%-30% of the general population, representing a serious and growing clinical problem due to the growing prevalence of obesity and overweight. Histologically, it resembles alcoholic liver injury but occurs in patients who deny significant alcohol consumption. NAFLD encompasses a spectrum of conditions, ranging from benign hepatocellular steatosis to inflammatory nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The majority of hepatocellular lipids are stored as triglycerides, but other lipid metabolites, such as free fatty acids, cholesterol, and phospholipids, may also be present and play a role in disease progression. NAFLD is associated with obesity and insulin resistance and is considered the hepatic manifestation of the metabolic syndrome, a combination of medical conditions including type 2 diabetes mellitus, hypertension, hyperlipidemia, and visceral adiposity. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to highlight the current information regarding epidemiology, diagnosis, and management of NAFLD as well as new information about pathogenesis, diagnosis and management of this disease. PMID:25937862

  13. [The effectiveness of the spa and health resort-based treatment with the application of Essentuki-type drinking mineral waters for the management of non-alcoholic fatty liver disease in the patients presenting with type 2 diabetes mellitus].

    Science.gov (United States)

    Efimenko, N V; Kaĭsinova, A S; Fedorova, T E; Botvineva, L A

    2015-01-01

    The objective of the present study was to estimate the effectiveness of the spa and health resort-based treatment of non-alcoholic fatty liver disease in 40 patients at the mean age of 48,8 ± 5.7 years suffering from type 2 diabetes mellitus. All of them received combined therapy including the application of potable Essentuki-Novaya mineral water (20 patients) or Essentuki No 4 water (20 patients). This therapeutic modality resulted in positive dynamics of clinical symptoms of the disease, the functional liver tests, and parameters of intra-hepatic hemodynamics, lipid peroxidation homeostasis, and the hormonal status. It is concluded that the spa and health resort-based treatment with the application of local drinking Essentuki-type mineral waters for the management of non-alcoholic fatty liver disease in the patients presenting with type 2 diabetes mellitus leads to the improvement of the main functions of the liver, stabilizes carbohydrate and lipid metabolism, and prevents progression of the pathological process.

  14. Practical approach to non-alcoholic fatty liver disease in patients with diabetes.

    Science.gov (United States)

    Tai, F W D; Syn, W-K; Alazawi, W

    2015-09-01

    The prevalence of Type 2 diabetes is expected to increase in parallel with obesity rates and the ageing population. Recent studies show that Type 2 diabetes is associated with a twofold increase in the risk of non-alcoholic fatty liver disease, a leading cause of chronic liver disease. Individuals with non-alcoholic steatohepatitis, a more advanced stage of non-alcoholic fatty liver disease, are specifically at risk of developing fibrosis/cirrhosis (end-stage liver disease) and hepatocellular carcinoma; therefore, identifying individuals (with Type 2 diabetes) who are likely to develop hepatic complications is paramount. In the present clinical review, we discuss the potential impact of non-alcoholic fatty liver disease diagnosis on Type 2 diabetes, and the putative risk factors for developing non-alcoholic steatohepatitis and non-alcoholic steatohepatitis fibrosis. We highlight the limitations of currently used tools in non-alcoholic fatty liver disease diagnosis and staging, and provide an insight into future developments in the field. We present an example of a non-alcoholic fatty liver disease screening protocol and discuss the therapeutic options currently available to our patients. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  15. Molecular pathways in non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Berlanga A

    2014-07-01

    Full Text Available Alba Berlanga,1,* Esther Guiu-Jurado,1,* José Antonio Porras,1,2 Teresa Auguet1,21Group GEMMAIR (AGAUR and Applied Medicine Research Group, Department of Medicine and Surgery, Universitat Rovira i Virgili (URV, IISPV, Hospital Universitari Joan XXIII, Tarragona, Spain; 2Department of Internal Medicine, Hospital Universitari Joan XXIII Tarragona, Tarragona, Spain *These authors contributed equally to this workAbstract: Non-alcoholic fatty liver disease (NAFLD is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the "double-hit" hypothesis. The primary insult or the "first hit" includes lipid accumulation in the liver, followed by a "second hit" in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA

  16. Focus on emerging drugs for the treatment of patients with non-alcoholic fatty liver disease

    Science.gov (United States)

    Federico, Alessandro; Zulli, Claudio; de Sio, Ilario; Del Prete, Anna; Dallio, Marcello; Masarone, Mario; Loguercio, Carmela

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder in Western countries and is increasingly being recognized in developing nations. Fatty liver disease encompasses a spectrum of hepatic pathology, ranging from simple steatosis to non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and end-stage liver disease. Moreover, NAFLD is often associated with other metabolic conditions, such as diabetes mellitus type 2, dyslipidemia and visceral obesity. The most recent guidelines suggest the management and treatment of patients with NAFLD considering both the liver disease and the associated metabolic co-morbidities. Diet and physical exercise are considered the first line of treatment for patients with NAFLD, but their results on therapeutic efficacy are often contrasting. Behavior therapy is necessary most of the time to achieve a sufficient result. Pharmacological therapy includes a wide variety of classes of molecules with different therapeutic targets and, often, little evidence supporting the real efficacy. Despite the abundance of clinical trials, NAFLD therapy remains a challenge for the scientific community, and there are no licensed therapies for NAFLD. Urgently, new pharmacological approaches are needed. Here, we will focus on the challenges facing actual therapeutic strategies and the most recent investigated molecules. PMID:25492998

  17. Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance.

    Science.gov (United States)

    Stål, Per

    2015-10-21

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.

  18. Modern approach to the clinical management of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Del Ben, Maria; Polimeni, Licia; Baratta, Francesco; Pastori, Daniele; Loffredo, Lorenzo; Angelico, Francesco

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is the most common and emerging form of chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis, which may progress to cirrhosis, liver cancer, and liver mortality. Common metabolic diseases, which are well established cardiovascular risk factors, have been associated to NAFLD and cardiovascular disease is the single most important cause of morbidity and mortality in this patient population. The pathogenesis of NAFLD appears multifactorial and many mechanisms have been proposed as possible causes of fatty liver infiltration. Management of fatty liver has become a major challenge to healthcare systems as the consequence of the increasing rates of obesity worldwide. First-line management focuses on lifestyle modifications. Moderate weight reduction either by dietary restriction or by increased habitual physical activity is safe and highly recommended. Several therapeutic interventions have been proposed. These include insulin sensitizer agents, lipid lowering drugs, antioxidants such as vitamin E and supplementation of vitamin D3. However, therapeutic strategies have been largely empirical so far, and experimental trials have mostly been carried out in uncontrolled settings with small sample sizes. Metabolic conditions such as diabetes mellitus, obesity, hypertension and hyperlipidemia, should be strongly considered and a multidisciplinary approach should be personalized for individual patients. Treatment of co-morbidities should be regarded as of paramount importance in the management of these patients. The purpose of this review is to examine different approaches for the clinical management of non-alcoholic fatty liver disease.

  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. Pathogenesis of non-alcoholic fatty liver disease

    OpenAIRE

    Dowman, J. K.; Tomlinson, J.W.; Newsome, P.N.

    2009-01-01

    Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disease ranging from hepatocellular steatosis through steatohepatitis to fibrosis and irreversible cirrhosis. The prevalence of NAFLD has risen rapidly in parallel with the dramatic rise in obesity and diabetes, and is rapidly becoming the most common cause of liver disease in Western countries. Indeed, NAFLD is now recognized to be the aetiology in many cases previously labelled as cryptogenic cirrhosis.

  1. [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.

  2. [Non-alcoholic fatty liver disease and hepatocellular carcinoma - 2016].

    Science.gov (United States)

    Pár, Alajos; Pár, Gabriella

    2016-06-19

    In the past decade non-alcoholic liver disease became the most frequently diagnosed liver disease in developed countries. At the same time, the dramatic rise in the incidence of hepatocellular carcinoma is attributed to this common metabolic disorder, and mainly to its severe form, non-alcoholic steatohepatitis. The risk factors of these associated diseases are genetic predisposition, obesity and diabetes as well as chronic low grade necro-infammation, which often leads to liver fibrosis. Free fatty acids, cytokines, lipotoxicity, insulin resistance, microRNS dysregulation and alteration in intestinal microbiota play a pivotal role in the pathogenesis. Treatment of non-alcoholic fatty liver disease - weight reduction and physical exercise in obesity, metformin in diabetes, statins in dyslipidemia and, as a new option, obeticholic acid - may diminish the risk of the hepatocellular carcinoma related to this metabolic disease.

  3. SIRT3 as a Regulator of Non-alcoholic Fatty Liver Disease

    OpenAIRE

    Cho, Eun-Hee

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a hepatic presentation of obesity and metabolic syndrome. NAFLD includes a large spectrum of hepatic pathologies that range from simple steatosis and non-alcoholic steatohepatitis (NASH), to liver cirrhosis without an all-encompassing approved therapeutic strategy. Mitochondrial dysfunction is a key component of many metabolic diseases, such as obesity, type 2 diabetes, cancer, NAFLD, and aging. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase tha...

  4. Roles of abnormal lipid metabolism in pathogenesis of non-alcoholic fatty liver disease

    OpenAIRE

    LU Ran; HONG Tianpei

    2015-01-01

    The prevalence of non-alcoholic fatty liver disease (NAFLD) keeps rising worldwide along with the increasing prevalence of metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia. Although most NAFLD patients present with simple steatosis of hepatocytes, some patients progress to non-alcoholic steatohepatitis, liver cirrhosis, and even cancer. In the Western world, NAFLD is the most common cause of elevated liver enzymes, and hence there has been a growing interest in this disea...

  5. Low physical activity and energy dense Malaysian foods are associated with non-alcoholic fatty liver disease in centrally obese but not in non-centrally obese patients with diabetes mellitus.

    Science.gov (United States)

    Chan, Wah-Kheong; Tan, Alexander Tong-Boon; Vethakkan, Shireene Ratna; Tah, Pei-Chien; Vijayananthan, Anushya; Goh, Khean-Lee

    2015-01-01

    To study the dietary intake and level of physical activity (PA) of patients with diabetes mellitus and the association with non-alcoholic fatty liver disease (NAFLD). Consecutive adult patients with type 2 diabetes mellitus seen in our hospital diabetes clinic were enrolled. The Global Physical Activity Questionnaire and a semi-quantitative food-frequency questionnaire were used to assess PA and dietary intake, respectively. Diagnosis of NAFLD was ultrasound-based and following exclusion of significant alcohol intake and other causes of chronic liver disease. Data for 299 patients were analyzed (mean age 63.3±10.5 years old, 41.1% male). Prevalence of NAFLD was 49.2%. Patients with low PA were more likely to have NAFLD (OR=1.75, 95% CI=1.03-2.99, p=0.029). There was no significant difference in energy intake, intake of macronutrients and percentage energy intake from each macronutrient, high sugar food, high cholesterol food and high SFA food between patients with and without NAFLD. Among centrally obese patients, patients with low PA and in the highest quartile of percentage energy intake from fat (OR=4.03, 95% CI=1.12-15.0, p=0.015), high cholesterol food (OR=3.61, 95% CI=1.37-9.72, p=0.004) and high SFA food (OR=2.67, 95% CI=1.08-6.67, p=0.019) were most likely to have NAFLD. Among those who were not centrally obese, PA and percentage energy intake from fat, high cholesterol food and high SFA food was not associated with NAFLD. Low PA and high percentage energy intake from fat, high cholesterol food and high SFA food is associated with NAFLD in centrally obese but not in non-centrally obese patients with diabetes mellitus.

  6. '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

  7. Hepatic Steatosis and Steatohepatitis Is the Inevitability of Mixed Genesis

    Directory of Open Access Journals (Sweden)

    Yu.M. Stepanov

    2014-11-01

    Full Text Available The analysis of the etiological and pathogenetic mechanisms of formation steatosis and steatohepatitis of mixed genesis is presented. It is shown that alcohol remains one of the main etiopathogenetic factors in the development of the hepatic steatosis and steatohepatitis, the role of which is observed in 46–65 % patients. There are strong evidence confirming that the obesity and insulin resistance are the independent factors of progression of steatosis and steatohepatitis of alcoholic, non-alcoholic and mixed etiology. The simultaneous influence of several etiological factors leads to the immediate development of steatosis and steatohepatitis in 95 % patients. Many trigger factors can be considered as complementary factors of liver damage of mixed genesis. Common approaches to the diagnosis, treatment, and the main group of drugs for the correction of steatosis and steatohepatitis of mixed origin are presented.

  8. 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

  9. Non-alcoholic fatty liver disease in 2016.

    Science.gov (United States)

    Townsend, S A; Newsome, Philip N

    2016-09-01

    Non-alcoholic fatty liver disease is the commonest cause of liver disease worldwide, and is rapidly becoming the leading indication for liver transplantation. Original articles, reviews and meta-analyses, guidelines. NAFLD strongly correlates with obesity and insulin resistance; currently, the best management strategy is weight loss and treatment of the metabolic syndrome. Recent data suggest that the presence of fibrosis and not non-alcoholic steatohepatitis (NASH) is the predictor of clinical outcome. Many phase 2 and 3 trials are underway. Drugs hoped to be effective are obeticholic acid, elafibranor, glucagon-like peptide-1 analogues and CCR2/5 inhibitors. Improved understanding of the pathophysiology of NAFLD should help us identify which patients progress to significant liver disease and to develop therapies to target this population. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Engin, Atilla

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is in parallel with the obesity epidemic and it is the most common cause of liver diseases. The development of hepatic steatosis in majority of patients is linked to dietary fat ingestion. NAFLD is characterized by excess accumulation of triglyceride in the hepatocyte due to both increased inflow of free fatty acids and de novo hepatic lipogenesis. Insulin resistance with the deficiency of insulin receptor substrate-2 (IRS-2)-associated phosphatidylinositol 3-kinase (PI3K) activity causes an increase in intracellular fatty acid-derived metabolites such as diacylglycerol, fatty acyl CoA or ceramides. Lipotoxicity-related mechanism of NAFLD could be explained still best by the "double-hit" hypothesis. Insulin resistance is the major mechanism in the development and progression of NAFLD/Non-alcoholic steatohepatitis (NASH). Metabolic oxidative stress, autophagy, and inflammation induce NASH progression. In the "first hit" the hepatic concentrations of diacylglycerol increase with rising saturated liver fat content in human NAFLD. Activities of mitochondrial respiratory chain complexes are decreased in liver tissue of patients with NASH. Furthermore, hepatocyte lipoapoptosis is a critical feature of NASH. In "second hit" reduced glutathione levels due to oxidative stress lead to overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling that induces cell death in the steatotic liver. Accumulation of toxic levels of reactive oxygen species (ROS) is caused by the ineffectual cycling of the endoplasmic reticulum (ER) oxidoreductin (Ero1)-protein disulfide isomerase oxidation cycle through the downstream of the inner membrane mitochondrial oxidative metabolism and Kelch like-ECH-associated protein 1 (Keap1)- Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway.

  11. Circulating dipeptidyl peptidase-4 activity correlates with measures of hepatocyte apoptosis and fibrosis in non-alcoholic fatty liver disease in type 2 diabetes mellitus and obesity: A dual cohort cross-sectional study.

    Science.gov (United States)

    Williams, Kathryn H; Vieira De Ribeiro, Ana Júlia; Prakoso, Emilia; Veillard, Anne-Sophie; Shackel, Nicholas A; Brooks, Belinda; Bu, Yangmin; Cavanagh, Erika; Raleigh, Jim; McLennan, Susan V; McCaughan, Geoffrey W; Keane, Fiona M; Zekry, Amany; Gorrell, Mark D; Twigg, Stephen M

    2015-11-01

    Intrahepatic expression of dipeptidyl peptidase-4 (DPP4), and circulating DPP4 (cDPP4) levels and its enzymatic activity, are increased in non-alcoholic fatty liver disease (NAFLD) and in type 2 diabetes mellitus and/or obesity. DPP4 has been implicated as a causative factor in NAFLD progression but few studies have examined associations between cDPP4 activity and NAFLD severity in humans. This study aimed to examine the relationship of cDPP4 activity with measures of liver disease severity in NAFLD in subjects with diabetes and/or obesity. cDPP4 was measured in 106 individuals with type 2 diabetes who had transient elastography (Cohort 1) and 145 individuals with morbid obesity who had liver biopsy (Cohort 2). Both cohorts had caspase-cleaved keratin-18 (ccK18) measured as a marker of apoptosis. Natural log increases in cDPP4 activity were associated with increasing quartiles of ccK18 (Cohorts 1 and 2) and with median liver stiffness ≥10.3 kPa (Cohort 1) and significant fibrosis (F ≥ 2) on liver biopsy (Cohort 2). In diabetes and/or obesity, cDPP4 activity is associated with current apoptosis and liver fibrosis. Given the pathogenic mechanisms by which DPP4 may progress NAFLD, measurement of cDPP4 activity may have utility to predict disease progression and DPP4 inhibition may improve liver histology over time. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

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

    Science.gov (United States)

    Yoneda, Masato; Naka, Shuhei; Nakano, Kazuhiko; Wada, Koichiro; Endo, Hiroki; Mawatari, Hironori; Imajo, Kento; Nomura, Ryota; Hokamura, Kazuya; Ono, Masafumi; Murata, Shogo; Tohnai, Iwai; Sumida, Yoshio; Shima, Toshihide; Kuboniwa, Masae; Umemura, Kazuo; Kamisaki, Yoshinori; Amano, Atsuo; Okanoue, Takeshi; Ooshima, Takashi; Nakajima, Atsushi

    2012-02-16

    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. 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. 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. Infection with high-virulence P. gingivalis might be an additional risk factor for the

  13. 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

  14. 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......), but this remains controversial. We aimed to investigate whether associations between various features of NAFLD and hs-CRP are independent of body mass index (BMI) in its broad range among obese patients....

  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. 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.

  17. Nonalcoholic steatohepatitis and obesity as one of the main predictors of metabolic syndrome development in children and adolescents

    Directory of Open Access Journals (Sweden)

    O.Yu. Belousova

    2017-03-01

    Full Text Available This article deals with the importance of isolating the metabolic syndrome in pediatric gastroenterological practice, since almost all the major components of the metabolic syndrome are already found in childhood. In addition, this condition diagnosed at early stages of the disease development is theoretically reversible, that is with the prescription of an adequate treatment, it is possible to reduce the severity of its main manifestations and to prevent diabetes mellitus type 2, dyslipidemia and cardiovascular diseases. The main predictors of the development of this pathology are obesity, whose growth tends to increase constantly, and non-alcoholic steatohepatitis, often manifested in adolescence. The advisability of using drugs that affect hepatic metabolism and are able to exert a lipid-regulating effects, in particular, essential phospholipids, is discussed.

  18. Non-alcoholic fatty pancreas disease.

    Science.gov (United States)

    Alempijevic, Tamara; Dragasevic, Sanja; Zec, Simon; Popovic, Dragan; Milosavljevic, Tomica

    2017-04-01

    Obesity is a growing problem worldwide and disorders associated with excess body fat including the metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular disease and malignant neoplasms are becoming a major cause of morbidity and mortality. Over the past decade, a vast amount of research has furthered our understanding of non-alcoholic fatty liver disease; however, only recently pancreatic fat infiltration is coming to the forefront of investigation. Termed non-alcoholic fatty pancreas disease (NAFPD), it is becoming evident that it has important associations with other diseases of obesity. It appears to arise as obesity progresses and after an initial phase of pancreatic hypertrophy and hyperplasia, fatty infiltration becomes apparent. Various studies have demonstrated that NAFPD may exacerbate the severity of acute pancreatitis, promote pancreatic dysfunction associated with insulin resistance and T2DM, and even have links to the development of pancreatic carcinoma, and therefore, it must be investigated in further detail. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. [Advances in the pathogenesis of non alcoholic fatty liver disease].

    Science.gov (United States)

    Pár, Alajos; Pár, Gabriella

    2017-06-01

    Non alcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome, and the most common liver disease. Its more aggressive form is the non alcoholic steatohepatitis. Multiple genetic and environmental factors lead to the accumulation of triglicerides and the inflammatory cascade. High fat diet, obesity, adipocyte dysfunction with cytokine production, insulin resistance and increased lipolysis with free fatty acid flux into the liver - all are the drivers of liver cell injury. Activation of inflammasome by damage- or pathogen-associated molecular patterns results in "steril inflammation" and immune response, while the hepatic stellate cells and progenitor cells lead to fibrogenesis. Small intestinal bacterial overgrowth and gut dysbiosis are also of pivotal importance in the inflammation. Among the susceptible genetic factors, mutations of patatin-like phospholipase domain containing 3 and the transmembrane 6 superfamily 2 genes play a role in the development and progression of the disease, similarly as do epigenetic regulators such as microRNAs and extracellular vesicles. Better understanding of the pathogenesis of non alcoholic fatty liver disease may identify novel therapeutic agents that improve the outcome of the disease. Orv Hetil. 2017; 158(23): 882-894.

  20. Managing non-alcoholic fatty liver disease.

    Science.gov (United States)

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

    2016-07-01

    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. Copyright: © Singapore Medical Association.

  1. Plasmatic higher levels of homocysteine in Non-alcoholic fatty liver disease (NAFLD)

    OpenAIRE

    Carvalho, Sylene Coutinho Rampche de; Muniz, Maria Tereza Cartaxo; Siqueira, Maria Deozete Vieira; Siqueira, Erika Rabelo Forte; Gomes, Adriana Vieira; Silva, Karina Alves; Bezerra, Lais Carvalho Luma; D'Almeida, Vania [UNIFESP; Oliveira, Claudia Pinto Marques Souza de; Pereira, Leila Maria M. Beltrao

    2013-01-01

    Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic mutations in the folate route may only mildly impair Hcy metabolism. The aim of this study was to investigate the relation between ...

  2. Fructose: A Dietary Sugar in Crosstalk with Microbiota Contributing to the Development and Progression of Non-Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Jessica Lambertz

    2017-09-01

    Full Text Available Fructose is one of the key dietary catalysts in the development of non-alcoholic fatty liver disease (NAFLD. NAFLD comprises a complex disease spectrum, including steatosis (fatty liver, non-alcoholic steatohepatitis, hepatocyte injury, inflammation, and fibrosis. It is also the hepatic manifestation of the metabolic syndrome, which covers abdominal obesity, insulin resistance, dyslipidemia, glucose intolerance, or type 2 diabetes mellitus. Commensal bacteria modulate the host immune system, protect against exogenous pathogens, and are gatekeepers in intestinal barrier function and maturation. Dysbalanced intestinal microbiota composition influences a variety of NAFLD-associated clinical conditions. Conversely, nutritional supplementation with probiotics and preobiotics impacting composition of gut microbiota can improve the outcome of NAFLD. In crosstalk with the host immune system, the gut microbiota is able to modulate inflammation, insulin resistance, and intestinal permeability. Moreover, the composition of microbiota of an individual is a kind of fingerprint highly influenced by diet. In addition, not only the microbiota itself but also its metabolites influence the metabolism and host immune system. The gut microbiota can produce vitamins and a variety of nutrients including short-chain fatty acids. Holding a healthy balance of the microbiota is therefore highly important. In the present review, we discuss the impact of long-term intake of fructose on the composition of the intestinal microbiota and its biological consequences in regard to liver homeostasis and disease. In particular, we will refer about fructose-induced alterations of the tight junction proteins affecting the gut permeability, leading to the translocation of bacteria and bacterial endotoxins into the blood circulation.

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

    OpenAIRE

    Betzel, Bark; Drenth, Joost PH

    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 its sensitivity is limited and liver biopsy is still considered to be the gold standard. Less invasive techniques that accurately quantify liver steatosis are warranted. Jimenez-Aguero and colleagues...

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

    NARCIS (Netherlands)

    van den Berg, Eline H.; Amini, Marzyeh; 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

  5. Autophagy and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Vanessa J. Lavallard

    2014-01-01

    Full Text Available Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD, have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH, steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma.

  6. Autophagy and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Lavallard, Vanessa J; Gual, Philippe

    2014-01-01

    Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD), have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH), steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma.

  7. Paediatric non-alcoholic fatty liver disease: an overview.

    Science.gov (United States)

    AlKhater, S A

    2015-05-01

    Non-alcoholic fatty liver disease (NAFLD) is a progressive disease that encompasses a spectrum of liver diseases, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Data related to survival in children are scarce, but these data firmly associate NAFLD with higher risks of hepatic and non-hepatic morbidities and mortalities compared with the general population. More recently, the association between NAFLD and cardiovascular disease among children has increasingly been recognized. Given that obesity is a major risk factor for the disease, paediatric NAFLD is becoming a global issue, paralleling the dramatic rise in obesity worldwide. NASH, which is more common in obese children, has the potential to advance to liver fibrosis and failure. It is unclear why certain patients undergo such transformation but this susceptibility is likely related to an interaction between a genetically susceptible host and the surrounding environment. Currently, treatment is largely conservative and includes lifestyle modification, attainable through healthy weight reduction via diet and exercise. In this review, current knowledge about NAFLD in children is summarized. This review aims to increase the awareness of the medical community about a hidden public health issue and to identify current gaps in the literature while providing directions for future research. © 2015 World Obesity.

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

    Directory of Open Access Journals (Sweden)

    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

  9. LDL receptor knock-out mice are a physiological model particularly vulnerable to study the onset of inflammation in non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Bieghs, Veerle; van Gorp, Patrick J.; Wouters, Kristiaan; Hendrikx, Tim; Gijbels, Marion J.; van Bilsen, Marc; Bakker, Jaap; Binder, Christoph J.; Lütjohann, Dieter; Staels, Bart; Hofker, Marten H.; Shiri-Sverdlov, Ronit

    2012-01-01

    Non-alcoholic steatohepatitis (NASH) involves steatosis combined with inflammation, which can progress into fibrosis and cirrhosis. Exploring the molecular mechanisms of NASH is highly dependent on the availability of animal models. Currently, the most commonly used animal models for NASH imitate

  10. LDL Receptor Knock-Out Mice Are a Physiological Model Particularly Vulnerable to Study the Onset of Inflammation in Non-Alcoholic Fatty Liver Disease

    NARCIS (Netherlands)

    Bieghs, Veerle; Van Gorp, Patrick J.; Wouters, Kristiaan; Hendrikx, Tim; Gijbels, Marion J.; van Bilsen, Marc; Bakker, Jaap; Binder, Christoph J.; Luetjohann, Dieter; Staels, Bart; Hofker, Marten H.; Shiri-Sverdlov, Ronit

    2012-01-01

    Background & Aims: Non-alcoholic steatohepatitis (NASH) involves steatosis combined with inflammation, which can progress into fibrosis and cirrhosis. Exploring the molecular mechanisms of NASH is highly dependent on the availability of animal models. Currently, the most commonly used animal models

  11. Global Epidemiology of Non-Alcoholic Fatty Liver Disease and Perspectives on US Minority Populations

    Science.gov (United States)

    Sherif, Zaki A.; Saeed, Armana; Ghavimi, Shima; Nouraie, Seyed-Mehdi; Laiyemo, Adeyinka O.; Brim, Hassan; Ashktorab, Hassan

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD), a clinical syndrome that is predicted to affect millions of people worldwide, will become the next global epidemic. The natural course of this disease, including its subtype, non-alcoholic steatohepatitis (NASH), is not clearly defined, especially in the US minority populations. The aim of this review is to report the global epidemiology of NAFLD, with emphasis on US minority populations on the basis of database searches using using Pubmed and other online databases. The US Hispanic population is the most disproportionately affected ethnic group with hepatic steatosis whereas African-Americans are the least affected. Genetic disparities involved in lipid metabolism seem to be the leading explanation for the lowest incidence and prevalence of both NAFLD and NASH in African-Americans. PMID:27038448

  12. Roles of abnormal lipid metabolism in pathogenesis of non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    LU Ran

    2015-07-01

    Full Text Available The prevalence of non-alcoholic fatty liver disease (NAFLD keeps rising worldwide along with the increasing prevalence of metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia. Although most NAFLD patients present with simple steatosis of hepatocytes, some patients progress to non-alcoholic steatohepatitis, liver cirrhosis, and even cancer. In the Western world, NAFLD is the most common cause of elevated liver enzymes, and hence there has been a growing interest in this disease. Given that fat deposition in the liver is the hallmark of NAFLD, we review the roles and the underlying mechanism of disturbed lipid metabolism in the development of NAFLD and suggest that more insights into the pathogenesis of NAFLD will help develop targeted strategies for the prevention and treatment of this disease.

  13. Role of Hedgehog signaling pathway in progression of non-alcoholic fatty liver fibrosis

    Directory of Open Access Journals (Sweden)

    AN Baiquan

    2015-03-01

    Full Text Available Obesity and related metabolic syndromes are prevalent on the global scale. Thus far, non-alcoholic fatty liver (NAFL disease has caused wide attention from domestic and overseas scholars. NAFL cirrhosis is considered to be the central part and inevitable stage of liver cirrhosis developed from simple fatty liver and non-alcoholic steatohepatitis. The effect of Hedgehog signaling pathway on hepatocytes in the progression of NAFL fibrosis was elucidated and investigated by a population study. Results showed that abnormal activation of the Hedgehog signaling pathway promoted the progression of NAFL fibrosis. In-depth study on the Hedgehog signaling pathway may provide a new approach for the treatment of NAFL fibrosis.

  14. Plasma fibrinogen-like protein 2 levels in patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Colak, Yasar; Senates, Ebubekir; Ozturk, Oguzhan; Yilmaz, Yusuf; Coskunpinar, Ender; Kahraman, Ozlem Timirci; Sahin, Onder; Zemheri, Ebru; Enc, Feruze Yilmaz; Ulasoglu, Celal; Kiziltas, Safak; Kurdas, Oya Ovunc; Tuncer, Ilyas

    2011-01-01

    Fibrinogen-like protein 2 (fgl2), has recently been identified as a new member of the fibrinogen-like family of proteins. In this study we assayed plasma levels of fgl2 in patients with biopsy proven non-alcoholic fatty liver disease (NAFLD) and examined their association with clinical, biochemical and histological phenotypes. Levels of plasma fgl2 were measured by enzyme linked immunosorbent assay and compared between the study groups. Moreover, concentrations of fgl2 were assessed in relation to the general characteristics of the study participants and the results of the liver biopsy. Levels of fgl2 were significantly higher in patients with definite non-alcoholic steatohepatitis (NASH) (788±190pg/mL, psubject to future confirmation, our data suggest that fgl2 levels are elevated in the more severe forms of NAFLD.

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

    Directory of Open Access Journals (Sweden)

    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

  16. Probiotics as a Novel Treatment for Non-Alcoholic Fatty Liver Disease; A Systematic Review on the Current Evidences

    Science.gov (United States)

    Kelishadi, Roya; Farajian, Sanam; Mirlohi, Maryam

    2013-01-01

    Context Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with 5-10% of liver having extra fat. Increase in its prevalence in all age groups is linked with obesity and Type II diabetes. The treatment of NAFLD remains controversial. A growing body of evidence suggests a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). The objective of this review is to provide an overview on experimental and clinical studies assessing all positive and negative effects of probiotics. Evidence Acquisition We made a critical appraisal on various types of documents published from 1999 to March 2012 in journals, electronic books, seminars, and symposium contexts including Medline, PubMed, and Cochrane Central Register of Controlled Trials databases. We used the key words: “non-alcoholic fatty liver disease, probiotics, non-alcoholic steatohepatitis, liver disease, and fatty liver”. Results Probiotics, as biological factors, control the gut microbiota and result in its progression. It is in this sense that they are suggestive of a new and a natural way of promoting liver function. Correspondingly, limited evidence suggests that probiotics could be considered as a new way of treatment for NAFLD. Conclusions Various experimental studies and clinical trials revealed promising effects of probiotics in improving NAFLD; however given the limited experience in this field, generalization of probiotics as treatment of NAFLD needs substantiation through more trials with a larger sample sizes and with longer-term follow up. PMID:23885277

  17. Probiotics as a novel treatment for non-alcoholic Fatty liver disease; a systematic review on the current evidences.

    Science.gov (United States)

    Kelishadi, Roya; Farajian, Sanam; Mirlohi, Maryam

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with 5-10% of liver having extra fat. Increase in its prevalence in all age groups is linked with obesity and Type II diabetes. The treatment of NAFLD remains controversial. A growing body of evidence suggests a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). The objective of this review is to provide an overview on experimental and clinical studies assessing all positive and negative effects of probiotics. We made a critical appraisal on various types of documents published from 1999 to March 2012 in journals, electronic books, seminars, and symposium contexts including Medline, PubMed, and Cochrane Central Register of Controlled Trials databases. We used the key words: "non-alcoholic fatty liver disease, probiotics, non-alcoholic steatohepatitis, liver disease, and fatty liver". Probiotics, as biological factors, control the gut microbiota and result in its progression. It is in this sense that they are suggestive of a new and a natural way of promoting liver function. Correspondingly, limited evidence suggests that probiotics could be considered as a new way of treatment for NAFLD. Various experimental studies and clinical trials revealed promising effects of probiotics in improving NAFLD; however given the limited experience in this field, generalization of probiotics as treatment of NAFLD needs substantiation through more trials with a larger sample sizes and with longer-term follow up.

  18. Pathogenesis of hepatic steatosis: the link between hypercortisolism and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Tarantino, Giovanni; Finelli, Carmine

    2013-10-28

    Based on the available literature, non alcoholic fatty liver disease or generally speaking, hepatic steatosis, is more frequent among people with diabetes and obesity, and is almost universally present amongst morbidly obese diabetic patients. Non alcoholic fatty liver disease is being increasingly recognized as a common liver condition in the developed world, with non alcoholic steatohepatitis projected to be the leading cause of liver transplantation. Previous data report that only 20% of patients with Cushing's syndrome have hepatic steatosis. Aiming at clarifying the reasons whereby patients suffering from Cushing's syndrome - a condition characterized by profound metabolic changes - present low prevalence of hepatic steatosis, the Authors reviewed the current concepts on the link between hypercortisolism and obesity/metabolic syndrome. They hypothesize that this low prevalence of fat accumulation in the liver of patients with Cushing's syndrome could result from the inhibition of the so-called low-grade chronic-inflammation, mainly mediated by Interleukin 6, due to an excess of cortisol, a hormone characterized by an anti-inflammatory effect. The Cushing's syndrome, speculatively considered as an in vivo model of the hepatic steatosis, could also help clarify the mechanisms of non alcoholic fatty liver disease.

  19. Non alcoholic fatty liver disease in a Nigerian population with type II ...

    African Journals Online (AJOL)

    Introduction: Worldwide, Non-alcoholic fatty liver disease (NAFLD) has become an important cause of chronic liver disease and cardiovascular morbidity, even more so in subjects with Type II Diabetes Mellitus (T2DM). The aim of this study was to determine the prevalence and risk factors of NAFLD in an African population ...

  20. Glucagon like peptide-1 receptor agonists for the management of obesity and non-alcoholic fatty liver disease: a novel therapeutic option.

    Science.gov (United States)

    Dhir, Gauri; Cusi, Kenneth

    2018-01-01

    Obesity is a major risk factor for the development of type 2 diabetes mellitus (T2DM), and is associated with a cluster of metabolic factors that lead to poor cardiovascular outcomes. In non-alcoholic fatty liver disease (NAFLD), liver fat (triglyceride) accumulation closely mirrors adipose tissue dysfunction and insulin resistance in obesity and T2DM. It is now recognized as the most common chronic liver disease in Westernized societies, often progressing to more severe forms of the disease such as nonalcoholic steatohepatitis (NASH), or cirrhosis and hepatocellular carcinoma. However, NAFLD remains largely overlooked by healthcare providers although it affects about two-thirds of patients with obesity and it promotes the development of T2DM. NAFLD mirrors adipose tissue and systemic insulin resistance, the liver being a 'barometer' of metabolic health. Although pioglitazone is emerging as the treatment of choice for NASH in patients with insulin-resistance, or those with T2DM, many other options are being tested. Due to their overall safety and efficacy, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming one of the cornerstones for the management of both obesity and T2DM, and a novel alternative for the treatment of NAFLD. In this review, we will briefly summarize the status of GLP-1RA for the treatment of obesity and NAFLD. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. 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?

    Directory of Open Access Journals (Sweden)

    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.

  2. Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations

    Science.gov (United States)

    Non-alcoholic fatty liver disease (NAFLD) is an important co-morbidity associated with obesity and a precursor to steatohepatitis. However, the contributions of gestational and early life influences on development of NAFLD and NASH remain poorly appreciated. Two independent studies were performed to...

  3. Non-alcoholic Fatty Liver Disease: Beneficial Effects of Flavonoids.

    Science.gov (United States)

    Akhlaghi, Masoumeh

    2016-10-01

    Non-alcoholic fatty liver disease (NAFLD) has been known as the hepatic feature of metabolic syndrome. Extra fat depots, especially in visceral areas, develop insulin resistance as a result of mild oxidation and inflammation. Insulin resistance induces lipolysis and releases free fatty acids into the circulation, where they are transported to the liver. In the liver, free fatty acids are converted to triglycerides and accumulate, causing simple steatosis that, if left untreated, can lead to steatohepatitis, and subsequently liver necrosis and cirrhosis.Flavonoids, a group of plant compounds with incredible biological characteristics, have shown advantages in pathological conditions. Beneficial effects of flavonoids against NAFLD and its related disorders have been observed in both animal and human studies. Various mechanisms have been found for their protection. Flavonoids prevent hepatosteatosis by increasing fatty acid oxidation in the liver. They can also reduce caloric intake and decrease body weight and fat deposition in visceral tissues. Flavonoids are unique antioxidants that exert their beneficial effects through inhibition of nuclear factor κB, thereby attenuating release of inflammatory cytokines, which are triggers of insulin resistance. Finally, flavonoids have shown to increase adiponectin, improve insulin sensitivity and glucose tolerance, correct dyslipidemia, and reduce blood pressure in patients with NAFLD. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Adipose tissue, obesity and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Polyzos, Stergios A; Kountouras, Jannis; Mantzoros, Christos S

    2017-06-01

    The association of obesity with non-alcoholic fatty liver disease (NAFLD) has been established. Obesity has been linked not only to initial stages of the disease, i.e., simple steatosis (SS), but also to its severity. From an epidemiologic point of view, both diseases has an increasing prevalence worldwide. From a pathogenetic point of view, obesity and its associate IR contribute to the initial fat accumulation in the hepatocyte (SS), but also to the progression of SS to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma (HCC). From a clinical point of view, obesity has increased morbidity and mortality when combined with NAFLD, owing to cardiovascular and liver-specific mortality, including higher HCC risk. From a therapeutic point of view, weight loss is regarded as the cornerstone for the disease prevention and treatment. Although diet and exercise are the first choice to this aim, they are both difficult to achieve and sustain. Thus, the need for pharmacological treatment is considered of high importance. To treat obesity through pharmacologic weight loss, orlistat has been investigated, though with limited efficacy. Currently, liraglutide appears to be more efficacious, but it has not been officially approved for specifically NASH patients. Bariatric surgery is another alternative for severely obese patients showing histological improvement in NASH patients. However, since relative data from randomized trials are very limited, morbid obesity-related NASH patients may be subjected to bariatric surgery only after a careful individualized risk-benefit assessment.

  5. Clinical approaches to non-alcoholic fatty liver disease

    Science.gov (United States)

    Schwenger, Katherine JP; Allard, Johane P

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), leading to fibrosis and potentially cirrhosis, and it is one of the most common causes of liver disease worldwide. NAFLD is associated with other medical conditions such as metabolic syndrome, obesity, cardiovascular disease and diabetes. NASH can only be diagnosed through liver biopsy, but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis, reducing the need for liver biopsy and risk to patients. Disease progression varies between individuals and is linked to a number of risk factors. Mechanisms involved in the pathogenesis are associated with diet and lifestyle, influx of free fatty acids to the liver from adipose tissue due to insulin resistance, hepatic oxidative stress, cytokines production, reduced very low-density lipoprotein secretion and intestinal microbiome. Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD. Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial. Omega 3 polyunsaturated fatty acids and statins may offer additional benefits. Bariatric surgery should be considered in morbidly obese patients. More research is needed to assess the impact of these treatments on a long-term basis. The objective of this article is to briefly review the diagnosis, management and treatment of this disease in order to aid clinicians in managing these patients. PMID:24587650

  6. Dorothy Hodgkin Lecture 2012: non-alcoholic fatty liver disease, insulin resistance and ectopic fat: a new problem in diabetes management.

    Science.gov (United States)

    Byrne, C D

    2012-09-01

    Non-alcoholic fatty liver disease is now recognized as the hepatic component of the metabolic syndrome. Non-alcoholic fatty liver disease is a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in non-alcoholic fatty liver disease and may progress to non-alcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. Prevalence estimates for non-alcoholic fatty liver disease range from 17 to 33% in the general populations and it has been estimated that non-alcoholic fatty liver disease exists in up to 70% of people with Type 2 diabetes. Non-alcoholic fatty liver disease increases risk of Type 2 diabetes and cardiovascular disease. In people with Type 2 diabetes, non-alcoholic fatty liver disease is the most frequent cause (∼80%) of fatty liver diagnosed by ultrasound. As non-alcoholic fatty liver disease is strongly associated with insulin resistance, the presence of non-alcoholic fatty liver disease with diabetes often contributes to poor glycaemic control. Consequently, strategies that decrease liver fat and improve whole-body insulin sensitivity may both contribute to prevention of Type 2 diabetes and to better glycaemic control in people who already have developed diabetes. This review summarizes the Dorothy Hodgkin lecture given by the author at the 2012 Diabetes UK annual scientific conference, proposing that fatty acid fluxes through the liver are crucial for the pathogenesis of non-alcoholic fatty liver disease and for increasing insulin resistance. © 2012 The Author. Diabetic Medicine © 2012 Diabetes UK.

