Fish oil prevents sucrose-induced fatty liver but exacerbates high-safflower oil-induced fatty liver in ddy mice.

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Yamazaki, Tomomi; Nakamori, Akiko; Sasaki, Eriko; Wada, Satoshi; Ezaki, Osamu

2007-12-01

Diets high in sucrose/fructose or fat can result in hepatic steatosis (fatty liver). We analyzed the effects of dietary fish oil on fatty liver induced by sucrose, safflower oil, and butter in ddY mice. In experiment I, mice were fed a high-starch diet [70 energy% (en%) starch] plus 20% (wt/wt) sucrose in the drinking water or fed a high-safflower oil diet (60 en%) for 11 weeks. As a control, mice were fed a high-starch diet with drinking water. Fish oil (10 en%) was either supplemented or not. Mice supplemented with sucrose or fed safflower oil showed a 1.7-fold or 2.2-fold increased liver triglyceride content, respectively, compared with that of control mice. Fish oil completely prevented sucrose-induced fatty liver, whereas it exacerbated safflower oil-induced fatty liver. Sucrose increased SREBP-1c and target gene messenger RNAs (mRNAs), and fish oil completely inhibited these increases. In experiment II, mice were fed a high-safflower oil or a high-butter diet, with or without fish oil supplementation. Fish oil exacerbated safflower oil-induced fatty liver but did not affect butter-induced fatty liver. Fish oil increased expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and target CD36 mRNA in safflower oil-fed mice. These increases were not observed in sucrose-supplemented or butter-fed mice. The effects of dietary fish oil on fatty liver differ according to the cause of fatty liver; fish oil prevents sucrose-induced fatty liver but exacerbates safflower oil-induced fatty liver. The exacerbation of fatty liver may be due, at least in part, to increased expression of liver PPARgamma.

Fatty Liver

International Nuclear Information System (INIS)

Filippone, A.; Digiovandomenico, V.; Digiovandomenico, E.; Genovesi, N.; Bonomo, L.

1991-01-01

The authors report their experience with the combined use of US and CT in the study of diffuse and subtotal fatty infiltration of the liver. An apparent disagreement was initially found between the two examinations in the study of fatty infiltration. Fifty-five patients were studied with US and CT of the upper abdomen, as suggested by clinics. US showed normal liver echogenicity in 30 patients and diffuse increased echogenicity (bright liver) in 25 cases. In 5 patients with bright liver, US demonstrated a solitary hypoechoic area, appearing as a 'skip area', in the quadrate lobe. In 2 patients with bright liver, the hypoechoic area was seen in the right lobe and exhibited no typical US features of 'Skip area'. Bright liver was quantified by measuring CT density of both liver and spleen. The relative attenuation values of spleen and liver were compared on plain and enhanced CT scans. In 5 cases with a hypoechoic area in the right lobe, CT findings were suggestive of hemangioma. A good correlation was found between broght liver and CT attenuation values, which decrease with increasing fat content of the liver. Moreover, CT attenuation values confirmed US findings in the study of typical 'skip area', by demonstrating normal density - which suggests that CT can characterize normal tissue in atypical 'skip area'

Correlation of hepatic 18F-fluorodeoxyglucose uptake with fatty liver

International Nuclear Information System (INIS)

An, Young Sil; Yoon, Joon Kee; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam

2006-01-01

Liver demonstrates heterogeneous FDG uptake and sometimes it shows abnormally increased uptake even though there is no malignant tissue. However, there was no previous study to correlate these various pattern of hepatic FDG uptake with benign liver disease. Therefore, we evaluated the significance of hepatic FDG uptake associated with various clinical factors including fatty liver, liver function tests and lipid profiles. We reviewed a total of 188 patients (male/female: 120/68, mean age: 50 ± 9) who underwent PET/CT for screening of malignancy. Patients with DM, impaired glucose tolerance, previous severe hepatic disease or long-term medication history were excluded. The FDG uptake in liver was analyzed semi-quantitatively using ROI on transaxial images (segment 8) and we compared mean standardized uptake value (SUV) between fatty liver and non-fatty liver group. We also evaluated the correlation between hepatic FDG uptake and various clinical factors including serum liver function test (ALT, AST), γ -GT, total cholesterol and triglyceride concentration. The effect of alcoholic history and body mass index on hepatic FDG uptake was analyzed within the fatty liver patients. The hepatic FDG uptake of fatty liver group was significantly higher than that of non-fatty liver group. Serum total cholesterol and triglyceride concentration showed significant correlation with hepatic FDG uptake. However, there was no significant correlation between other factors (ALT, AST, and γ -GT) and FDG uptake. Also there was no difference of mean SUV between normal and abnormal groups on the basis of alcoholic history and body mass index within fatty liver patients. Fatty liver and high serum triglyceride concentration were the independent factors affecting hepatic FDG uptake according to multivariate analysis. In conclusion, hepatic FDG uptake was strongly correlated with fatty liver and serum triglyceride concentration

Prevalence of Nonalcoholic Fatty Liver Disease in Normal-weight and Overweight Preadolescent Children in Haryana, India.

