Nonalcoholic Fatty Liver (nonalcoholic + fatty_liver)

Distribution by Scientific Domains

Terms modified by Nonalcoholic Fatty Liver

  • nonalcoholic fatty liver disease

  • Selected Abstracts


    Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease,,

    HEPATOLOGY, Issue 5 2010
    Kausik Das
    There is a paucity of community-based epidemiological data on nonalcoholic fatty liver (NAFL) among nonaffluent populations in developing countries. Available studies are radiological and/or biochemical and lack histological assessment, limiting their strength. We conducted a prospective epidemiological study comprising a 1:3 subsample of all adult (>18 years) inhabitants of a rural administrative unit of West Bengal, India. Subjects positive for hepatitis B virus and/or hepatitis C virus infection and consuming any amount of alcohol were excluded. Diagnosis of NAFL was by dual radiological screening protocol consisting of ultrasonographic and computed tomographic examination of the liver. Transient elastographic examination and liver biopsy were performed in a subset to identify significant liver disease. The risk factors of having NAFL were analyzed. A total of 1,911 individuals were analyzed, 7% of whom were overweight and 11% of whom had abdominal obesity. The prevalence of NAFL, NAFL with elevated alanine aminotransferase, and cryptogenic cirrhosis was 8.7%, 2.3%, and 0.2%, respectively. Seventy-five percent of NAFL subjects had a body mass index (BMI) <25 kg/m2, and 54% were neither overweight nor had abdominal obesity. The subjects with the highest risk of having NAFL were those with a BMI >25 kg/m2 (odds ratio 4.3, 95% confidence interval 1.6-11.5). Abdominal obesity, dysglycemia (fasting plasma glucose >100 mg/dL or elevated homeostatic model assessment of insulin resistance), and higher income were the other risk factors. Even having a normal BMI (18.5-24.9 kg/m2) was associated with a 2-fold increased risk of NAFL versus those with a BMI <18.5 kg/m2. Conclusion: There is a significant prevalence of NAFL and potentially significant liver disease, including cryptogenic cirrhosis, in this predominantly nonobese, nonaffluent population in a developing country. NAFL will be a major determinant of future liver disease burden in countries of the developing world. (HEPATOLOGY 2010) [source]


    Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression,

    HEPATOLOGY, Issue 6 2009
    Kimberley D. Bruce
    Nonalcoholic fatty liver disease (NAFLD) describes an increasingly prevalent spectrum of liver disorders associated with obesity and metabolic syndrome. It is uncertain why steatosis occurs in some individuals, whereas nonalcoholic steatohepatitis (NASH) occurs in others. We have generated a novel mouse model to test our hypothesis: that maternal fat intake contributes to the development of NAFLD in adult offspring. Female mice were fed either a high-fat (HF) or control chow (C) diet before and during gestation and lactation. Resulting offspring were fed either a C or a HF diet after weaning, to generate four offspring groups; HF/HF, HF/C, C/HF, C/C. At 15 weeks of age, liver histology was normal in both the C/C and HF/C offspring. Kleiner scoring showed that although the C/HF offspring developed nonalcoholic fatty liver, the HF/HF offspring developed NASH. At 30 weeks, histological analysis and Kleiner scoring showed that both the HF/C and C/HF groups had NAFLD, whereas the HF/HF had a more severe form of NASH. Therefore, exposure to a HF diet in utero and during lactation contributes toward NAFLD progression. We investigated the mechanisms by which this developmental priming is mediated. At 15 weeks of age, hepatic mitochondrial electron transport chain (ETC) enzyme complex activity (I, II/III, and IV) was reduced in both groups of offspring from HF-fed mothers (HF/C and HF/HF). In addition, measurement of hepatic gene expression indicated that lipogenesis, oxidative stress, and inflammatory pathways were up-regulated in the 15-week-old HF/C and HF/HF offspring. Conclusion: Maternal fat intake contributes toward the NAFLD progression in adult offspring, which is mediated through impaired hepatic mitochondrial metabolism and up-regulated hepatic lipogenesis. (HEPATOLOGY 2009.) [source]


    Dysfunctional very-low-density lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis,,