  7. 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.

  8. 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. © 2014 The Authors. Clinical Obesity © 2014 World Obesity.

  9. A clinical and biochemical profile of biopsy-proven non-alcoholic fatty liver disease subjects

    International Nuclear Information System (INIS)

    Khurram, M.; Mushraf, M.

    2007-01-01

    To describe clinical and biochemical features of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD). Fifty patients of either and of all ages were included, who had ultrasound evidence of fatty liver, deranged liver enzymes, and negative history of alcohol uptake. Serological/biochemical tests/markers of other liver diseases were negative. Each subject underwent liver biopsy reported by a single histopathologist. Clinical (symptoms, hypertension, hepatomegaly, and obesity) and biochemical evaluation (for diabetes, lipid abnormalities, and aspartate to alanine aminotransferase ratio (AST/ALT)) of each subject was done. Chi-square and t-tests were used for p-value calculation for finding significant difference between fatty liver and non-alcoholic steato-hepatitis groups. Thirty three (66%) patients were female and 34% were male. Mean age was 45.50+-11.50 years. Histopathologically, 62% subjects had fatty liver alone, while 38% had nonalcoholic steatohepatitis (NASH). Fatigue (100%), hypertriglyceridemia (80%), hepatomegaly (72%), AST/ALT ratio <1 (72%), and obesity/overweight (54%) were common NAFLD-related features. Except for hypertriglycedemia (p-value 0.008), no statistically significant association was noted between these features and histopathological subtypes of NAFLD. NAFLD-related clinical and biochemical features included fatigue, obesity, hepatomegaly, AST/ALT ratio <1, and hypertriglycedemia. Significant relationship existed between hypertriglyceridemia and NASH. (author)

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

    Science.gov (United States)

    Mouzaki, Marialena; Wang, Alice Y; Bandsma, Robert; Comelli, Elena M; Arendt, Bianca M; Zhang, Ling; Fung, Scott; Fischer, Sandra E; McGilvray, Ian G; Allard, Johane P

    2016-01-01

    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 (pLCA) (r = 0.526, p = 0.003) and inversely with unconjugated CA (r = -0.669, pinjury.

  11. [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

  12. The LXR inverse agonist SR9238 suppresses fibrosis in a model of non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Kristine Griffett

    2015-04-01

    Conclusions: Here, we demonstrate that an LXR inverse agonist, SR9238, is effective in reduction of hepatic steatosis, inflammation and fibrosis in an animal model of NASH. These results have important implications for the development of therapeutics for treatment NASH in humans.

  13. Salsalate attenuates diet induced non-alcoholic steatohepatitis in mice by decreasing lipogenic and inflammatory processes

    NARCIS (Netherlands)

    Liang, W.; Verschuren, L.; Mulder, P.; Hoorn, J.W.A. van der; Verheij, J.; Dam, A.D. van; Boon, M.R.; Princen, H.M.G.; Havekes, L.M.; Kleemann, R.; Hoek, A.M. van den

    2015-01-01

    BACKGROUND AND PURPOSE: Salsalate (salicylsalicylic acid) is an anti-inflammatory drug that was recently found to exert beneficial metabolic effects on glucose and lipid metabolism. Although its utility in the prevention and management of a wide range of vascular disorders, including type 2 diabetes

  14. Advances in hepatocellular carcinoma: Nonalcoholic steatohepatitis-related hepatocellular carcinoma

    OpenAIRE

    Khan, Fauzia Z; Perumpail, Ryan B; Wong, Robert J; Ahmed, Aijaz

    2015-01-01

    An increase in the prevalence of obesity and diabetes mellitus has been associated with the rise in nonalcoholic fatty liver disease (NAFLD). Two-thirds of the obese and diabetic populations are estimated to develop NAFLD. Currently, NAFLD is the most common etiology for chronic liver disease globally. The clinical spectrum of NAFLD ranges from simple steatosis, an accumulation of fat greater than 5% of liver weight, to nonalcoholic steatohepatitis (NASH), a more aggressive form with necroinf...

  15. 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.

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

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions NAFLD Non-alcoholic fatty liver disease Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Non-alcoholic fatty liver disease ( NAFLD ) is a buildup of excessive fat ...

  17. Translational Aspects of Diet and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Nicolas Goossens

    2017-09-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a spectrum of diseases ranging from simple steatosis without inflammation or fibrosis to nonalcoholic steatohepatitis (NASH. Despite the strong association between dietary factors and NAFLD, no dietary animal model of NAFLD fully recapitulates the complex metabolic and histological phenotype of the disease, although recent models show promise. Although animal models have significantly contributed to our understanding of human diseases, they have been less successful in accurate translation to predict effective treatment strategies. We discuss strategies to overcome this challenge, in particular the adoption of big data approaches combining clinical phenotype, genomic heterogeneity, transcriptomics, and metabolomics changes to identify the ideal NAFLD animal model for a given scientific question or to test a given drug. We conclude by noting that novel big data approaches may help to bridge the translational gap for selecting dietary models of NAFLD.

  18. Non-alcoholic fatty liver disease (NAFLD) in different populations: A clinical and epidemiological study - sample of São José do Rio Preto.

    Science.gov (United States)

    Andrade, Gabriel Costa de; Fujise, Luciana Harumi; Santana, Jaime Euclides de; Oliveira, Fabiane; Silva, Rita de Cássia Martins Alves da

    2016-01-01

    NAFLD is an heterogeneous condition that includes steatosis and non-alcoholic steatohepatitis (NASH), in the absence of significant alcohol consumption, reaching 30% of the population. The most common risk factors are: age, gender, ethnicity, diabetes mellitus (DM), obesity, predisposition, metabolic syndrome (MS), insulin resistance (IR), drugs, and polycystic ovary syndrome. To describe the profile of patients with NAFLD seen at Hospital de Base of Rio Preto, in the state of São Paulo. Patients with NAFLD were assessed, with medical and epidemiological data collected after informed consent. Of the 62 patients evaluated, 76% were women, 73% Caucasians, and 71% were aged between 50 and 69 years and had no symptoms. Ultrasonography results showed steatosis in 84%. NASH was diagnosed in 61% of the sample. 21 patients underwent liver biopsy, of which 36% had cirrhosis, 1 had liver cancer, and 1 pure steatosis (5% each). Risk factors were found in 70% of patients with metabolic syndrome, 87% with increased waist circumference, 63% with dyslipidemia, 61% (n=38) with high blood pressure (HBP), 28% with DM, 52% physically inactive, and 44% with insulin resistance (IR) (HOMA> 3.5). There was an association between IR and NASH (p=0.013), IR and obesity (p=0.027), IR and MS (p=0.006), and MS and steatosis on medical ultrasound (USG) (p=0.014). The most frequent risk factors were MS and its variables: increased waist circumference, dyslipidemia and HBP. This underscores the importance of metabolic control in NAFLD and confirms its role as the hepatic component of metabolic syndrome.

  19. Non-alcoholic fatty liver disease (NAFLD in different populations: A clinical and epidemiological study – sample of São José do Rio Preto

    Directory of Open Access Journals (Sweden)

    Gabriel Costa de Andrade

    2016-06-01

    Full Text Available SUMMARY Introduction: NAFLD is an heterogeneous condition that includes steatosis and non-alcoholic steatohepatitis (NASH, in the absence of significant alcohol consumption, reaching 30% of the population. The most common risk factors are: age, gender, ethnicity, diabetes mellitus (DM, obesity, predisposition, metabolic syndrome (MS, insulin resistance (IR, drugs, and polycystic ovary syndrome. Objective: To describe the profile of patients with NAFLD seen at Hospital de Base of Rio Preto, in the state of São Paulo. Method: Patients with NAFLD were assessed, with medical and epidemiological data collected after informed consent. Results: Of the 62 patients evaluated, 76% were women, 73% Caucasians, and 71% were aged between 50 and 69 years and had no symptoms. Ultrasonography results showed steatosis in 84%. NASH was diagnosed in 61% of the sample. 21 patients underwent liver biopsy, of which 36% had cirrhosis, 1 had liver cancer, and 1 pure steatosis (5% each. Risk factors were found in 70% of patients with metabolic syndrome, 87% with increased waist circumference, 63% with dyslipidemia, 61% (n=38 with high blood pressure (HBP, 28% with DM, 52% physically inactive, and 44% with insulin resistance (IR (HOMA> 3.5. There was an association between IR and NASH (p=0.013, IR and obesity (p=0.027, IR and MS (p=0.006, and MS and steatosis on medical ultrasound (USG (p=0.014. Conclusion: The most frequent risk factors were MS and its variables: increased waist circumference, dyslipidemia and HBP. This underscores the importance of metabolic control in NAFLD and confirms its role as the hepatic component of metabolic syndrome.

  20. 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.

  1. 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

    2014-01-01

    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. PMID:25024592

  2. Early life programming and the risk of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Lynch, C; Chan, C S; Drake, A J

    2017-06-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes and cardiovascular disease and can be considered the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of disease, from the relatively benign simple steatosis to the more serious non-alcoholic steatohepatitis, which can progress to liver cirrhosis, hepatocellular carcinoma and end-stage liver failure, necessitating liver transplantation. Although the increasing prevalence of NAFLD in developed countries has substantial implications for public health, many of the precise mechanisms accounting for the development and progression of NAFLD are unclear. The environment in early life is an important determinant of cardiovascular disease risk in later life and studies suggest this also extends to NAFLD. Here we review data from animal models and human studies which suggest that fetal and early life exposure to maternal under- and overnutrition, excess glucocorticoids and environmental pollutants may confer an increased susceptibility to NAFLD development and progression in offspring and that such effects may be sex-specific. We also consider studies aimed at identifying potential dietary and pharmacological interventions aimed at reducing this risk. We suggest that further human epidemiological studies are needed to ensure that data from animal models are relevant to human health.

  3. Non-alcoholic fatty liver disease: What the clinician needs to know

    Science.gov (United States)

    Machado, Mariana Verdelho; Cortez-Pinto, Helena

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis and advances on diagnosis and treatment. PMID:25278691

  4. 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

    2016-06-24

    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.

  5. 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

    2016-07-21

    To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease (NAFLD) patients. 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. 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. Prescribed exercise in subjects with NAFLD reduces IHTG independent of

  6. 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.

  7. 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.

  8. Effect of resveratrol on experimental non-alcoholic fatty liver disease depends on severity of pathology and timing of treatment.

    Science.gov (United States)

    Heebøll, Sara; El-Houri, Rime Bahij; Hellberg, Ylva Erika Kristina; Haldrup, David; Pedersen, Steen Bønløkke; Jessen, Niels; Christensen, Lars Porskjaer; Grønbaek, Henning

    2016-03-01

    Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with few therapeutic options. Resveratrol (RSV) prevents the development of steatosis in a number of experimental fatty liver (non-alcoholic fatty liver [NAFL]) models, but the preventive or therapeutic effects on experimental NASH are not yet clarified, and clinical results on non-alcoholic fatty liver disease are ambiguous. Thus, we aimed to compare the RSV-mediated preventive and therapeutic effects on experimental NAFL and NASH. We used a high-fat (HF) diet to generate a rat NAFL model and a high-fat, high-cholesterol (HFC) diet to generate a rat NASH model. The preventive and therapeutic potential of RSV was tested by adding RSV to the HF and HFC diet from study start or after 1 week of the diets. Animals were sacrificed after 8 weeks with appropriate controls. Blood and liver were harvested for analysis, including measurement of RSV metabolites. Resveratrol reduced the development of histological steatosis (P = 0.03) and partly triglyceride accumulation (fold change reduced from 3.6 to 2.4, P = 0.08) in the male NAFL model, although effects were moderate. In NASH prevention, RSV reduced the accumulation of triglyceride in hepatic tissue (P hepatic benefit of RSV treatment is seen in prevention of steatosis only. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  9. Development of a Representative Mouse Model with Nonalcoholic Steatohepatitis.

    Science.gov (United States)

    Verbeek, Jef; Jacobs, Ans; Spincemaille, Pieter; Cassiman, David

    2016-06-01

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the Western world. It represents a disease spectrum ranging from isolated steatosis to non-alcoholic steatohepatitis (NASH). In particular, NASH can evolve to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. The development of novel treatment strategies is hampered by the lack of representative NASH mouse models. Here, we describe a NASH mouse model, which is based on feeding non-genetically manipulated C57BL6/J mice a 'Western style' high-fat/high-sucrose diet (HF-HSD). HF-HSD leads to early obesity, insulin resistance, and hypercholesterolemia. After 12 weeks of HF-HSD, all mice exhibit the complete spectrum of features of NASH, including steatosis, hepatocyte ballooning, and lobular inflammation, together with fibrosis in the majority of mice. Hence, this model closely mimics the human disease. Implementation of this mouse model will lead to a standardized setup for the evaluation of (i) underlying mechanisms that contribute to the progression of NAFLD to NASH, and (ii) therapeutic interventions for NASH. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  10. L-carnitine prevents metabolic steatohepatitis in obese diabetic KK-Aymice.

    Science.gov (United States)

    Kon, Kazuyoshi; Ikejima, Kenichi; Morinaga, Maki; Kusama, Hiromi; Arai, Kumiko; Aoyama, Tomonori; Uchiyama, Akira; Yamashina, Shunhei; Watanabe, Sumio

    2017-03-01

    Pharmacological treatment for metabolic syndrome-related non-alcoholic steatohepatitis has not been established. We investigated the effect of L-carnitine, an essential substance for β-oxidation, on metabolic steatohepatitis in mice. Male KK-A y mice were fed a high-fat diet (HFD) for 8 weeks, with supplementation of L-carnitine (1.25 mg/mL) in drinking water for the latter 4 weeks. Serum total carnitine levels were decreased following HFD feeding, whereas the levels were reversed almost completely by L-carnitine supplementation. In mice given L-carnitine, exacerbation of hepatic steatosis and hepatocyte apoptosis was markedly prevented even though HFD feeding was continued. Body weight gain, as well as hyperlipidemia, hyperglycemia, and hyperinsulinemia, following HFD feeding were also significantly prevented in mice given L-carnitine. High-fat diet feeding elevated hepatic expression levels of carnitine palmitoyltransferase 1A mRNA; however, production of β-hydroxybutyrate in the liver was not affected by HFD alone. In contrast, L-carnitine treatment significantly increased hepatic β-hydroxybutyrate contents in HFD-fed mice. L-carnitine also blunted HFD induction in sterol regulatory element binding protein-1c mRNA in the liver. Furthermore, L-carnitine inhibited HFD-induced serine phosphorylation of insulin receptor substrate-1 in the liver. L-carnitine decreased hepatic free fatty acid content in 1 week, with morphological improvement of swollen mitochondria in hepatocytes, and increases in hepatic adenosine 5'-triphosphate content. L-carnitine ameliorates steatohepatitis in KK-A y mice fed an HFD, most likely through facilitating mitochondrial β-oxidation, normalizing insulin signals, and inhibiting de novo lipogenesis in the liver. It is therefore postulated that supplementation of L-carnitine is a promising approach for prevention and treatment of metabolic syndrome-related non-alcoholic steatohepatitis. © 2016 The Japan Society of Hepatology.

  11. ORIGINAL ARTICLE Non-Alcoholic Fatty Liver Disease and ...

    African Journals Online (AJOL)

    2018-01-01

    Jan 1, 2018 ... ABSTRACT. BACKGROUND: Non-alcoholic Fatty Liver Disease (NAFLD) among type 2 diabetic patients is completely ignored in developing regions like Africa paving the way for public health and economic burden in the region. Therefore, the main objective of this research was to evaluate non-alcoholic ...

  12. Effects of dietary supplementation with betaine on a nonalcoholic steatohepatitis (NASH) mouse model.

    Science.gov (United States)

    Kawakami, Sakura; Han, Kyu-Ho; Nakamura, Yumi; Shimada, Ken-ichiro; Kitano, Tomoko; Aritsuka, Tsutomu; Nagura, Taizo; Ohba, Kiyoshi; Nakamura, Kimihide; Fukushima, Michihiro

    2012-01-01

    The effects of betaine supplementation on non-alcoholic steatohepatitis (NASH) model mice were examined by measuring the accumulation of fat in the livers of NASH model mice compared to a control. Betaine from sugar beets was provided to the model mice as a dietary supplement. After 3 wk of dietary supplementation, there were no significant differences in body weight or liver weight between the groups. However, the liver to body weight ratio in the high-fat diet with betaine (HFB) group was significantly (pNASH model mice.

  13. 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.

  14. The effects of diet-induced obesity on hepatocyte insulin signaling pathways and induction of non-alcoholic liver damage

    Directory of Open Access Journals (Sweden)

    Sameer Fatani

    2011-03-01

    Full Text Available Sameer Fatani1, Imose Itua2, Paul Clark3, Christopher Wong3, Ebrahim K Naderali21Obesity Biology Unit, School of Clinical Sciences, University of Liverpool, Liverpool, UK; 2Department of Health and Applied Social Sciences, Liverpool Hope University, Hope Park, Liverpool UK; 3Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool, UKAbstract: The prevalence of diet-induced obesity is increasing amongst adults and children worldwide, predisposing millions of people to an array of health problems that include metabolic syndrome, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. In this study we used experimental animals to investigate the effects of dietary obesity on markers of hepatic insulin signaling as well as structural changes in hepatocytes. Adult male Wistar rats were randomized and assigned to either a control group or a test group. Controls were fed standard laboratory pelleted diet (chow-fed, while the test group had free access to a highly-palatable diet (HPD. After eight weeks, the HPD-fed animals were subdivided into three subgroups and their diets altered as follows: HPD-to-chow, HPD with the addition of fenofibrate given by oral gavage for a further seven weeks, or HPD with vehicle (1% carboxymethylcellulose at 1 mL/kg body weight given by oral gavage for a further seven weeks, respectively. Untreated diet-fed animals had significantly higher body weight, liver weight, and all measured metabolic profiles compared with chow-fed and treated diet-fed groups. Expression of kinases IRβ, IRS-1, AKt, eNOS, Shc and ERK1/2 were unaffected by obesity, while IRS-2 and P I3 kinase levels were significantly reduced in untreated HPD animals. Compared with chow-fed animals, steatosis and steatohepatitis were almost doubled in animals from untreated HPD, while removal of HPD and fenofibrate-treatment reduced steatosis by 40% and 80% respectively. These data suggest that diet-induced obesity affects

  15. Recent advances in understanding the role of adipocytokines during non-alcoholic fatty liver disease pathogenesis and their link with hepatokines.

    Science.gov (United States)

    Panera, Nadia; Della Corte, Claudia; Crudele, Annalisa; Stronati, Laura; Nobili, Valerio; Alisi, Anna

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is currently considered the main cause of chronic liver disease worldwide. Mechanisms leading to the development and progression of this disease are topics of great interest for researchers and clinicians. The current multi-hit hypothesis has thrown the crosstalk between liver and adipose tissue into sharp focus. It is well known that adipose tissue produces circulating factors, known as adipocytokines, which exert several effects on liver cells, promoting the onset of NAFLD and its progression to non-alcoholic steatohepatitis in obese subjects. In a similar way, hepatocytes may also respond to obesogenic stimuli by producing and releasing hepatokines into the circulation. Here, the authors provide an overview of recent advances in our understanding of the role of the most relevant adipocytokines and hepatokines in NAFLD pathogenesis, highlighting their possible molecular and functional interactions.

  16. Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Tang, Y; Bian, Z; Zhao, L; Liu, Y; Liang, S; Wang, Q; Han, X; Peng, Y; Chen, X; Shen, L; Qiu, D; Li, Z; Ma, X

    2011-11-01

    Mechanisms associated with the progression of simple steatosis to non-alcoholic fatty liver disease (NAFLD) remain undefined. Regulatory T cells (T(regs)) play a critical role in regulating inflammatory processes in non-alcoholic steatohepatitis (NASH) and because T helper type 17 (Th17) functionally oppose T(reg)-mediated responses, this study focused on characterizing the role of Th17 cells using a NAFLD mouse model. C57BL/6 mice were fed either a normal diet (ND) or high fat (HF) diet for 8 weeks. Mice in the HF group had a significantly higher frequency of liver Th17 cells compared to ND-fed mice. Neutralization of interleukin (IL)-17 in HF mice ameliorated lipopolysaccharide (LPS)-induced liver injury reflected by decreased serum alanine aminotransferase (ALT) levels and reduced inflammatory cell infiltrates in the liver. In vitro, HepG2 cells cultured in the presence of free fatty acids (FFA; oleic acid and palmitic acid) for 24 h and IL-17 developed steatosis via insulin-signalling pathway interference. IL-17 and FFAs synergized to induce IL-6 production by HepG2 cells and murine primary hepatocytes which, in combination with transforming growth factor (TGF-β), expanded Th17 cells. It is likely that a similar process occurs in NASH patients, as there were significant levels of IL-17(+) cell infiltrates in NASH patient livers. The hepatic expression of Th17 cell-related genes [retinoid-related orphan receptor gamma (ROR)γt, IL-17, IL-21 and IL-23] was also increased significantly in NASH patients compared to healthy controls. Th17 cells and IL-17 were associated with hepatic steatosis and proinflammatory response in NAFLD and facilitated the transition from simple steatosis to steatohepatitis. Strategies designed to alter the balance between Th17 cells and T(regs) should be explored as a means of preventing progression to NASH and advanced liver diseases in NAFLD patients. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for

  17. PNPLA3 as a Genetic Determinant of Risk for and Severity of Non-alcoholic Fatty Liver Disease Spectrum.

    Science.gov (United States)

    Salameh, Habeeb; Hanayneh, Muhannad Al; Masadeh, Maen; Naseemuddin, Mohammed; Matin, Tasnia; Erwin, Angelika; Singal, Ashwani K

    2016-09-28

    Background and Aims: Patatin-like phospholipase domain protein 3 ( PNPLA3 ) polymorphisms ( rs738409 C>G) are associated with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to examine the association of PNPLA3 polymorphisms with the spectrum and severity of this disease. Methods: Studies evaluating the association between the PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) and NAFLD were included. Pooled data are reported as odds ratios (ORs) with 95% confidence intervals. Results: Of 393 potentially relevant studies, 35 on NAFLD were included in the analysis. Compared to healthy controls, the pooled ORs for rs738409 CG and GG compared to CC among patients with non-alcoholic fatty liver (NAFL) were 1.46 (1.16-1.85) and 2.76 (2.30-3.13), and were 1.75 (1.24-2.46) and 4.44 (2.92-6.76) among patients with non-alcoholic steatohepatitis respectively. The respective ORs for CG and GG compared to the CC genotype were 2.35 (0.90-6.13) and 5.05 (1.47-17.29) when comparing non-alcoholic hepatocellular carcinoma to NAFL patients. Among the NAFLD patients, the ORs for G allele frequency when comparing steatosis grade 2-3 to grade 0-1 NAFL, when comparing the NAFLD activity score of ≥ 4 to score ≤ 3, when comparing NASH to NAFLD, when comparing the presence of lobular inflammation to absence, and when comparing the presence of hepatocyte ballooning to absence were 2.33 (1.43-3.80), 1.80 (1.36-2.37), 1.66 (1.42-1.94), 1.58 (1.19-2.10), and 2.63 (1.87-3.69) respectively. Subgroup analysis based on ethnicity showed similar results. Conclusions: PNPLA3 polymorphisms have strong association with the risk for and severity of NAFLDs. PNPLA3 polymorphism plays an evolving role in diagnosis and treatment decisions in patients with NAFLD.

  18. [Non-alcoholic fatty liver disease, as a component of the metabolic syndrome, and its causal correlations with other extrahepatic diseases].

    Science.gov (United States)

    Halmos, Tamás; Suba, Ilona

    2017-12-01

    Non-alcoholic fatty liver disease is the most common non-infectious chronic liver-disease in our age, and is a spectrum of all the diseases associated with increased fat accumulation in the hepatocytes. Its development is promoted by sedentary life-style, over-feeding, and certain genetic predisposition. Prevalence in the adult population, even in Hungary is ~30%. In a part of cases, this disease may pass into non-alcoholic steatohepatitis, later into fibrosis, rarely into primary hepatocellular cancer. Fatty liver is closely and bidirectionally related to the metabolic syndrome and type 2 diabetes, and nowadays there is a general consensus that fatty liver is the hepatic manifestation of the metabolic sycndrome. The importance of the fatty liver has been highly emphasized recently. In addition to the progression into steatohepatitis, its causal relationship with numerous extrahepatic disorders has been discovered. In our overview, we deal with the epidemiology, pathomechanism of the disease, discuss the possibilities of diagnosis, its relationship with the intestinal microbiota, its recently recognized correlations with bile acids and their receptors, and its supposed correlations with the circadian CLOCK system. Hereinafter, we overview those extrahepatic disorders, which have been shown to be causal link with the non-alcoholic fatty liver disease. Among these, we emphasize the metabolic syndrome/type 2 diabetes, cardiovascular disorders, chronic kidney disease, sleep apnea/hypoventilation syndrome, inflammatory bowel disease, Alzheimer's disease, osteoporosis, and psoriasis, as well. Based on the above, it can be stated, that high risk individuals with non-alcoholic fatty liver disease need systemic care, and require the detection of other components of this systemic pathological condition. While currently specific therapy for the disease is not yet known, life-style changes, adequate use of available medicines can prevent disease progression. Promising research

  19. Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Kato, Ken-Ichiro; Takeshita, Yumie; Misu, Hirofumi; Zen, Yoh; Kaneko, Shuichi; Takamura, Toshinari

    2015-03-01

    To examine the association between liver histological features and organ-specific insulin resistance indices calculated from 75-g oral glucose tolerance test data in patients with non-alcoholic fatty liver disease. Liver biopsy specimens were obtained from 72 patients with non-alcoholic fatty liver disease, and were scored for steatosis, grade and stage. Hepatic and skeletal muscle insulin resistance indices (hepatic insulin resistance index and Matsuda index, respectively) were calculated from 75-g oral glucose tolerance test data, and metabolic clearance rate was measured using the euglycemic hyperinsulinemic clamp method. The degree of hepatic steatosis, and grade and stage of non-alcoholic steatohepatitis were significantly correlated with Matsuda index (steatosis r = -0.45, P hepatic insulin resistance index. Multiple regression analyses adjusted for age, sex, body mass index and each histological score showed that the degree of hepatic steatosis (coefficient = -0.22, P steatosis and metabolic clearance rate (coefficient = -0.62, P = 0.059). Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in patients with non-alcoholic fatty liver disease, suggesting a central role of fatty liver in the development of peripheral insulin resistance and the existence of a network between the liver and skeletal muscle.

  20. Molecular pathways involved in the improvement of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Paz-Filho, Gilberto; Mastronardi, Claudio Alberto; Parker, Brian J; Khan, Ainy; Inserra, Antonio; Matthaei, Klaus I; Ehrhart-Bornstein, Monika; Bornstein, Stefan; Wong, Ma-Li; Licinio, Julio

    2013-01-01

    Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis are components of the metabolic syndrome. Serum leptin levels are elevated in obesity, but the role of leptin in the pathophysiology of the liver involvement is still unclear. To identify the effects and mechanisms by which leptin influences the pathogenesis of NAFLD, we performed epididymal white adipose tissue (eWAT) transplantation from congenic wild-type mice into the subcutaneous dorsal area of Lep(ob/ob) recipient mice and compared the results with those of the Lep(ob/ob) sham-operated mice. The mice were followed for 102-216 days. During killing, the transplanted mice had significantly lost body weight and exhibited significantly higher leptin levels, improved glucose tolerance, and lower liver injury scores than the sham-operated mice. Liver microarray analysis showed that novel pathways related to GA-binding protein (GABP) transcription factor targets, pheromone binding, and olfactory signaling were differentially expressed in the transplanted mice. Our data also replicate pathways known to be involved in NAFLD, such as those involved in the regulation of microRNAs, lipid, glucose, and glutathione metabolism, peroxisome proliferator-activated receptor signaling, cellular regulation, carboxylic acid processes, iron, heme, and tetrapyrrole binding, immunity and inflammation, insulin signaling, cytochrome P450 function, and cancer. wild-type eWAT transplantation into Lep(ob/ob) mice led to improvements in metabolism, body weight, and liver injury, possibly attributed to the production of leptin by the transplanted eWAT. These improvements were accompanied by the differential expression of novel pathways. The causal relationship between GABP downregulation and NAFLD improvement remains to be determined.

  1. Enhanced expression of BMP6 inhibits hepatic fibrosis in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Arndt, Stephanie; Wacker, Eva; Dorn, Christoph; Koch, Andreas; Saugspier, Michael; Thasler, Wolfgang E; Hartmann, Arndt; Bosserhoff, Anja Katrin; Hellerbrand, Claus

    2015-06-01

    Bone morphogenetic protein 6 (BMP6) has been identified as crucial regulator of iron homeostasis. However, its further role in liver pathology including non-alcoholic fatty liver disease (NAFLD) and its advanced form non-alcoholic steatohepatitis (NASH) is elusive. The aim of this study was to investigate the expression and function of BMP6 in chronic liver disease. BMP6 was analysed in hepatic samples from murine models of chronic liver injury and patients with chronic liver diseases. Furthermore, a tissue microarray comprising 110 human liver tissues with different degree of steatosis and inflammation was assessed. BMP6-deficient (BMP6(-/-)) and wild-type mice were compared in two dietary NASH-models, that is, methionine choline-deficient (MCD) and high-fat (HF) diets. BMP6 was solely upregulated in NAFLD but not in other murine liver injury models or diseased human livers. In NAFLD, BMP6 expression correlated with hepatic steatosis but not with inflammation or hepatocellular damage. Also, in vitro cellular lipid accumulation in primary human hepatocytes induced increased BMP6 expression. MCD and HF diets caused more hepatic inflammation and fibrosis in BMP6(-/-) compared with wild-type mice. However, only in the MCD and not in the HF diet model BMP6(-/-) mice developed marked hepatic iron overload, suggesting that further mechanisms are responsible for protective BMP6 effect. In vitro analysis revealed that recombinant BMP6 inhibited the activation of hepatic stellate cells (HSCs) and reduced proinflammatory and profibrogenic gene expression in already activated HSCs. Steatosis-induced upregulation of BMP6 in NAFLD is hepatoprotective. Induction of BMP6-signalling may be a promising antifibrogenic strategy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. 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 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.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.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.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 11β-HSD1 activity and consequent cortisol regeneration may

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

    Science.gov (United States)

    Ahmed, Adeeba; Rabbitt, Elizabeth; Brady, Theresa; Brown, Claire; Guest, Peter; Bujalska, Iwona J; Doig, Craig; Newsome, Philip N; Hubscher, Stefan; Elias, Elwyn; Adams, David H; Tomlinson, Jeremy W; Stewart, Paul M

    2012-01-01

    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). 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. 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. 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 11β-HSD1 activity and consequent cortisol regeneration may serve to

  4. 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.

  5. 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

  6. 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

  7. Effect of dietary fat to produce non-alcoholic fatty liver in the rat.

    Science.gov (United States)

    Ahmed, Umbreen; Redgrave, Trevor G; Oates, Phillip S

    2009-08-01

    Non-alcoholic steatohepatitis (NASH) belongs to a spectrum of non-alcoholic fatty liver disease (NAFLD). Oxidative stress is hypothesized to play an important role in the progression of the disease. We used the Lieber/DeCarli model for NASH to investigate the mechanisms involved in its progression. Male Sprague-Dawley rats were fed standard (35% of energy from fat) or high fat (71% of energy from fat) liquid diets, ad libitum or two-thirds of the amount consumed ad libitum initially for 3 weeks and then extended to 5 weeks. Steatosis was absent in rats at 3 weeks feeding, but by 5 weeks, the high fat/ad lib group showed microvesicular steatosis and foci of macrovesicular steatosis without inflammation. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were not different. By 5 weeks feeding, hepatic triglycerides were highest in the high fat ad lib group and the ad lib groups were higher compared with their restricted groups. The oxidative stress marker, hydroxyalkenal (HAE) was decreased in the standard ad lib compared with the high fat ad lib group. Liver mRNA of interleukin-6, haem oxygenase-1, and markers of endoplasmic stress: C/EBP homologous protein (CHOP), glucose responsive protein-78 (GRP78) and spliced X-box DNA binding protein (spliced XBP1) were similar in the ad lib groups. Extending the feeding period of the high fat/ad lib diet for 5 weeks placed our rats with Type I to II NAFLD compared to the more progressed Type III state previously obtained after 3 weeks feeding. The milder condition obtained raised the prospect of genetic modifiers present in our rats that resist disease progression.

  8. The expanding role of fish models in understanding non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Yoichi Asaoka

    2013-07-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a condition in which excessive fat accumulates in the liver of an individual who has not consumed excessive alcohol. Non-alcoholic steatohepatitis (NASH, a severe form of NAFLD, can progress to hepatic cirrhosis and/or hepatocellular carcinoma (HCC. NAFLD is considered to be a hepatic manifestation of metabolic syndrome, and its incidence has risen worldwide in lockstep with the increased global prevalence of obesity. Over the last decade, rodent studies have yielded an impressive list of molecules associated with NAFLD and NASH pathogenesis. However, the identification of currently unknown metabolic factors using mammalian model organisms is inefficient and expensive compared with studies using fish models such as zebrafish (Danio rerio and medaka (Oryzias latipes. Substantial advances in unraveling the molecular pathogenesis of NAFLD have recently been achieved through unbiased forward genetic screens using small fish models. Furthermore, these easily manipulated organisms have been used to great advantage to evaluate the therapeutic effectiveness of various chemical compounds for the treatment of NAFLD. In this Review, we summarize aspects of NAFLD (specifically focusing on NASH pathogenesis that have been previously revealed by rodent models, and discuss how small fish are increasingly being used to uncover factors that contribute to normal hepatic lipid metabolism. We describe the various types of fish models in use for this purpose, including those generated by mutation, transgenesis, or dietary or chemical treatment, and contrast them with rodent models. The use of small fish in identifying novel potential therapeutic agents for the treatment of NAFLD and NASH is also addressed.

  9. 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...... model. The preventive and therapeutic potential of RSV was tested by adding RSV to the HF and HFC diet from study start or after one week of the diets. Animals were sacrificed after 8 weeks with appropriate controls. Blood and liver were harvested for analysis, including measurement of RSV metabolites.......01), while there was no effect on biochemical, histopathological, or transcriptional NASH changes. Further, RSV had no therapeutic effect on established NASH. We found RSV metabolites but no parent RSV in serum or liver tissue, confirming low bioavailability. CONCLUSIONS: These experimental findings suggest...

  10. Determination of Caffeine Content in Non-Alcoholic Beverages and ...

    African Journals Online (AJOL)

    alcoholic energy drinks and prepared teas using reverse phase HPLC. Caffeine was extracted from 19 different types of non-alcoholic beverages and prepared teas sampled from supermarkets in Nairobi Central Business District, Kenya. These were ...

  11. Development and Quality Evaluation of a Non-Alcoholic Beverage ...

    African Journals Online (AJOL)

    % and 1.0% extracts of ginger and alligator pepper respectively. Two varieties of cocoyam, namely Colocasia esculenta and Xanthosoma sagittifolium were used. The purpose of this study is to develop an acceptable flavoured non alcoholic ...

  12. Improved Automated Classification of Alcoholics and Non-alcoholics

    OpenAIRE

    Ramaswamy Palaniappan

    2008-01-01

    In this paper, several improvements are proposed to previous work of automated classification of alcoholics and nonalcoholics. In the previous paper, multiplayer-perceptron neural network classifying energy of gamma band Visual Evoked Potential (VEP) signals gave the best classification performance using 800 VEP signals from 10 alcoholics and 10 non-alcoholics. Here, the dataset is extended to include 3560 VEP signals from 102 subjects: 62 alcoholics and 40 non-alcoholics...

  13. Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Jamali, Raika; Razavizade, Mohsen; Arj, Abbas; Aarabi, Mohammad Hossein

    2016-06-07

    To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease. Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score (NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic (ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis, lobular inflammation and fibrosis. Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08 (95%CI: 1.03-1.14), 1.04 (95%CI: 1.008-1.07), 1.04 (95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06 (95%CI: 1.002-1.12), 19.86 (95%CI: 2.79-141.19), 560.72 (95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P < 0.05]. Certain adipokines may

  14. In Vitro and in Vivo Models of Non-Alcoholic Fatty Liver Disease (NAFLD

    Directory of Open Access Journals (Sweden)

    Ina Bergheim

    2013-06-01

    Full Text Available By now, non-alcoholic fatty liver disease (NAFLD is considered to be among the most common liver diseases world-wide. NAFLD encompasses a broad spectrum of pathological conditions ranging from simple steatosis to steatohepatitis, fibrosis and finally even cirrhosis; however, only a minority of patients progress to end-stages of the disease, and the course of the disease progression to the later stages seems to be slow, developing progressively over several years. Key risk factors including overweight, insulin resistance, a sedentary life-style and an altered dietary pattern, as well as genetic factors and disturbances of the intestinal barrier function have been identified in recent years. Despite intense research efforts that lead to the identification of these risk factors, knowledge about disease initiation and molecular mechanisms involved in progression is still limited. This review summarizes diet-induced and genetic animal models, as well as cell culture models commonly used in recent years to add to the understanding of the mechanisms involved in NAFLD, also referring to their advantages and disadvantages.

  15. Non-alcoholic fatty liver disease phosphoproteomics: A functional piece of the precision puzzle.

    Science.gov (United States)

    Wattacheril, Julia; Rose, Kristie L; Hill, Salisha; Lanciault, Christian; Murray, Clark R; Washington, Kay; Williams, Brandon; English, Wayne; Spann, Matthew; Clements, Ronald; Abumrad, Naji; Flynn, Charles Robb

    2017-12-01

    Molecular signaling events associated with the necroinflammatory changes in nonalcoholic steatohepatitis (NASH) are not well understood. To understand the molecular basis of NASH, we evaluated reversible phosphorylation events in hepatic tissue derived from Class III obese subjects by phosphoproteomic means with the aim of highlighting key regulatory pathways that distinguish NASH from non-alcoholic fatty liver disease (also known as simple steatosis; SS). Class III obese subjects undergoing bariatric surgery underwent liver biopsy (eight normal patients, eight with simple steatosis, and eight NASH patients). Our strategy was unbiased, comparing global differences in liver protein reversible phosphorylation events across the 24 subjects. Of the 3078 phosphorylation sites assigned (2465 phosphoserine, 445 phosphothreonine, 165 phosphotyrosine), 53 were altered by a factor of 2 among cohorts, and of those, 12 were significantly increased or decreased by ANOVA (P < 0.05). Statistical analyses of canonical signaling pathways identified carbohydrate metabolism and RNA post-transcriptional modification among the most over-represented networks. Collectively, these results raise the possibility of abnormalities in carbohydrate metabolism as an important trigger for the development of NASH, in parallel with already established abnormalities in lipid metabolism. © 2017 The Japan Society of Hepatology.

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

    Science.gov (United States)

    Hernandez-Rodas, Maria Catalina; Valenzuela, Rodrigo; Videla, Luis A.

    2015-01-01

    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. PMID:26512643

  17. IL-17 Axis Driven Inflammation in Non-Alcoholic Fatty Liver Disease Progression

    Science.gov (United States)

    Giles, Daniel A.; Moreno-Fernandez, Maria E; Divanovic, Senad

    2016-01-01

    Obesity is a primary risk factor for the development of non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common chronic liver disease in the world, represents a spectrum of disorders that range from steatosis (NAFL) to steatohepatitis (NASH) to cirrhosis. It is anticipated that NAFLD will soon surpass chronic hepatitis C infection as the leading cause for needing liver transplantation. Despite its clinical and public health significance no specific therapies are available. Although the etiology of NAFLD is multifactorial and remains largely enigmatic, it is well accepted that inflammation is a central component of NAFLD pathogenesis. Despite the significance, critical immune mediators, loci of immune activation, the immune signaling pathways and the mechanism(s) underlying disease progression remain incompletely understood. Recent findings have focused on the role of Interleukin 17 (IL-17) family of proinflammatory cytokines in obesity and pathogenesis of obesity-associated sequelae. Notably, obesity favors a Th17 bias and is associated with increased IL-17A expression in both humans and mice. Further, in mice, IL-17 axis has been implicated in regulation of both obesity and NAFLD pathogenesis. However, despite these recent advances several important questions require further evaluation including: the relevant cellular source of IL-17A production; the critical IL-17RA-expressing cell type; the critical liver infiltrating immune cells; and the underlying cellular effector mechanisms. Addressing these questions may aid in the identification and development of novel therapeutic targets for prevention of inflammation-driven NAFLD progression. PMID:26028039

  18. Non-alcoholic Fatty Liver Disease in Lean Subjects: Characteristics and Implications.

    Science.gov (United States)

    Kumar, Ramesh; Mohan, Shantam

    2017-09-28

    Non-alcoholic fatty liver disease (NAFLD) is commonly diagnosed in obese subjects; however, it is not rare among lean individuals. Given the absence of traditional risk factors, it tends to remain under-recognised. The metabolic profiles of lean NAFLD patients are frequently comparable to those of obese NAFLD patients. Though results from several studies have been mixed, it has been generally revealed that lean subjects with NAFLD have minor insulin resistance compared to that in obese NAFLD. Several genetic variants are associated with NAFLD without insulin resistance. Some data suggest that the prevalence of steatohepatitis and advanced fibrosis do not differ significantly between lean and obese NAFLD; however, the former tend to have less severe disease at presentation. The underlying pathophysiology of lean NAFLD may be quite different. Genetic predispositions, fructose- and cholesterol-rich diet, visceral adiposity and dyslipidaemia have potential roles in the pathogenic underpinnings. Lean NAFLD may pose a risk for metabolic disturbances, cardiovascular morbidity or overall mortality. Secondary causes of hepatic steatosis are also needed to be ruled out in lean subjects with NAFLD. The effectiveness of various treatment modalities, such as exercise and pharmacotherapy, on lean NAFLD is not known. Weight loss is expected to help lean NAFLD patients who have visceral obesity. Further investigation is needed for many aspects of lean NAFLD, including mechanistic pathogenesis, risk assessment, natural history and therapeutic approach.