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Das, Manoja Kumar; Bhatia, Vidyut; Sibal, Anupam; Gupta, Abha; Gopalan, Sarath; Sardana, Raman; Sahni, Reeti; Roy, Ankur; Arora, Narendra K

2017-12-15

To document the prevalence of non-alcoholic fatty liver disease (NAFLD) and metabolic parameters among normal-weight and overweight schoolchildren. Cross-sectional study. Thirteen private schools in urban Faridabad, Haryana. 961 school children aged 5-10 years. Ultrasound testing was done, and 215 with fatty liver on ultrasound underwent further clinical, biochemical and virological testing. Prevalence of fatty liver on ultrasound, and NAFLD and its association with biochemical abnormalities and demographic risk factors. On ultrasound, 215 (22.4%) children had fatty liver; 18.9% in normal-weight and 45.6% in overweight category. Presence and severity of fatty liver disease increased with body mass index (BMI) and age. Among the children with NAFLD, elevated SGOT and SGPT was observed in 21.5% and 10.4% children, respectively. Liver enzyme derangement was significantly higher in overweight children (27% vs 19.4% in normal-weight) and severity of fatty liver (28% vs 20% in mild fatty liver cases). Eleven (8.1%) children with NAFLD had metabolic syndrome. Higher BMI (OR 35.9), severe fatty liver disease (OR 1.7) and female sex (OR 1.9) had strong association with metabolic syndrome. 22.4% of normal-weight and overweight children aged 5-10 years had fatty liver. A high proportion (18.9%) of normal-weight children with fatty liver on ultrasound indicates the silent burden in the population.

Nonalcoholic Fatty Liver Disease & NASH

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... Eating, Diet, & Nutrition Clinical Trials Wilson Disease Nonalcoholic Fatty Liver Disease & NASH View or Print All Sections Definition & Facts Nonalcoholic fatty liver disease (NAFLD) is a condition in which fat ...

External Validation of Fatty Liver Index for Identifying Ultrasonographic Fatty Liver in a Large-Scale Cross-Sectional Study in Taiwan

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Fang, Kuan-Chieh; Wang, Yuan-Chen; Huo, Teh-Ia; Huang, Yi-Hsiang; Yang, Hwai-I; Su, Chien-Wei; Lin, Han-Chieh; Lee, Fa-Yauh; Wu, Jaw-Ching; Lee, Shou-Dong

2015-01-01

Background and Aims The fatty liver index (FLI) is an algorithm involving the waist circumference, body mass index, and serum levels of triglyceride and gamma-glutamyl transferase to identify fatty liver. Although some studies have attempted to validate the FLI, few studies have been conducted for external validation among Asians. We attempted to validate FLI to predict ultrasonographic fatty liver in Taiwanese subjects. Methods We enrolled consecutive subjects who received health check-up services at the Taipei Veterans General Hospital from 2002 to 2009. Ultrasonography was applied to diagnose fatty liver. The ability of the FLI to detect ultrasonographic fatty liver was assessed by analyzing the area under the receiver operating characteristic (AUROC) curve. Results Among the 29,797 subjects enrolled in this study, fatty liver was diagnosed in 44.5% of the population. Subjects with ultrasonographic fatty liver had a significantly higher FLI than those without fatty liver by multivariate analysis (odds ratio 1.045; 95% confidence interval, CI 1.044–1.047, pfatty liver (AUROC: 0.827, 95% confidence interval, 0.822–0.831). An FLI fatty liver. Moreover, an FLI ≥ 35 (positive likelihood ratio (LR+) 3.12) for males and ≥ 20 (LR+ 4.43) for females rule in ultrasonographic fatty liver. Conclusions FLI could accurately identify ultrasonographic fatty liver in a large-scale population in Taiwan but with lower cut-off value than the Western population. Meanwhile the cut-off value was lower in females than in males. PMID:25781622

Diagnostic methods of fatty liver disease

International Nuclear Information System (INIS)

Kukuk, Guido Matthias; Sprinkart, Alois Martin; Traeber, Frank

2017-01-01

Fatty liver disease is defined as an abnormal accumulation of lipids into the cytoplasm of hepatocytes. Different kinds of fatty liver diseases are becoming the most important etiologies of end-stage liver disease in the western world. Because fatty liver is a theoretically reversible process, timely and accurate diagnosis is a prerequisite for potential therapeutic options. This work describes major diagnostic methods and discusses particular advantages and disadvantages of various techniques.