    HEPATOLOGY, Issue 3 2009
    Koji Fujita
    The specific mechanisms of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) pathogenesis remain unknown. In the present study we investigated the differences between NAFL and NASH in terms of liver lipid metabolites and serum lipoprotein. In all, 104 Japanese subjects (50 men and 54 postmenopausal women) with histologically verified NAFL disease (NAFLD) (51 with NAFL, 53 with NASH) were evaluated; all diagnoses were based on liver biopsy findings and the proposed diagnostic criteria. To investigate the differences between NAFL and NASH in humans, we carefully examined (1) lipid inflow in the liver, (2) lipid outflow from the liver, (3) very-low-density lipoprotein (VLDL) synthesis in the liver, (4) triglyceride (TG) metabolites in the liver, and (5) lipid changes and oxidative DNA damage. Most of the hepatic lipid metabolite profiles were similar in the NAFL and NASH groups. However, VLDL synthesis and lipid outflow from the liver were impaired, and surplus TGs might have been produced as a result of lipid oxidation and oxidative DNA damage in the NASH group. Conclusion: A growing body of literature suggests that a deterioration in fatty acid oxidation and VLDL secretion from the liver, caused by the impediment of VLDL synthesis, might induce serious lipid oxidation and DNA oxidative damage, impacting the degree of liver injury and thereby contributing to the progression of NASH. Therefore, dysfunctional VLDL synthesis and release may be a key factor in progression to NASH. (HEPATOLOGY 2009.) [source]


    Alcoholic fatty liver differentially induces a neutrophil-chemokine and hepatic necrosis after ischemia-reperfusion in rat

    HEPATOLOGY, Issue 2 2000
    Shinwa Yamada M.D.
    Primary graft nonfunction of steatotic liver allograft is one of the factors causing shortage of donor livers. Ischemia/reperfusion (I/R) injury is an important contributory factor to primary graft nonfunction. In this study, we investigated the complex chain of events from transcription factor activation to necrosis through cytokine induction and apoptosis in steatotic rat liver after warm I/R. Rats with alcoholic or nonalcoholic fatty liver were subjected to hepatic warm I/R and compared with control rats. Rats fed an ethanol diet for 6 to 8 weeks developed severe hepatic necrosis accompanied by increased neutrophil recruitment after I/R, compared with rats with nonalcoholic fatty liver or control. Hepatic apoptosis as assessed by DNA fragmentation at 4 hours after I/R, however, increased to a similar degree in each of the 2 fatty liver models compared with the control. Alcoholic fatty liver exposed to I/R showed a rapid increase in nuclear factor-,B (NF-,B) binding activity at 1 hour after I/R, which preceded an increased expression of tumor necrosis factor , (TNF-,) and cytokine-induced neutrophil chemoattractant-1 (CINC-1). In contrast, nonalcoholic fatty liver did not show such potentiation of either NF-,B activation or cytokine induction after I/R. Our results have indicated that alcoholic fatty liver may differentially induce CINC-1 production and hepatic necrosis after I/R. Furthermore, our results suggest that apoptosis per se does not always lead to necrosis in the liver following I/R. [source]


    Melatonin ameliorates nonalcoholic fatty liver induced by high-fat diet in rats

    JOURNAL OF PINEAL RESEARCH, Issue 1 2006
    Min Pan
    Abstract:, Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition that may progress to end-stage liver disease, which ranges from simple steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. Oxidative stress and lipid peroxidation are key pathophysiological mechanisms in NAFLD. We investigate the preventive effects of intraperitoneal administration of melatonin (2.5, 5, 10 mg/kg, daily, respectively) in NAFLD rats induced by high-fat diets for 12 wk. Liver damage was evaluated by serological analysis, serum and hepatic lipid assay as well as hematoxylin,eosin staining in liver sections. Oxidative stress and lipid peroxidation were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver. The results showed that high-fat diet induced oxidative stress with extensive liver steatosis in rats. Melatonin (5 or 10 mg/kg) was effective in reducing hepatic steatosis and inflammation with lowering serum alanine aminotransferase, aspartate aminotransferase, and levels liver total cholesterol and triglycerides in high-fat diet rats. Moreover, melatonin (2.5, 5, 10 mg/kg) increased SOD and GSH-Px activities and the 10 mg/kg dose of melatonin reduced MDA levels in liver. This study shows that melatonin exerts protective effects against fatty liver in rats induced by high-fat diet possibly through its antioxidant actions. [source]


    MicroRNA Expression Profile in Lieber-DeCarli Diet-Induced Alcoholic and Methionine Choline Deficient Diet-Induced Nonalcoholic Steatohepatitis Models in Mice