  19. Ginkgolide A ameliorates non-alcoholic fatty liver diseases on high fat diet mice.

    Science.gov (United States)

    Jeong, Hyeon-Soo; Kim, Kang-Hoon; Lee, In-Seung; Park, Ji Young; Kim, Yumi; Kim, Ki-Suk; Jang, Hyeung-Jin

    2017-04-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases worldwide and has continuously increased. NAFLD refers to a spectrum of diseases ranging from fatty liver to steatohepatitis, cirrhosis, and even to hepatocyte carcinoma. Excessive fatty acid enters the cell and the mitochondria undergo stress and unremoved ROS can trigger a form of cell apoptosis known as 'lipoapoptosis'. NASH arises from damaged liver hepatocytes due to lipotoxicity. NASH not only involves lipid accumulation and apoptosis but also inflammation. Ginkgo biloba has been tested clinical trials as a traditional medicine for asthma, bronchitis and cardiovascular disease. The effects of Ginkgolide A (GA), derived from the ginkgo biloba leaf, are still unknown in NAFLD. To determine the protective effects of GA in NAFLD, we examined the fatty liver disease condition in the non-esterified fatty acid (NEFA)-induced HepG2 cell line and in a high fat diet mouse model. The findings of this study suggest that GA is non-toxic at high concentrations in hepatocytes. Moreover, GA was found to inhibit cellular lipogenesis and lipid accumulation by causing mitochondrial oxidative stress. GA showed hepatoprotective efficacy by inducing cellular lipoapoptosis and by inhibiting cellular inflammation. The results demonstrated that GA may be feasible as a therapeutic agent for NAFLD patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Increased prevalence and risk of non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes in South China.

    Science.gov (United States)

    Yi, M; Chen, R-P; Yang, R; Chen, H

    2017-04-01

    To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes mellitus. We recruited patients with Type 2 diabetes with a BMI ≥ 24 kg/m 2 , who visited the diabetes clinics of 60 hospitals in 21 cities in Guangdong Province, China from August 2011 to March 2012. Anthropometric measurements, biochemical tests and abdominal ultrasonography were performed for all the patients. The study included 3861 patients (1860 men) with a mean ± sd (range) age of 58.91 ± 13.06 (18-90) years. Non-alcoholic fatty liver disease was found in 1751 patients (45.4%), with a significantly higher prevalence among men than women (48.0 vs 42.9%). The peak of non-alcoholic fatty liver disease prevalence was in patients with a BMI of 34-35 kg/m 2 , those with a triglyceride/HDL cholesterol ratio of 5.5-6.0, men aged non-alcoholic fatty liver disease, while heart rate and female gender were protective factors. The prevalence of non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes in South China is high. Multiple metabolic disorders were significantly associated with non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes. © 2016 Diabetes UK.

  1. Evaluation of multiple-scoring system for non-alcoholic fatty liver patients based on CK18 levels, lipid profile and liver enzymes

    Directory of Open Access Journals (Sweden)

    Nahid Teimouri

    2017-04-01

    Full Text Available Background: Non-alcoholic fatty liver disease (NAFLD, the most common liver disease is usually associated with conditions such as steatosis, steatohepatitis and cirrhosis. Liver biopsy, which is the reference, gold standard and invasive method for the diagnosis of the disease may have complications. Scoring systems are among the noninvasive diagnostic methods. Numerous noninvasive scoring systems based on routinely measured clinical and laboratory parameters were provided that identifies the steatosis and advanced fibrosis in patients with NAFLD. In this study, several scoring system in patients with NAFLD were evaluated. Materials and Methods: This case-control study was carried out on sonographically established NAFLD (n=51 patients and healthy individuals (n=30. Anthropometric factors, biochemical tests and CK-18 fragment levels were evaluated. Then the scores for hepatic steatosis index, fatty liver index, aspartate aminotransferase (AST to platelets ratio index (APRI were calculated. In addition, the BARD and (non-alcoholic steatohepatitis (NASH scores were calculated. Results: In this study, as expected, except for FIB-4, there was no significant difference between the two groups. Conclusions: Scoring systems examined in this study can help to predict the presence or absence of fibrosis and NAFLD or NASH.

  2. Non-Alcoholic Fatty Liver Disease (NAFLD): new challenge for general practitioners and important burden for health authorities?

    Science.gov (United States)

    Ahmed, Mohamed H; Abu, Emmanuel O; Byrne, Christopher D

    2010-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of hepatic dysfunction encountered in general practice. A large proportion of individuals with type 2 diabetes and the metabolic syndrome develop NAFLD. NAFLD is associated with severe insulin resistance and increased risk of cardiovascular disease and can progress to non-alcoholic steato-hepatitis, liver cirrhosis and cancer. Currently the only known effective treatments for NAFLD are lifestyle changes including stable weight loss and a diet low in calories. General practitioners will increasingly play a key role in dealing with this evolving but serious epidemic of NAFLD and associated metabolic complications. However, success will depend on the appropriate systems and mechanisms being in place in primary care and the proper motivation, support and education of the patient. This review provides the primary care physician with: (a) a step-by step guide of how to identify NAFLD, (b) information to exclude common other causes of liver fat accumulation and (c) additional insight into relationships between NAFLD and other conditions such as obesity, cardiovascular disease and type 2 diabetes. Copyright © 2010 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  3. Mediterranean Diet and Multi-Ingredient-Based Interventions for the Management of Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Suárez, Manuel; Boqué, Noemí; del Bas, Josep M.; Arola, Lluís; Caimari, Antoni

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprises a wide spectrum of hepatic disorders, from simple steatosis to hepatic necro-inflammation leading to non-alcoholic steatohepatitis (NASH). Although the prevalence of these multifactorial pathologies is continuously increasing in the population, there is still not an established methodology for their treatment other than weight loss and a change in lifestyle habits, such as a hypocaloric diet and physical exercise. In this framework, there is increasing evidence that several food bioactives and dietary patterns are effective for reversing and preventing the onset of these pathologies. Some studies have claimed that better responses are obtained when treatments are performed under a multifaceted approach, using different bioactive compounds that act against complementary targets. Thus, in this work, current strategies for treating NAFLD and NASH based on multi-ingredient-based supplements or the Mediterranean diet, a dietary pattern rich in bioactive compounds, are reviewed. Furthermore, the usefulness of omics techniques to design effective multi-ingredient nutritional interventions and to predict and monitor their response against these disorders is also discussed. PMID:28937599

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. Status of antiviral immunity in patients with non-alcoholic liver fatty disease, who were Chornobyl NPP accident liquidators

    Directory of Open Access Journals (Sweden)

    A.A. Chumak

    2017-11-01

    Full Text Available 34 men were examined, who after participating in the liquidation of the Chornobyl NPP accident developed non-alcoholic fatty liver disease. The state of antiviral defense was evaluated by the levels of immunoglobulin (Ig G and IgM antibodies in the blood serum. In most patients with non-alcoholic steatohepatitis, who were Chornobyl NPP accident liquidators, antibodies of the IgG, but not IgM class to the persistent mixed infection with herpes simplex virus types 1 and 2, cytomegaly and Epstein-Barr were found. A positive correlation was established between the antibody titers to the herpes simplex virus types 1 and 2 (anti-HSV-1/2 IgG and cytomegalovirus (anti-CMV IgG (rs = 0.383, p = 0.040, as well as between the antibodies titers to the nuclear antigen of Epstein-Barr virus (anti-EBV NA IgG and antibodies to core antigen of Epstein-Barr (anti-EBV VCA IgG (rs = 0.584, p = 0.002 in patients with persistent mixed infection of these herpesviruses.

  7. Changes in drug transport and metabolism and their clinical implications in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Dietrich, Christoph G; Rau, Monika; Jahn, Daniel; Geier, Andreas

    2017-06-01

    The incidence of non-alcoholic fatty liver disease (NAFLD) is rising, especially in Western countries. Drug treatment in patients with NAFLD is common since it is linked to other conditions like diabetes, obesity, and cardiovascular disease. Consequently, changes in drug metabolism may have serious clinical implications. Areas covered: A literature search for studies in animal models or patients with obesity, fatty liver, non-alcoholic steatohepatitis (NASH) or NASH cirrhosis published before November 2016 was performed. After discussing epidemiology and animal models for NAFLD, we summarized both basic as well as clinical studies investigating changes in drug transport and metabolism in NAFLD. Important drug groups were assessed separately with emphasis on clinical implications for drug treatment in patients with NAFLD. Expert opinion: Given the frequency of NAFLD even today, a high degree of drug treatment in NAFLD patients appears safe and well-tolerated despite considerable changes in hepatic uptake, distribution, metabolism and transport of drugs in these patients. NASH causes changes in biliary excretion, systemic concentrations, and renal handling of drugs leading to alterations in drug efficacy or toxicity under specific circumstances. Future clinical drug studies should focus on this special patient population in order to avoid serious adverse events in NAFLD patients.

  8. 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

    2016-04-27

    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.

  9. Tissue Inhibitors of Metalloproteinase-1 and 2 and Obesity Related Non-Alcoholic Fatty Liver Disease: Is There a Relationship.

    Science.gov (United States)

    Abdelaziz, Rokaya; Elbasel, Mohamed; Esmat, Serag; Essam, Kareem; Abdelaaty, Sahar

    2015-01-01

    Non-alcoholic fatty liver disease is a spectrum of clinical conditions, including simple steatosis and non-alcoholic steatohepatitis (NASH). The aim of the study is to evaluate the tissue inhibitors of metalloproteinase-1 and 2 (TIMPs) as noninvasive predictors of NASH. Three groups were included in the study. Obese patients (n = 30) with normal liver enzymes were included in group I and obese patients (n = 30) with elevated liver enzymes with liver biopsy-based diagnosis of NASH were included in group II. Age-matched subjects (n = 30) formed the control as group III. The lipid profile, liver enzyme levels and levels of TIMPs were compared among all the patients and subjects. Comparison of groups I and II showed significantly elevated levels of TIMP-1 and TIMP-2 in group II as compared to group I (p < 0.05). Similarly, comparison between groups II and III showed significantly increased levels of TIMP-1 and TIMP-2 in group II as compared to group III (p < 0.05). TIMP-1 (sensitivity 96.7%, specificity 100%) and TIMP-2 (sensitivity 93.3%, specificity 100%) showed high accuracy in NASH diagnosis. TIMP-1 and TIMP-2 may be considered noninvasive markers for the diagnosis of NASH. © 2015 S. Karger AG, Basel.

  10. Mediterranean Diet and Multi-Ingredient-Based Interventions for the Management of Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Manuel Suárez

    2017-09-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD comprises a wide spectrum of hepatic disorders, from simple steatosis to hepatic necro-inflammation leading to non-alcoholic steatohepatitis (NASH. Although the prevalence of these multifactorial pathologies is continuously increasing in the population, there is still not an established methodology for their treatment other than weight loss and a change in lifestyle habits, such as a hypocaloric diet and physical exercise. In this framework, there is increasing evidence that several food bioactives and dietary patterns are effective for reversing and preventing the onset of these pathologies. Some studies have claimed that better responses are obtained when treatments are performed under a multifaceted approach, using different bioactive compounds that act against complementary targets. Thus, in this work, current strategies for treating NAFLD and NASH based on multi-ingredient-based supplements or the Mediterranean diet, a dietary pattern rich in bioactive compounds, are reviewed. Furthermore, the usefulness of omics techniques to design effective multi-ingredient nutritional interventions and to predict and monitor their response against these disorders is also discussed.

  11. Preventive effects of citrulline on Western diet-induced non-alcoholic fatty liver disease in rats.

    Science.gov (United States)

    Jegatheesan, Prasanthi; Beutheu, Stéphanie; Freese, Kim; Waligora-Dupriet, Anne-Judith; Nubret, Esther; Butel, Marie-Jo; Bergheim, Ina; De Bandt, Jean-Pascal

    2016-07-01

    A Western diet induces insulin resistance, liver steatosis (non-alcoholic fatty liver disease (NAFLD)) and intestinal dysbiosis, leading to increased gut permeability and bacterial translocation, thus contributing to the progression of NAFLD to non-alcoholic steatohepatitis. In the present study, we sought, in a model of Western diet-induced NAFLD, to determine whether citrulline (Cit), an amino acid that regulates protein and energy metabolism, could decrease Western diet-induced liver injuries, as well as the mechanisms involved. Sprague-Dawley rats were fed a high-fat diet (45 %) and fructose (30 %) in drinking water or a control diet associated with water (group C) for 8 weeks. The high-fat, high-fructose diet (Western diet) was fed either alone (group WD) or with Cit (1 g/kg per d) (group WDC) or an isonitrogenous amount of non-essential amino acids (group WDA). We evaluated nutritional and metabolic status, liver function, intestinal barrier function, gut microbiota and splanchnic inflammatory status. Cit led to a lower level of hepatic TAG restricted to microvesicular lipid droplets and to a lower mRNA expression of CCAAT-enhancer-binding protein homologous protein, a marker of endoplasmic reticulum stress, of pro-inflammatory cytokines Il6 (PWestern diet alone. Cit improves Western diet-induced liver injuries via decreased lipid deposition, increased insulin sensitivity, lower inflammatory process and preserved antioxidant status. This may be related in part to its protective effects at the gut level.

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

    Directory of Open Access Journals (Sweden)

    Eline H van den Berg

    Full Text Available 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.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 <18 years, immigrants, missing data to assess FLI and metabolic syndrome, excessive alcohol use, previous-diagnosed hepatitis or cirrhosis and non-fasting blood sampling.Out of 37,496 included participants (median age 44 years, 62.1% female, 8,259 (22.0% had a FLI≥60. Individuals with a FLI≥60 were more often male, older, 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.Twenty

  13. Comparative analysis and modeling of the severity of steatohepatitis in DDC-treated mouse strains.

    Directory of Open Access Journals (Sweden)

    Vikash Pandey

    Full Text Available BACKGROUND: Non-alcoholic fatty liver disease (NAFLD has a broad spectrum of disease states ranging from mild steatosis characterized by an abnormal retention of lipids within liver cells to steatohepatitis (NASH showing fat accumulation, inflammation, ballooning and degradation of hepatocytes, and fibrosis. Ultimately, steatohepatitis can result in liver cirrhosis and hepatocellular carcinoma. METHODOLOGY AND RESULTS: In this study we have analyzed three different mouse strains, A/J, C57BL/6J, and PWD/PhJ, that show different degrees of steatohepatitis when administered a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC containing diet. RNA-Seq gene expression analysis, protein analysis and metabolic profiling were applied to identify differentially expressed genes/proteins and perturbed metabolite levels of mouse liver samples upon DDC-treatment. Pathway analysis revealed alteration of arachidonic acid (AA and S-adenosylmethionine (SAMe metabolism upon other pathways. To understand metabolic changes of arachidonic acid metabolism in the light of disease expression profiles a kinetic model of this pathway was developed and optimized according to metabolite levels. Subsequently, the model was used to study in silico effects of potential drug targets for steatohepatitis. CONCLUSIONS: We identified AA/eicosanoid metabolism as highly perturbed in DDC-induced mice using a combination of an experimental and in silico approach. Our analysis of the AA/eicosanoid metabolic pathway suggests that 5-hydroxyeicosatetraenoic acid (5-HETE, 15-hydroxyeicosatetraenoic acid (15-HETE and prostaglandin D2 (PGD2 are perturbed in DDC mice. We further demonstrate that a dynamic model can be used for qualitative prediction of metabolic changes based on transcriptomics data in a disease-related context. Furthermore, SAMe metabolism was identified as being perturbed due to DDC treatment. Several genes as well as some metabolites of this module show differences between A

  14. Assessment of Some Adipo cytokines Levels In Serum of Egyptian Patients Suffering From Non-Alcoholic Steatohepatitis (NASH)

    International Nuclear Information System (INIS)

    Mohammed, A.A.

    2011-01-01

    In the present study, thirty five patients with biopsy proven NASH and twenty age and sex matched healthy individuals were enrolled. Serum adiponectin, ghrelin, TNF-α and leptin levels were estimated in the serum of NASH patients and control subjects. Also, fasting insulin and blood glucose levels were measured and insulin resistance (IR) were calculated. In addition, liver function enzymes (AST, ALT), total cholesterol and triglycerides were measured, and body mass index (BMI) was calculated. The results showed significant decrease in adiponectin and ghrelin levels and significant increase in TNF-α and leptin levels in NASH group as compared to controls. Ten patients were diabetic and seven patients had BMI > 30 kg/m 2 . Also, significant positive relationship was recorded between adiponectin and ghrelin and AST/ALT ratio in the NASH group, and significant negative relationship between them and BMI and HOMA-IR

  15. Resolution of non-alcoholic steatohepatitis after growth hormone replacement in a pediatric liver transplant patient with panhypopituitarism

    DEFF Research Database (Denmark)

    Gilliland, Thomas; Dufour, Sylvie; Shulman, Gerald I.

    2016-01-01

    NAFLD is a common condition linked to obesity, type 2 diabetes, and metabolic syndrome. Simple hepatic steatosis is a risk factor for inflammatory reactions in the liver (NASH), which may lead to cirrhosis. While the mechanism is unclear, NAFLD and NASH are associated with panhypopituitarism, which...... in the pediatric population often results from craniopharyngioma or pituitary adenoma and the sequelae of treatment, causing hypothyroidism, adrenal insufficiency, hypogonadotropic hypogonadism, and GH deficiency. Refractory NAFLD in panhypopituitarism may be amenable to GH replacement. Here, we report a pediatric....... Pediatric patients with NASH cirrhosis secondary to panhypopituitarism can be good candidates for liver transplantation, but hormone deficiencies predispose to recurrence after transplant. High-dose GH replacement should be considered in pediatric patients with GH deficiency and recurrent disease...

  16. Effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix components in experimentally induced non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Surapaneni Krishna Mohan

    2015-08-01

    Results:The experimental NASH rats treated with pioglitazone showed significant decrease in the levels of hyaluronic acid and significant increase in adiponectin levels when compared to experimentally induced NASH group, but did not show any effect on the levels of leptin. Contrary to these two drugs, viz. pioglitazone and hydroxy citric acid, the group treated with quercetin showedsignificant decrease in the levels of hyaluronic acid and leptin and significant decrease in adiponectin levels compared with that of experimentally induced NASH NASH group, offering maximum protection against NASH. Conclusion: Considering our findings, it could be concluded that quercetin may offer maximum protection against NASH by significantly increasing the levels of adiponectin, when compared to pioglitazone and hydroxy citric acid.

  17. Clinical and histological features of nonalcoholic steatohepatitis in Iranian patients

    Directory of Open Access Journals (Sweden)

    Haghpanah Babak

    2003-10-01

    Full Text Available Abstract Background Although several studies have been performed on risk factors and natural course of NASH, it seems that NASH tends to be more than a disease confined to strict boundaries. The objective of this study was to assess the clinical and paraclinical features and risk factors for non-alcoholic steatohepatitis (NASH patients in an Iranian population Methods Patients with histologically confirmed NASH who had elevated liver aminotransaminases, negative serologic markers of viral or autoimmune hepatitis and no findings in favor of metabolic liver disease were enrolled. A careful history was taken regarding alcohol intake. Results 53 patients consisting of 32 male and 21 female entered the study. The mean age was 37.8 ± 11.3 years. Twenty-six patients (55.3% were overweight, 15 (31.9% obese, 40 (75.5% dyslipidemic, and three patients (5.7% were diabetic. Liver biopsy showed mild steatosis in 35.7%, moderate steatosis in 53.6%, and severe forms in 10.7%. In 80.2% of patients, portal inflammation was present, and 9.4% had cirrhosis. The amount of increase in liver enzymes bore no relationship with fibrosis, portal inflammation, and degree of steatosis. Conclusions The patients in our study showed a male predominancy and were somewhat younger than other studies.

  18. Expression of resistin in the liver of patients with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Piotr Gierej

    2017-11-01

    Full Text Available Adipokines are cytokines that presumably connect the pathologies of metabolic syndrome. One of the adipokines is resistin, the role of which in insulin resistance, obesity, and non-alcoholic fatty liver disease (NAFLD needs to be determined. Liver biopsy specimens were obtained intraoperatively from 214 obese patients. Histological assessment was based on NAFLD activity score according to Kleiner. Statistical analysis involved semi-quantitive immunohistochemistry assessment of resistin staining and: NAFLD status in obese patients compared with a non-obese control group, selected clinical data (age, sex, body mass index – BMI, selected biochemical data, comorbidities (hypertension, type 2 diabetes mellitus, dyslipidaemia, and metformin treatment in patients with type 2 diabetes mellitus. Resistin expression was observed in the histiocytes of inflammatory infiltrate, Kupffer cells, and histiocytes surrounding the hepatocytes with steatosis. There was a positive correlation between the total expression of resistin and: (1 NAFLD advancement (NAFLD Activity Score- NAS, (2 AST, ALT, BMI, glucose, insulin, Homeostasis Model Assessment (HOMA, LDH, GGT, triglycerides (TG, and glycated haemoglobin (HbA1c. Resistin expression was more intense in patients with type 2 diabetes mellitus and dyslipidaemia and less intense in the control group. Resistin probably plays a role in the pathogenesis of hepatic insulin resistance and aggravates pathologic changes in the liver of patients with NAFLD.

  19. Non-Alcoholic Fatty Liver Disease (NAFLD) in Obesity

    OpenAIRE

    Patell, Rushad; Dosi, Rupal; Joshi, Harshal; Sheth, Smit; Shah, Purav; Jasdanwala, Sarfaraz

    2014-01-01

    Background and Objectives: Limited studies have been undertaken to characterize Non-Alcoholic Fatty Liver Disease (NAFLD) in the Indian population. The main objective of our study was to document the prevalence of NAFLD amongst a cohort of obese Indian patients and demonstrate its relationship with other components of the metabolic syndrome.

  20. Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver Disease

    NARCIS (Netherlands)

    ter Horst, Kasper W.; Serlie, Mireille J.

    2017-01-01

    Increased fructose consumption has been suggested to contribute to non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and insulin resistance, but a causal role of fructose in these metabolic diseases remains debated. Mechanistically, hepatic fructose metabolism yields precursors that can be

  1. 7853 DEMAND FOR NON-ALCOHOLIC BEVERAGES AMONG ...

    African Journals Online (AJOL)

    Win7Ent

    2013-06-03

    Jun 3, 2013 ... cross-price sensitivity, substitutability and complementarities among beverages are very important to ... elicit information on household demography, income, food and non-food expenditure and prices as well as individual ... Non-alcoholic beverages (NABs) market in Nigeria is oligopolistic. Each of the NAB.

  2. Determinants of Non Alcoholic Beverages (NAB) Consumption in ...

    African Journals Online (AJOL)

    ABSTRACT: Non alcoholic beverages (NAB) consumption in Nigeria has been steadily increasing over the years to the point where nearly half of the populace are ... caffeine (Valentine, 2001). Demand for fruit juice in Nigeria has grown ... According to economic theory and observed behavior age has a negative effect on ...

  3. Monitoring food and non-alcoholic beverage promotions to children.

    Science.gov (United States)

    Kelly, B; King, L; Baur, L; Rayner, M; Lobstein, T; Monteiro, C; Macmullan, J; Mohan, S; Barquera, S; Friel, S; Hawkes, C; Kumanyika, S; L'Abbé, M; Lee, A; Ma, J; Neal, B; Sacks, G; Sanders, D; Snowdon, W; Swinburn, B; Vandevijvere, S; Walker, C

    2013-10-01

    Food and non-alcoholic beverage marketing is recognized as an important factor influencing food choices related to non-communicable diseases. The monitoring of populations' exposure to food and non-alcoholic beverage promotions, and the content of these promotions, is necessary to generate evidence to understand the extent of the problem, and to determine appropriate and effective policy responses. A review of studies measuring the nature and extent of exposure to food promotions was conducted to identify approaches to monitoring food promotions via dominant media platforms. A step-wise approach, comprising 'minimal', 'expanded' and 'optimal' monitoring activities, was designed. This approach can be used to assess the frequency and level of exposure of population groups (especially children) to food promotions, the persuasive power of techniques used in promotional communications (power of promotions) and the nutritional composition of promoted food products. Detailed procedures for data sampling, data collection and data analysis for a range of media types are presented, as well as quantifiable measurement indicators for assessing exposure to and power of food and non-alcoholic beverage promotions. The proposed framework supports the development of a consistent system for monitoring food and non-alcoholic beverage promotions for comparison between countries and over time. © 2013 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of the International Association for the Study of Obesity.

  4. Demand for non-alcoholic beverages among urban households in ...

    African Journals Online (AJOL)

    This study examined the roles of income, prices and household demography in household demand for non-alcoholic beverages (NABs) in two cities – Abeokuta and Ibadan in Southwest Nigeria. The study was based on primary data obtained from a cross-section of 407 households (211 from Abeokuta and 198 from ...

  5. 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

    2015-06-08

    To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. 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 and S

  6. Disturbed Vitamin A Metabolism in Non-Alcoholic Fatty Liver Disease (NAFLD

    Directory of Open Access Journals (Sweden)

    Ali Saeed

    2017-12-01

    Full Text Available Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A’s functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs and retinoid X receptors (RXRs.The liver plays a central role in vitamin A metabolism: (1 it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2 it produces retinol binding protein 4 (RBP4 that distributes vitamin A, as retinol, to peripheral tissues; and (3 it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs. In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 μmol/L, sufficient to provide the body with this vitamin for months. Liver diseases, in particular those leading to fibrosis and cirrhosis, are associated with impaired vitamin A homeostasis and may lead to vitamin A deficiency. Liver injury triggers HSCs to transdifferentiate to myofibroblasts that produce excessive amounts of extracellular matrix, leading to fibrosis. HSCs lose the retinyl ester stores in this process, ultimately leading to vitamin A deficiency. Non-alcoholic fatty liver disease (NAFLD is the hepatic manifestation of metabolic syndrome and is a spectrum of conditions ranging from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH; it may progress to cirrhosis and liver cancer. NASH is projected to be the main cause of liver failure in the near future. Retinoic acids are key regulators of glucose and lipid metabolism in the liver and adipose tissue, but it is unknown whether impaired vitamin A homeostasis contributes to or suppresses the development of NAFLD. A genetic variant of patatin-like phospholipase domain-containing 3 (PNPLA3-I148M is the most prominent

  7. 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

  8. Systems-level organization of non-alcoholic fatty liver disease progression network

    Directory of Open Access Journals (Sweden)

    K. Shubham

    2017-10-01

    Full Text Available Non-Alcoholic Fatty Liver Disease (NAFLD is a hepatic metabolic disorder that is commonly associated with sedentary lifestyle and high fat diets. NAFLD is prevalent in individuals with obesity, insulin resistance and Type 2 Diabetes (T2D. The clinical spectrum of NAFLD ranges from simple steatosis to Non-Alcoholic Steatohepatitis (NASH with fibrosis, which can progress to cirrhosis and hepatocellular carcinoma.The pathogenesis of NAFLD is complex, involving crosstalk between multiple organs, cell-types, and environmental and genetic factors. Dysfunction of White Adipose Tissue (WAT plays a central role in the development of NAFLD and other metabolic disorders. WAT is an active endocrine organ that regulates whole-body energy homeostasis, lipid metabolism, insulin sensitivity and food intake by secreting biologically active molecules (lipokines, adipokines and cytokines. WAT dynamically reacts to nutrient excess or deprivation by remodelling the number (called hyperplasia and/or size (called hypertrophy of adipocytes to store fat or supply nutrients to other tissues by lipolysis, respectively. Adipose tissue remodelling is also accompanied by changes in the composition or function of stromal vascular cells and ECM. The major objective of our study was to identify and characterize the metabolic and signaling modules associated with the progression of NAFLD in the VAT. We performed Weighted Gene Co-expression Network Analysis (WGCNA to organize microarray data obtained from the VAT of patients at different stages of NAFLD into functional modules. In order to obtain insights into the metabolism and its regulation at the genome scale, a co-expression network of metabolic genes in the Human Metabolic Network (HMR2 was constructed and compared with the co-expression network constructed based on all the varying genes. We also used the prior network information on adipocyte metabolism (GEM to verify and extract reporter metabolites. Our analysis revealed

  9. Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing.

    Science.gov (United States)

    Zhou, Can-Can; Yang, Xi; Hua, Xia; Liu, Jian; Fan, Mao-Bing; Li, Guo-Qiang; Song, Jie; Xu, Tian-Ying; Li, Zhi-Yong; Guan, Yun-Feng; Wang, Pei; Miao, Chao-Yu

    2016-08-01

    Ageing is an important risk factor of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether the deficiency of nicotinamide adenine dinucleotide (NAD(+) ), a ubiquitous coenzyme, links ageing with NAFLD. Hepatic concentrations of NAD(+) , protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD(+) biosynthesis, were compared in middle-aged and aged mice or patients. The influences of NAD(+) decline on the steatosis and steatohepatitis were evaluated in wild-type and H247A dominant-negative, enzymically-inactive NAMPT transgenic mice (DN-NAMPT) given normal or high-fat diet (HFD). Hepatic NAD(+) level decreased in aged mice and humans. NAMPT-controlled NAD(+) salvage, but not de novo biosynthesis pathway, was compromised in liver of elderly mice and humans. Given normal chow, middle-age DN-NAMPT mice displayed systemic NAD(+) reduction and had moderate NAFLD phenotypes, including lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver. All these NAFLD phenotypes, especially release of pro-inflammatory factors, Kupffer cell accumulation, monocytes infiltration, NLRP3 inflammasome pathway and hepatic fibrosis (Masson's staining and α-SMA staining), deteriorated further under HFD challenge. Oral administration of nicotinamide riboside, a natural NAD(+) precursor, completely corrected these NAFLD phenotypes induced by NAD(+) deficiency alone or HFD, whereas adenovirus-mediated SIRT1 overexpression only partially rescued these phenotypes. These results provide the first evidence that ageing-associated NAD(+) deficiency is a critical risk factor for NAFLD, and suggest that supplementation with NAD(+) substrates may be a promising therapeutic strategy to prevent and treat NAFLD. © 2016 The British Pharmacological Society.

  10. Obstructive Sleep Apnea and Non-alcoholic Fatty Liver Disease: Is the Liver Another Target?

    Directory of Open Access Journals (Sweden)

    Aibek eMirrakhimov

    2012-10-01

    Full Text Available Obstructive sleep apnea (OSA is recurrent obstruction of the upper airway during sleep leading to intermittent hypoxia (IH. OSA has been associated with all components of the metabolic syndrome as well as with non-alcoholic fatty liver disease (NAFLD. NAFLD is a common condition ranging in severity from uncomplicated hepatic steatosis to steatohepatitis (NASH, liver fibrosis and cirrhosis. The gold standard for the diagnosis and staging of NAFLD is liver biopsy. Obesity and insulin resistance lead to liver steatosis, but the causes of the progression to NASH are not known. Emerging evidence suggests that OSA may play a role in the progression of hepatic steatosis and the development of NASH. Several cross-sectional studies showed that the severity of IH in patients with OSA predicted the severity of NAFLD on liver biopsy. However, neither prospective nor interventional studies with continuous positive airway pressure (CPAP treatment have been performed. Studies in a mouse model showed that IH causes triglyceride accumulation in the liver and liver injury as well as hepatic inflammation. The mouse model provided insight in the pathogenesis of liver injury showing that (1 IH accelerates the progression of hepatic steatosis by inducing adipose tissue lipolysis and increasing free fatty acids (FFA flux into the liver; (2 IH up-regulates lipid biosynthetic pathways in the liver; (3 IH induces oxidative stress in the liver; (4 IH up-regulates hypoxia inducible factor 1 alpha and possibly HIF-2 alpha, which may increase hepatic steatosis and induce liver inflammation and fibrosis. However, the role of FFA and different transcription factors in the pathogenesis of IH-induced NAFLD is yet to be established. Thus, multiple lines of evidence suggest that IH of OSA may contribute to the progression of NAFLD but definitive clinical studies and experiments in the mouse model have yet to be done.

  11. 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 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.This study sought to identify factors predictive of normal liver histology in a bariatric cohort.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.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.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.

  12. Curcumin ameliorates hepatic fibrosis in type 2 diabetes mellitus – insights into its mechanisms of action

    Science.gov (United States)

    Stefanska, B

    2012-01-01

    A wide variety of beneficial effects have been attributed to curcumin, a major polyphenol from the golden spice Curcuma longa known as turmeric, including amelioration of severe complications of type 2 diabetes such as hepatic fibrosis, retinopathy, neuropathy and nephropathy. In the present issue of BJP, Lin and colleagues reveal new mechanisms by which curcumin inhibits the activation of hepatic stellate cells in vitro, a hallmark of non-alcoholic steatohepatitis and hepatic fibrogenesis associated with type 2 diabetes mellitus. They demonstrated that curcumin suppresses the advanced glycation end-products (AGEs)-mediated induction of the receptor for AGEs (RAGE) gene expression by increasing PPARγ activity and stimulating de novo synthesis of glutathione. As a result, downstream elements of RAGE-activated pathways are inhibited, which prevents oxidative stress, inflammation and hepatic stellate cell activation. This report suggests that curcumin may have potential as an anti-fibrotic agent in type 2 diabetes and opens the door to the evaluation of curcumin therapeutic effects in liver conditions of different aetiology and in other disorders linked to the impairment of PPARγ activity, such as obesity and atherosclerosis. LINKED ARTICLE This article is a commentary on Lin et al., pp. 2212–2227 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.01910.x PMID:22452372

  13. Curcumin ameliorates hepatic fibrosis in type 2 diabetes mellitus - insights into its mechanisms of action.

    Science.gov (United States)

    Stefanska, B

    2012-08-01

    A wide variety of beneficial effects have been attributed to curcumin, a major polyphenol from the golden spice Curcuma longa known as turmeric, including amelioration of severe complications of type 2 diabetes such as hepatic fibrosis, retinopathy, neuropathy and nephropathy. In the present issue of BJP, Lin and colleagues reveal new mechanisms by which curcumin inhibits the activation of hepatic stellate cells in vitro, a hallmark of non-alcoholic steatohepatitis and hepatic fibrogenesis associated with type 2 diabetes mellitus. They demonstrated that curcumin suppresses the advanced glycation end-products (AGEs)-mediated induction of the receptor for AGEs (RAGE) gene expression by increasing PPARγ activity and stimulating de novo synthesis of glutathione. As a result, downstream elements of RAGE-activated pathways are inhibited, which prevents oxidative stress, inflammation and hepatic stellate cell activation. This report suggests that curcumin may have potential as an anti-fibrotic agent in type 2 diabetes and opens the door to the evaluation of curcumin therapeutic effects in liver conditions of different aetiology and in other disorders linked to the impairment of PPARγ activity, such as obesity and atherosclerosis. This article is a commentary on Lin et al., pp. 2212-2227 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.01910.x. © 2012 The Author. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  14. 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. © 2016 World Obesity.

  15. Pomegranate juice prevents development of non-alcoholic fatty liver disease in rats by attenuating oxidative stress and inflammation.

    Science.gov (United States)

    Noori, Maryam; Jafari, Bahar; Hekmatdoost, Azita

    2017-06-01

    The effects of pomegranate juice (PJ) on the risk factors of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) have been reported previously; however, the effects on NAFLD and its prevention have not yet been clarified. The present study aimed to evaluate the effects of PJ consumption with respect to the prevention of NAFLD/NASH development. Sprague-Dawley rats were fed either a high-fat, high sugar diet (model group); a high-fat, high sugar diet plus PJ (model+PJ); or a chow diet ad libitum for 7 weeks. Serum levels of fasting glucose, triglyceride, cholesterol, liver enzymes, insulin and hepatic tumor necrosis factor-α and tissue growth factor-β gene expression were determined. Hepatic histology was examined by hemotoxylin and eosin staining. The model+PJ group had significantly lower hepatic steatosis, ballooning, lobular inflammation and portal inflammation (P hepatic pro-inflammatory and pro-fibrotic gene expression (P < 0.001); and lower plasma levels of alanine aminotransferase (P = 0.026), aspartate aminotransferase (P = 0.041), insulin (P < 0.001), triglycerides (P = 0.041) and glucose (P = 0.009) compared to the model group; however, weight gain, food intake and plasma high-density lipoprotein levels were not significantly different between these two groups. The data obtained in the present study indicate that the regular consumption of PJ can prevent NAFLD even in the presence of the other risk factors such as obesity, hypercholesterolemia, and high energy, fat and sugar intakes. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

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

    Directory of Open Access Journals (Sweden)

    Christine Bernsmeier

    Full Text Available 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.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.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.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.

  17. 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.

  18. Taking care: Creating a non-alcoholic cocktail for Generation X

    African Journals Online (AJOL)

    A non-alcoholic cocktail is a mixed drink containing no alcohol. The owner of De Pleats thinks that, ... created on an economic, social and environmental dimension,. Taking care: Creating a non-alcoholic cocktail for .... be used in marketing non-alcoholic cocktails, because they are. Table 1: The basic characteristics of the ...

  19. 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.

  20. The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice.

    Science.gov (United States)

    Ideta, Takayasu; Shirakami, Yohei; Miyazaki, Tsuneyuki; Kochi, Takahiro; Sakai, Hiroyasu; Moriwaki, Hisataka; Shimizu, Masahito

    2015-12-08

    Non-alcoholic fatty liver disease (NAFLD), which is strongly associated with metabolic syndrome, is increasingly a major cause of hepatic disorder. Dipeptidyl peptidase (DPP)-4 inhibitors, anti-diabetic agents, are expected to be effective for the treatment of NAFLD. In the present study, we established a novel NAFLD model mouse using monosodium glutamate (MSG) and a high-fat diet (HFD) and investigated the effects of a DPP-4 inhibitor, teneligliptin, on the progression of NAFLD. Male MSG/HFD-treated mice were divided into two groups, one of which received teneligliptin in drinking water. Administration of MSG and HFD caused mice to develop severe fatty changes in the liver, but teneligliptin treatment improved hepatic steatosis and inflammation, as evaluated by the NAFLD activity score. Serum alanine aminotransferase and intrahepatic triglyceride levels were significantly decreased in teneligliptin-treated mice (p Hepatic mRNA levels of the genes involved in de novo lipogenesis were significantly downregulated by teneligliptin (p hepatic expression levels of phosphorylated AMP-activated protein kinase (AMPK) protein. These findings suggest that teneligliptin attenuates lipogenesis in the liver by activating AMPK and downregulating the expression of genes involved in lipogenesis. DPP-4 inhibitors may be effective for the treatment of NAFLD and may be able to prevent its progression to non-alcoholic steatohepatitis.

  1. Altered fatty acid metabolism-related gene expression in liver from morbidly obese women with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Auguet, Teresa; Berlanga, Alba; Guiu-Jurado, Esther; Martinez, Salomé; Porras, José Antonio; Aragonès, Gemma; Sabench, Fátima; Hernandez, Mercé; Aguilar, Carmen; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2014-12-02

    Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis.

  2. Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Teresa Auguet

    2014-12-01

    Full Text Available Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD. We aimed to evaluate gene expression of different fatty acid (FA metabolism-related genes in morbidly obese (MO women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS, FA uptake and transport (PPARγ, CD36, FABP4, FA oxidation (PPARα, and inflammation (IL6, TNFα, CRP, PPARδ were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13, simple steatosis (SS, n = 47 and non-alcoholic steatohepatitis (NASH, n = 67. Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively. Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively. Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis.

  3. The potential role of prebiotic fibre for treatment and management of non-alcoholic fatty liver disease and associated obesity and insulin resistance.

    Science.gov (United States)

    Parnell, Jill A; Raman, Maitreyi; Rioux, Kevin P; Reimer, Raylene A

    2012-05-01

    Non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH) represent a spectrum of diseases involving hepatic fat accumulation and histological features essentially identical to alcoholic liver disease; however, they occur in the absence of excessive alcohol intake. They typically arise in conjunction with one or more features of the metabolic syndrome. Lifestyle mediated weight loss remains the primary mode of therapy for NAFLD and NASH, but this is often ineffective and adjunctive medical and surgical treatments are presently lacking. Prebiotic fibres are a group of non-digestible carbohydrates that modulate the human microbiota in a manner that is advantageous to host health. Rodent studies suggest that dietary supplementation with prebiotic fibres positively impacts NAFLD by modifying the gut microbiota, reducing body fat, and improving glucoregulation. Future research should focus on placebo-controlled, human, clinical trials using histological endpoints to address the effects of prebiotics on NAFLD and NASH. The aim of this review is to summarize current knowledge about prebiotics as an emerging therapeutic target for NAFLD. © 2011 John Wiley & Sons A/S.