Effects of elastase on fatty liver

International Nuclear Information System (INIS)

Ogura, Kazuo; Shimizu, Yoshikazu; Hihara, Masafumi; Ando, Hideki; Nishiyama, Masateru; Tano, Hironobu

1984-01-01

Elastase (Elaszym 6T) was administered, in addition to the dietary instruction, to three patients with fatty liver. CT scanning revealed marked improvement in fatty liver. Transaminase levels returned to normal, total cholesterol levels tended to decrease, and HDL-cholesterol levels tended to increase. These results suggest that elastase is effective in the treatment of fatty liver. (Namekawa, K.)

External validation of fatty liver index for identifying ultrasonographic fatty liver in a large-scale cross-sectional study in Taiwan.

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Bi-Ling Yang

Full Text Available The fatty liver index (FLI is an algorithm involving the waist circumference, body mass index, and serum levels of triglyceride and gamma-glutamyl transferase to identify fatty liver. Although some studies have attempted to validate the FLI, few studies have been conducted for external validation among Asians. We attempted to validate FLI to predict ultrasonographic fatty liver in Taiwanese subjects.We enrolled consecutive subjects who received health check-up services at the Taipei Veterans General Hospital from 2002 to 2009. Ultrasonography was applied to diagnose fatty liver. The ability of the FLI to detect ultrasonographic fatty liver was assessed by analyzing the area under the receiver operating characteristic (AUROC curve.Among the 29,797 subjects enrolled in this study, fatty liver was diagnosed in 44.5% of the population. Subjects with ultrasonographic fatty liver had a significantly higher FLI than those without fatty liver by multivariate analysis (odds ratio 1.045; 95% confidence interval, CI 1.044-1.047, p< 0.001. Moreover, FLI had the best discriminative ability to identify patients with ultrasonographic fatty liver (AUROC: 0.827, 95% confidence interval, 0.822-0.831. An FLI < 25 (negative likelihood ratio (LR- 0.32 for males and <10 (LR- 0.26 for females rule out ultrasonographic fatty liver. Moreover, an FLI ≥ 35 (positive likelihood ratio (LR+ 3.12 for males and ≥ 20 (LR+ 4.43 for females rule in ultrasonographic fatty liver.FLI could accurately identify ultrasonographic fatty liver in a large-scale population in Taiwan but with lower cut-off value than the Western population. Meanwhile the cut-off value was lower in females than in males.

Correlation of hepatic {sup 18}F-fluorodeoxyglucose uptake with fatty liver

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An, Young Sil; Yoon, Joon Kee; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam [Ajou University School of Medicine, Suwon (Korea, Republic of)

2006-10-15

Liver demonstrates heterogeneous FDG uptake and sometimes it shows abnormally increased uptake even though there is no malignant tissue. However, there was no previous study to correlate these various pattern of hepatic FDG uptake with benign liver disease. Therefore, we evaluated the significance of hepatic FDG uptake associated with various clinical factors including fatty liver, liver function tests and lipid profiles. We reviewed a total of 188 patients (male/female: 120/68, mean age: 50 {+-} 9) who underwent PET/CT for screening of malignancy. Patients with DM, impaired glucose tolerance, previous severe hepatic disease or long-term medication history were excluded. The FDG uptake in liver was analyzed semi-quantitatively using ROI on transaxial images (segment 8) and we compared mean standardized uptake value (SUV) between fatty liver and non-fatty liver group. We also evaluated the correlation between hepatic FDG uptake and various clinical factors including serum liver function test (ALT, AST), {gamma} -GT, total cholesterol and triglyceride concentration. The effect of alcoholic history and body mass index on hepatic FDG uptake was analyzed within the fatty liver patients. The hepatic FDG uptake of fatty liver group was significantly higher than that of non-fatty liver group. Serum total cholesterol and triglyceride concentration showed significant correlation with hepatic FDG uptake. However, there was no significant correlation between other factors (ALT, AST, and {gamma} -GT) and FDG uptake. Also there was no difference of mean SUV between normal and abnormal groups on the basis of alcoholic history and body mass index within fatty liver patients. Fatty liver and high serum triglyceride concentration were the independent factors affecting hepatic FDG uptake according to multivariate analysis. In conclusion, hepatic FDG uptake was strongly correlated with fatty liver and serum triglyceride concentration.