    ALCOHOLISM, Issue 10 2009
    Angela Dolganiuc
    Background:, Alcoholic and nonalcoholic steatohepatitis are leading causes of liver diseases worldwide. While of different etiology, these share common pathophysiological mechanisms and feature abnormal fat metabolism, inflammation and fibrosis. MicroRNAs (miRNA) are highly conserved noncoding RNAs that control gene expression at the post-transcriptional level either via the degradation of target mRNAs or the inhibition of translation. Each miRNA controls the expression of multiple targets; miRNAs have been linked to regulation of lipid metabolism and inflammation. Methods:, We fed Lieber-DeCarli alcohol or methionine-choline-deficient (MCD) diets to C57Bl6 and analyzed livers for histopathology, cytokines by ELISA, alanine aminotransferase (ALT) by biochemical assay, and microRNA profile by microarray. Results:, Both Lieber-DeCarli and MCD diets lead to development of liver steatosis, liver injury, indicated by increased ALT, and elevated levels of serum TNF,, suggesting that animal models portray the pathophysiological features of alcoholic and nonalcoholic fatty liver, respectively. We identified that Lieber-deCarli diet up-regulated 1% and down-regulated 1% of known miRNA; MCD diet up-regulated 3% and down-regulated 1% of known miRNA, compared to controls. Of miRNAs that changed expression levels, 5 miRNAs were common in alcoholic and nonalcoholic fatty livers: the expression of both miR-705 and miR-1224 was increased after Lieber-DeCarli or MCD diet feeding. In contrast, miR-182, miR-183, and miR-199a-3p were down-regulated in Lieber-deCarli feeding, while MCD diet lead to their up-regulation, compared to corresponding controls. Conclusions:, Our findings indicate etiology-specific changes in miRNA expression profile during steatohepatitis models, which opens new avenues for research in the pathophysiology of alcoholic and nonalcoholic fatty liver disease. [source]


    Predictive Factors for Pure Steatosis in Alcoholic Patients

    ALCOHOLISM, Issue 6 2009
    Sylvie Naveau
    Background:, Bearing in mind the mechanisms involved in nonalcoholic fatty liver disease, this study aims to verify whether metabolic syndrome or its various individual components are independent predictive factors for steatosis ,10% in alcoholic patients. Methods:, This study included 281 consecutive alcoholic patients with abnormal liver tests and either normal liver histology or steatosis <10% (n = 119) or steatosis ,10% (n = 162). Logistic regression analysis was used to study the relationship between metabolic syndrome components and various risk factors and the presence of steatosis ,10%. We assessed apolipoprotein A1 (ApoA-1) levels, a major protein component of plasma high-density lipoprotein (HDL), rather than HDL-cholesterol levels. Results:, Plasma ApoA-1 levels (p < 0.01), body mass index (BMI) (p < 0.01), and waist circumference (p < 0.05) were significantly higher in patients with steatosis ,10% than in patients with normal liver histology or steatosis <10%. A higher percentage of patients with steatosis ,10% had high blood pressure (p = 0.003) than patients with normal liver histology or steatosis <10%. In the logistic regression, ApoA-1 [odds ratio (OR) = 1.57 (1.10,2.22)], BMI [OR = 1.10 (1.01,1.23)], and high blood pressure [OR = 1.84 (1.10,3.06)] were positively and independently correlated with the presence of steatosis ,10%. In the multivariate regression high blood pressure was independently and positively correlated with steatosis score (r = 0.55 0.26; p < 0.05). On the other hand, when the presence of high blood pressure was the dependent variable, the presence of steatosis ,10% positively and independently correlated with it [OR = 1.82 (1.05,3.15)]. Conclusion:, In alcoholic patients without fibrosis, ApoA-1, BMI, and high blood pressure on the next morning after the admission were predictive of steatosis ,10%. High blood pressure was the only metabolic syndrome component associated with the presence of alcoholic steatosis ,10% and was not correlated with other metabolic syndrome components. These findings suggest that steatosis mechanisms are different in alcoholic and nonalcoholic fatty liver. [source]


    Endocannabinoid receptor CB2 in nonalcoholic fatty liver disease

    LIVER INTERNATIONAL, Issue 2 2007
    N. Mendez-Sanchez
    Abstract Background and Aim: Fatty infiltration and fibrosis are major issues in chronic liver disease. Recent reports suggest a role for the endocannabinoid system in these processes. Aim: To characterize localization and expression of CB2 in normal liver and nonalcoholic fatty liver. Methods: We studied 64 liver biopsies: eight were considered normal; 56 had a diagnosis of nonalcoholic fatty liver disease (NAFLD); 32 with nonalcoholic steatosis and 24 nonalcoholic steatohepatitis (NASH). CB2 immunolocalization was studied in 38 samples in paraffin blocks using immunohistochemistry, and a computerized semiquantitative analysis was carried out. CB2 mRNA expression was assessed through RT-PCR in 26 frozen liver samples and the ratio CB2/,-actin was used to evaluate differences between groups. Statistical analysis was performed with central tendency measures and the Mann,Whitney U -test. We considered as significant differences those with a P -value <0.05. Results: Neither parenchymal nor nonparenchymal cells in normal liver tissue react towards anti-CB2 antibodies. All the samples from patients with steatosis and nonalcoholic steatohepatitis showed hepatocellular immunoreactivity. Cholangiocytes were positive only in the NAFLD group. Normal liver tissue showed a normalized CB2/,-actin ratio of 0.0010.01, steatosis 6.5217.3 (P=0.05 vs normal) and NASH 6.4912.2 (P=0.06 vs normal and P=0.6 vs steatosis). Conclusion: CB2 receptors are expressed by hepatocytes in nonalcoholic fatty liver disease but not in normal liver. [source]