  4. 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.

  5. Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Auguet, Teresa; Berlanga, Alba; Guiu-Jurado, Esther; Martinez, Salomé; Porras, José Antonio; Aragonès, Gemma; Sabench, Fátima; Hernandez, Mercé; Aguilar, Carmen; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2014-01-01

    Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis. PMID:25474087

  6. NON-ALCOHOLIC FATTY LIVER DISEASE IN CHILDREN

    Directory of Open Access Journals (Sweden)

    L.V. Chistova

    2010-01-01

    Full Text Available Metabolic syndrome that represents a totality of interrelated carbohydrate metabolism and lipid disorders, as well as a mechanism regulating arterial tension and endothelium function is one of the critical issues in pediatrics. In recent years, children with metabolic syndrome are increasingly diagnosed with liver injuries symptoms that are associated with a fatty transformation of the liver [1–3]. In this case, non-alcoholic fatty liver disease (NAFLD, a liver manifestation of metabolic syndrome is diagnosed. The diagnosis is confirmed in the absence of alcohol abuse in the past medical history, virus and autoimmune liver disease markers, elimination of toxic and drug influence, as wells as disorders of copper and iron exchange in the patient’s system. One of the key risk factors for developing NAFLD in children is overeating and reduced physical activities. It was believed in the past that NAFLD is relatively benign, however, there is evidence in current literature that this is a pathological condition that may develop and result in extreme fibrotic alterations in the liver parenchymatous tissue all the way to cirrhosis and hepatocellular carcinoma [4]. Early-stage identification and timely launch of therapy for NAFLD in children represents one of the most important objectives in modern healthcare. Key words: metabolic syndrome, non-alcoholic fatty liver disease, children, steatohepatosis. (Pediatric Pharmacology. – 2010; 7(6:68-72

  7. Plasmatic higher levels of homocysteine in non-alcoholic fatty liver disease (NAFLD).

    Science.gov (United States)

    de Carvalho, Sylene Coutinho Rampche; Muniz, Maria Tereza Cartaxo; Siqueira, Maria Deozete Vieira; Siqueira, Erika Rabelo Forte; Gomes, Adriana Vieira; Silva, Karina Alves; Bezerra, Laís Carvalho Luma; D'Almeida, Vânia; de Oliveira, Claudia Pinto Marques Souza; Pereira, Leila Maria M Beltrão

    2013-04-02

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic mutations in the folate route may only mildly impair Hcy metabolism. The aim of this study was to investigate the relation between liver steatosis with plasma homocysteine level and MTHFR C677T and A1298C polymorphisms in Brazilian patients with NAFLD. Thirty-five patients diagnosed with NAFLD by liver biopsy and forty-five healthy controls neither age nor sex matched were genotyped for C677T and A1298C MTHFR polymorphisms using PCR-RFLP and PCR-ASA, respectively, and Hcy was determined by HPLC. All patients were negative for markers of Wilson's, hemochromatosis and autoimmune diseases. Their daily alcohol intake was less than 100 g/week. A set of metabolic and serum lipid markers were also measured at the time of liver biopsies. The plasma Hcy level was higher in NAFLD patients compared to the control group (p = 0.0341). No statistical difference for genotypes 677C/T (p = 0.110) and 1298A/C (p = 0.343) in patients with NAFLD and control subjects was observed. The genotypes distribution was in Hardy-Weinberg equilibrium (677C/T p = 0.694 and 1298 A/C p = 0.188). The group of patients and controls showed a statistically significant difference (p MTHFR C677T and A1298C polymorphisms did not differ significantly between groups, despite the 677TT homozygous frequency was higher in patients (17.14%) than in controls (677TT = 4.44%) (p > 0.05). The suggested genetic susceptibility to the MTHFR C677T and A1298C should be confirmed in large population based studies.

  8. Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage.

    Science.gov (United States)

    Neuman, Manuela G; French, Samuel W; Zakhari, Samir; Malnick, Stephen; Seitz, Helmut K; Cohen, Lawrence B; Salaspuro, Mikko; Voinea-Griffin, Andreea; Barasch, Andrei; Kirpich, Irina A; Thomes, Paul G; Schrum, Laura W; Donohue, Terrence M; Kharbanda, Kusum K; Cruz, Marcus; Opris, Mihai

    2017-02-01

    This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases. We aimed to (1) describe the immuno-pathology of ALD, (2) examine the role of genetics in the development of alcoholic hepatitis (ASH) and NAFLD, (3) propose diagnostic markers of ASH and non-alcoholic steatohepatitis (NASH), (4) examine age and ethnic differences as well as analyze the validity of some models, (5) develop common research tools and biomarkers to study alcohol-induced effects, 6) examine the role of alcohol in oral health and colon and gastrointestinal cancer and (7) focus on factors that aggravate the severity of organ-damage. The present review includes pre-clinical, translational and clinical research that characterizes ALD and NAFLD. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD with simple fatty infiltrations and chronic alcoholic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes and cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus were discussed

  9. PATHOGENESIS OF HEPATOCELLULAR CARCINOMA DEVELOPMENT IN NON ALCOHOLIC FATTY LIVER DISEASE.

    Science.gov (United States)

    Shetty, Kirti; Chen, Jian; Shin, Ji-Hyun; Jogunoori, Wilma; Mishra, Lopa

    2015-06-01

    Non-alcoholic fatty liver disease (NAFLD) is being recognized as an increasingly important contributor to the burden of hepatocellular carcinoma (HCC) worldwide. It is often accompanied by obesity and diabetes mellitus and is believed to be the hepatic representation of the metabolic syndrome. HCC development in NAFLD is multifactorial and complex. It is dependent on not only the well-described mechanisms noted in chronic liver injury, but also on the molecular derangements associated with obesity and dysmetabolism. These include adipocyte remodeling, adipokine secretion, lipotoxicity and insulin resistance. Recent advances focus on the importance of the gut-liver axis in accelerating the process of oncogenesis in NAFLD. The farnesoid X nuclear receptor (FXR) has been demonstrated to have important metabolic effects and its pharmacological activation by obeticholic acid has been recently reported to produce histological improvement in NASH. It is hoped that delineating the mechanisms of hepatic fibrosis and oncogenesis in NASH will lead to enhanced strategies for cancer prevention, surveillance and therapy in this population.

  10. Exercise and spirulina control non-alcoholic hepatic steatosis and lipid profile in diabetic Wistar rats

    Science.gov (United States)

    2011-01-01

    Background Diabetes mellitus is associated with metabolic dysfunctions, including alterations in circulating lipid levels and fat tissue accumulation, which causes, among other pathologies, non-alcoholic fatty liver disease (NAFLD). Aim of the study The objective of this study was to analyse the effects of physical exercise and spirulina intake on the control of NAFLD in diabetic Wistar rats. Methods Diabetes was induced in the animals through intravenous administration of alloxan. The rats were divided into four groups: Diabetic Control (DC) - diabetic rats fed with a control diet and no physical exercise; Diabetic Spirulina (DS) - diabetic rats fed with a diet that included spirulina; Diabetic Spirulina and Exercise (DSE) - diabetic rats fed with a diet that included Spirulina and that exercised; and Diabetic Exercise (DE) - diabetic rats fed with a control diet and that exercised. Results The groups DS, DSE, and DE presented lower plasma concentrations of LDL cholesterol than DC, as well as lower levels of total liver lipids in groups DS, DSE, and DE in comparison to DC. Conclusion Thus, spirulina appears to be effective in reducing total circulating levels of LDL-cholesterol and hepatic lipids, alone or in conjunction with physical exercise in diabetic rats. PMID:21569626

  11. Epidemiological modifiers of non-alcoholic fatty liver disease: focus on high-risk groups

    OpenAIRE

    Lonardo, A.; Bellentani, S.; Argo, C.K.; Ballestri, S.; Byrne, Christopher D.; Caldwell, S.H.; Cortez-Pinto, H.; Grieco, A.; Machado, M.V.; Miele, L.; Targher, G.

    2015-01-01

    An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identification of individuals at high risk of developing chronic liver disease and extra-hepatic complications, thus contributing to more effective case finding of non-alcoholic fatty liver disease among selected groups.We aimed to illustrate the epidemiology of non-alcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to r...

  12. Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions.

    Science.gov (United States)

    Adolph, Timon E; Grander, Christoph; Grabherr, Felix; Tilg, Herbert

    2017-07-29

    Accumulating evidence links obesity with low-grade inflammation which may originate from adipose tissue that secretes a plethora of pro- and anti-inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as crucial signals in many obesity-related pathologies including non-alcoholic fatty liver disease (NAFLD). Whereas adiponectin deficiency might be critically involved in the pro-inflammatory state associated with obesity and related disorders, overproduction of leptin, a rather pro-inflammatory mediator, is considered of equal relevance. An imbalanced adipokine profile in obesity consecutively contributes to metabolic inflammation in NAFLD, which is associated with a substantial risk for developing hepatocellular carcinoma (HCC) also in the non-cirrhotic stage of disease. Both adiponectin and leptin have been related to liver tumorigenesis especially in preclinical models. This review covers recent advances in our understanding of some adipokines in NAFLD and associated HCC.

  13. Non-alcoholic fatty liver disease: A poorly known pandemic.

    Science.gov (United States)

    Augustin, Salvador; Graupera, Isabel; Caballeria, Juan

    2017-12-20

    Non-alcoholic fatty liver disease (NAFLD) consists of an excessive depositing of fat in the liver, which can end up by causing inflammation, fibrosis and also cirrhosis with the corresponding complications including liver cancer. NAFLD has become the most common liver disease worldwide. The incidence has increased in parallel with the obesity, diabetes and metabolic syndrome epidemic, thus resulting in becoming one of the main indications for liver transplant. The diagnosis has principally been through histology but with the development of non-invasive methods, these have helped in simplifying the management of these patients in clinical practice. The only therapeutic strategies currently available are focused on weight loss (lifestyle changes or bariatric surgery). There is still no approved pharmacological option for the treatment of NAFLD, however there are a number of molecular studies in advanced stages of development. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  14. Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions

    Directory of Open Access Journals (Sweden)

    Timon E. Adolph

    2017-07-01

    Full Text Available Accumulating evidence links obesity with low-grade inflammation which may originate from adipose tissue that secretes a plethora of pro- and anti-inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as crucial signals in many obesity-related pathologies including non-alcoholic fatty liver disease (NAFLD. Whereas adiponectin deficiency might be critically involved in the pro-inflammatory state associated with obesity and related disorders, overproduction of leptin, a rather pro-inflammatory mediator, is considered of equal relevance. An imbalanced adipokine profile in obesity consecutively contributes to metabolic inflammation in NAFLD, which is associated with a substantial risk for developing hepatocellular carcinoma (HCC also in the non-cirrhotic stage of disease. Both adiponectin and leptin have been related to liver tumorigenesis especially in preclinical models. This review covers recent advances in our understanding of some adipokines in NAFLD and associated HCC.

  15. Non-alcoholic Fatty Liver Disease: East Versus West

    Science.gov (United States)

    Agrawal, Swastik; Duseja, Ajay K

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease worldwide with prevalence ranging from 10% to 30% in various countries. It has become an important cause of unexplained rise in transaminases, cryptogenic cirrhosis, and cryptogenic hepatocellular carcinoma. Pathogenesis is related to obesity, insulin resistance, oxidative stress, lipotoxicity, and resultant inflammation in the liver progressing to fibrosis. Pharmacological treatment in patients with NAFLD is still evolving and the treatment of these patients rests upon lifestyle modification with diet and exercise being the cornerstones of therapy. While there are many similarities between patients with NAFLD from Asia and the West, there are certain features which make the patients with NAFLD from Asia stand apart. This review highlights the data on NAFLD from Asia comparing it with the data from the West. PMID:25755421

  16. Hypogonadism and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Mintziori, Gesthimani; Poulakos, Pavlos; Tsametis, Christos; Goulis, Dimitrios G

    2017-06-01

    Non-alcoholic fatty liver disease (NAFLD) is more common in men than in women. Thus, it has been suggested that sex steroids do have a role in the development of NAFLD. The aim of the current paper is to illustrate the association between NAFLD and hypogonadism, by reviewing data derived from both human and animal studies. The prevalence of NAFLD is high in men with hypogonadism, including those with idiopathic hypogonadotropic hypogonadism (IHH), as well as in women in post-menopause, those under estrogen receptor antagonist treatment or women with Turner syndrome. Estrogens seem to play a pivotal role in hepatic lipid homeostasis, as demonstrated in animal models with diminished ovarian estrogens (i.e., ovariectomized mice) and low serum testosterone (T) concentration is independently associated with NAFLD. The elucidation of the exact role of sex steroids in NAFLD pathogenesis would create a unique opportunity to develop novel therapies to tackle NAFLD disease.

  17. Glycosyltransferases and non-alcoholic fatty liver disease

    Science.gov (United States)

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

    2016-01-01

    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. PMID:26937136

  18. Production and storage stability of non alcoholic banana beverage powder.

    Science.gov (United States)

    Mugula, J K; Lyimo, M H; Kessy, F L

    1994-02-01

    Powder for an instant, non-alcoholic beverage formulation was manufactured by sundrying and ovendrying of a popular dessert ('silk') banana variety. The reconstituted beverage was organoleptically acceptable. The effect of traditional sundrying on mats and ovendrying methods on product quality was investigated. Sundrying resulted in losses of Vitamin A, C and total sugar contents by 74, 91 and 63%, while ovendrying losses were 73, 90 and 62%, respectively. Nutrient losses during storage for three months in transparent polythene bags reached 93, 93 and 70% in sundried samples and 84, 99 and 55% in ovendried samples, respectively. The moisture content of sundried and ovendried samples increased by 12 and 17%, respectively, during storage. The increase in microbial load in this period was higher in sundried samples.

  19. Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.

    Science.gov (United States)

    Alonso, Cristina; Fernández-Ramos, David; Varela-Rey, Marta; Martínez-Arranz, Ibon; Navasa, Nicolás; Van Liempd, Sebastiaan M; Lavín Trueba, José L; Mayo, Rebeca; Ilisso, Concetta P; de Juan, Virginia G; Iruarrizaga-Lejarreta, Marta; delaCruz-Villar, Laura; Mincholé, Itziar; Robinson, Aaron; Crespo, Javier; Martín-Duce, Antonio; Romero-Gómez, Manuel; Sann, Holger; Platon, Julian; Van Eyk, Jennifer; Aspichueta, Patricia; Noureddin, Mazen; Falcón-Pérez, Juan M; Anguita, Juan; Aransay, Ana M; Martínez-Chantar, María Luz; Lu, Shelly C; Mato, José M

    2017-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a consequence of defects in diverse metabolic pathways that involve hepatic accumulation of triglycerides. Features of these aberrations might determine whether NAFLD progresses to nonalcoholic steatohepatitis (NASH). We investigated whether the diverse defects observed in patients with NAFLD are caused by different NAFLD subtypes with specific serum metabolomic profiles, and whether these can distinguish patients with NASH from patients with simple steatosis. We collected liver and serum from methionine adenosyltransferase 1a knockout (MAT1A-KO) mice, which have chronically low levels of hepatic S-adenosylmethionine (SAMe) and spontaneously develop steatohepatitis, as well as C57Bl/6 mice (controls); the metabolomes of all samples were determined. We also analyzed serum metabolomes of 535 patients with biopsy-proven NAFLD (353 with simple steatosis and 182 with NASH) and compared them with serum metabolomes of mice. MAT1A-KO mice were also given SAMe (30 mg/kg/day for 8 weeks); liver samples were collected and analyzed histologically for steatohepatitis. Livers of MAT1A-KO mice were characterized by high levels of triglycerides, diglycerides, fatty acids, ceramides, and oxidized fatty acids, as well as low levels of SAMe and downstream metabolites. There was a correlation between liver and serum metabolomes. We identified a serum metabolomic signature associated with MAT1A-KO mice that also was present in 49% of the patients; based on this signature, we identified 2 NAFLD subtypes. We identified specific panels of markers that could distinguish patients with NASH from patients with simple steatosis for each subtype of NAFLD. Administration of SAMe reduced features of steatohepatitis in MAT1A-KO mice. In an analysis of serum metabolomes of patients with NAFLD and MAT1A-KO mice with steatohepatitis, we identified 2 major subtypes of NAFLD and markers that differentiate steatosis from NASH in each subtype. These might be

  20. Low hepatic copper content and PNPLA3 polymorphism in non-alcoholic fatty liver disease in patients without metabolic syndrome.

    Science.gov (United States)

    Stättermayer, Albert Friedrich; Traussnigg, Stefan; Aigner, Elmar; Kienbacher, Christian; Huber-Schönauer, Ursula; Steindl-Munda, Petra; Stadlmayr, Andreas; Wrba, Friedrich; Trauner, Michael; Datz, Christian; Ferenci, Peter

    2017-01-01

    The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is multifactorial including metabolic, genetic (e.g. PNPLA3 [patatin-like phospholipase domain-containing 3 gene]), viral factors and drugs. Besides, there is evidence for a role of copper deficiency. Aim of the study was to evaluate the role of hepatic copper content, PNPLA3 in NAFLD patients with and without metabolic syndrome (MetS). One-hundred seventy-four NAFLD patients, who underwent liver biopsy for diagnostic work-up, were studied. Diagnosis of MetS was based on the WHO Clinical Criteria. Steatosis was semiquantified as percentage of fat containing hepatocytes and was graded according to Brunt. Histological features of non-alcoholic steatohepatitis (NASH) were assessed using the Bedossa classification. Hepatic copper content (in μg/g dry weight) was measured by flame atomic absorption spectroscopy. SNP rs738409 in PNPLA3 was investigated by RT-PCR. Mean hepatic copper content was 22.3 (19.6-25.1) μg/g. The mean percentage of histologically lipid containing hepatocytes was 42.2% (38.3-46.0) and correlated inversely with hepatic copper content (ρ=-0.358, Psteatosis (≥33%) both in patients with (OR: 2.405 [CI95%: 1.220-4.744], P=0.011) and without MetS (OR: 2.481 [CI95%: 1.172-5.250], P=0.018), but was only associated with NASH (OR: 2.002 [CI95%: 1.062-3.772], P=0.032) and liver fibrosis (OR: 2.646 [CI95%: 1.299-5.389], P=0.007) in patients without MetS. Hepatic copper content and PNPLA3 mutations are associated with disease activity in NAFLD patients without MetS. Presence of MetS appears to mask the effects of hepatic copper and PNPLA3. Copyright © 2016 Elsevier GmbH. All rights reserved.

  1. Non-alcoholic fatty liver disease - histological scoring systems: a large cohort single-center, evaluation study.

    Science.gov (United States)

    Rastogi, Archana; Shasthry, Saggere Muralikrishna; Agarwal, Ayushi; Bihari, Chhagan; Jain, Priyanka; Jindal, Ankur; Sarin, Shiv

    2017-11-01

    Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause of chronic liver disease. Till date, liver biopsy remains the gold standard for identification and quantification of the wide histological spectra of NAFLD. Histological scorings are very useful and widely applied for the diagnosis and management in clinical trials and follow-up studies of non-alcoholic steatohepatitis (NASH). However, in view of scarce published literature, there is a need to evaluate them in large cohort of NAFLD. This study was aimed to evaluate the two histological scoring systems (NAS-CRN, SAF) in the diagnosis of NAFLD and to assess the role of histological characteristics as injury markers in NAFLD. Retrospective histological study of liver biopsies of 1000 patients diagnosed as NAFLD, between 2010 and 2016, was conducted. Histopathologic evaluation and semiquantiative scoring based on NAS-CRN and SAF algorithm and their correlation with serum aminotransferase and fibrosis were performed. Liver biopsies were classified according to the NAS-CRN scoring, as NAS <3 (not NASH) in 72 (7.2%), NAS 3-4 (borderline NASH) in 310 (31%), and NAS ≥5 (definite NASH) in 618 (61.8%), and SAF classified 117 (11.7%) not NASH and 883 (88.3%) definite NASH. There was excellent concordance for definite NASH and not NASH; however, 88.06% of borderline NASH was classified as NASH by SAF. 76.39% by NAS and 78.63% by SAF algorithm who were diagnosed as not NASH showed the presence of fibrosis; however, higher stages of fibrosis were significantly more prevalent in definite NASH, excluding burnt-out cirrhosis. Serum ALT was significantly associated with increasing stages of fibrosis (p < 0.001) and the three categories (not NASH, borderline NASH, and definite NASH) when classified as with/without fibrosis (p < 0.001). Steatosis of higher grades, more ballooned cells, and more foci of Lobular Inflammation were found in significantly higher proportion of patients with NASH (p < 0

  2. Non-alcoholic fatty liver disease and associated factors among type ...

    African Journals Online (AJOL)

    Background: Non-alcoholic Fatty Liver Disease (NAFLD) among type 2 diabetic patients is completely ignored in developing regions like Africa paving the way for public health and economic burden in the region. Therefore, the main objective of this research was to evaluate non-alcoholic fatty liver disease and associated

  3. Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups.

    Science.gov (United States)

    Lonardo, Amedeo; Bellentani, Stefano; Argo, Curtis K; Ballestri, Stefano; Byrne, Christopher D; Caldwell, Stephen H; Cortez-Pinto, Helena; Grieco, Antonio; Machado, Mariana V; Miele, Luca; Targher, Giovanni

    2015-12-01

    An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identification of individuals at high risk of developing chronic liver disease and extra-hepatic complications, thus contributing to more effective case finding of non-alcoholic fatty liver disease among selected groups. We aimed to illustrate the epidemiology of non-alcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published until May 2015 using relevant and pertinent keywords "nonalcoholic fatty liver disease" and "diabetes", "obesity", "hyperlipidaemia", "familial heterozygous hypobetalipoproteinaemia", "hypertension", "metabolic syndrome", "ethnicity", "family history" or "genetic polymorphisms". We found that age, sex and ethnicity are major physiological modifiers of the risk of non-alcoholic fatty liver disease, along with belonging to "non-alcoholic fatty liver disease families" and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolaemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of non-alcoholic fatty liver disease risk. Compared with these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of non-alcoholic fatty liver disease. A better understanding of the epidemiology of non-alcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  4. Non-alcoholic fatty liver disease and colorectal cancer.

    Science.gov (United States)

    Mikolasevic, I; Orlic, L; Stimac, D; Hrstic, I; Jakopcic, I; Milic, S

    2017-03-01

    As a significant cause of cancer death worldwide, colorectal cancer (CRC) is still one of the most common cancers in the world. The most efficient strategies to reduce CRC incidence include identifying risk factors for CRC and performing a preventive colonoscopy in high-risk populations. Some well-established risk factors for CRC development include hereditary syndromes and inflammatory bowel disease. Of note, in recent years, attention has been given to new evidence indicating that more than 75%-95% of CRC occurs in individuals with little or no genetic risk. For these individuals, the risk for CRC is associated with their lifestyle and dietary factors, including central obesity, overweight and physical inactivity. Recently, evidence demonstrated a connection between non-alcoholic fatty liver disease (NAFLD) and CRC. Insulin resistance and metabolic syndrome (MetS) are common risks that NAFLD and colorectal neoplasms share. The incidence of NAFLD is increasing in parallel with an increasing prevalence of MetS and obesity. Consequently, the question arises: will the incidence of CRC increase together with this dramatic increase in obesity, MetS and ultimately NAFLD prevalence? Recent studies of adenomatous polyps, CRC and NAFLD are discussed in this manuscript. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. Iron and non-alcoholic fatty liver disease.

    Science.gov (United States)

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

    2016-09-28

    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.

  6. Non-alcoholic fatty liver disease: An expanded review

    Science.gov (United States)

    Benedict, Mark; Zhang, Xuchen

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing epidemic, not only in the United States, but worldwide in part due to obesity and insulin resistance leading to liver accumulation of triglycerides and free fatty acids. Numerous risk factors for the development of NAFLD have been espoused with most having some form of metabolic derangement or insulin resistance at the core of its pathophysiology. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality, and NAFLD is rapidly becoming the leading indication for liver transplantation. Liver biopsy remains the gold standard for definitive diagnosis, but the development of noninvasive advanced imaging, biochemical and genetic tests will no doubt provide future clinicians with a great deal of information and opportunity for enhanced understanding of the pathogenesis and targeted treatment. As it currently stands several medications/supplements are being used in the treatment of NAFLD; however, none seem to be the “magic bullet” in curtailing this growing problem yet. In this review we summarized the current knowledge of NAFLD epidemiology, risk factors, diagnosis, pathogenesis, pathologic changes, natural history, and treatment in order to aid in further understanding this disease and better managing NAFLD patients. PMID:28652891

  7. Adrenal disorders and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Papanastasiou, Labrini; Fountoulakis, Stelios; Vatalas, Ioannis-Anastasios

    2017-06-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the developed world and its pathogenesis is complex and multifactorial. It is considered the hepatic manifestation of the metabolic syndrome and is the leading cause of hepatic cirrhosis. This review aims to present current knowledge on the involvement of the adrenal glands in the development of NAFLD. Clinical and animal studies have shown that excess glucocorticoids (GC) have been implicated in the pathogenesis of NAFLD. Patients with NAFLD seem to have a subtle chronic activation of the hypothalamic pituitary adrenal axis leading to a state of subclinical hypercortisolism. Regulators of GC such as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that regenerates cortisol from inactive cortisone, and 5α/5β-reductases, enzymes that increase cortisol clearance, are implicated in the development of NAFLD by amplifying local GC action. Adrenal androgen (dehydroepiandrosterone) abnormalities and increased aldosterone levels may also have a role in the development of NAFLD whereas the contribution of adrenergic signaling in NAFLD pathogenesis remains unclear.

  8. Non-alcoholic fatty liver disease: An expanded review.

    Science.gov (United States)

    Benedict, Mark; Zhang, Xuchen

    2017-06-08

    Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing epidemic, not only in the United States, but worldwide in part due to obesity and insulin resistance leading to liver accumulation of triglycerides and free fatty acids. Numerous risk factors for the development of NAFLD have been espoused with most having some form of metabolic derangement or insulin resistance at the core of its pathophysiology. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality, and NAFLD is rapidly becoming the leading indication for liver transplantation. Liver biopsy remains the gold standard for definitive diagnosis, but the development of noninvasive advanced imaging, biochemical and genetic tests will no doubt provide future clinicians with a great deal of information and opportunity for enhanced understanding of the pathogenesis and targeted treatment. As it currently stands several medications/supplements are being used in the treatment of NAFLD; however, none seem to be the "magic bullet" in curtailing this growing problem yet. In this review we summarized the current knowledge of NAFLD epidemiology, risk factors, diagnosis, pathogenesis, pathologic changes, natural history, and treatment in order to aid in further understanding this disease and better managing NAFLD patients.

  9. Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Ter Horst, Kasper W; Serlie, Mireille J

    2017-09-06

    Increased fructose consumption has been suggested to contribute to non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and insulin resistance, but a causal role of fructose in these metabolic diseases remains debated. Mechanistically, hepatic fructose metabolism yields precursors that can be used for gluconeogenesis and de novo lipogenesis (DNL). Fructose-derived precursors also act as nutritional regulators of the transcription factors, including ChREBP and SREBP1c, that regulate the expression of hepatic gluconeogenesis and DNL genes. In support of these mechanisms, fructose intake increases hepatic gluconeogenesis and DNL and raises plasma glucose and triglyceride levels in humans. However, epidemiological and fructose-intervention studies have had inconclusive results with respect to liver fat, and there is currently no good human evidence that fructose, when consumed in isocaloric amounts, causes more liver fat accumulation than other energy-dense nutrients. In this review, we aim to provide an overview of the seemingly contradicting literature on fructose and NAFLD. We outline fructose physiology, the mechanisms that link fructose to NAFLD, and the available evidence from human studies. From this framework, we conclude that the cellular mechanisms underlying hepatic fructose metabolism will likely reveal novel targets for the treatment of NAFLD, dyslipidemia, and hepatic insulin resistance. Finally, fructose-containing sugars are a major source of excess calories, suggesting that a reduction of their intake has potential for the prevention of NAFLD and other obesity-related diseases.

  10. Reduced hepatic aquaporin-9 and glycerol permeability are related to insulin resistance in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Rodríguez, A; Gena, P; Méndez-Giménez, L; Rosito, A; Valentí, V; Rotellar, F; Sola, I; Moncada, R; Silva, C; Svelto, M; Salvador, J; Calamita, G; Frühbeck, G

    2014-09-01

    Glycerol represents an important metabolite for the control of lipid accumulation and hepatic gluconeogenesis. We investigated whether hepatic expression and functionality of aquaporin-9 (AQP9), a channel mediating glycerol influx into hepatocytes, is impaired in non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in the context of insulin resistance. Liver biopsies were obtained from 66 morbid obese patients undergoing bariatric surgery (66% women, mean body mass index (BMI) 46.1±1.0 kg m(-2)) with available liver echography and pathology analysis of the biopsies in this cross-sectional study. Subjects were classified according to normoglycemia (NG), impaired glucose tolerance (IGT) or type 2 diabetes (T2D). Hepatic expression of AQP9 was analyzed by real-time PCR, western blotting and immunohistochemistry, while glycerol permeability (P(gly)) was measured by stopped-flow light scattering. AQP9 was the most abundantly (PAQP3>AQP7>AQP10). Obese patients with T2D showed increased plasma glycerol as well as lower P(gly) and hepatic AQP9 expression. The prevalence of NAFLD and NASH in T2D patients was 100 and 65%, respectively. Interestingly, AQP9 expression was decreased in patients with NAFLD and NASH as compared with those without hepatosteatosis, in direct relation to the degree of steatosis and lobular inflammation, being further reduced in insulin-resistant individuals. The association of AQP9 with insulin sensitivity was independent of BMI and age. Consistent with these data, fasting insulin and C-reactive protein contributed independently to 33.1% of the hepatic AQP9 mRNA expression variance after controlling for the effects of age and BMI. AQP9 downregulation together with the subsequent reduction in hepatic glycerol permeability in insulin-resistant states emerges as a compensatory mechanism whereby the liver counteracts further triacylglycerol accumulation within its parenchyma as well as reduces hepatic gluconeogenesis in patients

  11. The impact of cereal grain consumption on the development and severity of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Georgoulis, Michael; Kontogianni, Meropi D; Tileli, Nafsika; Margariti, Aikaterini; Fragopoulou, Elisabeth; Tiniakos, Dina; Zafiropoulou, Rodessa; Papatheodoridis, George

    2014-12-01

    There is evidence that dietary habits contribute to the presence and severity of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to explore any associations between consumption of grains and the development and severity of NAFLD. Seventy-three consecutive NAFLD patients were enrolled. Additionally, 58 controls matched for age, sex and body mass index with 58 patients were also included. Consumption of grains was estimated through a semi-quantitative food frequency questionnaire. Medical history, anthropometric indices, body composition analysis, physical activity data, biochemical and inflammatory markers were available for all the participants. Liver stiffness measurement by transient elastography was performed in 58 and liver biopsy in 34 patients. In patients, consumption of whole grains was associated with lower abdominal fat level (β = -0.24, p = 0.02) and lower levels of insulin resistance index (β = -0.28, p = 0.009), while it also correlated inversely with interleukin-6 levels (ρ = -0.23, p = 0.05). Consumption of whole grains was associated with lower likelihood of having histological steatohepatitis (OR 0.97, 95% CI 0.94-1.000), after adjusting for sex and energy intake, but the association became weaker after further adjusting for abdominal fat or interleukin-6 levels. In the case-control analysis, consumption of refined grains was associated with higher odds of having NAFLD (OR 1.021, 95% CI 1.001-1.042), after adjusting for age, sex, energy intake, abdominal fat level, HOMA-IR, LDL, adiponectin and TNF-α. Although refined grain consumption increased the likelihood of having NAFLD, whole-grain consumption favorably affected clinical characteristics of patients with NAFLD and tended to be associated with less severe disease.

  12. Genome-based nutrition: An intervention strategy for the prevention and treatment of obesity and nonalcoholic steatohepatitis

    Science.gov (United States)

    Roman, Sonia; Ojeda-Granados, Claudia; Ramos-Lopez, Omar; Panduro, Arturo

    2015-01-01

    Obesity and nonalcoholic steatohepatitis are increasing in westernized countries, regardless of their geographic location. In Latin America, most countries, including Mexico, have a heterogeneous admixture genome with Amerindian, European and African ancestries. However, certain high allelic frequencies of several nutrient-related polymorphisms may have been achieved by past gene-nutrient interactions. Such interactions may have promoted the positive selection of variants adapted to regional food sources. At present, the unbalanced diet composition of the Mexicans has led the country to a 70% prevalence rate of overweightness and obesity due to substantial changes in food habits, among other factors. International guidelines and intervention strategies may not be adequate for all populations worldwide because they do not consider disparities in genetic and environmental factors, and thus there is a need for differential prevention and management strategies. Here, we provide the rationale for an intervention strategy for the prevention and management of obesity-related diseases such as non-alcoholic steatohepatitis based on a regionalized genome-based diet. The components required to design such a diet should focus on the specific ancestry of each population around the world and the convenience of consuming traditional ethnic food. PMID:25834309

  13. Fructose, high fructose corn syrup, sucrose, and non-alcoholic liver disease

    Science.gov (United States)

    Nonalcoholic fatty liver disease (NAFLD), formerly called nonalcoholic steatohepatitis, is characterized by hepatic steatosis and abnormal triglyceride accumulation in liver cells. Its etiology, pathophysiology, and pathogenesis are still poorly understood. Some have suggested that the increased in...

  14. Non-alcohol fatty liver disease in Asia: Prevention and planning.

    Science.gov (United States)

    Ashtari, Sara; Pourhoseingholi, Mohamad Amin; Zali, Mohamad Reza

    2015-07-08

    To review all of epidemiological aspects of non-alcoholic fatty liver disease (NAFLD) and also prevent this disease is examined. We conducted a systematic review according to the PRISMA guidelines. All searches for writing this review is based on the papers was found in PubMed (MEDLINE), Cochrane database and Scopus in August and September 2014 for topic of NAFLD in Asia and the way of prevention of this disease, with no language limitations. All relevant articles were accessed in full text and all relevant materials was evaluated and reviewed. NAFLD is the most common liver disorder in worldwide, with an estimated with 20%-30% prevalence in Western countries and 2%-4% worldwide. The prevalence of NAFLD in Asia, depending on location (urban vs rural), gender, ethnicity, and age is variable between 15%-20%. According to the many studies in the world, the relationship between NAFLD, obesity, diabetes mellitus, and metabolic syndrome (MS) is quiet obvious. Prevalence of NAFLD in Asian countries seems to be lower than the Western countries but, it has increased recently due to the rise of obesity, type 2 diabetes and MS in this region. One of the main reasons for the increase in obesity, diabetes and MS in Asia is a lifestyle change and industrialization. Today, NAFLD is recognized as a major chronic liver disease in Asia. Therefore, prevention of this disease in Asian countries is very important and the best strategy for prevention and control of NAFLD is lifestyle modifications. Lifestyle modification programs are typically designed to change bad eating habits and increase physical activity that is associated with clinically significant improvements in obesity, type 2 diabetes and MS. Prevention of NAFLD is very important in Asian countries particularly in Arab countries because of high prevalence of obesity, diabetes and MS.

  15. Prevalence of metabolic risk factors in non-alcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Ashraf, N.; Sarfraz, T.; Mumtaz, Z.; Rizwan, M.

    2017-01-01

    Objective: To determine the frequency of factors leading to metabolic syndrome among non-alcoholic fatty liver disease (NAFLD) patients at a tertiary care hospital. Study Design: Descriptive cross sectional study. Place and Duration of Study: Department of Medicine, Combined Military Hospital, Kharian. Study was carried out over a period of six months from Jan 2015 to Jun 2015. Material and Methods: A total of 110 patients were included in this study. Past history was taken to rule out alcohol intake, viral and drug induced etiology, to determine the presence of co-morbidities like obesity, type 2 diabetes mellitus, arterial hypertension and dyslipidemia. Physical examination was carried to determine the arterial blood pressure and to determine anthropometric data that is weight, height, body mass index (BMI) and abdominal obesity by measuring waist circumference. Results: Mean age of the patients was 49.95 +- 8.86 years. There were 72 male patients (65.5%) while 38 (34.5%) patients were female. Different metabolic factors were central obesity in 82 patients (74.5%), raised high density lipoprotein (HDL) in 19 patients (17.3%), raised cholesterol in 87 patients (79.1%), raised blood pressure in 65 patients (59.1%) and raised fasting plasma glucose in 82 patients (74.5%). Mean BMI was 26.31 kg/m2 +- 2.68, mean waist circumference was 109.82 cm +- 18.41, mean cholesterol was 237.50 +- 48.47mg/dl, mean systolic blood pressure was 148.88mmHg +- 22.10, mean diastolic blood pressure was 90.41mmHg +- 12.25 and mean fasting plasma glucose was 113.28mg/dl +- 22.80. Stratification with regard to age was carried out. Conclusion: A considerable number of patients with NAFLD had metabolic syndrome. There was a close correlation between NAFLD and metabolic syndrome. (author)

  16. [Dietetary recommendation for non-alcoholic fatty liver disease].

    Science.gov (United States)

    Jeznach-Steinhagen, Anna; Ostrowska, Joanna; Czerwonogrodzka-Senczyna, Aneta; Boniecka, Iwona; Gronostajska, Wioletta

    2017-12-22

    Non-alcoholic Fatty Liver Disease (NAFLD) is currently the most common chronic liver disease in the developed world. Nowadays, in the adult population of Europe it is estimated at 14% to 21%. Its most important risk factors are obesity and metabolic syndrome. Introducing lifestyle changes such as: dietary intervention and increased physical activity are the first-line treatment and are intended to support not only NAFLD but also associated diseases such as obesity, insulin resistance, diabetes and dyslipidemia. Dietary management focuses on weight reduction of overweight or obese people by decreasing energy in diet. It is recommended to limit the intake of saturated fats and trans fatty acids as well as cholesterol. Instead, it is important to increase the proportion of polyunsaturated fatty acid diets, mainly from the n-3 family, which exhibit anti-inflammatory activity. It is also beneficial to eat nuts, despite their high energy value, as a source of alpha linolenic acid, which lowers LDL cholesterol. It is important to increase the share of vegetable protein (eg. soya) and limit the intake of fat meat, milk and the dairy products. A key role in the treatment and prevention of NAFLD is also a reduction of simple sugars and total exclusion of added sugar in the diet. The rise of NAFLD in developed countries is analogous to the increase of fructose consumption, which high intake is directly indicated as the main cause of the disease. Choosing foods with high fiber content, low glycemic index and meals composed with low glycemic load, is conducive to weight reduction. An important role in supporting NAFLD treatment is also attributed to vitamin D, C and E supplementation and some probiotic bacteria, as well as cinnamon and turmeric, which improve insulin sensitivity. Daily physical activity is strongly recommended as the supplement of healthy lifestyle.

  17. Insulin resistance index (HOMA-IR) in the differentiation of patients with non-alcoholic fatty liver disease and healthy individuals.

    Science.gov (United States)

    Salgado, Ana Lúcia Farias de Azevedo; Carvalho, Luciana de; Oliveira, Ana Claudia; Santos, Virgínia Nascimento dos; Vieira, Jose Gilberto; Parise, Edison Roberto

    2010-01-01

    Due to its good correlation to glycemic clamp, HOMA-IR has been widely utilized as insulin resistance index in clinical and epidemiological studies involving non-alcoholic fatty liver disease carriers. However, values used for this parameter have shown large variability. To identify the HOMA-IR cut value that best distinguishes non-diabetic non-alcoholic fatty liver disease patients from a control group. One hundred sixteen non-alcoholic fatty liver disease patients were studied, diagnosed by clinical, biochemical, and liver image or biopsy criteria, and 88 healthy individuals, without any liver disease and testing for oral glucose tolerance within normality. These groups did not differ in age and gender. All were submitted to oral glucose tolerance test and blood samples were collected for glucose and insulin measurements by immunofluorometric method. HOMA-IR was calculated according to the formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. NAFLD patients showed higher insulin, glycemia, and HOMA-IR values than control group, even when excluding glucose intolerant and diabetes mellitus patients by their glycemic curves. HOMA-IR 75th percentile for control group was 1.78 and the best area under the curve index was obtained for HOMA-IR values of 2.0 [AUC= 0.840 (0.781-0.899 CI 95%), sensitivity (Se): 85%, specificity (Sp): 83%] while value 2.5 showed best specificity without important loss in sensitivity [AUC=0,831 (0.773-0.888) Se = 72%, Sp = 94%]. HOMA-IR values above or equal to 2.0 or 2.5 show enhanced diagnostic value in distinguishing non-alcoholic fatty liver disease carriers from control group individuals.

  18. Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver disease to hepatocarcinoma: Current and innovative therapeutic approaches.

    Science.gov (United States)

    Borrelli, Antonella; Bonelli, Patrizia; Tuccillo, Franca Maria; Goldfine, Ira D; Evans, Joseph L; Buonaguro, Franco Maria; Mancini, Aldo

    2018-05-01

    Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD progresses through the inflammatory phase of non-alcoholic steatohepatitis (NASH) to fibrosis and cirrhosis, with some cases developing liver failure or hepatocellular carcinoma (HCC). Liver biopsy remains the gold standard approach to a definitive diagnosis of NAFLD and the distinction between simple steatosis and NASH. The pathogenesis of NASH is still not clear. Several theories have been proposed ranging from the "Two Hit Theory" to the "Multiple Hit Theory". However, the general consensus is that the gut microbiota, oxidative stress, and mitochondrial damage play key roles in the pathogenesis of NASH. The interaction between the gut epithelia and some commensal bacteria induces the rapid generation of reactive oxygen species (ROS). The main goal of any therapy addressing NASH is to reverse or prevent progression to liver fibrosis/cirrhosis. This problem represents the first "Achilles' heel" of the new molecules being evaluated in most ongoing clinical trials. The second is the inability of these molecules to reach the mitochondria, the primary sites of energy production and ROS generation. Recently, a variety of non-pharmacological and pharmacological treatment approaches for NASH have been evaluated including vitamin E, the thiazolidinediones, and novel molecules related to NASH pathogenesis (including obeticholic acid and elafibranor). Recently, a new isoform of human manganese superoxide dismutase (MnSOD) was isolated and obtained in a synthetic recombinant form designated rMnSOD. This protein has been shown to be a powerful antioxidant capable of mediating ROS dismutation, penetrating biological barriers via its uncleaved leader peptide, and reducing portal hypertension and fibrosis in rats affected by liver cirrhosis. Based on these distinctive characteristics, it can be hypothesized that this novel recombinant protein (r

  19. Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver disease to hepatocarcinoma: Current and innovative therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Antonella Borrelli

    2018-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD represents the most common chronic liver disease in industrialized countries. NAFLD progresses through the inflammatory phase of non-alcoholic steatohepatitis (NASH to fibrosis and cirrhosis, with some cases developing liver failure or hepatocellular carcinoma (HCC. Liver biopsy remains the gold standard approach to a definitive diagnosis of NAFLD and the distinction between simple steatosis and NASH. The pathogenesis of NASH is still not clear. Several theories have been proposed ranging from the “Two Hit Theory” to the “Multiple Hit Theory”. However, the general consensus is that the gut microbiota, oxidative stress, and mitochondrial damage play key roles in the pathogenesis of NASH. The interaction between the gut epithelia and some commensal bacteria induces the rapid generation of reactive oxygen species (ROS. The main goal of any therapy addressing NASH is to reverse or prevent progression to liver fibrosis/cirrhosis. This problem represents the first “Achilles’ heel” of the new molecules being evaluated in most ongoing clinical trials. The second is the inability of these molecules to reach the mitochondria, the primary sites of energy production and ROS generation. Recently, a variety of non-pharmacological and pharmacological treatment approaches for NASH have been evaluated including vitamin E, the thiazolidinediones, and novel molecules related to NASH pathogenesis (including obeticholic acid and elafibranor. Recently, a new isoform of human manganese superoxide dismutase (MnSOD was isolated and obtained in a synthetic recombinant form designated rMnSOD. This protein has been shown to be a powerful antioxidant capable of mediating ROS dismutation, penetrating biological barriers via its uncleaved leader peptide, and reducing portal hypertension and fibrosis in rats affected by liver cirrhosis. Based on these distinctive characteristics, it can be hypothesized that this novel

  20. Gastric bypass surgery is protective from high-fat diet-induced non-alcoholic fatty liver disease and hepatic endoplasmic reticulum stress.

    Science.gov (United States)

    Mosinski, J D; Pagadala, M R; Mulya, A; Huang, H; Dan, O; Shimizu, H; Batayyah, E; Pai, R K; Schauer, P R; Brethauer, S A; Kirwan, J P

    2016-06-01

    High-fat diets are known to contribute to the development of obesity and related co-morbidities including non-alcoholic fatty liver disease (NAFLD). The accumulation of hepatic lipid may increase endoplasmic reticulum (ER) stress and contribute to non-alcoholic steatohepatitis and metabolic disease. We hypothesized that bariatric surgery would counter the effects of a high-fat diet (HFD) on obesity-associated NAFLD. Sixteen of 24 male Sprague Dawley rats were randomized to Sham (N = 8) or Roux-en-Y gastric bypass (RYGB) surgery (N = 8) and compared to Lean controls (N = 8). Obese rats were maintained on a HFD throughout the study. Insulin resistance (HOMA-IR), and hepatic steatosis, triglyceride accumulation, ER stress and apoptosis were assessed at 90 days post-surgery. Despite eating a HFD for 90 days post-surgery, the RYGB group lost weight (-20.7 ± 6%, P Hepatic steatosis and ER stress, specifically glucose-regulated protein-78 (Grp78, P < 0.001), X-box binding protein-1 (XBP-1) and spliced XBP-1 (P < 0.01), and fibroblast growth factor 21 (FGF21) gene expression, were normalized in the RYGB group compared to both Sham and Lean controls. Significant TUNEL staining in liver sections from the Obese Sham group, indicative of accelerated cell death, was absent in the RYGB and Lean control groups. Additionally, fasting plasma glucagon like peptide-1 was increased in RYGB compared to Sham (P < 0.02). These data suggest that in obese rats, RYGB surgery protects the liver against HFD-induced fatty liver disease by attenuating ER stress and excess apoptosis. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  1. Controlled attenuation parameter using the FibroScan® XL probe for quantification of hepatic steatosis for non-alcoholic fatty liver disease in an Asian population.

    Science.gov (United States)

    Chan, Wah-Kheong; Nik Mustapha, Nik Raihan; Wong, Grace Lai-Hung; Wong, Vincent Wai-Sun; Mahadeva, Sanjiv

    2017-02-01

    The FibroScan® XL probe reduces failure of liver stiffness measurement (LSM) and unreliable results in obese patients. The objective of this article is to evaluate the accuracy of controlled attenuation parameter (CAP) obtained using the XL probe for the estimation of hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD). Adult NAFLD patients with a liver biopsy within six months were included and were examined with the FibroScan® M and XL probes. Histopathological findings were reported according to the Non-Alcoholic Steatohepatitis Clinical Research Network Scoring System. Participants who did not have fatty liver on ultrasonography were recruited as controls. A total of 57 NAFLD patients and 22 controls were included. The mean age of the NAFLD patients and controls was 50.1 ± 10.4 years and 20.2 ± 1.3 years, respectively ( p  = 0.000). The mean body mass index was 30.2 ± 5.0 kg per m 2 and 20.5 ± 2.4 kg per m 2 , respectively ( p  = 0.000). The distribution of steatosis grades were: S0, 29%; S1, 17%; S2, 35%; S3, 19%. The AUROC for estimation of steatosis grade ≥ S1, S2 and S3 was 0.94, 0.80 and 0.69, respectively, using the M probe, and 0.97, 0.81 and 0.67, respectively, using the XL probe. CAP obtained using the XL probe had similar accuracy as the M probe for the estimation of hepatic steatosis in NAFLD patients.

  2. Increased Expression Profile and Functionality of TLR6 in Peripheral Blood Mononuclear Cells and Hepatocytes of Morbidly Obese Patients with Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Arias-Loste, María Teresa; Iruzubieta, Paula; Puente, Ángela; Ramos, David; Santa Cruz, Carolina; Estébanez, Ángel; Llerena, Susana; Alonso-Martín, Carmen; San Segundo, David; Álvarez, Lorena; López Useros, Antonio; Fábrega, Emilio; López-Hoyos, Marcos; Crespo, Javier

    2016-11-10

    Current evidence suggests that gut dysbiosis drives obesity and non-alcoholic fatty liver disease (NAFLD) pathogenesis. Toll-like receptor 2 (TLR2) and TLR6 specifically recognize components of Gram-positive bacteria. Despite the potential implications of TLR2 in NAFLD pathogenesis, the role of TLR6 has not been addressed. Our aim is to study a potential role of TLR6 in obesity-related NAFLD. Forty morbidly obese patients undergoing bariatric surgery were prospectively studied. Cell surface expression of TLR2 and TLR6 was assessed on peripheral blood mononuclear cells (PBMCs) by flow cytometry. Freshly isolated monocytes were cultured with specific TLR2/TLR6 agonists and intracellular production of cytokines was determined by flow-cytometry. In liver biopsies, the expression of TLR2 and TLR6 was analyzed by immunohistochemistry and cytokine gene expression using RT-qPCR. TLR6 expression in PBMCs from non-alcoholic steatohepatitis (NASH) patients was significantly higher when compared to those from simple steatosis. The production of pro-inflammatory cytokines in response to TLR2/TLR6 stimulation was also significantly higher in patients with lobular inflammation. Hepatocyte expression of TLR6 but not that of TLR2 was increased in NAFLD patients compared to normal liver histology. Deregulated expression and activity of peripheral TLR6 in morbidly obese patients can mirror the liver inflammatory events that are well known drivers of obesity-related NASH pathogenesis. Moreover, TLR6 is also significantly overexpressed in the hepatocytes of NAFLD patients compared to their normal counterparts. Thus, deregulated TLR6 expression may potentiate TLR2-mediated liver inflammation in NAFLD pathogenesis, and also serve as a potential peripheral biomarker of obesity-related NASH.

  3. [The importance of AST / ALT rate in nonalcoholic steatohepatitis diagnosis].

    Science.gov (United States)

    Zamin, Júnior Idilio; de Mattos, Angelo Alves; Perin, Christiano; Ramos, Gabriel Zatti

    2002-01-01

    There is a histologic similarity between nonalcoholic steatohepatitis and alcoholic liver disease and in some cases differential diagnosis may be difficult, since some patients do not report abusive alcohol consumption. Evaluating the usefulness of setting the rate AST/ALT for the differential diagnosis of nonalcoholic steatohepatitis and alcoholic liver disease. Twenty nine obese patients with nonalcoholic steatohepatitis were compared with 28 patients with alcoholic liver disease. The diagnosis of nonalcoholic steatohepatitis was made after exclusion of other causes of liver disease and by histologic findings of, at least, macrovesicular steatosis and hepatocellular necrosis. In patients with nonalcoholic steatohepatitis the medium AST value was 52.3 +/- 21.2 U/L and ALT of 90.1 +/- 37.9 U/L, being the AST/ALT rate lower than 1 in all patients. In patients with alcoholic liver disease the medium AST value was 140 +/- 82.5 U/L and ALT was 50.6 +/- 40.3 U/L. The rate was higher than 1 in all cases and higher than 2 in 24 (85.7%), being statistically significant when compared with patients with nonalcoholic steatohepatitis. The AST/ALT rate seems to be useful in the differential diagnosis of liver diseases, while lower than 1 is highly suggestive of nonalcoholic steatohepatitis.

  4. Mouse Models of Diet-Induced Nonalcoholic Steatohepatitis Reproduce the Heterogeneity of the Human Disease

    Science.gov (United States)

    Machado, Mariana Verdelho; Michelotti, Gregory Alexander; Xie, Guanhua; de Almeida, Thiago Pereira; Boursier, Jerome; Bohnic, Brittany; Guy, Cynthia D.; Diehl, Anna Mae

    2015-01-01

    Background and aims Non-alcoholic steatohepatitis (NASH), the potentially progressive form of nonalcoholic fatty liver disease (NAFLD), is the pandemic liver disease of our time. Although there are several animal models of NASH, consensus regarding the optimal model is lacking. We aimed to compare features of NASH in the two most widely-used mouse models: methionine-choline deficient (MCD) diet and Western diet. Methods Mice were fed standard chow, MCD diet for 8 weeks, or Western diet (45% energy from fat, predominantly saturated fat, with 0.2% cholesterol, plus drinking water supplemented with fructose and glucose) for 16 weeks. Liver pathology and metabolic profile were compared. Results The metabolic profile associated with human NASH was better mimicked by Western diet. Although hepatic steatosis (i.e., triglyceride accumulation) was also more severe, liver non-esterified fatty acid content was lower than in the MCD diet group. NASH was also less severe and less reproducible in the Western diet model, as evidenced by less liver cell death/apoptosis, inflammation, ductular reaction, and fibrosis. Various mechanisms implicated in human NASH pathogenesis/progression were also less robust in the Western diet model, including oxidative stress, ER stress, autophagy deregulation, and hedgehog pathway activation. Conclusion Feeding mice a Western diet models metabolic perturbations that are common in humans with mild NASH, whereas administration of a MCD diet better models the pathobiological mechanisms that cause human NAFLD to progress to advanced NASH. PMID:26017539

  5. Hyperuricemia Inversely Correlates with Disease Severity in Taiwanese Nonalcoholic Steatohepatitis Patients.

    Directory of Open Access Journals (Sweden)

    Jee-Fu Huang

    Full Text Available Asians are more susceptible to non-alcoholic steatohepatitis (NASH as well as metabolic disorder than other ethnicities. We aimed to assess the interaction between metabolic factors and fibrosis in Taiwanese NASH patients.A total of 130 biopsy-proven Taiwanese NASH patients (94 males, age = 43.0 ± 13.0 years were consecutively enrolled. Their demographic, metabolic profiles and histopathological manifestations were analyzed.Twenty-four (18.5% NASH patients were non-obese. Thirty-three (25.4% patients had significant fibrosis (F2 or more: 22 (16.9% patients were of F2, whilst 11 (8.5% patients were of advanced fibrosis (F3-4. The prevalence of metabolic syndrome, diabetes and hypertension were 60.8%, 39.4%, and 61.5%, respectively. There was a significant inverse correlation between hyperuricemia and fibrosis stages, ranging from 48.4% of F0-1, 33.3% of F2, and 9.1% of F3-4, respectively (P = 0.01, linear trend. Multivariate logistic regression analysis showed that a decreased serum albumin level (OR = 40.0, 95% CI = 4.5-300, P = 0.001 and normal uric acid level (OR = 5.6, 95% CI = 1.5-21.7, P = 0.01 were the significant factors associated with significant fibrosis.Hyperuricemia inversely predicts fibrosis stages. Females might carry a more disease severity than males in Taiwanese NASH patients.

  6. Impact of Renal Impairment on Cardiovascular Disease Mortality After Liver Transplantation for Nonalcoholic Steatohepatitis Cirrhosis

    Science.gov (United States)

    VanWagner, Lisa B.; Lapin, Brittany; Skaro, Anton I.; Lloyd-Jones, Donald M.; Rinella, Mary E.

    2016-01-01

    BACKGROUND & AIMS Non-alcoholic steatohepatitis (NASH) is an independent risk factor for cardiovascular disease (CVD) morbidity after liver transplantation, but its impact on CVD mortality is unknown. We sought to assess the impact of NASH on CVD mortality after liver transplantation and to predict which NASH recipients are at highest risk of a CVD-related death following a liver transplant. METHODS Using the Organ Procurement and Transplantation Network database we examined associations between NASH and post liver transplant CVD mortality, defined as primary cause of death from thromboembolism, arrhythmia, heart failure, myocardial infarction, or stroke. A physician panel reviewed cause of death. RESULTS Of 48,360 liver transplants (2/2002–12/2011), 5,057 (10.5%) were performed for NASH cirrhosis. NASH recipients were more likely to be older, female, obese, diabetic, and have history of renal failure or prior CVD versus non-NASH (ptransplant diabetes, renal impairment or CVD. A risk score comprising age ≥ 55, male sex, diabetes and renal impairment was developed for prediction of post liver transplant CVD mortality (c-statistic 0.60). CONCLUSION NASH recipients have an increased risk of CVD mortality after liver transplantation explained by a high prevalence of co-morbid cardiometabolic risk factors that in aggregate identify those at highest risk of post-transplant CVD mortality. PMID:25977117

  7. Mouse models of diet-induced nonalcoholic steatohepatitis reproduce the heterogeneity of the human disease.

    Directory of Open Access Journals (Sweden)

    Mariana Verdelho Machado

    Full Text Available Non-alcoholic steatohepatitis (NASH, the potentially progressive form of nonalcoholic fatty liver disease (NAFLD, is the pandemic liver disease of our time. Although there are several animal models of NASH, consensus regarding the optimal model is lacking. We aimed to compare features of NASH in the two most widely-used mouse models: methionine-choline deficient (MCD diet and Western diet.Mice were fed standard chow, MCD diet for 8 weeks, or Western diet (45% energy from fat, predominantly saturated fat, with 0.2% cholesterol, plus drinking water supplemented with fructose and glucose for 16 weeks. Liver pathology and metabolic profile were compared.The metabolic profile associated with human NASH was better mimicked by Western diet. Although hepatic steatosis (i.e., triglyceride accumulation was also more severe, liver non-esterified fatty acid content was lower than in the MCD diet group. NASH was also less severe and less reproducible in the Western diet model, as evidenced by less liver cell death/apoptosis, inflammation, ductular reaction, and fibrosis. Various mechanisms implicated in human NASH pathogenesis/progression were also less robust in the Western diet model, including oxidative stress, ER stress, autophagy deregulation, and hedgehog pathway activation.Feeding mice a Western diet models metabolic perturbations that are common in humans with mild NASH, whereas administration of a MCD diet better models the pathobiological mechanisms that cause human NAFLD to progress to advanced NASH.

  8. Menopausal age and sex hormones in postmenopausal women with alcoholic and non-alcoholic liver disease

    DEFF Research Database (Denmark)

    Becker, U; Gluud, C; Farholt, S

    1991-01-01

    , elevated concentrations of oestrone and sex hormone binding globulin (SHBG) and reduced levels of 5 alpha-dihydrotestosterone (DHT), while women with non-alcoholic cirrhosis had significantly elevated concentrations of SHBG and reduced levels of oestrone sulphate, DHT, androstenedione...

  9. [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.

  10. Effect of Non-Alcoholic Compounds of Alcoholic Drinks on the Pancreas

    OpenAIRE

    Feick, Peter; Gerloff, Andreas; Singer, Manfred V.

    2007-01-01

    Over the past 30 years the role of alcohol (ethanol) in the development of acute and chronic pancreatitis has been intensively investigated. However, ethanol is generally consumed in form of alcoholic beverages which contain numerous non-alcoholic compounds. At least on gastric acid secretion it has been convincingly demonstrated that alcohol and alcoholic beverages have markedly different effects. In the present article, we provide an overview about the effect of different non-alcoholic cons...

  11. Colchicine for alcoholic and non-alcoholic liver fibrosis or cirrhosis

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2001-01-01

    Colchicine is an anti-inflammatory and anti-fibrotic drug. Several randomized clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic as well as non-alcoholic fibrosis and cirrhosis. The objectives were to assess the efficacy of colchicine...... evaluated in randomized trials on mortality, liver related mortality, liver related complications, liver fibrosis markers, liver histology, alcohol consumption, quality of life, and health economics in patients with alcoholic and non-alcoholic fibrosis or cirrhosis....

  12. Associations of Fatty Liver Disease with Hypertension, Diabetes, and Dyslipidemia: Comparison between Alcoholic and Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Nobuyuki Toshikuni

    2017-01-01

    Full Text Available Alcoholic steatohepatitis (ASH and nonalcoholic steatohepatitis (NASH are representative types of fatty liver disease (FLD and have similar histologic features. In this study, we aimed to compare the associations of the two FLD types with hypertension (HT, diabetes mellitus (DM, and dyslipidemia (DL. A nationwide survey investigating FLD status included 753 Japanese subjects (median age 55 years; male 440, female 313 with biopsy-proven ASH (n=172 or NASH (n=581. We performed a multiple logistic regression analysis to identify the factors associated with HT, DM, or DL. Older age and a higher body mass index were significant factors associated with HT. Older age, female sex, a higher body mass index, advanced liver fibrosis, and the NASH type of FLD (odds ratio 2.77; 95% confidence interval 1.78–4.31; P<0.0001 were significant factors associated with DM. Finally, the NASH type of FLD (odds ratio 4.05; 95% confidence interval 2.63–6.24; P<0.0001 was the only significant factor associated with DL. Thus, the associations of NASH with DM and DL were stronger than those of ASH with DM and DL. In the management of FLD subjects, controlling DM and DL is particularly important for NASH subjects.

  13. Free fatty acids, not triglycerides, are associated with non-alcoholic liver injury progression in high fat diet induced obese rats.

    Science.gov (United States)

    Liu, Jiali; Han, Lina; Zhu, Leilei; Yu, Yerong

    2016-02-11

    The incidence of non-alcoholic fatty liver disease (NAFLD), commonly associated with obesity and metabolic syndrome, is increasing worldwide. However, the specific mechanisms that mediate the progression from simple steatosis to non-alcoholic steatohepatitis remain largely unclear. This study aimed to investigate the time dependent changes of triglyceride (TG) and free fatty acid (FFA) levels in the blood and liver over 24 weeks in high-fat diet-induced obese rats with NAFLD and to clarify the role of high FFA levels in the progression of liver injury. Male Wistar rats were randomly divided into three groups (n = 30 per group): the Control group, fed standard chow; the High-fat diet (HFD) group, fed high-fat chow; and the Acipimox group, fed an HFD plus acipimox (100 mg/kg/d, ig) for 8, 16 and 24 weeks. After treatment, blood and liver samples were collected for biochemical analyses, western blotting analysis and a histopathological study. The visceral fat/weight and liver/body weight ratios were higher in both the HFD and Acipimox groups than in the Control group. The TG and FFA concentrations in blood and liver were increased in the HFD group and associated with elevated serum alanine aminotransferase (ALT) and liver malondialdehyde (MDA) levels and macro/microvesicular steatosis on hepatic fragments. Although the TG levels in the liver were similar between the HFD and Acipimox groups (p > 0.05), the FFA concentrations in the blood and liver were much lower in the latter group (p 0.05), but the protein expression level of carnitine palmitoyltransferase 1a (CPT-1a) was higher in the Acipimox group. Liver TG accumulation does not cause cellular injury in the liver; rather, FFAs or their metabolites are responsible for liver injury via increased oxidative stress. It is suggested that the therapeutic efforts to prevent non-alcoholic liver injury progression should be focused on reducing the burden of fatty acids transported to the liver or those being synthesized in

  14. 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.

  15. Different Effects of Eicosapentaenoic and Docosahexaenoic Acids on Atherogenic High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice.

    Directory of Open Access Journals (Sweden)

    Noriko Suzuki-Kemuriyama

    Full Text Available 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.

  16. [Non-alcoholic fatty liver: 10 years' experience at the Insituto Nacional de la Nutrición Salvador Zubirán].

    Science.gov (United States)

    de la Mora, G; Olivera, M; de la Cerda, R; Arista, J; Kershenobich, D; Uribe, M

    1994-01-01

    To describe the characteristics of non-alcoholic steatohepatitis (NASH) at the Instituto Nacional de la Nutricion Salvador Zubiran. We reviewed all liver biopsy reports from January 1982 to December 1991. From patient records we obtained the following data: clinical, biochemical, imaging studies and we reviewed the histological material. We correlated clinical, biochemical and histological data. From 2963 biopsies reviewed we obtained 16 cases of NASH. We found a 7:1 female/male ratio. Median age was 30 years and six patients were obese. Eleven patients had concomitant disease (diabetes in seven) and nine were using drugs. All had been studied for biochemical abnormalities and were asymptomatic. Ten patients had hepatomegaly and six splenomegaly. Ultrasound suggested the diagnosis in 50% of the cases. All had steatosis, inflammatory infiltrate, necrosis, fibrosis and Mallory bodies at different stages. One case had cirrhosis on initial biopsy and two developed cirrhosis on follow-up (one and eight years later). We did not find any correlation between clinical, biochemical or imaging characteristics and histological findings. When we compared these findings between obese and non obese patients and primary and secondary NASH we did not find any differences between groups. NASH is infrequent in our institution. The underlying pathogenesis seems to be multifactorial. There is no biochemical-histological correlation. Cirrhosis can develop in some cases.

  17. 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.

  18. [Sugar content in non-alcoholic beverages and dietary recemmendations for children and adolescents].

    Science.gov (United States)

    Bilek, Maciej; Rybakowa, Maria

    2015-01-01

    Increase the intake of sugars among the inhabitants of developed countries is related to, among others, increasing consumption of non-alcoholic beverages, for which the relationship with the epidemic of obesity, particularly among children and adolescents, has been proven. The most frequently cited are non-alcoholic beverages, sweetened glucose-fructose syrup, ie. colas, tonics, ice teas, lemonades. Fruit drinks, fruit juices and nectars are commonly cited as a healthy alternative to non-alcoholic beverages and, however, we do not pay attention to the high content of sugars in these products. Determine the content of sugars in non-alcohollic beverages popular among children and adolescents. 80 non-alcoholic beverages such as cola, tonic, lemonade, ice tea, flavored waters, fruit juices, fruit nectars and fruit drinks. Evaluation of the content of monosaccharides and sucrose was performed by high performance liquid chromatography method (HPLC). In the tested non-alcohollic beverages, monosaccharides ie. glucose and fructose and the disaccharide sucrose were detected in different proportions. The product with the lowest content of the total sugars content was flavored water with lemon flavor based on the mineral water (2.72 g/100 ml). In the group of fruit juices, fruit nectars and fruit drinks highest sugars content have been reported (12.94 g/100 ml for aronia nectar and 12.76 g/100ml for the juice of pomegranate and grapes). Significant monosaccharides and sucrose content in the tested non-alcohollic beverages tends to claim that their manufacturers should be obliged to place warnings on the labels addressed to patients suffering from disorders of carbohydrate metabolism. Educational programs for children and adolescents with diabetes should include information about the content of a large amount of sugars in fruit products: fruit juices, fruit drinks and fruit nectar. © Polish Society for Pediatric Endocrinology and Diabetology.

  19. High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs

    DEFF Research Database (Denmark)

    Ipsen, David Højland; Tveden-Nyborg, Pernille; Rolin, Bidda

    2016-01-01

    /cholesterol on the development of dyslipidemia and NAFLD. Methods Seventy female guinea pigs were block-randomized (based on weight) into five groups and fed a normal chow diet (control: 4 % fat), a very high-sucrose diet (vHS: 4 % fat, 25 % sucrose), a high-fat diet (HF: 20 % fat, 0.35 % cholesterol), a high...

  20. 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

  1. Non-Alcoholic Fatty Liver Disease: Lipids and Insulin Resistance

    Science.gov (United States)

    Berk, Paul D; Verna, Elizabeth C

    2016-01-01

    Abstract/Synopsis Obesity and its major co-morbidities, including type 2 diabetes mellitus, nonalcoholic fatty liver disease (NAFLD), obesity cardiomyopathy, and certain cancers, are major public health problems worldwide. They are responsible for substantial morbidity and mortality, to a degree that life expectancy in the United States has actually declined in recent years because of it. Obesity is the increased accumulation of fat, i.e. triglycerides (TG), which are synthesized from glycerol and long chain fatty acids (LCFA), throughout the body. Although long believed to enter cells solely by passive diffusion, it has been established over the past 30 years that LCFA enter adipocytes, hepatocytes and cardiomyocytes via specific, facilitated transport processes, and that these processes are hormonally up-regulated in obesity. Metabolism of increased cellular TG content in obesity may lead to cell-specific lipotoxicity, contributing to co-morbidities such as NAFLD and cardiomyopathy. In contrast to the popular perception, dietary control and bariatric surgery can each achieve major initial weight loss in many patients. However several mechanisms, including persistent up-regulation of LCFA transport, contribute to weight regain in the large majority of patients. Better understanding of these transport processes and their regulation may be a key to successful future strategies to treat obesity and NAFLD. PMID:27063267

  2. Could metabolic syndrome lead to hepatocarcinoma via non-alcoholic fatty liver disease?

    Science.gov (United States)

    Scalera, Antonella; Tarantino, Giovanni

    2014-07-28

    It was estimated that from 2002 to 2008 the risk of developing cancer increased a quarter-fold in men and two-fold in women due to excessive BMI. Obesity, metabolic syndrome and type 2 diabetes mellitus are strictly related and are key pathogenetic factors of non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease worldwide. The most important consequence of the "metabolic epidemics" is the probable rise in the incidence of hepatocarcinoma (HCC), and NAFLD is the major causative factor. Adipose tissue is not merely a storage organ where lipids are preserved as an energy source. It is an active organ with important endocrine, paracrine, and autocrine actions in addition to immune functions. Adipocytes produce a wide range of hormones, cytokines, and growth factors that can act locally in the adipose tissue microenvironment and systemically. In this article, the main roles of insulin growth factor (IGF)-1 and IGF-2 are discussed. The role of IGF-2 is not only confined to HCC, but it may also act in early hepato-carcinogenesis, as pre-neoplastic lesions express IGF-2 mRNA. IGF-1 and IGF-2 interact with specific receptors (IGF-1R and IGF-2R). IGF-1R is over-expressed in in vitro and in animal models of HCC and it was demonstrated that IGF ligands exerted their effects on HCC cells through IGF-1R and that it was involved in the degeneration of pre-neoplastic lesions via an increase in their mitotic activity. Both IGF-2R and TGF β, a growth inhibitor, levels are reduced in human HCC compared with adjacent normal liver tissues. Another key mechanism involves peroxisome proliferator-activated receptor (PPAR)γ. In in vitro studies, PPARγ inhibited various carcinomas including HCC, most probably by regulating apoptosis via the p21, p53 and p27 pathways. Finally, as a clinical consequence, to improve survival, efforts to achieve a "healthier diet" should be promoted by physicians and politicians.

  3. Body mass index and the visceral adipose tissue expression of IL-6 and TNF-alpha are associated with the morphological severity of non-alcoholic fatty liver disease in individuals with class III obesity.

    Science.gov (United States)

    Jorge, Antônio Sérgio Barcala; Andrade, João Marcus Oliveira; Paraíso, Alanna Fernandes; Jorge, Gislaine Candida Batista; Silveira, Christine Mendes; de Souza, Ludmilla Regina; Santos, Erivelton Pereira; Guimaraes, André Luiz Sena; Santos, Sérgio Henrique Sousa; De-Paula, Alfredo Maurício Batista

    To analyze the mRNA expression of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in the liver and white adipose tissue samples of individuals with class III obesity (body mass index ≥40.0kg/m 2 ) with non-alcoholic fatty liver disease (NAFLD). This cross-sectional study included patients with class III obesity exhibiting early or late morphological presentation of NAFLD (non-alcoholic hepatic steatosis [NAFL], n=8 and non-alcoholic steatohepatitis [NASH], n=13, respectively). All patients underwent bariatric surgery and peripheral blood, liver, and visceral white adipose tissue (WAT) samples were collected. Socio-demographic, anthropometric, clinical, plasma biochemical, and nutritional characteristics of each study subject were assessed and compared between patients presenting with NAFL and NASH. IL-6 and TNF-α mRNA expression in the liver and WAT samples were measured by using quantitative real time-polymerase chain reaction (qRT-PCR). Individuals with class III obesity and NASH showed higher body mass index (BMI) and higher IL-6 and TNF-α mRNA expression in the WAT compared to that of patients with NAFL (p=0.01, for all associations). Individuals with class III obesity with higher morphological severity of NAFLD exhibited higher BMI and higher IL-6 and TNF-α expression in the WAT. Future prospective studies are warranted to determine how BMI, IL-6, and TNF-α affect the progression of NAFLD in individuals with class III obesity. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  4. Omega-3 fatty acids and non-alcoholic fatty liver disease: Evidence of efficacy and mechanism of action.

    Science.gov (United States)

    Scorletti, Eleonora; Byrne, Christopher D

    2018-03-22

    For many years it has been known that high doses of long chain omega-3 fatty acids are beneficial in the treatment of hypertriglyceridaemia. Over the last three decades, there has also been a wealth of in vitro and in vivo data that has accumulated to suggest that long chain omega-3 fatty acid treatment might be beneficial to decrease liver triacylglycerol. Several biological mechanisms have been identified that support this hypothesis; notably, it has been shown that long chain omega-3 fatty acids have a beneficial effect: a) on bioactive metabolites involved in inflammatory pathways, and b) on alteration of nuclear transcription factor activities such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), involved in inflammatory pathways and liver lipid metabolism. Since the pathogenesis of non alcoholic fatty liver disease (NAFLD) begins with the accumulation of liver lipid and progresses with inflammation and then several years later with development of fibrosis; it has been thought in patients with NAFLD omega-3 fatty acid treatment would be beneficial in treating liver lipid and possibly also in ameliorating inflammation. Meta-analyses (of predominantly dietary studies and small trials) have tended to support the assertion that omega-3 fatty acids are beneficial in decreasing liver lipid, but recent randomised controlled trials have produced conflicting data. These trials have suggested that omega-3 fatty acid might be beneficial in decreasing liver triglyceride (docosahexanoic acid also possibly being more effective than eicosapentanoic acid) but not in decreasing other features of steatohepatitis (or liver fibrosis). The purpose of this review is to discuss recent evidence regarding biological mechanisms by which long chain omega-3 fatty acids might act to ameliorate liver disease in NAFLD; to consider the recent evidence from randomised

  5. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Giovanni Musso

    2014-07-01

    Full Text Available BACKGROUND: Chronic kidney disease (CKD is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD. METHODS AND FINDINGS: English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR, and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants, we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66 and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95 CKD. Non-alcoholic steatohepatitis (NASH was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05 and incidence (HR 2.12, 95% CI 1.42-3.17 of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3

  6. Non-alcoholic Korsakoff syndrome in psychiatric patients with a history of undiagnosed Wernicke's encephalopathy.

    Science.gov (United States)

    Nikolakaros, Georgios; Ilonen, Tuula; Kurki, Timo; Paju, Janina; Papageorgiou, Sokratis G; Vataja, Risto

    2016-11-15

    Wernicke's encephalopathy is often undiagnosed, particularly in non-alcoholics. There are very few reports of non-alcoholic patients diagnosed with Korsakoff syndrome in the absence of a prior diagnosis of Wernicke's encephalopathy and no studies of diffusion tensor imaging in non-alcoholic Korsakoff syndrome. We report on three non-alcoholic psychiatric patients (all women) with long-term non-progressive memory impairment that developed after malnutrition accompanied by at least one of the three Wernicke's encephalopathy manifestations: ocular abnormalities, ataxia or unsteadiness, and an altered mental state or mild memory impairment. In neuropsychological examination, all patients had memory impairment, including intrusions. One patient had mild cerebellar vermis atrophy in MRI taken after the second episode of Wernicke's encephalopathy. The same patient had mild hypometabolism in the lateral cortex of the temporal lobes. Another patient had mild symmetrical atrophy and hypometabolism of the superior frontal lobes. Two patients were examined with diffusion tensor imaging. Reduced fractional anisotropy values were found in the corona radiata in two patients, and the uncinate fasciculus and the inferior longitudinal fasciculus in one patient. Our results suggest that non-alcoholic Korsakoff syndrome is underdiagnosed. Psychiatric patients with long-term memory impairment may have Korsakoff syndrome and, therefore, they should be evaluated for a history of previously undiagnosed Wernicke's encephalopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Consuming non-alcoholic beer and other beverages during pregnancy and breastfeeding.

    Science.gov (United States)

    Adiong, John Patrick; Kim, Eunji; Koren, Gideon; Bozzo, Pina

    2014-08-01

    An increasing number of my patients are asking about the safety of consuming non-alcoholic beer and other alcohol-free versions of alcoholic beverages during pregnancy and breastfeeding, as they believe that these drinks might be a "safer" alternative to regular alcoholic beverages. What are Motherisk's recommendations regarding these products? Such drinks might contain higher ethanol levels than what is indicated on their labels. As there is no known safe level of alcohol intake in pregnancy, abstinence from non-alcoholic beverages would eliminate any risk of fetal alcohol spectrum disorder. Although it is likely that moderate intake of non-alcoholic beverages would pose no harm to breastfed infants, briefly delaying breastfeeding after consumption of such drinks would ensure that the infant is not exposed to alcohol. Copyright© the College of Family Physicians of Canada.

  8. Effects of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease and inflammation.

    Science.gov (United States)

    Wang, Xing-Chun; Gusdon, Aaron M; Liu, Huan; Qu, Shen

    2014-10-28

    Glucagon-like peptide1 (GLP-1) is secreted from Langerhans cells in response to oral nutrient intake. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of incretin-based anti-diabetic drugs. They function to stimulate insulin secretion while suppressing glucagon secretion. GLP-1-based therapies are now well established in the management of type 2 diabetes mellitus (T2DM), and recent literature has suggested potential applications of these drugs in the treatment of obesity and for protection against cardiovascular and neurological diseases. As we know, along with change in lifestyles, the prevalence of non-alcoholic fatty liver disease (NAFLD) in China is rising more than that of viral hepatitis and alcoholic fatty liver disease, and NAFLD has become the most common chronic liver disease in recent years. Recent studies further suggest that GLP-1RAs can reduce transaminase levels to improve NAFLD by improving blood lipid levels, cutting down the fat content to promote fat redistribution, directly decreasing fatty degeneration of the liver, reducing the degree of liver fibrosis and improving inflammation. This review shows the NAFLD-associated effects of GLP-1RAs in animal models and in patients with T2DM or obesity who are participants in clinical trials.

  9. Clinical utility of red cell distribution width in alcoholic and non-alcoholic liver cirrhosis.

    Science.gov (United States)

    Milić, Sandra; Mikolasević, Ivana; Radić, Mladen; Hauser, Goran; Stimac, Davor

    2011-09-01

    Red blood cell distribution width (RDW) is a measure of the variation of red blood cell width that is reported as apart of standard complete blood count. Red blood cell distribution width results are often used together with mean corpuscular volume (MCV) results to figure out mixed anemia. The aim of our study was to compare the values of RDW in alcoholic and non-alcoholic liver cirrhosis and to determine if RDW follows the severity of disease according to Child-Pugh score. We retrospectively analyzed 241 patients (176 men and 65 women) with liver cirrhosis and anemia, defined as a hemoglobin value reference range is 11-15%. Alcoholic liver cirrhosis had 204 patients (85%) while non-alcoholic cirrhosis had 37 patients (15%). In group of alcoholic cirrhosis the average RDW was 16.8%. In relation to severity of disease the average RDW for Child-Pugh A was 16.80%, for Child-Pugh B was 16.92%, for Child-Pugh C was 17.10%. In the group of non-alcoholic cirrhosis the average RDW was 16.73% and in relation to severity of disease for Child-Pugh A was 16.25%, for Child-Pugh B 17.01% and for Child-Pugh C was 16.87%. We didn't find statistically significant difference of RDW between alcoholic and non alcoholic cirrhosis (p > 0.05) and we didn't proved any statistically significant increase of RDW in relation to severity of disease in group of alcoholic cirrhosis (p = 0.915) nor in group of patients with non-alcoholic cirrhosis (p = 0.697). Our study showed that RDW had not any clinical value in differentiation of anemia neither in alcoholic and non-alcoholic liver cirrhosis nor in severity of liver disease.

  10. TO STUDY AND EVALUATE DIASTOLIC DYSFUNCTION IN PATIENTS OF ALCOHOLIC AND NON-ALCOHOLIC CIRRHOSIS

    Directory of Open Access Journals (Sweden)

    Gaurav Sudhir

    2016-04-01

    Full Text Available BACKGROUND Cardiovascular dysfunction is the major component of morbidity in patients of liver cirrhosis and a cardinal prognostic indicator in patients undergoing liver transplantation. The constellation of hyperdynamic circulation, peripheral vasodilation and volume overload alters the systolic and diastolic dysfunction leading to cirrhotic cardiomyopathy (CCM. In this study, we evaluated and compared the diastolic dysfunction among alcoholic and non-alcoholic cirrhotic patients. AIMS 1 To Study the Prevalence of Diastolic Dysfunction in Alcoholic & Non-Alcoholic Cirrhotics and Controls. 2 To Compare the Diastolic functional status between alcoholic and non-alcoholic cirrhosis patients. MATERIALS AND METHODS A cross-sectional case control study was conducted in 100 male cirrhotic patients consisting of alcoholic and non-alcoholic cirrhotic subjects with age matched 50 controls in Pt. JNM Medical College & Dr. BRAM Hospital, Raipur. Left ventricular diastolic dysfunction was assessed using echocardiographic parameters. STATISTICAL ANALYSIS The range, median, standard deviation and statistical significance were calculated. Most of the data is analysed by Student Ttest, Mann Whitney U test, while the data with frequency distribution is analysed by Fisher’s exact. With p value 1. CONCLUSION Our study showed that patients with alcoholic and non-alcoholic cirrhosis have higher occurrence of DD (49% and 46% respectively than controls owing to alterations in the myocardial contractile and relaxation function. It also shows that although DD is a frequent event in cirrhosis, it is usually of mild degree and does not correlate with severity of liver dysfunction. There were no significant differences in diastolic parameters between alcoholic and non-alcoholic cirrhosis concluding that alcohol likely plays a non-significant role in cardiovascular dysfunction in cirrhotics.