    Serum thioredoxin elucidates the significance of serum ferritin as a marker of oxidative stress in chronic liver diseases

    LIVER INTERNATIONAL, Issue 5 2001
    Yoshio Sumida
    Abstract:Background/Aims: Serum thioredoxin (TRX) levels have recently been established as an indicator of oxidative stress in various diseases. The aim of the present study was to clarify the clinical significance of serum ferritin in chronic liver diseases. Methods: Levels of ferritin, transferrin saturation (TS), aspartate aminotransferase (AST), and TRX were measured in the sera of patients with chronic hepatitis C (CH-C, n=92), chronic hepatitis B (CH-B, n=28), nonalcoholic fatty liver (FL, n=31), or alcoholic liver diseases (ALD, n=17). Serum TRX levels were evaluated with a recently established sandwich enzyme-linked immunosorbent assay kit. Results: Serum TRX levels were significantly higher in CH-C, FL, and ALD than in healthy volunteers. A larger proportion of patients with CH-C, FL, and ALD had elevated levels of serum ferritin than CH-B. Serum ferritin levels were positively correlated with levels of TS, AST, and TRX in CH-C, but were merely correlated with TS values in CH-B. Ferritin levels were also well correlated with AST and TRX, but not with TS in FL and ALD. Conclusion: Oxidative stress, which was evaluated by measuring serum TRX, in addition to storage iron and hepatocyte damage is a cause of increasing serum ferritin levels in chronic liver diseases. An elevated serum ferritin level, which was correlated with TS, indicates that iron-induced oxidative stress contributes to CH-C. Elevated ferritin levels in FL and ALD may be mostly due to iron-unrelated stresses. [source]


    MicroRNA Expression Profile in Lieber-DeCarli Diet-Induced Alcoholic and Methionine Choline Deficient Diet-Induced Nonalcoholic Steatohepatitis Models in Mice

    ALCOHOLISM, Issue 10 2009
    Angela Dolganiuc
    Background:, Alcoholic and nonalcoholic steatohepatitis are leading causes of liver diseases worldwide. While of different etiology, these share common pathophysiological mechanisms and feature abnormal fat metabolism, inflammation and fibrosis. MicroRNAs (miRNA) are highly conserved noncoding RNAs that control gene expression at the post-transcriptional level either via the degradation of target mRNAs or the inhibition of translation. Each miRNA controls the expression of multiple targets; miRNAs have been linked to regulation of lipid metabolism and inflammation. Methods:, We fed Lieber-DeCarli alcohol or methionine-choline-deficient (MCD) diets to C57Bl6 and analyzed livers for histopathology, cytokines by ELISA, alanine aminotransferase (ALT) by biochemical assay, and microRNA profile by microarray. Results:, Both Lieber-DeCarli and MCD diets lead to development of liver steatosis, liver injury, indicated by increased ALT, and elevated levels of serum TNF,, suggesting that animal models portray the pathophysiological features of alcoholic and nonalcoholic fatty liver, respectively. We identified that Lieber-deCarli diet up-regulated 1% and down-regulated 1% of known miRNA; MCD diet up-regulated 3% and down-regulated 1% of known miRNA, compared to controls. Of miRNAs that changed expression levels, 5 miRNAs were common in alcoholic and nonalcoholic fatty livers: the expression of both miR-705 and miR-1224 was increased after Lieber-DeCarli or MCD diet feeding. In contrast, miR-182, miR-183, and miR-199a-3p were down-regulated in Lieber-deCarli feeding, while MCD diet lead to their up-regulation, compared to corresponding controls. Conclusions:, Our findings indicate etiology-specific changes in miRNA expression profile during steatohepatitis models, which opens new avenues for research in the pathophysiology of alcoholic and nonalcoholic fatty liver disease. [source]