  11. Standardized Salvia miltiorrhiza Extract Suppresses Hepatic Stellate Cell Activation and Attenuates Steatohepatitis Induced by a Methionine-Choline Deficient Diet in Mice

    Directory of Open Access Journals (Sweden)

    Hak Sung Lee

    2014-06-01

    Full Text Available The aim of this study was to examine the effect of standardized extract of Salvia miltiorrhiza (SME on gene and protein expression of non-alcoholic steatohepatitis (NASH-related factors in activated human hepatic stellate cells (HSC, and in mice with steatohepatitis induced by a methionine-choline deficient (MCD diet. Male C57BL/6J mice were placed on an MCD or control diet for 8 weeks and SME (0, 0.1, 0.5 and 1 mg/kg body weight was administered orally every other day for 4 or 6 weeks. HSCs from the LX-2 cell line were treated with transforming growth factor β-1 (TGF-β1 or TGF-β1 plus SME (0.1–10 μg/mL. To investigate the effect of SME on reactive oxygen species (ROS-induced condition, LX-2 cells were treated with hydrogen peroxide (H2O2 or H2O2 plus SME (0.1–100 μg/mL. MCD administration for 12 weeks increased mRNA expression of tumor necrosis factor (TNF-α, TGF-β1, interleukin-1β (IL-1β, C-reactive protein (CRP, α-smooth muscle actin (α-SMA, type I collagen, matrix metalloproteinase-2 (MMP-2 and MMP-9. TGF-β1-induced LX-2 cells exhibited similar gene expression patterns. SME treatment significantly reduced the mRNA and protein expression of NASH-related factors in the mouse model and HSCs. Histopathological liver analysis showed improved non-alcoholic fatty liver disease (NAFLD activity and fibrosis score in SME-treated mice. The in vivo studies showed that SME had a significant effect at low doses. These results suggest that SME might be a potential therapeutic candidate for NAFLD treatment.

  12. The Risk of Abdominal Obesity according to the Degree of Non-Alcoholic Fatty Liver Disease in Korean Men

    OpenAIRE

    Park, Sung Keun; Ryoo, Jae-Hong; Choi, Joong-Myung; Seo, Min Woo; Park, Chung Min

    2016-01-01

    Although non-alcoholic fatty liver disease has been reported as a cardiometabolic risk factor, the effect of non-alcoholic fatty liver is yet to be clarified on abdominal obesity. Therefore, this study was conducted to investigate the longitudinal relationship of non-alcoholic fatty liver on the development of abdominal obesity. The study participants were composed of 11,212 Korean men without abdominal obesity. They were followed up from 2005 to 2010 to be monitored for the development of ab...

  13. Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease.

    Science.gov (United States)

    Reilly, Norelle R; Lebwohl, Benjamin; Hultcrantz, Rolf; Green, Peter H R; Ludvigsson, Jonas F

    2015-06-01

    Non-alcoholic fatty liver disease is a common cause of chronic liver disease. Celiac disease alters intestinal permeability and treatment with a gluten-free diet often causes weight gain, but so far there are few reports of non-alcoholic fatty liver disease in patients with celiac disease. Population-based cohort study. We compared the risk of non-alcoholic fatty liver disease diagnosed from 1997 to 2009 in individuals with celiac disease (n = 26,816) to matched reference individuals (n = 130,051). Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of non-alcoholic fatty liver disease. Cox regression estimated hazard ratios for non-alcoholic fatty liver disease were determined. During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of non-alcoholic fatty liver disease (21/100,000 person-years). In comparison, we identified 85 reference individuals diagnosed with non-alcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95% CI 2.0-3.8), with the highest risk estimates seen in children (HR = 4.6; 95% CI 2.3-9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95% CI 3.5-50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR = 2.5; 95% CI 1.0-5.9). Individuals with celiac disease are at increased risk of non-alcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years after diagnosis with celiac disease. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  14. Motor performance during and following acute alcohol intoxication in healthy non-alcoholic subjects

    DEFF Research Database (Denmark)

    Poulsen, Mette Buch; Jakobsen, Johannes Klitgaard; Andersen, Henning

    2007-01-01

    ). To detect a reduced activation of the central motor pathways superimposed external electrical stimulations during voluntary contractions were applied. Creatine kinase (CK) was measured to detect any alcohol-induced changes in sarcolemmal integrity. No change was seen in isokinetic as well as in isometric...... muscle performance during or following the alcohol intoxication as compared to the non-alcoholic condition. Also, no central activation failure was observed. No significant difference in CK increment was observed comparing the alcoholic- and non-alcoholic condition. In conclusion, a single episode...

  15. Estimated intake of intense sweeteners from non-alcoholic beverages in Denmark, 2005

    DEFF Research Database (Denmark)

    Leth, Torben; Jensen, U.; Fagt, Sisse

    2008-01-01

    In 2005, 76 out of 177 analysed samples of non-alcoholic beverages were found to contain the intense sweeteners cyclamate, acesulfame-K, aspartame, and saccharin. The content of cyclamate did not exceed the now permitted maximum level in the European Union of 250 mg l(-1) in soft drinks. The esti......In 2005, 76 out of 177 analysed samples of non-alcoholic beverages were found to contain the intense sweeteners cyclamate, acesulfame-K, aspartame, and saccharin. The content of cyclamate did not exceed the now permitted maximum level in the European Union of 250 mg l(-1) in soft drinks...

  16. Pharmacological inhibition of the chemokine CXCL16 diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury.

    Directory of Open Access Journals (Sweden)

    Alexander Wehr

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a major cause of morbidity and mortality in developed countries, resulting in steatohepatitis (NASH, fibrosis and eventually cirrhosis. Modulating inflammatory mediators such as chemokines may represent a novel therapeutic strategy for NAFLD. We recently demonstrated that the chemokine receptor CXCR6 promotes hepatic NKT cell accumulation, thereby controlling inflammation in experimental NAFLD. In this study, we first investigated human biopsies (n = 20, confirming that accumulation of inflammatory cells such as macrophages is a hallmark of progressive NAFLD. Moreover, CXCR6 gene expression correlated with the inflammatory activity (ALT levels in human NAFLD. We then tested the hypothesis that pharmacological inhibition of CXCL16 might hold therapeutic potential in NAFLD, using mouse models of acute carbon tetrachloride (CCl4- and chronic methionine-choline-deficient (MCD diet-induced hepatic injury. Neutralizing CXCL16 by i.p. injection of anti-CXCL16 antibody inhibited the early intrahepatic NKT cell accumulation upon acute toxic injury in vivo. Weekly therapeutic anti-CXCL16 administrations during the last 3 weeks of 6 weeks MCD diet significantly decreased the infiltration of inflammatory macrophages into the liver and intrahepatic levels of inflammatory cytokines like TNF or MCP-1. Importantly, anti-CXCL16 treatment significantly reduced fatty liver degeneration upon MCD diet, as assessed by hepatic triglyceride levels, histological steatosis scoring and quantification of lipid droplets. Moreover, injured hepatocytes up-regulated CXCL16 expression, indicating that scavenging functions of CXCL16 might be additionally involved in the pathogenesis of NAFLD. Targeting CXCL16 might therefore represent a promising novel therapeutic approach for liver inflammation and steatohepatitis.

  17. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Wahlang, Banrida; Song, Ming; Beier, Juliane I.; Cameron Falkner, K.; Al-Eryani, Laila; Clair, Heather B.; Prough, Russell A.; Osborne, Tanasa S.; Malarkey, David E.; Christopher States, J.; Cave, Matthew C.

    2014-01-01

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced

  18. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Wahlang, Banrida [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Song, Ming [Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Beier, Juliane I. [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Cameron Falkner, K. [Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Al-Eryani, Laila [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Clair, Heather B.; Prough, Russell A. [Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Osborne, Tanasa S.; Malarkey, David E. [Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Christopher States, J. [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Cave, Matthew C., E-mail: matt.cave@louisville.edu [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202 (United States); The Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206 (United States)

    2014-09-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced

  19. 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

  20. The contribution of metabolic and adipose tissue inflammation to non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Mulder, P.C.A.

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common cause of chronic liver disease, and its worldwide prevalence continues to increase in parallel of the obesity epidemic. NAFLD comprises a wide spectrum of liver damage ranging fat accumulation (steatosis) to steatosis with

  1. Screening for non-alcoholic fatty liver disease in children: do guidelines provide enough guidance?

    NARCIS (Netherlands)

    Koot, B. G. P.; Nobili, V.

    2017-01-01

    Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the industrialized world in children. Its high prevalence and important health risks make NAFLD highly suitable for screening. In practice, screening is widely, albeit not consistently, performed. Aim:

  2. Preserved hemostatic status in patients with non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Potze, Wilma; Siddiqui, Mohammad S.; Boyett, Sherry L.; Adelmeijer, Jelle; Daita, Kalyani; Sanyal, Arun J.; Lisman, Ton

    2016-01-01

    Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of thrombosis. However, it remains unclear if hypercoagulability contributes to this risk. We, therefore, determined an in-depth hemostatic profile in a cohort of well-defined patients with NAFLD.

  3. New insights in the pathogenesis of non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Gaemers, Ingrid C.; Groen, Albert K.

    2006-01-01

    PURPOSE OF REVIEW: The hallmark of non-alcoholic fatty liver disease is hepatic steatosis. This is mostly a benign condition, but for largely unknown reasons it progresses to liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma in about 10% of patients. In this review we discuss recent

  4. Taking care: Creating a non-alcoholic cocktail for Generation X ...

    African Journals Online (AJOL)

    It is recommended that De Pleats puts this non-alcoholic cocktail on their menu. For future research it would be recommended to duplicate this same experiment with the cocktails in a different order, and with another target group like Generation Y. Keywords: sustainability, taste testing, flavour styles, taste preferences ...

  5. Consuming non-alcoholic beer and other beverages during pregnancy and breastfeeding

    OpenAIRE

    Adiong, John Patrick; Kim, Eunji; Koren, Gideon; Bozzo, Pina

    2014-01-01

    Question An increasing number of my patients are asking about the safety of consuming non-alcoholic beer and other alcohol-free versions of alcoholic beverages during pregnancy and breastfeeding, as they believe that these drinks might be a “safer” alternative to regular alcoholic beverages. What are Motherisk’s recommendations regarding these products?

  6. Functional or emotional? How Dutch and Portuguese conceptualise beer, wine and non-alcoholic beer consumption

    NARCIS (Netherlands)

    Silva, Ana Patricia; Jager, Gerry; Bommel, van Roelien; Zyl, van Hannelize; Voss, Hans Peter; Hogg, Tim; Pintado, Manuela; Graaf, de Kees

    2016-01-01

    Non-alcoholic beer (NAB) may be a healthier alternative to wine and beer consumption, however has little appeal to consumers. Conceptualisations, i.e. functional and emotional associations that consumers have with foods/beverages, were explored to understand how NAB consumption is perceived, and

  7. Implications for the pathogenesis of non-alcoholic fatty liver disease

    African Journals Online (AJOL)

    Aim. Explore the possibility that increased gastrointestinal alcohol production may play a role in the pathogenesis of non-alcoholic fatty liver disease in patients with the metabolic syndrome. Methods. Blood, urine and breath levels of alcohol measured in 20 patients with the metabolic syndrome were compared with those of ...

  8. Estimated intake of intense sweeteners from non-alcoholic beverages in Denmark

    DEFF Research Database (Denmark)

    Leth, Torben; Fabricius, N.; Fagt, Sisse

    2007-01-01

    In 1999, 116 samples of non-alcoholic beverages were analysed for the intense sweeteners cyclamate, acesulfame-K, aspartame and saccharin. High contents of cyclamate close to the maximum permitted level in 1999 of 400 mgl(-1) were found in many soft drinks. The estimated intake of the sweeteners...

  9. Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring

    NARCIS (Netherlands)

    Pruis, M. G. M.; Lendvai, A.; Bloks, V. W.; Zwier, M. V.; Baller, J. F. W.; de Bruin, A.; Groen, A. K.; Plosch, T.

    AimMetabolic programming via components of the maternal diet during gestation may play a role in the development of different aspects of the metabolic syndrome. Using a mouse model, we aimed to characterize the role of maternal western-type diet in the development of non-alcoholic fatty liver

  10. Colchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2005-01-01

    Alcohol and hepatotropic viruses cause the majority of liver cirrhosis cases in the Western World. Colchicine is an anti-inflammatory and anti-fibrotic medication. Several randomised clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic or non-alcoholic...

  11. Neonatal monosodium glutamate treatment causes obesity, diabetes, and macrovesicular steatohepatitis with liver nodules in DIAR mice.

    Science.gov (United States)

    Tsuneyama, Koichi; Nishida, Takeshi; Baba, Hayato; Taira, Shu; Fujimoto, Makoto; Nomoto, Kazuhiro; Hayashi, Shinichi; Miwa, Shigeharu; Nakajima, Takahiko; Sutoh, Mitsuko; Oda, Emu; Hokao, Ryoji; Imura, Johji

    2014-09-01

    Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome (MS). Monosodium glutamate (MSG)-treated ICR mice is a useful model of MS and NASH, but it shows the different patterns of steatosis from human NASH. Because inbred aged DIAR (ddY, Institute for Animal Reproduction) mice spontaneously show the similar pattern of steatosis as NASH, we analyzed their liver pathology after administering MSG. MSG-treated DIAR mice (DIAR-MSG) and untreated DIAR mice (DIAR-controls) were sacrificed and assessed histopathologically at 29, 32, 40, 48, and 54 weeks of age. The NASH activity score, body mass index, blood glucose level, and oral glucose tolerance test were also assessed. The body mass index and blood glucose levels of DIAR-MSG were significantly higher than controls. The oral glucose tolerance test revealed a type 2 diabetes pattern in DIAR-MSG. The livers of DIAR-MSG mice showed macrovesicular steatosis, lobular inflammation with neutrophils, and ballooning degeneration after 29 weeks. At 54 weeks, mild fibrosis was observed in 5/6 DIAR-MSG and 2/5 DIAR-control mice. In imaging mass spectrometry analysis, cholesterol as well as triglyceride accumulated in the liver of DIAR-MSG mice. Atypical liver nodules were also observed after 32 weeks in DIAR-MSG, some with cellular and structural atypia mimicking human hepatocellular carcinoma. The NASH activity score of DIAR-MSG after 29 weeks was higher than that of control mice, suggesting the development of NASH. DIAR-MSG had NASH-like liver pathology and liver nodules typically associated with MS symptoms. DIAR-MSG provides a valuable animal model to analyze NASH pathogenesis and carcinogenesis. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  12. 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

  13. Lack of ClC-2 Alleviates High Fat Diet-Induced Insulin Resistance and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Dongxia Fu

    2018-03-01

    Full Text Available Background/Aims: Non-alcoholic fatty liver disease (NAFLD is the most common cause of chronic liver disease. This study aims to investigate whether chloride channel 2 (ClC-2 is involved in high fat diet (HFD-induced NAFLD and possible molecular mechanisms. Methods: ClC-2 expression was liver-specifically downregulated using adeno-associated virus in C57BL/6 mice treated with a chow diet or HFD for 12 weeks. Peripheral blood and liver tissues were collected for biochemical and pathological estimation respectively. Western blotting was applied to detect the protein expressions of lipid synthesis-related enzymes and the phosphorylated level of IRS-1, Akt and mTOR. Results: ClC-2 mRNA level was significantly increased in patients with non-alcoholic steatohepatitis, which positively correlated with the plasma levels of alanine transaminase (ALT, aspartate transaminase (AST and insulin. Knockdown of ClC-2 in liver attenuated HFD-induced weight gain, obesity, hepatocellular ballooning, and liver lipid accumulation and fibrosis, accompanied by reduced plasma free fatty acid (FFA, triglyceride (TG, total cholesterol (TC, ALT, AST, glucose and insulin levels and homeostasis model of insulin resistance (HOMA-IR value. Moreover, HFD-treated mice lacking ClC-2 showed inhibited hepatic lipid accumulation via regulating lipid metabolism through decreasing sterol regulatory element binding protein (SREBP-1c expression and its downstream targeting enzymes such as fatty acid synthase (FAS, HMG-CoA reductase (HMGCR and acetyl-Coenzyme A carboxylase (ACCα. In addition, in vivo and in vitro results demonstrated that ClC-2 downregulation in HFD-treated mice or HepG2 cells increased the sensitivity to insulin via activation of IRS-1/Akt/mTOR signaling pathway. Conclusion: Our present study reveals a critical role of ClC-2 in regulating metabolic diseases. Mice lacking ClC-2 are associated with a remarkably beneficial metabolic phenotype, suggesting that decreasing Cl

  14. Health and economic benefits of reducing sugar intake in the USA, including effects via non-alcoholic fatty liver disease: a microsimulation model

    Science.gov (United States)

    Vreman, Rick A; Goodell, Alex J; Rodriguez, Luis A; Porco, Travis C; Lustig, Robert H; Kahn, James G

    2017-01-01

    Objectives Excessive consumption of added sugars in the human diet has been associated with obesity, type 2 diabetes (T2D), coronary heart disease (CHD) and other elements of the metabolic syndrome. Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is a critical pathway to metabolic syndrome. This model assesses the health and economic benefits of interventions aimed at reducing intake of added sugars. Methods Using data from US National Health Surveys and current literature, we simulated an open cohort, for the period 2015–2035. We constructed a microsimulation model with Markov chains for NAFLD (including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)), body mass index, T2D and CHD. We assessed reductions in population disease prevalence, disease-attributable disability-adjusted life years (DALYs) and costs, with interventions that reduce added sugars consumption by either 20% or 50%. Findings The model estimated that a 20% reduction in added sugars intake will reduce prevalence of hepatic steatosis, NASH, cirrhosis, HCC, obesity, T2D and CHD. Incidence of T2D and CHD would be expected to decrease by 19.9 (95% CI 12.8 to 27.0) and 9.4 (95% CI 3.1 to 15.8) cases per 100 000 people after 20 years, respectively. A 20% reduction in consumption is also projected to annually avert 0.767 million (M) DALYs (95% CI 0.757M to 0.777M) and a total of US$10.3 billion (B) (95% CI 10.2B to 10.4B) in discounted direct medical costs by 2035. These effects increased proportionally when added sugars intake were reduced by 50%. Conclusions The decrease in incidence and prevalence of disease is similar to results in other models, but averted costs and DALYs were higher, mainly due to inclusion of NAFLD and CHD. The model suggests that efforts to reduce consumption of added sugars may result in significant public health and economic benefits. PMID:28775179

  15. The Galician Beverage Picture Set (GBPS): A standardized database of alcohol and non-alcohol images.

    Science.gov (United States)

    López-Caneda, E; Carbia, C

    2018-03-01

    The available picture sets in alcohol research are scarce and display a number of limitations, including poor picture quality, limited number of stimuli and absence of non-alcohol and/or real-life images. In the present study, we developed the Galician Beverage Picture Set (GBPS), a database of high-quality alcohol and non-alcohol pictures embedded in real-life scenarios. A total of 201 college students (∼59% females) were assessed by the Alcohol Use Disorders Identification Test, ∼54% being characterized as no/low drinkers (N/LDs) and ∼46% as risky drinkers (RDs). The GBPS included six types of beverages: beer, wine, liquor (alcoholic drinks); water, juice, milk (non-alcoholic drinks). Additionally, two subcategories were considered: orientation (landscape, portrait) and number of people (0, 1, ≥2 people). Participants rated the images for valence, arousal and visual complexity. Objective measures of brightness and color and recognition rates were also assessed. Internal consistency was estimated using Cronbach's alpha coefficient. There was a high degree of internal consistency within each category (alcoholic and non-alcoholic drinks) for valence, arousal and visual complexity scores. A mixed-model ANOVA revealed that RDs rated alcohol pictures as more pleasant and arousing than N/LDs. Conversely, N/LDs displayed greater valence and arousal ratings than RDs for non-alcohol pictures. The GBPS provides normative data on affective (valence/arousal), perceptual (visual complexity) and physical (brightness/color) values for a large number of images that may be useful for alcohol-related research. Differences in subjective assessments between N/LDs and RDs support the picture set's suitability for studies in young drinkers. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Association between non-alcoholic hepatic steatosis and hyper reactive blood pressure response on the exercise treadmill test

    OpenAIRE

    Laurinavicius, A.G.; Bittencourt, M.S.; Blaha, M.J.; Nary, F.C.; Kashiwagi, N.M.; Conceiçao, R.D.; Meneghelo, R.S.; Prado, R.R.; Carvalho, J.A.M.; Nasir, K.; Blumenthal, R.S.; Santos, R.D.

    2016-01-01

    Aims: Non-alcoholic hepatic steatosis (HS) is associated with hypertension and increased cardiovascular risk. While Blood pressure hyper-reactive response (HRR) during peak exercise indicates an increased risk of incident hypertension and increased cardiovascular risk, no data on the association of non-alcoholic HS and HRR exists. In this study, we have evaluated the association of HS with HRR.

  17. The Risk of Abdominal Obesity according to the Degree of Non-Alcoholic Fatty Liver Disease in Korean Men.

    Science.gov (United States)

    Park, Sung Keun; Ryoo, Jae-Hong; Choi, Joong-Myung; Seo, Min Woo; Park, Chung Min

    2016-03-01

    Although non-alcoholic fatty liver disease has been reported as a cardiometabolic risk factor, the effect of non-alcoholic fatty liver is yet to be clarified on abdominal obesity. Therefore, this study was conducted to investigate the longitudinal relationship of non-alcoholic fatty liver on the development of abdominal obesity. The study participants were composed of 11,212 Korean men without abdominal obesity. They were followed up from 2005 to 2010 to be monitored for the development of abdominal obesity according to their degree of non-alcoholic fatty liver disease (normal, mild, and moderate to severe). Cox-proportional hazard model was used to calculate the hazard ratios for abdominal obesity according to the degree of non-alcoholic fatty liver disease. While the average incidence was 15.5%, the incidence of abdominal obesity increased according to the degree of non-alcoholic fatty liver (normal: 11.6%, mild: 25.2%, moderate to severe: 41.0%, P obesity independently increased proportionally to the degree of NAFLD (mild [1.07; 0.94-1.23], moderate to severe [1.58; 1.11-2.26], P for trend obesity increased proportionally to the degree of non-alcoholic fatty liver disease. This finding guarantees further studies to reveal the incidental relationship of abdominal obesity with non-alcoholic fatty liver disease.

  18. Severe steatohepatitis with hepatic decompensation resulting from malnutrition after pancreaticoduodenectomy

    Directory of Open Access Journals (Sweden)

    Eun Hui Sim

    2012-12-01

    Full Text Available The most common finding related to nonalcoholic steatohepatitis is obesity, but a status of severe malnutrition can also induce the steatohepatitis. The authors report a rare case of steatohepatitis leading to hepatic decompensation caused by malnutrition after pancreaticoduodenectomy. A 68-year-old female patient who had been previously diagnosed with pancreatic cancer and had undergone pancreaticoduodenectomy 5 months previously presented with abdominal distension. Routine CT performed 3 months after the surgery revealed severe fatty liver without evidence of tumor recurrence. After undergoing pancreaticoduodenectomy her food intake had reduced, and as a result she had lost 7 kg of body weight over 2 months. At this admission, CT revealed moderate amounts of ascites without tumor recurrence. Furthermore, her albumin and lipid profile levels were markedly decreased, and she had a flapping tremor and slurred speech suggestive of hepatic encephalopathy. Her liver biopsy findings were consistent with steatohepatitis and disclosed macrovesicular steatosis without definite fibrosis. After careful nutritional control, her symptoms disappeared and her laboratory findings improved.

  19. Ursodeoxycholic Acid and Atorvastatin in the Treatment of Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Murat Kiyici

    2003-01-01

    Full Text Available BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH is a serious disorder with the potential to gradually progress to cirrhosis. It is generally associated with obesity, diabetes and hyperlipidemia. Currently, there is no established therapy for NASH. The aim of the present study was to evaluate the effectiveness of atorvastatin and ursodeoxycholic acid (UDCA in the treatment of NASH.

  20. Type 2 Diabetes in Non-Alcoholic Fatty Liver Disease and Hepatitis C Virus Infection--Liver: The "Musketeer" in the Spotlight.

    Science.gov (United States)

    Ballestri, Stefano; Nascimbeni, Fabio; Romagnoli, Dante; Baldelli, Enrica; Targher, Giovanni; Lonardo, Amedeo

    2016-03-09

    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.

  1. 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.

  2. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Wahlang, Banrida; Song, Ming; Beier, Juliane I; Cameron Falkner, K; Al-Eryani, Laila; Clair, Heather B; Prough, Russell A; Osborne, Tanasa S; Malarkey, David E; Christopher States, J; Cave, Matthew C

    2014-09-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20mg/kg or 200mg/kg in corn oil) for 12weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260+HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant "second hit" in the transformation of steatosis to steatohepatitis. Copyright © 2014. Published by Elsevier Inc.

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

    Science.gov (United States)

    Ballestri, Stefano; Nascimbeni, Fabio; Romagnoli, Dante; Baldelli, Enrica; Targher, Giovanni; Lonardo, Amedeo

    2016-01-01

    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. PMID:27005620

  4. AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Beale, Gary; Reeves, Helen; Chattopadhyay, Dipankar; Gray, Joe; Stewart, Stephen; Hudson, Mark; Day, Christopher; Trerotoli, Paolo; Giannelli, Gianluigi; Manas, Derek

    2008-01-01

    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. 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. 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. 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 that the choice of optimal biomarkers for HCC

  5. A case of insulinoma with non-alcoholic fatty liver disease: Roles of hyperphagia and hyperinsulinemia in pathogenesis of the disease.

    Science.gov (United States)

    Rokutan, Mariyo; Yabe, Daisuke; Komoto, Izumi; Kurose, Takeshi; Kawai, Jun; Nakamura, Takefumi; Imamura, Masayuki; Seino, Yutaka

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a serious health-related condition all over the world; the number of patients is increasing in Asian countries including Japan. Better understanding of its pathophysiology is required to develop effective therapeutics, as patients may go on to develop non-alcoholic steatohepatitis and hepatocellular carcinomas. While NAFLD is believed to be associated with metabolic risk factors such as obesity, diabetes, and dyslipidemia, its etiology remains largely unknown and the development or co-existence of NAFLD in patients with insulinoma has not been investigated. A 33-year-old male with an insulinoma, who had been hypoglycemic during the previous four years, developed abnormally elevated levels of liver enzymes and histological fatty liver characteristic of NAFLD by the time of admission to our hospital for resection of an insulinoma. His medical records for the previous eight years revealed that his bodyweight had increased gradually from 60 kg to 71 kg for seven years and then acutely increased to 79 kg in the latest one-year period. This sudden increase was thought to be due to the patient's self-described overeating of fruits to forestall hypoglycemia. Fresh fruits are rich in fructose, and the patient's triglycerides, alanine and aspartate transaminases showed an acute increase in the previous one-year period. After resection of the insulinoma, the levels of these parameters all were mostly restored, which suggests that hyperinsulinemia and subsequent hyperphagia played a role in the development of NAFLD in this case. This is the first report of patient with NAFLD and an insulinoma.

  6. Effect of a Low Glycemic Index Mediterranean Diet on Non-Alcoholic Fatty Liver Disease. A Randomized Controlled Clinici Trial.

    Science.gov (United States)

    Misciagna, G; Del Pilar Díaz, M; Caramia, D V; Bonfiglio, C; Franco, I; Noviello, M R; Chiloiro, M; Abbrescia, D I; Mirizzi, A; Tanzi, M; Caruso, M G; Correale, M; Reddavide, R; Inguaggiato, R; Cisternino, A M; Osella, A R

    2017-01-01

    Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the most common form of liver disease worldwide affecting all ages and ethnic groups and it has become a consistent threat even in young people. Our aim was to estimate the effect of a Low Glycemic Index Mediterranean Diet (LGIMD) on the NAFLD score as measured by a Liver Ultrasonography (LUS). NUTRIzione in EPAtologia (NUTRIEPA) is a population-based Double-Blind RCT. Data were collected in 2011 and analyzed in 2013-14. 98 men and women coming from Putignano (Puglia, Southern Italy) were drawn from a previous randomly sampled population-based study and identified as having moderate or severe NAFLD. The intervention strategy was the assignment of a LGIMD or a control diet. The main outcome measure was NAFLD score, defined by LUS. After randomization, 50 subjects were assigned to a LGIMD and 48 to a control diet. The study lasted six months and all participants were subject to monthly controls/checks. Adherence to the LGIMD as measured by Mediterranean Adequacy Index (MAI) showed a median of 10.1. A negative interaction between time and LGIMD on the NAFLD score (-4.14, 95% CI -6.78,-1.49) was observed, and became more evident at the sixth month (-4.43, 95%CI -7.15, -1.71). A positive effect of the interaction among LGIMD, time and age (Third month: 0.07, 95% CI 0.02, 0.12; Sixth month: 0.08, 95% CI 0.03,0.13) was also observed. LGIMD was found to decrease the NAFLD score in a relatively short time. Encouraging those subjects who do not seek medical attention but still have NAFLD to follow a LGIMD and other life-style interventions, may reduce the degree of severity of the disease. Dietary intervention of this kind, could also form the cornerstone of primary prevention of Type 2 Diabetes Mellitus (T2DM) and cardiovascular disease.

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

    OpenAIRE

    Temple, J. L.; Cordero, P.; Li, J.; Vi, N.; Oben, J. 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 ...

  8. Can Diet Help Non-Obese Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD)?

    OpenAIRE

    Merchant, Hamid A.

    2017-01-01

    Subjects diagnosed with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis are usually obese or overweight. NAFLD has also been reported in many non-obese healthy subjects as an incidental finding during imaging. Subjects with early-stage NAFLD who are otherwise healthy are often left unmanaged in current clinical practice; it is not clear if an early intervention in those individuals would be of any benefit in preventing NAFLD progression to more serious conditions. Since many of...

  9. Dietary Composition Independent of Weight Loss in the Management of Non-Alcoholic Fatty Liver Disease

    OpenAIRE

    Eslamparast, Tannaz; Tandon, Puneeta; Raman, Maitreyi

    2017-01-01

    Poor dietary composition is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD). The majority of NAFLD patients follow diets with overconsumption of simple carbohydrates, total and saturated fat, with reduced intake of dietary fiber and omega-3 rich foods. Although lifestyle modifications including weight loss and exercise remain the keystone of NAFLD management, modifying dietary composition with or without a calorie-restricted diet may also be a feasible and ...

  10. Serum acid sphingomyelinase is upregulated in chronic hepatitis C infection and non alcoholic fatty liver disease.

    Science.gov (United States)

    Grammatikos, Georgios; Mühle, Christiane; Ferreiros, Nerea; Schroeter, Sirkka; Bogdanou, Dimitra; Schwalm, Stephanie; Hintereder, Gudrun; Kornhuber, Johannes; Zeuzem, Stefan; Sarrazin, Christoph; Pfeilschifter, Josef

    2014-07-01

    Sphingolipids constitute bioactive molecules with functional implications in homeostasis and pathogenesis of various diseases. However, the role of sphingolipids as possible disease biomarkers in chronic liver disease remains largely unexplored. In the present study we used mass spectrometry and spectrofluorometry methods in order to quantify various sphingolipid metabolites and also assess the activity of an important corresponding regulating enzyme in the serum of 72 healthy volunteers as compared to 69 patients with non-alcoholic fatty liver disease and 69 patients with chronic hepatitis C virus infection. Our results reveal a significant upregulation of acid sphingomyelinase in the serum of patients with chronic liver disease as compared to healthy individuals (phepatitis C infection acid sphingomyelinase activity correlated significantly with markers of hepatic injury (r=0.312, p=0.009) and showed a high discriminative power. Accumulation of various (dihydro-) ceramide species was identified in the serum of patients with non-alcoholic fatty liver disease (pliver disease (phepatic injury was identified. Chronic hepatitis C virus infection and non-alcoholic fatty liver disease induce a significant upregulation of serum acid sphingomyelinase which appears as a novel biomarker in chronic hepatopathies. Further studies are required to elucidate the potential of the sphingolipid signaling pathway as putative therapeutic target in chronic liver disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Parent-child relationship in children of alcoholic and non-alcoholic parents

    Directory of Open Access Journals (Sweden)

    Babita Mahato

    2009-01-01

    Full Text Available Aim: Overall aim of the study was to see parent-child relationship in children of alcoholic and non-alcoholic parents. Materials and Methods: The sample consisted of 30 alcoholic and 30 non-alcoholic parents and their children taken from Kanke Block of Ranchi district. The sample was selected on the basis of inclusion and exclusion criteria. Socio-demographic data sheet and Parent Child Relationship Scale (Rao, 1978 were administered to the children. Results: In a child′s perception of father in various domains of parent-child relationship, significant difference at P < 0.01 was found in the domain of symbolic punishment, rejecting, objective punishment, demanding, indifferent, symbolic reward in loving and neglecting, and in child′s perception of the mother. Significant difference at P < 0.01 was found in the domain of symbolic punishment, rejecting, object punishment, indifferent and in neglecting. Conclusion: The result showed that the children of alcoholic parents tended to have more symbolic punishment, rejecting, objective punishment, demanding, indifferent, symbolic reward loving and in neglecting than children of non alcoholic parents.

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

    Directory of Open Access Journals (Sweden)

    Zhi-Jun He

    2016-07-01

    Full Text Available 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.

  13. [Content of carbohydrates and trace elements in a group of non-alcoholic drinks].

    Science.gov (United States)

    Elena, M; Pérez, M; Jansà, M; Déulofeu, R; Esmatjes, E; Schinca, N; Mas, E; Molina, R; Ballesta, A M

    1998-03-21

    In order to elaborate recommendations for the dietetic care of diabetic patients and other clinical disorders we have measured the concentration of carbohydrates and trace elements in a group of non alcoholic refreshments of current use in Spain. Thirty refreshments were classified into 10 groups. Glucose and phosphate were measured by hexokinase and reduction of phospho-molybdate methods respectively in an autoanalyzer Dax-72. Glucose and fructose were analyzed by cellulose thin-layer chromatography; glucose, fructose and sucrose by gas chromatographys. Sodium and potassium by emission spectrophotometry and calcium, magnesium, iron, copper and zinc by atomic absorption spectrophotometry. Light refreshments and soft drinks have no carbohydrates. Isotonic beverages, fruit juices, cool tea and non alcoholic beers had less than 10 g/dl. Tonic waters, Fanta, different coles, non alcoholic bitter and others had more than 10 g/dl. Sodium levels between 15-20 mEq/l were found in the isotonic beverages and 7-Up and levels of 7 mEq/l in the others. Potassium values between 15-40 mEq/l were found in the fruit juices, 3-4 mEq/l in Gatorade and less than 1 mEq/l in the others. Light refreshments and soft drinks contain low concentrations of carbohydrates and sodium. Fruit juices have high potassium concentration. Such information can be especially useful for dietetic care of diabetic patients.

  14. Composition and Nutrient Information of Non-Alcoholic Beverages in the Spanish Market: An Update.

    Science.gov (United States)

    Serrano Iglesias, María; de Lourdes Samaniego Vaesken, María; Varela Moreiras, Gregorio

    2016-10-08

    The aim of this study was to draw an updated map of the nutrition facts in the different categories of non-alcoholic beverages in the Spanish market based on the information declared on the labels of these products; we expect this first step to justify the need for the coordination and harmonization of food composition tables in Spain so that there will be an updated database available to produce realistic scientific nutrient intake estimates in accordance with the actual market scenario. The nutrition facts declared on the labels of non-alcoholic beverages by manufacturers in Spain were compiled and studied. The database included 211 beverages classified in 7 groups with energy/carbohydrate content per 100 mL ranging from 0-55 kcal/0-13 g for soft drinks; 2-60 kcal/0-14.5 g for energy drinks; 24-31 kcal/5.8-7.5 g for sports drinks; 1-32 kcal/0-7.3 g for drinks containing mineral salts in their composition; 14-69 kcal/2.6-17 g for fruit juice, nectar, and grape musts; 43-78 kcal/6.1-14.4 g for vegetable drinks; and 33-88 kcal/3.6-14 g for dairy drinks. The current non-alcoholic beverage market is a dynamic, growing, and highly innovative one, allowing consumers to choose according to their preferences, needs, or level of physical activity at any moment of the day.

  15. Research of Household Expenditure for Food and Non-Alcoholic Beverages in the Republic of Croatia

    Directory of Open Access Journals (Sweden)

    Krsto Kero

    2011-12-01

    Full Text Available The aim of this paper is to investigate household spending by income deciles. Only the most important one among the expenditure categories was considered, food and non-alcoholic beverages. Research and analysis were based on the results of the Questionnaire on Household Expenditure in the Republic of Croatia. Adequate mathematical and statistical models of expenditure for food and non-alcoholic beverages by income deciles were established. The defined models were used in further research to calculate the coefficient of elasticity. The research showed that expenditure for food and non-alcoholic beverages is non-elastic, thus confirming the first Engel’s law. The obtained results can be used in planning household expenditure also in future periods, considering the fact that the model of expenditure by income deciles referring to the period 200 – 2009 was developed. A model for measuring elasticity was constructed as well. It refers to a 10-year period and can be used to forecast future coefficients of elasticity.

  16. Australian print news media coverage of sweet, non-alcoholic drinks sends mixed health messages.

    Science.gov (United States)

    Bonfiglioli, Catriona; Hattersley, Libby; King, Lesley

    2011-08-01

    This study aimed to analyse the contribution of Australian print news coverage to the public profile of sweet, non-alcoholic beverages. News media portrayal of health contributes to individuals' decision-making. The focus on sugar-sweetened beverages reflects their contribution to excessive energy intake. One year's coverage of sweet, non-alcoholic beverages by major Australian newspapers was analysed using content and frame analysis. Research questions addressed which sweet drinks are most prominently covered, what makes sweet drinks newsworthy and how are the health aspects of sweet drinks framed? Fruit juice was the most widely covered sweet drink, closely followed by carbonated, sugar-sweetened soft drinks. Overall coverage was positively oriented towards sweet drinks, with fruit juice primarily portrayed as having health benefits. Some coverage mentioned risks of sweet drinks, such as obesity, tooth decay, metabolic syndrome and heart attack. Sweet drinks often enjoy positive coverage, with their health benefits and harms central to their ability to attract journalists' attention. However, the mix of coverage may be contributing to consumer confusion about whether it is safe and/or healthy to consume sweet non-alcoholic drinks. Framing of sweet drinks as healthy may undermine efforts to encourage individuals to avoid excess consumption of energy-dense drinks which offer few or minimal health benefits. © 2011 The Authors. ANZJPH © 2011 Public Health Association of Australia.

  17. 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

    2015-01-01

    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. PMID:25941433

  18. Beer and its Non-Alcoholic Compounds: Role in Pancreatic Exocrine Secretion, Alcoholic Pancreatitis and Pancreatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Peter Feick

    2010-03-01

    Full Text Available : In this article we provide an overview of the newest data concerning the effect of non-alcoholic constituents of alcoholic beverages, especially of beer, on pancreatic secretion, and their possible role in alcoholic pancreatitis and pancreatic carcinoma. The data indicate that non-alcoholic constituents of beer stimulate pancreatic enzyme secretion in humans and rats, at least in part, by direct action on pancreatic acinar cells. Some non-alcoholic compounds of beer, such as quercetin, resveratrol, ellagic acid or catechins, have been shown to be protective against experimentally induced pancreatitis by inhibiting pancreatic secretion, stellate cell activation or by reducing oxidative stress. Quercetin, ellagic acid and resveratrol also show anti-carcinogenic potential in vitro and in vivo. However, beer contains many more non-alcoholic ingredients. Their relevance in beer-induced functional alterations of pancreatic cells leading to pancreatitis and pancreatic cancer in humans needs to be further evaluated.

  19. Beer and its Non-Alcoholic Compounds: Role in Pancreatic Exocrine Secretion, Alcoholic Pancreatitis and Pancreatic Carcinoma

    Science.gov (United States)

    Gerloff, Andreas; Singer, Manfred V; Feick, Peter

    2010-01-01

    In this article we provide an overview of the newest data concerning the effect of non-alcoholic constituents of alcoholic beverages, especially of beer, on pancreatic secretion, and their possible role in alcoholic pancreatitis and pancreatic carcinoma. The data indicate that non-alcoholic constituents of beer stimulate pancreatic enzyme secretion in humans and rats, at least in part, by direct action on pancreatic acinar cells. Some non-alcoholic compounds of beer, such as quercetin, resveratrol, ellagic acid or catechins, have been shown to be protective against experimentally induced pancreatitis by inhibiting pancreatic secretion, stellate cell activation or by reducing oxidative stress. Quercetin, ellagic acid and resveratrol also show anti-carcinogenic potential in vitro and in vivo. However, beer contains many more non-alcoholic ingredients. Their relevance in beer-induced functional alterations of pancreatic cells leading to pancreatitis and pancreatic cancer in humans needs to be further evaluated. PMID:20617020

  20. Notch signaling and progenitor/ductular reaction in steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Carola M Morell

    Full Text Available Persistent hepatic progenitor cells (HPC activation resulting in ductular reaction (DR is responsible for pathologic liver repair in cholangiopathies. Also, HPC/DR expansion correlates with fibrosis in several chronic liver diseases, including steatohepatitis. Increasing evidence indicates Notch signaling as a key regulator of HPC/DR response in biliary and more in general liver injuries. Therefore, we aimed to investigate the role of Notch during HPC/DR activation in a mouse model of steatohepatitis.Steatohepatitis was generated using methionine-choline deficient (MCD diet. For hepatocyte lineage tracing, R26R-YFP mice were infected with AAV8-TBG-Cre.MCD diet promoted a strong HPC/DR response that progressively diffused in the lobule, and correlated with increased fibrosis and TGF-β1 expression. Notch signaling was unchanged in laser-capture microdissected HPC/DR, whereas Notch receptors were down regulated in hepatocytes. However, in-vivo lineage tracing experiments identified discrete hepatocytes showing Notch-1 activation and expressing (the Notch-dependent Sox9. Stimulation of AML-12 hepatocyte-cell line with immobilized Jag1 induced Sox9 and down-regulated albumin and BSEP expression. TGF-β1 treatment in primary hepatic stellate cells (HSC induced Jag1 expression. In MCD diet-fed mice, αSMA-positive HSC were localized around Sox9 expressing hepatocytes, suggesting that Notch activation in hepatocytes was promoted by TGF-β1 stimulated HSC. In-vivo Notch inhibition reduced HPC response and fibrosis progression.Our data suggest that Notch signaling is an important regulator of DR and that in steatohepatitis, hepatocytes exposed to Jag1-positive HSC, contribute to pathologic DR by undergoing Notch-mediated differentiation towards an HPC-like phenotype. Given the roles of Notch in fibrosis and liver cancer, these data suggest mesenchymal expression of Jag1 as an alternative therapeutic target.

  1. Impact of bariatric surgery on non-alcoholic fatty liver disease.

    Science.gov (United States)

    Major, Piotr; Pędziwiatr, Michał; Rubinkiewicz, Mateusz; Stanek, Maciej; Głuszewska, Anna; Pisarska, Magdalena; Małczak, Piotr; Budzyński, Andrzej; Budzyński, Piotr

    2017-04-30

    Introduction; p to 300 million people have the body mass index (BMI) greater than 30 kg/m2. Obesity is the cause of many serious diseases, such as type 2 diabetes, hypertension, and non-alcoholic fatty liver disease (NAFLD). Bariatric surgery is the only effective method of achieving weight loss in patients with morbid obesity. The aim of the study was to assess the impact of bariatric surgery on non-alcoholic fatty liver disease in patients operated on due to morbid obesity. We included 20 patients who were qualified for bariatric procedures based on BMI > 40 kg/ m2 or BMI > 35kg/m2 with the presence of comorbidities. The average body weight in the group was 143.85kg, with an average BMI of 49.16kg/m2. Before the procedure, we evaluated the severity of non-alcoholic fatty liver disease in each patient using the Sheriff-Saadeh ultrasound scale. We also evaluated the levels of liver enzymes. Follow-up evaluation was performed twelve months after surgery. Twelve months after surgery, the average weight was 102.34 kg. The mean %WL was 33.01%, %EWL was 58.8%, and %EBMIL was 61.37%. All patients showed remission of fatty liver disease. Liver damage, evaluated with ultrasound imaging, decreased from an average of 1.85 on the Sheriff-Saadeh scale, before surgery, to 0.15 twelve months after surgery (p < 0.001). As regards liver enzymes, the level of alanine aminotransferase decreased from 64.5 (U/l) to 27.95 (U/l) (p < 0.001), and the level of aspartate aminotransferase decreased from 54.4 (U/l) to 27.2 (U/l). Bariatric procedures not only lead to a significant and lasting weight loss, but they also contribute to the reduction of fatty liver disease and improve liver function.

  2. Composition and Nutrient Information of Non-Alcoholic Beverages in the Spanish Market: An Update

    Directory of Open Access Journals (Sweden)

    María Serrano Iglesias

    2016-10-01

    Full Text Available The aim of this study was to draw an updated map of the nutrition facts in the different categories of non-alcoholic beverages in the Spanish market based on the information declared on the labels of these products; we expect this first step to justify the need for the coordination and harmonization of food composition tables in Spain so that there will be an updated database available to produce realistic scientific nutrient intake estimates in accordance with the actual market scenario. Materials and Methods: The nutrition facts declared on the labels of non-alcoholic beverages by manufacturers in Spain were compiled and studied. Results: The database included 211 beverages classified in 7 groups with energy/carbohydrate content per 100 mL ranging from 0–55 kcal/0–13 g for soft drinks; 2–60 kcal/0–14.5 g for energy drinks; 24–31 kcal/5.8–7.5 g for sports drinks; 1–32 kcal/0–7.3 g for drinks containing mineral salts in their composition; 14–69 kcal/2.6–17 g for fruit juice, nectar, and grape musts; 43–78 kcal/6.1–14.4 g for vegetable drinks; and 33–88 kcal/3.6–14 g for dairy drinks. Conclusion: The current non-alcoholic beverage market is a dynamic, growing, and highly innovative one, allowing consumers to choose according to their preferences, needs, or level of physical activity at any moment of the day.

  3. Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice.

    Science.gov (United States)

    Ou, Rongying; Liu, Jia; Lv, Mingfen; Wang, Jingying; Wang, Jinmeng; Zhu, Li; Zhao, Liang; Xu, Yunsheng

    2017-07-01

    Non-alcoholic fatty liver disease is highly associated with morbidity and mortality in population. Although studies have already demonstrated that the immune response plays a pivotal role in the development of non-alcoholic fatty liver disease, the comprehensive regulation is unclear. Therefore, present study was carried out to investigate the non-alcoholic fatty liver disease development under neutrophil depletion. To achieve the aim of the study, C57BL/6 J mice were fed with high fat diet for 6 weeks before treated with neutrophil deplete antibody 1A8 or isotype control (200 μg/ mouse every week) for another 4 weeks. Treated with 1A8 antibody, obese mice exhibited better whole body metabolic parameters, including reduction of body weight gain and fasting blood glucose levels. Neutrophil depletion also effectively reduced hepatic structural disorders, dysfunction and lipid accumulation. Lipid β-oxidative markers, phosphorylated-AMP-activated protein kinase α and phosphorylated-acetyl-CoA carboxylase levels were increased in 1A8 antibody-treated obese mouse group. The mitochondrial number and function were also reversed after 1A8 antibody treatment, including increased mitochondrial number, reduced lipid oxidative damage and enhanced mitochondrial activity. Furthermore, the expression of inflammatory cytokines, tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 were obviously reduced after neutrophil depletion, accompanied with decreased F4/80 mRNA level and macrophage percentage in liver. The decreased NF-κB signaling activity was also involved in the beneficial effect of neutrophil depletion. Taken together, neutrophil depletion could attenuate metabolic syndromes and hepatic dysfunction.

  4. Further evidence for GHB naturally occurring in common non-alcoholic beverages.

    Science.gov (United States)

    Elliott, Simon P; Fais, Paolo

    2017-08-01

    GHB has been implicated in many cases of suspected surreptitious administration with the purpose of increasing victim vulnerability to sexual assault. Low amounts of endogenous (or naturally occurring) GHB, which do not reach pharmacologically active levels, have been detected in alcoholic and non-alcoholic beverages. Due to the continued requirement to obtain data on the presence of endogenous GHB in various beverage types, GHB concentrations were measured in a series of non-alcoholic beverages. Tonic water and lemon flavoured tonic water beverages were analysed at 0, 24 and 96h after the bottle opening using gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) on an Agilent 6890/7000C Triple Quadrupole. GHB was detected in all beverages at very low amounts ranging from 89 to 145ng/mL (0.089-0.145mg/L) and did not demonstrate a general trend of variation for concentration along the tested time span (96h). The presented data provide additional evidence for the endogenous nature of GHB in non-alcoholic beverages at very low concentrations, which are many orders of magnitude lower than those described to produce any pharmacological effect on the subject. However, when considering a case of alleged drug-facilitated sexual assault, a low level of GHB detected in a drink may be related both to a surreptitiously GHB administration with subsequent dilution for concealment or to the presence of endogenous GHB. On this basis, a comprehensive analysis of all the available information, including circumstantial data demonstrating possible attempts to conceal GHB administration and an assessment of levels of endogenous GHB in the suspected beverage type, is of the utmost importance for a proper interpretation of the toxicological results. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Lifestyle Modification through Dietary Intervention: Health Promotion of Patients with Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Manoochehr Khoshbaten

    2011-12-01

    Full Text Available Background: Prevalence of non-alcoholic fatty liver disease (NAFLD is more common worldwide and no certain treatment apart from lifestyle modification has been established yet. Available data consistently show that energy intake is significantly higher in patients with NAFLD than in individuals with no evidence of fatty liver. Changing nutritional behaviors seems to be the primary approach for treatment, simultaneously addressing all the clinical and biochemical defects. This study was aimed to examine the effects of two different composition of low energy diet (diet I vs. diet II on non-alcoholic fatty liver disease patients.Methods: In this double-blind randomized controlled trial, 44 ultrasonography-proven overweight non-alcoholic fatty liver disease patients were divided into two groups and received two low-energy diets (-500 kcal less than energy requirement individually inc. diet I (Carbohydrate: Fat: Protein: 55:25:20 and diet II (Carbohydrate: Fat: Protein: 40:40:20 for six weeks. Anthropometric and biochemical measures as well as liver enzymes were assessed after 12 hours fasting.Results: After diet I and diet II, weight decreased significantly (%1.82 and %2.45, respectively. Liver enzymes and echogenicity decreased significantly by both diet I and diet II. Mean of triglyceride concentration decreased (%18.09 after diet II (P=0.023, while there was no significant change after diet I. Significant correlations were found between changes in aspartate aminotransferase with triglyceride and LDL-C diet I.Conclusion: Low energy diets can decrease liver enzymes regardless of their composition, while diet II seems to be more effective than diet I in reduction of weight and triglyceride level.

  6. Application of localized 31P 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

    International Nuclear Information System (INIS)

    Valkovic, Ladislav; Gajdosik, Martin; Chmelik, Marek; Trattnig, Siegfried; Traussnigg, Stefan; Kienbacher, Christian; Trauner, Michael; Wolf, Peter; Krebs, Michael; Bogner, Wolfgang; Krssak, Martin

    2014-01-01

    Saturation transfer (ST) phosphorus MR spectroscopy ( 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 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 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 ( 1 H) MRS, measured at 3 T. The mean exchange rate constant (k) in healthy volunteers was 0.31 ± 0.03 s -1 with a coefficient of variation of 9.0 %. Significantly lower exchange rates (p -1 ) when compared to healthy volunteers, and NAFL patients (k = 0.30 ± 0.05 s -1 ). Significant correlation was found between the k value and the liver fat content (r = 0.824, p 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.)

  7. The Association between Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk in Children

    Directory of Open Access Journals (Sweden)

    Anna Di Sessa

    2017-07-01

    Full Text Available The rising prevalence of childhood obesity in the past decades has made Non-Alcoholic Fatty Liver Disease (NAFLD the most common cause of pediatric chronic liver disease worldwide. Currently, a growing body of evidence links NAFLD with cardiovascular disease (CVD even at an early age. Data on the pediatric population have shown that NAFLD could represent an independent risk factor not only for cardiovascular events but also for early subclinical abnormalities in myocardial structure and function. Briefly, we review the current knowledge regarding the relationship between pediatric NAFLD and cardiovascular risk in an attempt to clarify our understanding of NAFLD as a possible cardiovascular risk factor in childhood.

  8. Omic studies reveal the pathogenic lipid droplet proteins in non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Xuelin Zhang

    2016-10-01

    Full Text Available Abstract Non-alcoholic fatty liver disease (NAFLD is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet (LD, the main organelle involved in neutral lipid storage and hydrolysis, is a potential target for NAFLD therapeutic treatment. In this review, we summarize recent progress elucidating the connections between LD-associated proteins and NAFLD found by genome-wide association studies (GWAS, genomic and proteomic studies. Finally, we discuss a possible mechanism by which the protein 17β-hydroxysteroid dehydrogenase 13 (17β-HSD13 may promote the development of NAFLD.

  9. Association between non-alcoholic fatty liver disease, insulin resistance and Helicobacter pylori.

    Science.gov (United States)

    Abenavoli, Ludovico; Milic, Natasa; Masarone, Mario; Persico, Marcello

    2013-11-01

    Here we report a case of a 55-year Caucasian man, who improved the metabolic profile after the treatment for Helicobacter pylori eradication. In particular, we report the changes in homeostatic model assessment of insulin resistance, fatty liver index and echographic liver pattern. We hypothesize the co-factorial role of H. pylori in the mechanisms involved in non-alcoholic fatty liver disease pathogenesis and insulin resistance, by the cytokine serum changes. If this correlation is confirmed, the H. pylori treatment may represent an option in the clinical management of liver steatosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. 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......-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...

  11. Clinical Utility of Red Cell Distribution Width in Alcoholic and Non-alcoholic Liver Cirrhosis

    OpenAIRE

    Milić, Sandra; Mikolašević, Ivana; Radić, Mladen; Hauser, Goran; Štimac, Davor

    2011-01-01

    Red blood cell distribution width (RDW) is a measure of the variation of red blood cell width that is reported as a part of standard complete blood count. Red blood cell distribution width results are often used together with mean corpuscular volume (MCV) results to figure out mixed anemia. The aim of our study was to compare the values of RDW in alcoholic and non-alcoholic liver cirrhosis and to determine if RDW follows the severity of disease according to Child-Pugh score. We re...

  12. Demand for Non-Alcoholic Beverages: Evidence From The ACNielsen Home Scan Panel

    OpenAIRE

    Pofahl, Geoffrey M.; Capps, Oral, Jr.; Clauson, Annette L.

    2005-01-01

    Using the ACNielsen HomeScan Panel over the period 1998 to 2001 as the source of data, we entertain various demand systems, namely, the LA/AIDS, the AIDS, and the QUAIDS to investigate the demand for eight non-alcoholic beverages. Own-price, cross-price, and expenditure elasticities are obtained by year and by demand system for milk, bottled water, carbonated soft drinks, powdered soft drinks, coffee, tea, fruit juices and drinks, and isotonics. Emphasis is placed on the magnitude of price se...

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

    OpenAIRE

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

    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...

  14. Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy

    Science.gov (United States)

    Kristiansen, Maria Nicoline Baandrup; Veidal, Sanne Skovgård; Rigbolt, Kristoffer Tobias Gustav; Tølbøl, Kirstine Sloth; Roth, Jonathan David; Jelsing, Jacob; Vrang, Niels; Feigh, Michael

    2016-01-01

    AIM: To characterize development of diet-induced nonalcoholic steatohepatitis (NASH) by performing liver biopsy in wild-type and genetically obese mice. METHODS: Male wild-type C57BL/6J (C57) mice (DIO-NASH) and male Lepob/Lepob (ob/ob) mice (ob/ob-NASH) were maintained on a diet high in trans-fat (40%), fructose (22%) and cholesterol (2%) for 26 and 12 wk, respectively. A normal chow diet served as control in C57 mice (lean chow) and ob/ob mice (ob/ob chow). After the diet-induction period, mice were liver biopsied and a blinded histological assessment of steatosis and fibrosis was conducted. Mice were then stratified into groups counterbalanced for steatosis score and fibrosis stage and continued on diet and to receive daily PO dosing of vehicle for 8 wk. Global gene expression in liver tissue was assessed by RNA sequencing and bioinformatics. Metabolic parameters, plasma liver enzymes and lipids (total cholesterol, triglycerides) as well as hepatic lipids and collagen content were measured by biochemical analysis. Non-alcoholic fatty liver disease activity score (NAS) (steatosis/inflammation/ballooning degeneration) and fibrosis were scored. Steatosis and fibrosis were also quantified using percent fractional area. RESULTS: Diet-induction for 26 and 12 wk in DIO-NASH and ob/ob-NASH mice, respectively, elicited progressive metabolic perturbations characterized by increased adiposity, total cholesterol and elevated plasma liver enzymes. The diet also induced clear histological features of NASH including hepatosteatosis and fibrosis. Overall, the metabolic NASH phenotype was more pronounced in ob/ob-NASH vs DIO-NASH mice. During the eight week repeated vehicle dosing period, the metabolic phenotype was sustained in DIO-NASH and ob/ob-NASH mice in conjunction with hepatomegaly and increased hepatic lipids and collagen accumulation. Histopathological scoring demonstrated significantly increased NAS of DIO-NASH mice (0 vs 4.7 ± 0.4, P NASH mice (2.4 ± 0.3 vs 6.3

  15. Knowing What's Out There: Awareness of Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Ghevariya, Vishal; Sandar, Nan; Patel, Kishor; Ghevariya, Nehal; Shah, Ruchit; Aron, Joshua; Anand, Sury

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic disorder, which poses a significant health burden in the western countries. As the epidemic of obesity slides health downward, the incidence of NAFLD is evidently increasing. We aimed to ascertain the awareness of NAFLD and its risk factors in the general population, which may be helpful in designing educational tools to promote prevention, early detection, and treatment of this disorder. A survey of 5000 non-institutionalized residents of Brooklyn, NY, USA was conducted. Sixteen items were included in the survey questionnaire including awareness of fatty liver, predisposing factors of NAFLD, awareness of cirrhosis, and conditions that advance to cirrhosis. The questionnaire also addressed awareness of prevention, diagnostic methods and treatment of NAFLD, and education of physicians to their patients about NAFLD. Overwhelming majority of the subjects was not aware of NAFLD and stated that their physicians did not have a discussion about NAFLD. Non-alcoholic fatty liver disease is a preventable liver disorder with limited treatment options. Thorough counseling by primary care physicians can be of paramount importance in preventive strategy for NAFLD. We should target our teenage population in an era of obesity epidemics of all times.

  16. Beneficial effects of non-alcoholic grape-derived products on human health: A literature review

    Directory of Open Access Journals (Sweden)

    Di Lorenzo Chiara

    2015-01-01

    Full Text Available Vine is widely cultivated due to the economic value of wine and other grape derivatives. The grape berry is character- ized by the presence of a wide variety of flavonoids, which have been investigated for their health promoting properties. Several epidemiological studies have shown that a moderate consumption of wine is associated with a J-shaped effect on some risk fac- tors for chronic diseases. On the other hand, the wine market has shown a decreasing trend due to the frequent abuse of alcoholic beverages also by young people, as denounced by WHO. Accordingly, the scientific research in the field of non-alcoholic grape products has been further stimulated. The aim of this paper was a preliminary collection of data on human studies supporting the beneficial properties of unfermented grape products. The most convincing positive effects, observed in humans, consisted in the reduction of risk factors for cardiovascular diseases, such as hypertension and oxidative stress. Other human trials have been published in the area of: immune system, diabetes, cognitive functions, oral health, and cancer. Generally speaking, the findings listed in this review support the use of non-alcoholic grape derivatives, as a source of beneficial compounds for the human diet, even though further studies are necessary.

  17. The regulation of food and non-alcoholic beverage advertising to children in Brazil

    Directory of Open Access Journals (Sweden)

    Hartung P. A. D.

    2017-02-01

    Full Text Available The objective of this present article is to understand the regulation of food and non-alcoholic beverage advertising aimed at children in Brazil. It is argued that this discussion must be contextualized within the broader debate on advertising that targets children of less than 12 years of age, of any product, service or brand, given that the advertising of food and drinks to children is a species of the broader commercial practice of advertising, which is considered abusive and therefore illegal under Brazilian rules and by the recommendations of interna-tional organizations. Advertising directly to children utilizes their hyper-vulnerability and their unfinished development to persuade them to consume, violating their rights guaran-teed by law, such as the right to respect comprising physical, mental and moral inviolability. Specifically, advertising of food and non-alcoholic beverages with low nutritional value to children, in addition to leveraging children’s vulnerability, directly impacts increasing rates of childhood and weight, therefore becoming an important public health issue to be regulated. In Brazil, the regulation of this commercial activity takes place within the broader context of restricting marketing communication directed at children under 12 years of age,, which has been discussed extensively at various state levels, including through lawsuits that generated a historical precedent in the Brazilian Superior Court of Justice, which considered ins his decision this practice to be abusive and, therefore, illegal.

  18. Non-Alcoholic Beverages from Fermented Cereals with Increased Oligosaccharide Content.

    Science.gov (United States)

    Basinskiene, Loreta; Juodeikiene, Grazina; Vidmantiene, Daiva; Tenkanen, Maija; Makaravicius, Tomas; Bartkiene, Elena

    2016-03-01

    The aim of this study is to develop a new technology for making traditional Lithuanian non-alcoholic beverage kvass from fermented cereals by extending the spectrum of raw materials (extruded rye) and applying new biotechnological resources (xylanolytic enzymes and lactic acid bacteria (LAB)) to improve its functional properties. Arabinoxylans in extruded rye were very efficiently hydrolysed into oligosaccharides by xylanolytic complex Ceremix Plus MG. Using Ceremix Plus MG and LAB fermentation, the yield of arabinoxylooligosaccharides and xylooligosaccharides in beverage was increased to 300 and 1100 mg/L, respectively. Beverages fermented by LAB had lower pH values and ethanol volume fraction compared to the yeast-fermented beverage. The acceptability of the beverage fermented by Lactobacillus sakei was higher than of Pediococcus pentosaceus- or yeast- -fermented beverages and similar to the acceptability of commercial kvass made from malt extract. The results showed that extruded rye, xylanolytic enzymes and LAB can be used for production of novel and safe high-value non-alcoholic beverages.

  19. Screening potential intakes of colour additives used in non-alcoholic beverages.

    Science.gov (United States)

    Tennant, David R

    2008-06-01

    The Union of European Beverages Associations (UNESDA) has undertaken a screening exercise to determine whether any of the colours used in non-alcoholic beverages has the potential for high consumers to exceed the acceptable daily intake (ADI). The organisation undertook a survey of its membership to identify current use levels in non-alcoholic beverages. Information about the consumption of beverages and other foods that can contain the colours was derived from UK survey data because UK consumers were shown to represent some of the highest in the EU. A methodology was developed which added the intake of high level consumers of beverages to average intakes from all other uses to estimate total high level intake. A hierarchical approach used maximum approved use levels (where available) at the first tier and, if intakes exceed the ADI or maximum use levels were not available, UNESDA usage survey data at the second tier. Of the 33 colours approved for use in beverages nine were eliminated from further consideration at Tier 1. A further 22 colours were eliminated from further consideration at Tier 2. Two colours (E101 riboflavins and E110 sunset yellow) required further evaluation but under practical use conditions neither of these colours had the potential to exceed its ADI. Some colours used in beverages are permitted quantum satis in other foods and so permitted use levels were not available. Further information is required about these uses to determine whether total intakes from all foods have the potential to exceed ADIs.

  20. Non-Alcoholic Beverages from Fermented Cereals with Increased Oligosaccharide Content

    Directory of Open Access Journals (Sweden)

    Grazina Juodeikiene

    2016-01-01

    Full Text Available The aim of this study is to develop a new technology for making traditional Lithuanian non-alcoholic beverage kvass from fermented cereals by extending the spectrum of raw materials (extruded rye and applying new biotechnological resources (xylanolytic enzymes and lactic acid bacteria (LAB to improve its functional properties. Arabinoxylans in extruded rye were very efficiently hydrolysed into oligosaccharides by xylanolytic complex Ceremix Plus MG. Using Ceremix Plus MG and LAB fermentation, the yield of arabinoxylooligosaccharides and xylooligosaccharides in beverage was increased to 300 and 1100 mg/L, respectively. Beverages fermented by LAB had lower pH values and ethanol volume fraction compared to the yeast-fermented beverage. The acceptability of the beverage fermented by Lactobacillus sakei was higher than of Pediococcus pentosaceus- or yeast-fermented beverages and similar to the acceptability of commercial kvass made from malt extract. The results showed that extruded rye, xylanolytic enzymes and LAB can be used for production of novel and safe high-value non-alcoholic beverages.

  1. Noninvasive Tests Do Not Accurately Differentiate Nonalcoholic Steatohepatitis From Simple Steatosis: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Verhaegh, Pauline; Bavalia, Roisin; Winkens, Bjorn; Masclee, Ad; Jonkers, Daisy; Koek, Ger

    2017-08-22

    Non-alcoholic fatty liver disease is a rapidly increasing health problem. Liver biopsy analysis is the most sensitive test to differentiate between non-alcoholic steatohepatitis (NASH) and simple steatosis (SS), but non-invasive methods are needed. We performed a systematic review and meta-analysis of non-invasive tests for differentiating NASH from SS, focusing on blood markers. We performed a systematic search of the PubMed, Medline and Embase (1990-2016) databases using defined keywords, limited to full-text papers in English and human adults, and identified 2608 articles. Two independent reviewers screened the articles and identified 122 eligible articles that used liver biopsy as reference standard. If at least 2 studies were available, pooled sensitivity (sens p ) and specificity (spec p ) values were determined using the Meta-Analysis Package for R (metafor). In the 122 studies analyzed, 219 different blood markers (107 single markers and 112 scoring systems) were identified to differentiate NASH from simple steatosis, and 22 other diagnostic tests were studied. Markers identified related to several pathophysiological mechanisms. The markers analyzed in the largest proportions of studies were alanine aminotransferase (sens p , 63.5% and spec p , 74.4%) within routine biochemical tests, adiponectin (sensp, 72.0% and spec p , 75.7%) within inflammatory markers, CK18-M30 (sens p , 68.4% and spec p , 74.2%) within markers of cell death or proliferation and homeostatic model assessment of insulin resistance (sens p , 69.0% and spec p , 72.7%) within the metabolic markers. Two scoring systems could also be pooled: the NASH test (differentiated NASH from borderline NASH plus simple steatosis with 22.9% sens p and 95.3% spec p ) and the GlycoNASH test (67.1% sens p and 63.8% spec p ). In the meta-analysis, we found no test to differentiate NASH from SS with a high level of pooled sensitivity and specificity (≥80%). However, some blood markers, when included in

  2. Frequency of non alcoholic fatty liver disease (NAFLD) and its biochemical derangements in Type-2 diabetic patients

    International Nuclear Information System (INIS)

    Taseer, I.H.; Hussain, L.; Safdar, S.; Mirbahar, A.M.; Ahmad, I.

    2010-01-01

    Objective: To see the frequency of non-alcoholic fatty liver disease in Type-2 diabetic patients and to see iochemical derangements in NAFLD patients. Methodology: It is a cross-sectional study, conducted at Diabetic Research Centre and outpatient department Nishtar Hospital and PMRC Research Centre Nishtar Medical College, Multan. One hundred patients of either sex having type 2 diabetes mellitus attending diabetic out-patient department Nishtar Hospital Multan were included in the study. A pre-designed study proforma was filled with relevant investigations and clinical assessments were carried out in all cases. All the patients underwent abdominal ultrasonography. Data were entered in SPSS-11 and analyzed. Results: Out of one hundred patients, 51 (51%) were female and 49 (49%) were male. Mean age of the patients was 47.93 +- 8.57 years. Fifty one (51%) of the diabetic patients had fatty liver. Out of these 32 (62.75%) were female and 19 (37.25%) were male. Fatigue was present in 49 (53.26%), generalized weakness in 48 (52.18%), heaviness right upper abdomen in 22 (64.70%) and pain right upper abdomen in 20 (58.82%) of fatty liver patients. Corresponding figure in Non Fatty Liver Patients were 43 (46.74%), 44 (47.82%), 12 (35.30%) and 14(41.18%), respectively. Itching was noted in 19 (44.18%) patients of fatty liver while it was 24(55.82%) in non-fatty liver patients. Serum triglyceride level more than 160 mg/dl in 47 (92.15%) patients of fatty liver while serum cholesterol level more than 200 mg/dl was seen in 24(47.05%). Aspartate amino transferase (AST) more than 35 u/l was noted in seven (13.72%), alanine amino-transferase (ALT) more than 40u/l was noted in 6(11.76%) fatty liver patients while serum albumin and serum bilirubin were within normal range in all fatty liver and non-fatty liver patients. Conclusion: Nonalcoholic fatty liver disease (NAFLD) is more commonly seen in Type-2 diabetic patients. Serum triglyceride and serum cholesterol are significantly

  3. Endothelial dysfunction and morphofunctional properties of erythrocytes in non-alcoholic steathohepatitis combined with chronic obstructive pulmonary disease in patients with obesity

    Directory of Open Access Journals (Sweden)

    T.P. Cyntar

    2017-09-01

    Full Text Available Background. The investigation of violation of the functional state of the endothelium and morphofunctional properties of erythrocytes in non-alcoholic steatohepatitis (NASH combined with chronic obstructive pulmonary disease (COPD in patients with obesity was the purpose of our study. Materials and methods. We have examined 30 patients with NASH on the background of degree I obesity (group 1, 30 patients with COPD and normal body weight (group 2, 60 patients with NASH in combination with COPD (group 3 and 20 apparently healthy persons. The functional state of the endothelium was studied by the content of stable metabolites of nitrogen monoxide (nitrites/nitrates, endothelin-1 (ET-1, and the number of circulating excised endothelial cells (CEEC with soluble vascular cell adhesion molecule-1 (sVCAM-1 content in the blood. The erythrocyte deformity index (EDI, the relative viscosity of the erythrocytic suspension (RVES and the percentage of peroxide hemolysis of erythrocytes (PHE were also determined. Results. The conducted study showed that the course of NASH in its combination with COPD in patients with degree I obesity is accompanied by an increase in the level of ET-1 (by 5.8 times, sVCAM-1 (5.6-fold, CEEC (2.1-fold, RVES (by 65 % and the percentage of PHE (2.1-fold while simultaneously reducing the content of stable metabolites of nitrogen monoxide (nitrites/nitrates (2.1-fold and EDI (by 36.2 % compared to those in apparently healthy subjects. Conclusions. With a combined course of NASH and COPD in patients with degree I obesity, endothelial dysfunction develops, which is characterized by elevated levels of ET-1, sVCAM in the blood serum and CEEC, with the maximum decrease in the content of nitrites/nitrates in the blood. One of the factors leading to the aggravation of microcirculatory disorders in NASH combined with COPD is the changes in the morphofunctional state of erythrocytes (reduction of the EDI with simultaneous increase in RVES and

  4. Fuzheng Huayu recipe prevents nutritional fibrosing steatohepatitis in mice

    Directory of Open Access Journals (Sweden)

    Jia Yan-Hong

    2012-03-01

    Full Text Available Abstract Background Fuzheng Huayu recipe (FZHY, a compound of Chinese herbal medicine, was reported to improve liver function and fibrosis in patients with hepatitis B virus infection. However, its effect on nutritional fibrosing steatohepatitis is unclear. We aimed to elucidate the role and molecular mechanism of FZHY on this disorder in mice. Methods C57BL/6 J mice were fed with methionine-choline deficient (MCD diet for 8 weeks to induce fibrosing steatohepatitis. FZHY and/or heme oxygenase-1 (HO-1 chemical inducer (hemin were administered to mice, respectively. The effect of FZHY was assessed by comparing the severity of hepatic injury, levels of hepatic lipid peroxides, activation of hepatic stellate cells (HSCs and the expression of oxidative stress, inflammatory and fibrogenic related genes. Results Mice fed with MCD diet for 8 weeks showed severe hepatic injury including hepatic steatosis, necro-inflammation and fibrosis. Administration of FZHY or hemin significantly lowered serum levels of alanine aminotransferase, aspartate aminotransferase, reduced hepatic oxidative stress and ameliorated hepatic inflammation and fibrosis. An additive effect was observed in mice fed MCD supplemented with FZHY or/and hemin. These effects were associated with down-regulation of pro-oxidative stress gene cytochrome P450 2E1, up-regulation of anti-oxidative gene HO-1; suppression of pro-inflammation genes tumor necrosis factor alpha and interleukin-6; and inhibition of pro-fibrotic genes including α-smooth muscle actin, transforming growth factor beta 1, collagen type I (Col-1 and Col-3. Conclusions Our study demonstrated the protective role of FZHY in ameliorating nutritional fibrosing steatohepatitis. The effect was mediated through regulating key genes related to oxidative stress, inflammation and fibrogenesis.

  5. Oxidized low-density lipoprotein antibodies/high-density lipoprotein cholesterol ratio is linked to advanced non-alcoholic fatty liver disease lean patients.

    Science.gov (United States)

    Ampuero, Javier; Ranchal, Isidora; Gallego-Durán, Rocío; Pareja, María Jesús; Del Campo, Jose Antonio; Pastor-Ramírez, Helena; Rico, María Carmen; Picón, Rocío; Pastor, Luis; García-Monzón, Carmelo; Andrade, Raúl; Romero-Gómez, Manuel

    2016-09-01

    A small but significant proportion of patients with normal body mass index show non-alcoholic fatty liver disease (NAFLD). Oxidized low-density lipoprotein (LDL) is a powerful immunogenic molecule, which causes oxidative stress and produces antibodies (oxLDL-ab). We aimed to analyze the role of oxLDL-ab on histological features in lean-NAFLD patients. Seventy-two biopsy-proven NAFLD patients were included. Lean patients showed body index mass of Liver biopsies were assessed by one pathologist blinded to clinical data. Histological features were non-alcoholic steatohepatitis (NASH), steatosis, hepatocellular ballooning, and liver fibrosis. Metabolic and hepatic profiles were analyzed, and lipid-lowering medication was recorded. OxLDL-ab levels were measured by ELISA. OxLDL-ab-based lipid indexes analyzed: oxLDL-ab/total cholesterol ratio; oxLDL-ab/LDL-c ratio; oxLDL-ab/high-density lipoprotein cholesterol (HDL-c) ratio; and oxLDL-ab/oxLDL ratio. Lean-NAFLD patients presented 26.5% (9/34) of NASH. OxLDL-ab/HDL-c ratio (r = 0.570; n = 34; P = 0.001) correlated with NAS score and was the only variable associated with NASH in the multivariate analysis [odds ratio, OR, 1.10 (95% confidence interval, CI: 1.01-1.21); P = 0.039]. Severe steatosis was present in 41.2% (14/34) of lean-NAFLD patients. OxLDL-ab/HDL-c ratio was higher in patients with grade-III steatosis (54.9 (37.3-124.6)) than those with grade II (37.1 (20.2-71.1)) and grade I (17.7 (13.1-22.8)) (P = 0.018). Hepatocellular ballooning was present in 20.6% (7/34) of lean-NAFLD patients, and OxLDL-ab/HDL-c ratio (OR 1.03 [95% CI: 1.01-1.05]; P = 0.050) was independently associated with histological features. OxLDL-ab/HDL-c ratio was higher in patients with advanced fibrosis (39.8 (22.9-121.6) vs 17.7 (13.9-30.9); P = 0.025), increasing gradually with the fibrosis stage (P = 0.042) and remained in the final multivariate model [OR 1.05 (95% CI: 1.00-1.11); P = 0.05]. However, in

  6. Homicide in Chicago from 1890 to 1930: prohibition and its impact on alcohol- and non-alcohol-related homicides.

    Science.gov (United States)

    Asbridge, Mark; Weerasinghe, Swarna

    2009-03-01

    The aim of the current paper is to examine the impact of the enactment of constitutional prohibition in the United States in 1920 on total homicides, alcohol-related homicides and non-alcohol-related homicides in Chicago. Data are drawn from the Chicago Historical Homicide Project, a data set chronicling 11 018 homicides in Chicago between 1870 and 1930. Interrupted time-series and autoregression integrated moving average (ARIMA) models are employed to examine the impact of prohibition on three separate population-adjusted homicide series. All models control for potential confounding from World War I demobilization and from trend data drawn from Wesley Skogan's Time-Series Data from Chicago. Total and non-alcohol-related homicide rates increased during prohibition by 21% and 11%, respectively, while alcohol-related homicides remained unchanged. For other covariates, alcohol-related homicides were related negatively to the size of the Chicago police force and positively to police expenditures and to the proportion of the Chicago population aged 21 years and younger. Non-alcohol-related homicides were related positively to police expenditures and negatively to the size of the Chicago police force. While total and non-alcohol-related homicides in the United States continued to rise during prohibition, a finding consistent with other studies, the rate of alcohol-related homicides remained unchanged. The divergent impact of prohibition on alcohol- and non-alcohol-related homicides is discussed in relation to previous studies of homicide in this era.

  7. Iatrogenic hyperadrenocorticism and steatohepatitis caused by unapproved medicine.

    Science.gov (United States)

    Kitahara, Akira; Saga, Kumiko; Koide, Shigeki; Isobe, Tomoaki; Oki, Yutaka; Nakamura, Hirotoshi

    2008-01-01

    A 54-year-old man experienced weight gain. He was diagnosed as having hyperglycemia, hypertension and liver damage. Liver biopsy showed steatohepatitis. We initially suspected him as having hyperadrenocorticism. However, both adrenocorticotropic hormone and cortisol levels were low. Later, it was revealed that he took medicine to relieve his gonalgia. His hyperglycemia, hypertension and liver damage improved after he discontinued taking the medicine. An analysis of this medicine showed that it contained desoximetasone, a glucocorticoid compound that had not been approved for medical use in Japan. To adequately diagnose clinical conditions, it is necessary to survey the patient's medicinal history in detail.

  8. A Simple Diet- and Chemical-Induced Murine NASH Model with Rapid Progression of Steatohepatitis, Fibrosis and Liver Cancer.

    Science.gov (United States)

    Tsuchida, Takuma; Lee, Youngmin A; Fujiwara, Naoto; Ybanez, Maria; Allen, Brittany; Martins, Sebastiao; Fiel, M Isabel; Goossens, Nicolas; Chou, Hsin-I; Hoshida, Yujin; Friedman, Scott L

    2018-03-20

    Although the majority of patients with nonalcoholic fatty liver disease (NAFLD) have only steatosis without progression, a sizable fraction develop non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis and hepatocellular carcinoma (HCC). Many established diet-induced mouse models for NASH require 24-52 weeks, which makes testing for drug response costly and time consuming. We have sought to establish a murine NASH model with rapid progression of extensive fibrosis and HCC by using a western diet (WD), which is high-fat, high-fructose and high-cholesterol, combined with low dose weekly intraperitoneal carbon tetrachloride (CCl 4 ), which served as an accelerator. C57BL/6J mice were fed a normal chow diet (ND) ± CCl 4 or WD ± CCl 4 for 12 and 24 weeks. Addition of CCl 4 exacerbated histological features of NASH, fibrosis, and tumor development induced by WD, which resulted in stage 3 fibrosis at 12 weeks and HCC development at 24 weeks. Furthermore, whole liver transcriptomic analysis indicated that dysregulated molecular pathways in WD/CCl 4 mice and immunologic features were closely similar to those of human NASH. Our mouse NASH model exhibits rapid progression of advanced fibrosis and HCC, and mimics histological, immunological and transcriptomic features of human NASH, suggesting that it will be a useful experimental tool for preclinical drug testing. A carefully characterized model has been developed in mice that recapitulates the progressive stages of human fatty liver disease, from simple steatosis, to inflammation, fibrosis and cancer. The functional pathways of gene expression and immune abnormalities in this model closely resemble human disease. The ease and reproducibility of this model makes it ideal to study disease pathogenesis and test new treatments. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  9. Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations.

    Directory of Open Access Journals (Sweden)

    Umesh D Wankhade

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is an important co-morbidity associated with obesity and a precursor to steatohepatitis. However, the contributions of gestational and early life influences on development of NAFLD and NASH remain poorly appreciated.Two independent studies were performed to examine whether maternal over-nutrition via exposure to high fat diet (HFD leads to exacerbated hepatic responses to post-natal HFD and methionine choline deficient (MCD diets in the offspring. Offspring of both control diet- and HFD-fed dams were weaned onto control and HFD, creating four groups.When compared to their control diet-fed littermates, offspring of HF-dams weaned onto HFD gained greater body weight; had increased relative liver weight and showed hepatic steatosis and inflammation. Similarly, this group revealed significantly greater immune response and pro-fibrogenic gene expression via RNA-seq. In parallel, 7-8 week old offspring were challenged with either control or MCD diets for 3 weeks. Responses to MCD diets were also exacerbated due to maternal HFD as seen by gene expression of classical pro-fibrogenic genes. Quantitative genome-scale DNA methylation analysis of over 1 million CpGs showed persistent epigenetic changes in key genes in tissue development and metabolism (Fgf21, Ppargc1β with maternal HFD and in cell adhesion and communication (VWF, Ephb2 in the combination of maternal HFD and offspring MCD diets. Maternal HFD also influenced gut microbiome profiles in offspring leading to a decrease in α-diversity. Linear regression analysis revealed association between serum ALT levels and Coprococcus, Coriobacteriacae, Helicobacterioceae and Allobaculum.Our findings indicate that maternal HFD detrimentally alters epigenetic and gut microbiome pathways to favor development of fatty liver disease and its progressive sequelae.

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

    International Nuclear Information System (INIS)

    Werven, J.R. van; Schreuder, T.C.M.A.; Nederveen, A.J.; Lavini, C.; Jansen, P.L.M.; Stoker, J.

    2010-01-01

    Rationale and objective: Non-alcoholic fatty liver disease (NAFLD) is related to the metabolic syndrome and obesity. Proton magnetic resonance spectroscopy ( 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 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. 1 H MRS measurements were performed at 3.0 T. From the 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 1 H MRS. 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 1 H MRS to assess hepatic UFA in vivo.

  11. The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

    Science.gov (United States)

    Faghihzadeh, Forouzan; Adibi, Payman; Hekmatdoost, Azita

    2015-09-14

    Non-alcoholic fatty liver disease (NAFLD) is usually associated with insulin resistance, central obesity, reduced glucose tolerance, type 2 diabetes mellitus and hypertriacylglycerolaemia. The beneficial effects of resveratrol on metabolic disorders have been shown previously. The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD. In this randomised double-blinded placebo-controlled clinical trial, fifty NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. resveratrol supplementation reduced alanine aminotransferase (ALT) and hepatic steatosis significantly more than placebo (P0·05). There were no significant changes in blood pressure, insulin resistance markers and TAG in either group (P>0·05). Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements, insulin resistance markers, lipid profile and blood pressure; however, it reduced ALT and hepatic steatosis in patients with NAFLD.

  12. Effect of non-alcoholic fatty liver disease on carotid artery intima-media thickness as a risk factor for atherosclerosis

    Science.gov (United States)

    Nahandi, Maryam Zaare; Ramazanzadeh, Elham; Abbaszadeh, Leili; Javadrashid, Reza; Shirazi, Koorosh Masnadi; Gholami, Nasrin

    2014-01-01

    Aim This study aimed to evaluate the effect of NAFLD on CIMT as a risk factor for atherosclerosis. Background The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide due to rise of obesity and diabetes mellitus (DM) prevalence. Non-invasive assessment of carotid intima-media thickness (CIMT) by high-resolution carotid B-mode ultrasonography is widely used for determining the atherosclerosis. Patients and methods In this case-control setting, 151 subjects were categorized in three groups: group I including 49 patients with NAFLD and DM; group II including 50 non-diabetic NAFLD patients; and the control including 52 normal subjects as group III. The right and left CIMTs and its maximum reading (CIMTmax) were measured by a skilled sonographist blind to the groups. The sonographic grading of the NAFLD was determined in group I and II. Results Median CIMTmax was significantly higher in group I comparing with group II and control group (pliver enzymes (in both groups, 0.6 mm, p= 0.402). Conclusion Based on our findings, there is a significant association between the presence of NAFLD and atherosclerosis. This association was independent to the DM presence. The grade of NAFLD and elevated liver function tests had no effect on severity of atherosclerosis. PMID:25436098

  13. Modeling Advertising Expenditures and Spillover Effects Applied to the U.S. Non-Alcoholic Beverage Industry: Vector Autoregression (VAR) and Polynomial Distributed Lag (PDL) Approaches

    OpenAIRE

    Dharmasena, Senarath; Capps, Oral, Jr.; Bessler, David A.

    2012-01-01

    The non-alcoholic beverage market in the U.S. is a multi-billion dollar industry growing steadily over the past decade. Also, non-alcoholic beverages are among the most heavily advertised food and beverage groups in the United States. Several studies pertaining to non-alcoholic beverages including the incorporation of advertising effects have been conducted, but most of these have centered attention on milk consumption. Some studies have considered demand interrelationships for several bevera...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Sanna, Claudia; Rosso, Chiara; Marietti, Milena; Bugianesi, Elisabetta

    2016-05-12

    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.

  16. Relationship between hepatocellular carcinoma, metabolic syndrome and non-alcoholic fatty liver disease: which clinical arguments?

    Science.gov (United States)

    Rosmorduc, Olivier

    2013-05-01

    Obesity and the metabolic syndrome are growing epidemics associated with an increased risk for many types of cancer. In the liver, inflammatory and angiogenic changes due to insulin resistance and fatty liver disease are associated with an increased incidence of liver cancer. Regardless of underlying liver disease, cirrhosis remains the most important risk factor for hepatocellular carcinoma (HCC) although are cases of HCC arising without cirrhosis raise the possibility of a direct carcinogenesis secondary to Non-alcoholic Fatty Liver Disease (NAFLD). Moreover, metabolic syndrome and its different features may also increase the risk of HCC in the setting of chronic liver diseases of other causes such as viral hepatitis or alcohol abuse. Taking into account all these data, it is necessary to better determine the risk of developing HCC in patients with metabolic syndrome to improve the screening guidelines and develop prophylactic treatments in this setting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  17. Fluid milk consumption and demand response to advertising for non-alcoholic beverages

    Directory of Open Access Journals (Sweden)

    K. RICKERTSEN

    2008-12-01

    Full Text Available Norwegian fluid milk consumption has declined steadily over the last twenty years, despite the dairy industry spending increasing amounts of money on advertising. Using a two-stage model, we investigate whether advertising has increased the demand for milk. No effect of advertising on the demand for non-alcoholic beverages is found in the first stage. In the second stage, an almost ideal demand system including advertising expenditures on competing beverages is estimated. The effects of generic advertising within the beverage group are positive and significant for whole milk and negative and significant for lower fat milk. The own-advertising elasticity for the combined fluid milk group is 0.0008. This highly inelastic elasticity suggests that increased advertising will not be profitable for the producers. Several cross-advertising effects are statistically significant, emphasizing the usefulness of a demand system approach.

  18. 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.

  19. 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 (phepatic markers between flaxseed and control group, respectively: ALT [-11.12 compared with -3.7 U/L; Psteatosis 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. The Possible Role of Helicobacter pylori Infection in Non-alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Dan-dan Cheng

    2017-05-01

    Full Text Available Helicobacter pylori (H. pylori which colonizes the stomach can cause a wide array of gastric disorders, including chronic gastritis, peptic ulcer, and gastric cancer. Recently, accumulating evidence has implicated H. pylori infection in extragastrointestinal diseases such as cardiovascular diseases, neurological disorders, and metabolic diseases. At the same time, many scholars have noted the relationship between H. pylori infection and non-alcoholic fatty liver disease (NAFLD. Despite the positive association between H. pylori and NAFLD reported in some researches, there are opposite perspectives denying their relationship. Due to high prevalence, unclear etiology and difficult treatment of NAFLD, confirming the pathogenicity of H. pylori infection in NAFLD will undoubtedly provide insights for novel treatment strategies for NAFLD. This paper will review the relationship between H. pylori infection and NAFLD and the possible pathogenic mechanisms.

  2. Non-alcoholic fatty liver disease as a consequence of autonomic imbalance and circadian desynchronization.

    Science.gov (United States)

    Sabath, E; Báez-Ruiz, A; Buijs, R M

    2015-10-01

    The circadian system, headed by the suprachiasmatic nucleus, synchronizes behaviour and metabolism according to the external light-dark cycle through neuroendocrine and autonomic signals. Metabolic diseases, such as steatosis, obesity and glucose intolerance, have been associated with conditions of circadian misalignment wherein the feeding schedule has been moved to the resting phase. Here we describe the physiological processes involved in liver lipid accumulation and show how they follow a circadian pattern importantly regulated by both the autonomic nervous system and the feeding-fasting cycle. We propose that an unbalanced activity of the sympathetic-parasympathetic branches between organs induced by circadian misalignment provides the conditions for the development and progression of non-alcoholic fatty liver disease. © 2015 World Obesity.

  3. What is the role of adiponectin in obesity related non-alcoholic fatty liver disease?

    Science.gov (United States)

    Finelli, Carmine; Tarantino, Giovanni

    2013-02-14

    Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries. Insulin resistance is a key factor in the pathogenesis of NAFLD, the latter being considered as the hepatic component of insulin resistance or obesity. Adiponectin is the most abundant adipose-specific adipokine. There is evidence that adiponectin decreases hepatic and systematic insulin resistance, and attenuates liver inflammation and fibrosis. Adiponectin generally predicts steatosis grade and the severity of NAFLD; however, to what extent this is a direct effect or related to the presence of more severe insulin resistance or obesity remains to be addressed. Although there is no proven pharmacotherapy for the treatment of NAFLD, recent therapeutic strategies have focused on the indirect upregulation of adiponectin through the administration of various therapeutic agents and/or lifestyle modifications. In this adiponectin-focused review, the pathogenetic role and the potential therapeutic benefits of adiponectin in NAFLD are analyzed systematically.

  4. Gastrointestinal complications of obesity: non-alcoholic fatty liver disease (NAFLD) and its sequelae.

    Science.gov (United States)

    Karlas, Thomas; Wiegand, Johannes; Berg, Thomas

    2013-04-01

    Obesity is a major risk factor for malign and non-malign diseases of the gastrointestinal tract. Non-alcoholic fatty liver disease (NAFLD) is an outstanding example for the complex pathophysiology of the metabolic system and represents both source and consequence of the metabolic syndrome. NAFLD has a growing prevalence and will become the leading cause of advanced liver disease and cirrhosis. Obesity has a negative impact on NAFLD at all aspects and stages of the disease. The growing epidemic will strain health care resources and demands new concepts for prevention, screening and therapeutic approaches. A better understanding of the interplay of liver, gut and hormonal system is necessary for new insights in the underlying mechanisms of NAFLD and the metabolic syndrome including obesity. Identification of patients at risk for progressive liver disease will allow a better adaption of treatment strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. 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.

  6. Liver fat content, non-alcoholic fatty liver disease, and ischaemic heart disease

    DEFF Research Database (Denmark)

    Lauridsen, Bo Kobberø; Stender, Stefan; Kristensen, Thomas Skårup

    2018-01-01

    Aims: In observational studies, non-alcoholic fatty liver disease (NAFLD) is associated with high risk of ischaemic heart disease (IHD). We tested the hypothesis that a high liver fat content or a diagnosis of NAFLD is a causal risk factor for IHD. Methods and results: In a cohort study...... of the Danish general population (n = 94 708/IHD = 10 897), we first tested whether a high liver fat content or a diagnosis of NAFLD was associated observationally with IHD. Subsequently, using Mendelian randomization, we tested whether a genetic variant in the gene encoding the protein patatin......-like phospholipase domain containing 3 protein (PNPLA3), I148M (rs738409), a strong and specific cause of high liver fat content and NAFLD, was causally associated with the risk of IHD. We found that the risk of IHD increased stepwise with increasing liver fat content (in quartiles) up to an odds ratio (OR) of 2...

  7. Peer influence in a micro-perspective: imitation of alcoholic and non-alcoholic beverages.

    Science.gov (United States)

    Larsen, Helle; Engels, Rutger C M E; Souren, Pierre M; Granic, Isabela; Overbeek, Geertjan

    2010-01-01

    Ample experimental research has found evidence for imitation of alcohol consumption in social encounters. However, these studies cannot reveal whether imitation is specifically related to alcohol and not to consumption in general. We investigated whether imitation is more evident when peers drink alcohol compared to other beverages. We observed sipping behavior during a 30-minute interaction between same-sex confederates and participants in an ad lib semi-naturalistic drinking context (bar lab). We expected a stronger imitation effect when both participant and confederate drank alcoholic beverages. A random occasion multilevel analysis was conducted to take repeated measurements into account. Findings showed that participants imitated the sips of the confederates, but that the likelihood of participants imitating a sip was lower when confederates were drinking alcoholic beverages and participants non-alcoholic beverages compared to when both were consuming alcohol.

  8. What does irritable bowel syndrome share with non-alcoholic fatty liver disease?

    Science.gov (United States)

    Scalera, Antonella; Di Minno, Matteo Nicola Dario; Tarantino, Giovanni

    2013-09-07

    Non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) are two very common diseases in the general population. To date, there are no studies that highlight a direct link between NAFLD and IBS, but some recent reports have found an interesting correlation between obesity and IBS. A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD, leading to an increased cardiovascular risk, and IBS, leading to microbial dysbiosis, impaired intestinal barrier and altered intestinal motility. It is not known when considering local and systemic inflammation/immune system activation, which one has greater importance in NAFLD and IBS pathogenesis. Also, the nervous system is implicated. In fact, inflammation participates in the development of mood disorders, such as anxiety and depression, characteristics of obesity and consequently of NAFLD and, on the other hand, in intestinal hypersensitivity and dysmotility.

  9. Dietary Composition Independent of Weight Loss in the Management of Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Eslamparast, Tannaz; Tandon, Puneeta; Raman, Maitreyi

    2017-07-26

    Poor dietary composition is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD). The majority of NAFLD patients follow diets with overconsumption of simple carbohydrates, total and saturated fat, with reduced intake of dietary fiber and omega-3 rich foods. Although lifestyle modifications including weight loss and exercise remain the keystone of NAFLD management, modifying dietary composition with or without a calorie-restricted diet may also be a feasible and sustainable strategy for NAFLD treatment. In the present review article, we highlight the potential therapeutic role of a "high quality healthy diet" to improve hepatic steatosis and metabolic dysfunction in patients with NAFLD, independent of caloric restriction and weight loss. We provide a literature review evaluating the evidence behind dietary components including fiber-, meat- and omega-3-rich diets and, pending further evidence, we concur with the EASL-EASD-EASO Clinical Guidelines recommendation of the Mediterranean diet as the diet of choice in these patients.

  10. Alimentary regimen in non-alcoholic fatty liver disease: Mediterranean diet

    Science.gov (United States)

    Abenavoli, Ludovico; Milic, Natasa; Peta, Valentina; Alfieri, Francesco; De Lorenzo, Antonino; Bellentani, Stefano

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The mechanisms of the underlying disease development and progression are awaiting clarification. Insulin resistance and obesity-related inflammation status, among other possible genetic, dietary, and lifestyle factors, are thought to play the key role. There is no consensus concerning the pharmacological treatment. However, the dietary nutritional management to achieve weight loss is an essential component of any treatment strategy. On the basis of its components, the literature reports on the effectiveness of the Mediterranean diet in reducing cardiovascular risk and in preventing major chronic diseases, including obesity and diabetes. New evidence supports the idea that the Mediterranean diet, associated with physical activity and cognitive behaviour therapy, may have an important role in the prevention and the treatment of NAFLD. PMID:25492997

  11. Non-alcoholic fatty liver disease: the role of nuclear receptors and circadian rhythmicity.

    Science.gov (United States)

    Mazzoccoli, Gianluigi; Vinciguerra, Manlio; Oben, Jude; Tarquini, Roberto; De Cosmo, Salvatore

    2014-09-01

    Non-alcoholic fatty liver disease (NAFLD) is the accumulation of triglycerides in the hepatocytes in the absence of excess alcohol intake, and is caused by an imbalance between hepatic synthesis and breakdown of fats, as well as fatty acid storage and disposal. Liver metabolic pathways are driven by circadian biological clocks, and hepatic health is maintained by proper timing of circadian patterns of metabolic gene expression with the alternation of anabolic processes corresponding to feeding/activity during wake times, and catabolic processes characterizing fasting/resting during sleep. A number of nuclear receptors in the liver are expressed rhythmically, bind hormones and metabolites, sense energy flux and expenditure, and connect the metabolic pathways to the molecular clockwork throughout the 24-h day. In this review, we describe the role played by the nuclear receptors in the genesis of NAFLD in relationship with the circadian clock circuitry. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. State of the art: treatment of nonalcoholic steatohepatitis.

    Science.gov (United States)

    Pearlman, Michelle; Loomba, Rohit

    2014-05-01

    Nonalcoholic fatty liver disease is the most common cause of chronic liver disease in Western countries, and consists of a spectrum of histopathological changes that range in severity from simple steatosis to steatohepatitis to cirrhosis. The use of pharmacological agents as adjunctive therapy to lifestyle modification is crucial, because weight loss is often difficult to achieve and maintain. The purpose of this review is to analyze the most recent literature pertaining to current therapies for nonalcoholic steatohepatitis (NASH), as there are currently no Food and Drug Administration-approved medications. Recent studies suggest that vitamin E may improve liver histology in NASH without affecting insulin resistance; however, long-term risks remain to be studied. Pioglitazone is beneficial in improving liver histology and insulin resistance, but is associated with weight gain. Emerging data suggest that pentoxifylline may also be beneficial in improving serum aminotransferase and liver histology in patients with biopsy-proven NASH. Ongoing research evaluating potential pharmacological agents for NASH is critical, because these patients are at an increased risk for cirrhosis and hepatocellular carcinoma. The current therapies being used for the treatment of NASH include the use of vitamin E and pioglitazone, in addition to dietary counseling and regular exercise.

  13. Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease

    Directory of Open Access Journals (Sweden)

    Liane Rabinowich

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI. The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial β-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis.

  14. Treatment of Nonalcoholic Steatohepatitis in Adults: Present and Future

    Directory of Open Access Journals (Sweden)

    S. Gitto

    2015-01-01

    Full Text Available Nonalcoholic steatohepatitis has become one of the most common liver-related health problems. This condition has been linked to an unhealthy diet and weight gain, but it can also be observed in nonobese people. The standard of care is represented by the lifestyle intervention. However, because this approach has several limitations, such as a lack of compliance, the use of many drugs has been proposed. The first-line pharmacological choices are vitamin E and pioglitazone, both showing a positive effect on transaminases, fat accumulation, and inflammation. Nevertheless, vitamin E has no proven effect on fibrosis and on long-term morbidity and mortality and pioglitazone has a negative impact on weight. Other drugs have been studied such as metformin, ursodeoxycholic acid, statins, pentoxiphylline, and orlistat with only partially positive results. Among the emerging treatments, telmisartan is particularly interesting as it seems to have an impact on insulin resistance, liver steatosis, inflammation, and fibrosis. However, the pathogenesis of steatohepatitis is highly complex and is determined by different parallel hits; indeed, the association of different drugs that act on various levels has been suggested. In conclusion, lifestyle intervention should be optimised and the associations of different drugs should be tested in large studies with long-term outcomes.

  15. [EFFICIENCY OF URSODEOXYCHOLIC ACID APPLICATION IN NONALCOCHOLIC STEATOHEPATITIS].

    Science.gov (United States)

    Dudanova, O P; Belavina, L A; Kurbatova, I V; Larina, A A; Topchieva, L V

    2015-01-01

    to estimate the efficiency of ursodeoxycholic acid (UDHC) in nonalcocholic steatohepatitis (NASH) by analysis of conventional clinical datas, apoptosis and liver perfusion parameters. UDHC was used as monotherapy in treatment of 92 NASH patients in daily dose 10-15 mg/kg. We have observed 44 (47.8%) males, 48 (52.2%) females, age was 56.8 ± 7.2 years, BMI was 28.4 ± 2.3 kg/m2, waist circumference was 93.8 ± 8.3 cm. Functional liver tests (ALAT, ASAT, alcaline phosphatase--APh, gamma-glutamyltranspeptidase--GGTP), abdominal ultrasonography and dopplerography of liver blood flow, kaspase-3, 6, 8, 9 genes expression in blood leucocytes were estimated. Periods of controls research and UDCA treatment were: 4-8 weeks in 92 patients, 20-24 weeks in 18 (19.6%) patients and 40-48 weeks in 13 (14.1%) patients. Significant positive dynamics of liver functional tests and decrease of kaspase-3, 6, 9 genes expression in blood leucocytes were observed over 4-8 weeks, normalization of liver tests--over 20-24 weeks and significant amelioration of venous and arterial liver perfusion parameters--over 40-48 weeks. Ursodeoxycholic acid in daily dose of 10-15 mg/kg in nonalcocholic steatohepatitis caused positive dynamics of cytolytic and cholestasis parameters, leucocytic apoptosis and venous and arterial liver blood flow parameters.

  16. Mediterranean diet and non-alcoholic fatty liver disease: the need of extended and comprehensive interventions.

    Science.gov (United States)

    Trovato, Francesca M; Catalano, Daniela; Martines, G Fabio; Pace, Patrizia; Trovato, Guglielmo M

    2015-02-01

    Non-alcoholic fatty liver disease (NAFLD) is mostly related to increased BMI and sedentary life, even if it not directly attributable only to these or to single specific factors. Unhealthy lifestyle and obesity are the most probable causes, also in non-diabetic and without alcohol abuse patients, even if lean individuals can be involved. NAFLD treatment is currently warranted and driven by comprehensive lifestyle intervention, a valuable objective that is more often wished for than actually achieved. The aim is to re-assess the effectiveness of an intervention focused to increase the Adherence to Mediterranean Diet Score (AMDS) and the level of physical exercise, investigating the factors associated with failure and reporting the time that must elapse before such intervention becomes effective. The study included 90 (F 46, M 44) non-alcoholic non-diabetic patients, aged 50.13 ± 13.68 years, BMI 31.01 ± 5.18 with evidence of fatty liver by ultrasound. A significant decrease of Bright Liver Score (BLS) was observed only after 6 months of intervention: differently, at the first and third month of monitoring fatty liver changes were still not significant. By a multiple linear regression model Adherence to Mediterranean Diet change (p:0.015) and body mass index changes (p:Diet is a significant predictor of changes in the fat content of the liver in overweight patients with NAFLD. The effect of the diet is gradual and favorable and it is independent of other lifestyle changes. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  17. Comparison of serum lipid profile in non alcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Latif, A.; Ain, Q.U.A.; Ahmed, N.; Shafiq, A.M.; Sapna, K.

    2017-01-01

    Objective: To compare serum lipid profile in different ultrasonographic grades of non alcoholic fatty liver disease (NAFLD). Study Design: Cross sectional study. Place and Duration of Study: PNS SHIFA hospital, Karachi, from Oct 2015 to Jul 2016. Material and Methods: Seventy three adults of either gender were consecutively inducted after diagnosis of non alcoholic fatty liver disease (NAFLD) on ultrasonography (USG). These individuals were further classified into grade I, II and III of NAFLD depending on US findings. Fasting blood sample of all the subjects was analyzed for serum fasting lipid profile comprising of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Serum non HDL cholesterol (nonHDL-C) was calculated by subtracting HDL-C from TC. Results: Among 73 subjects with NAFLD, 42.5%, 37% and 20.5% had grade I, II and III NAFLD respectively. All parameters showed significant increase in frequency of abnormal results with increasing grade of NAFLD except TG. Significant difference was found in mean TC (p=0.000), LDL-C (p=0.000), HDL-C (p=0.005) and nonHDL-C (p=0.000) between grades of NAFLD. Post hoc analysis revealed that only mean nonHDL-C was significantly different amongst all the grades of NAFLD. Conclusion: The increasing severity of NAFLD was found associated with increased frequency of dyslipidemia. Though most frequent dyslipidemia in NAFLD was low serum HDL-C followed by hypertriglyceridemia, only serum nonHDL-C was statistically different amongst all the grades of NAFLD. (author)

  18. Consumption estimation of non alcoholic beverages, sodium, food supplements and oil.

    Science.gov (United States)

    López Díaz-Ufano, María Luisa

    2015-02-26

    The interest in the type and quantity of non alcoholic beverage, sodium, food supplements and oil consumption is not new, and numerous approaches have been used to assess beverage intake, but the validity of these approaches has not been well established. The need to intake liquids varies depending on the diet, the physical activity carried out, the environmental temperature, the humidity, etc. The variety of beverages in the diet can contribute to increasing the micro nutrient intake: vitamins, antioxidants, minerals. Risks associated to high sodium consumption are: an increase in high blood pressure, vascular endothelial deterioration, bone demineralisation, kidney disease, stomach cancer. Progress in health, investigation, education, etc. are leading to an increase in food supplement consumption. Olive oil represents one of the basic pillars of the Mediterranean diet and its normal presence in nutrition guarantees an adequate content of some important nutrients; not only oleic acid and linoleic acid but also tocopherols, phytoesterols and phenolic compounds. Biomarkers of intake are able to objectively assess dietary intake/status without the bias of self-reported dietary intake errors and also overcome the problem of intra-individual diet variability. Furthermore, some methods of of measuring dietary intake used biomarkers to validate the data it collects. Biological markers may offer advantages and be able to improve the estimates of dietary intake assessment, which impact into the statistical power of the study. There is a surprising paucity of studies that systematically examine the correlation of beverages intake and hydration biomarker in different populations. There is no standardized questionnaire developed as a research tool for the evaluation of non alcoholic beverages, sodium, food supplements and oil intake in the general population. Sometimes, the information comes from different sources or from different methodological characteristics which raises

  19. CORRECTION OF MICROCIRCULATORY DISORDERS IN NON-ALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH CHRONIC HEART FAILURE PATIENTS

    Directory of Open Access Journals (Sweden)

    M. E. Statsenko

    2016-01-01

    Full Text Available Combined liver damage in patients with chronic heart failure and non-alcoholic fatty liver disease leads to the formation of pathological hemodynamic types of microcirculation with prevalence of shunt blood flow, nutritional deficiency, that correlated with changes in the functional state of the liver. Using cytoprotector mexicor for 16 weeks as part of the basic treatment of patients with chronic heart failure and non-alcoholic fatty liver disease can correct these microcirculatory disorders, has a beneficial effect on endothelial function, autonomic tone of microvessels, which is accompanied by the positive dynamics of indicators of cytolysis and cholestasis.

  20. Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects : The Lifelines Cohort Study

    NARCIS (Netherlands)

    van den Berg, Eline H.; van Tienhoven-Wind, Lynnda J. N.; Amini, Marzyeh; Schreuder, Tim C.M.A.; Faber, Klaas Nico; Blokzijl, Hans; Dullaart, Robin P. F.

    Objective. Overt hypothyroidism confers an increased risk of non-alcoholic fatty liver disease (NAFLD). The liver plays a crucial role in the metabolism of cholesterol and triglycerides; thyroid hormones interact on hepatic lipid homeostasis. Thyroid function within the euthyroid range affects a

  1. Intensive lifestyle treatment for non-alcoholic fatty liver disease in children with severe obesity: inpatient versus ambulatory treatment

    NARCIS (Netherlands)

    Koot, B. G. P.; van der Baan-Slootweg, O. H.; Vinke, S.; Bohte, A. E.; Tamminga-Smeulders, C. L. J.; Jansen, P. L. M.; Stoker, J.; Benninga, M. A.

    2016-01-01

    Lifestyle intervention is the only established therapy for non-alcoholic fatty liver disease (NAFLD). The optimal treatment schedule and predictors of response of this treatment have not been established in children. We aimed to evaluate the 2-year efficacy of an inpatient versus ambulatory

  2. 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.

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

    Science.gov (United States)

    Völzke, Henry

    2012-07-21

    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 obesity-related 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.

  4. 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

  5. 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

  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. The unique contribution of attitudes toward non-alcoholic drinks to the prediction of adolescents' and young adults' alcohol consumption

    NARCIS (Netherlands)

    Roek, M.A.E.; Spijkerman, R.; Poelen, E.A.P.; Lemmers, A.C.J.; Engels, R.C.M.E.

    2010-01-01

    Attitudes toward alternative behaviors, such as drinking soda instead of alcohol, might contribute to the prediction of young people's drinking behavior. The current study explored the associations between late adolescents' and young adults' attitudes toward alcoholic and non-alcoholic drinks and

  8. The unique contribution of attitudes toward non-alcoholic drinks to the prediction of adolescents' and young adults' alcohol consumption.

    Science.gov (United States)

    Roek, Marion A E; Spijkerman, Renske; Poelen, Evelien A P; Lemmers, Lex; Engels, Rutger C M E

    2010-06-01

    Attitudes toward alternative behaviors, such as drinking soda instead of alcohol, might contribute to the prediction of young people's drinking behavior. The current study explored the associations between late adolescents' and young adults' attitudes toward alcoholic and non-alcoholic drinks and their alcohol consumption, and whether these associations were moderated by participants' sex, age and education level. Cross-sectional data were collected among 1012 15 to 25-year-olds. Participants completed an online questionnaire on attitudes toward alcoholic and non-alcoholic drinks, binge drinking and monthly alcohol consumption. Data were analyzed by employing structural equation modeling in Mplus. After controlling for the shared variance in both attitudes, attitudes toward alcoholic drinks were positively related and attitudes toward non-alcoholic drinks were negatively related to participants' monthly alcohol use and binge drinking. Relations between attitudes towards alcoholic drinks and monthly alcohol consumption were stronger for boys than for girls and stronger for participants with intermediate education background. Relations between both attitudes and binge drinking were strongest for high educated participants. According to our data, non-alcohol attitudes provide a unique contribution to the prediction of alcohol use. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. High prevalence of apolipoprotein B dyslipoproteinemias in non-alcoholic fatty liver disease : The lifelines cohort study

    NARCIS (Netherlands)

    Nass, Karlijn J.; van den Berg, Eline H.; Faber, Klaas Nico; Schreuder, Tim C.M.A.; Blokzijl, Hans; Dullaart, Robin P. F.

    Objective. Cardiovascular disease (CVD) is a major adverse consequence of non-alcoholic fatty liver disease (NAFLD). The association of NAFLD with various apolipoprotein B (apoB) dyslipoproteinemias is unclear. We determined the prevalence of specific apoB dyslipoproteinemias in subjects with

  10. Free triiodothyronine as determinant of non-alcoholic fatty liver disease in euthyroid subjects: The lifelines cohort study

    NARCIS (Netherlands)

    Van Den Berg, Eline; van Tienhoven-Wind, Lynnda; Amini, Marzyeh; Schreuder, Tim C.M.A.; Faber, Klaas Nico; Blokzijl, H.; Dullaart, Robin P.F.

    2016-01-01

    Background: Non-alcoholic fatty live disease (NAFLD) is becoming the leading cause of chronic liver disease in de Western world. The liver plays a crucial role in the metabolism of cholesterol and triglycerides and thyroid hormones interact on hepatic lipid homeostasis. Given the importance of

  11. Sales impact of displaying alcoholic and non-alcoholic beverages in end-of-aisle locations: an observational study.

    Science.gov (United States)

    Nakamura, Ryota; Pechey, Rachel; Suhrcke, Marc; Jebb, Susan A; Marteau, Theresa M

    2014-05-01

    In-store product placement is perceived to be a factor underpinning impulsive food purchasing but empirical evidence is limited. In this study we present the first in-depth estimate of the effect of end-of-aisle display on sales, focussing on alcohol. Data on store layout and product-level sales during 2010-11 were obtained for one UK grocery store, comprising detailed information on shelf space, price, price promotion and weekly sales volume in three alcohol categories (beer, wine, spirits) and three non-alcohol categories (carbonated drinks, coffee, tea). Multiple regression techniques were used to estimate the effect of end-of-aisle display on sales, controlling for price, price promotion, and the number of display locations for each product. End-of-aisle display increased sales volumes in all three alcohol categories: by 23.2% (p = 0.005) for beer, 33.6% (p non-alcohol beverage categories: by 51.7% (p alcohol categories, and a decrease in price of between 22% and 62% per volume for non-alcohol categories. End-of-aisle displays appear to have a large impact on sales of alcohol and non-alcoholic beverages. Restricting the use of aisle ends for alcohol and other less healthy products might be a promising option to encourage healthier in-store purchases, without affecting availability or cost of products. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Non-alcoholic fatty liver disease, obesity and the metabolic syndrome.

    Science.gov (United States)

    Dietrich, Peter; Hellerbrand, Claus

    2014-08-01

    Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most common cause of chronic liver disease worldwide. Its prevalence has increased to more than 30% of adults in developed countries and its incidence is still rising. The majority of patients with NAFLD have simple steatosis but in up to one third of patients, NAFLD progresses to its more severe form nonalcoholic steatohepatitis (NASH). NASH is characterized by liver inflammation and injury thereby determining the risk to develop liver fibrosis and cancer. NAFLD is considered the hepatic manifestation of the metabolic syndrome. However, the liver is not only a passive target but affects the pathogenesis of the metabolic syndrome and its complications. Conversely, pathophysiological changes in other organs such as in the adipose tissue, the intestinal barrier or the immune system have been identified as triggers and promoters of NAFLD progression. This article details the pathogenesis of NAFLD along with the current state of its diagnosis and treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. [Polycystic ovarian syndrome incidence in young women with non-alcoholic fatty liver disease].

    Science.gov (United States)

    Ciotta, L; Pagano, I; Stracquadanio, M; Formuso, C

    2011-10-01

    Recently, numerous studies have shown significant correlation between hyperandrogenism and elevated insulin levels in many patients with polycystic ovarian syndrome (PCOS). Insuline-Resistance (IR) results in increased circulating levels of this hormone and it is the basis of the metabolic syndrome, characterized by the presence of fatty liver disease (NAFLD), which is pathologically characterized by the accumulation of triglycerides as macro or micro vesicles, in more than 5% of hepatocytes. The aim of our study was to evaluate the incidence of NAFLD in young women with PCOS, who were lean, overweight or obese. Particularly, the levels of glucose and insulin, the lipidic profile, and all liver function indices were evaluated; the severity and degree of steatosis were established on the basis of parenchymal echogenicity and the view of intrahepatic venous circulation. Our study showed that NAFLD is a common disease in women with polycystic ovaries, especially with high BMI, but an incidence rate of 40% in lean women too was found. Because steatohepatitis is a risk factor for the developmente of cirrhosis and hepatocellular carcinoma, it is therefore prudent to carry out an ultrasound evaluation of liver in all young patients suffering from polycystic ovary syndrome, regardless of their BMI and the results of serological evaluation of liver. This collateral diagnosis that accompanies the diagnosis of Polycystic Ovary Syndrome seems important since this type of patients could be treated with metformin or with thiazoles to reduce insulin-resistance and steatosis as well.

  14. A Series of microRNA in the Chromosome 14q32.2 Maternally Imprinted Region Related to Progression of Non-Alcoholic Fatty Liver Disease in a Mouse Model.

    Directory of Open Access Journals (Sweden)

    Kinya Okamoto

    Full Text Available Simple steatosis (SS and non-alcoholic steatohepatitis (NASH are subtypes of non-alcoholic fatty liver disease (NAFLD, and the pathogenic differences between SS and NASH remain unclear. MicroRNAs (miRNAs are endogenous, non-coding, short RNAs that regulate gene expression. The aim of this study was to use animal models and human samples to examine the relationship between miRNA expression profiles and each type of NAFLD (SS and NASH.DD Shionogi, Fatty Liver Shionogi (FLS and FLS ob/ob mice were used as models for normal control, SS and NASH, respectively. Microarray analysis and real-time PCR were used to identify candidate NAFLD-related miRNAs. Human serum samples were used to examine the expression profiles of these candidate miRNAs in control subjects and patients with SS or NASH.Fourteen miRNAs showed clear expression differences among liver tissues from SS, NASH, and control mice with good reproducibility. Among these NAFLD candidate miRNAs, seven showed similar expression patterns and were upregulated in both SS and NASH tissues; these seven candidate miRNAs mapped to an miRNA cluster in the 14q32.2 maternally imprinted region delineated by delta-like homolog 1 and type III iodothyronine deiodinase (Dlk1-Dio3 mat. Software-based predictions indicated that the transforming growth factor-β pathway, insulin like growth factor-1 and 5' adenosine monophosphate activated protein kinase were potential targets of theses Dlk1-Dio3 mat NAFLD candidate miRNAs. In addition, serum samples from patients with SS or NASH differed markedly with regard to expression of the putative Dlk1-Dio3 mat miRNAs, and these differences accurately corresponded with NAFLD diagnosis.The expression profiles of seven miRNAs in 14q32.2 mat have high potential as biomarkers for NAFLD and for improving future research on the pathogenesis and treatment of NASH.

  15. Multiple Focal Nodular Hyperplasia and Steatohepatitis: Atypical Imaging Characteristics

    Directory of Open Access Journals (Sweden)

    Robert P Myers

    2001-01-01

    Full Text Available Focal nodular hyperplasia is a rare, benign condition of the liver. A 28-year-old woman with malignant melanoma, mild liver enzyme abnormalities, steatohepatitis and newly documented hepatic lesions is described. Ultrasound, computed tomography and magnetic resonance imaging suggested only areas of focal fatty sparing but could not eliminate the concern for metastases. A 99mtechnetium-labelled sulphur colloid scan, however, revealed areas of increased uptake consistent with multiple focal nodular hyperplasia. This diagnosis was ultimately confirmed with a liver biopsy. The investigation of a patient with a malignancy and expanding hepatic lesions is challenging. This case illustrates the usefulness of the 99mtechnetium-labelled sulphur colloid scan in the evaluation of patients with hepatic lesions.

  16. Aerobic vs. resistance exercise in non-alcoholic fatty liver disease: A systematic review.

    Science.gov (United States)

    Hashida, Ryuki; Kawaguchi, Takumi; Bekki, Masafumi; Omoto, Masayuki; Matsuse, Hiroo; Nago, Takeshi; Takano, Yoshio; Ueno, Takato; Koga, Hironori; George, Jacob; Shiba, Naoto; Torimura, Takuji

    2017-01-01

    Exercise is a first-line therapy for patients with non-alcoholic fatty liver disease (NAFLD). We sought to: 1) summarize effective aerobic and resistance exercise protocols for NAFLD; and 2) compare the effects and energy consumption of aerobic and resistance exercises. A literature search was performed using PubMed, Web of Science, and Scopas to January 28, 2016. From a total of 95 articles, 23 studies including 24 aerobic and 7 resistance exercise protocols were selected for the summary of exercise protocols. Twelve articles including 13 aerobic and 4 resistance exercise protocols were selected for the comparative analysis. For aerobic exercise, the median effective protocol was 4.8 metabolic equivalents (METs) for 40min/session, 3times/week for 12weeks. For resistance exercise, the median effective protocol was 3.5 METs for 45min/session, 3times/week for 12weeks. Aerobic and resistance exercise improved hepatic steatosis. No significant difference was seen in the duration, frequency, or period of exercise between the two exercise groups; however, %VO 2 max and energy consumption were significantly lower in the resistance than in the aerobic group (50% [45-98] vs. 28% [28-28], p=0.0034; 11,064 [6394-21,087] vs. 6470 [4104-12,310] kcal/total period, p=0.0475). Resistance exercise improves NAFLD with less energy consumption. Thus, resistance exercise may be more feasible than aerobic exercise for NAFLD patients with poor cardiorespiratory fitness or for those who cannot tolerate or participate in aerobic exercise. These data may indicate a possible link between resistance exercise and lipid metabolism in the liver. Both aerobic and resistance exercise reduce hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) with similar frequency, duration, and period of exercise (40-45min/session 3times/week for 12weeks); however, the two forms of exercise have different characteristics. Intensity and energy consumption were significantly lower for resistance than for

  17. Resistin expression correlates with steatohepatitis in morbidly obese patients.

    Science.gov (United States)

    Edwards, Claire R; Hindle, A Katharine; Latham, Patricia S; Fu, Sidney W; Brody, Fred J

    2013-04-01

    Morbidly obese patients are at risk for nonalcoholic steatohepatitis (NASH) even in the absence of risk factors for liver disease. Unfortunately, NASH is usually not clinically evident, and a definitive, noninvasive test for NASH does not exist. Resistin, a cytokine originating from adipose tissue, is involved in insulin resistance and also initiates proinflammatory signaling from hepatic stellate cells. This study explores the relationship between resistin expression and liver pathology in bariatric surgery patients. Blood samples from 30 patients undergoing bariatric surgery were collected. Total RNA was extracted and cDNA was synthesized. Quantitative RT-PCR was used to quantify relative gene expression using 18s rRNA gene as an internal control. Wedge liver biopsies from these patients were sectioned and stained. Based on a previously published scoring method, biopsies were assigned an overall NASH severity score and subscores for steatosis, inflammation, and fibrosis. Results were analyzed by using Student's t test. Resistin mRNA levels ranged from 0.5 to 9.7. A group of five patients with very high resistin expression (>4) was identified. These patients had a significantly higher average NASH score compared with the rest of the group (7.9 vs. 4.48, p = 0.019). Steatosis and inflammation scores were significantly higher in the high-resistin group (p < 0.05 for both comparisons). There also was a trend toward higher fibrosis score in this group, which approached statistical significance (p = 0.051). In morbidly obese patients, high resistin expression in serum is associated with hepatic steatosis, inflammation, and fibrosis. The development of elevated resistin expression may represent a link between obesity and the onset of steatohepatitis.

  18. Psoralea corylifolia L. Attenuates Nonalcoholic Steatohepatitis in Juvenile Mouse

    Directory of Open Access Journals (Sweden)

    Lishan Zhou

    2017-11-01

    Full Text Available Psoralea corylifolia L. (PC is a traditional Chinese herb used to treat yang deficiency of the spleen and kidney in pediatric disease. Recent studies have shown its liver protection and anti-oxidative effects. The aim of this study was to explore the effect and mechanism of PC on nonalcoholic steatohepatitis in juvenile mice. The juvenile mouse model of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH was established by being fed a high-fat diet in maternal-offspring manner. PC granules were prepared and the quality was assessed. The main components were identified by high performance liquid chromatography. Then, different dosages of PC were administered for 6 weeks. Homeostatic model assessment of insulin resistance, plasma liver enzymes, hepatic morphology, hepatic superoxide anion, and triglyceride/total cholesterol levels were examined. The changes of nuclear factor-κB (NF-κB activity phosphatidylinositol 3 kinase (PI3K/protein kinase B (Akt and protein kinase C-α (PKC-α/nicotinamide-adenine dinucleotide phosphate (NADPH oxidase signaling pathways in hepatic tissues were also determined. Our data demonstrated that PC significantly improved liver dysfunction, liver triglyceride/total cholesterol accumulation and insulin resistance in juvenile NAFLD/NASH mice. PC also alleviated hepatic steatosis, inflammatory cell infiltration, and fibroplasia in the portal area. Additionally, PC inhibited the activation of NF-κB and the mRNA expression of inflammatory factors while enhancing PI3K/Akt signaling in hepatic tissues. PC could also reduce hepatic superoxide anion levels, and NADPH oxidase activity as well as p47phox protein expression and PKCα activation in hepatic tissues. The results suggest that PC is effective in the treatment of NASH in juvenile mice. The mechanism may be related to the attenuation of hepatic oxidative stress through the PKC-α/NADPH oxidase signaling pathway.

  19. Prevalence of Non-Alcoholic Fatty Liver Disease in Morbidly Obese Patients Undergoing Sleeve Bariatric Surgery in Iran and Association With Other Comorbid Conditions

    Directory of Open Access Journals (Sweden)

    Karimi-Sari

    2015-04-01

    Full Text Available Background Nonalcoholic fatty liver disease (NAFLD is one of the most common causes of chronic liver disease including simple steatosis to nonalcoholic steatohepatitis (NASH. NASH could progress to cirrhosis and liver cancer. The pr