CT number of the fatty liver

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Maeda, Hiroko; Kawai, Takeshi; Kanasaki, Yoshiki; Akagi, Hiroaki

1981-01-01

This report is studied on CT number and CT images of the eight cases with fatty liver. Five of these cases showed the reversal of densities of the liver and vessels. In these cases, the diagnoses of the fatty liver were easible. In other cases, the diagnoses were possible only by comparison of the CT number of the liver and spleen because the CT number of normal liver were higher than those of the spleen. In the results which we examined the correlation of the CT number and specific gravities of the blood, normal saline, distilled water, mayonnaise, eatable iol, ethyl alcohol and lard, we observed the linear relationship between CT number and specific gravities. And so, we think that the diagnosis of the fatty liver and the degree of fatty infiltration can be guessed by the CT number of the liver and spleen. (author)

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

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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

Gallstone disease is associated with more severe liver damage in patients with non-alcoholic fatty liver disease.

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Anna Ludovica Fracanzani

Full Text Available BACKGROUND: Nonalcoholic fatty liver disease (NAFLD and gallstone disease (GD are both highly prevalent in the general population and associated with obesity and insulin resistance. We aimed to evaluate the prevalence of GD in a cross sectional study of NAFLD patients and to define whether the presence of GD is associated with diabetes and predicts more severe liver disease. METHODOLOGY/PRINCIPAL FINDINGS: We merged databases of four Liver Units, comprising 524 consecutive biopsy-proven NAFLD (373 males observed between January 2003 and June 2010. GD was diagnosed in 108 (20%, and 313 cases (60% were classified by liver biopsy as nonalcoholic steatohepatitis (NASH. The GD subgroup was characterized by a significantly higher prevalence of females, prediabetes/diabetes, abdominal obesity and metabolic syndrome, older age, higher BMI, fasting glucose, HOMA-IR and lower ALT. The prevalence of GD progressively increased with advancing fibrosis and with the severity of necroinflammatory activity (p for trend  = 0.0001 and  = 0.01, respectively, without differences in the severity of steatosis. At multivariate analysis GD was associated with female gender (OR 1.37, 95% CI 1.04-1.8, age (OR 1.027, 95% CI1.003-1.05, fasting glucose (OR 1.21, 95% CI 1.10-1.33 and NASH (OR 1.40,95% CI 1.06-1.89, whereas ALT levels were associated with a lower GD risk (OR 0.98, 95% CI 0.97-0.99. When subjects with cirrhosis were excluded from analysis, the association between GD and fasting glucose, female gender, and NASH was maintained. CONCLUSION: Patients with NAFLD have a high prevalence of GD, which characterizes subjects with altered glucose regulation and more advanced liver disease.

Genetics Home Reference: non-alcoholic fatty liver disease

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... individual is considered to have a fatty liver (hepatic steatosis) if the liver contains more than 5 to ... Resources Genetic Testing (2 links) Genetic Testing Registry: Fatty liver disease, nonalcoholic 1 Genetic Testing Registry: Fatty liver ...

Non-alcoholic fatty liver disease, to struggle with the strangle: Oxygen availability in fatty livers.

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Anavi, Sarit; Madar, Zecharia; Tirosh, Oren

2017-10-01

Nonalcoholic fatty liver diseases (NAFLD) is one of the most common chronic liver disease in Western countries. Oxygen is a central component of the cellular microenvironment, which participate in the regulation of cell survival, differentiation, functions and energy metabolism. Accordingly, sufficient oxygen supply is an important factor for tissue durability, mainly in highly metabolic tissues, such as the liver. Accumulating evidence from the past few decades provides strong support for the existence of interruptions in oxygen availability in fatty livers. This outcome may be the consequence of both, impaired systemic microcirculation and cellular membrane modifications which occur under steatotic conditions. This review summarizes current knowledge regarding the main factors which can affect oxygen supply in fatty liver. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Fatty liver incidence and predictive variables

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Tsuneto, Akira; Seto, Shinji; Maemura, Koji; Hida, Ayumi; Sera, Nobuko; Imaizumi, Misa; Ichimaru, Shinichiro; Nakashima, Eiji; Akahoshi, Masazumi

2010-01-01

Although fatty liver predicts ischemic heart disease, the incidence and predictors of fatty liver need examination. The objective of this study was to determine fatty liver incidence and predictive variables. Using abdominal ultrasonography, we followed biennially through 2007 (mean follow-up, 11.6±4.6 years) 1635 Nagasaki atomic bomb survivors (606 men) without fatty liver at baseline (November 1990 through October 1992). We examined potential predictive variables with the Cox proportional hazard model and longitudinal trends with the Wilcoxon rank-sum test. In all, 323 (124 men) new fatty liver cases were diagnosed. The incidence was 19.9/1000 person-years (22.3 for men, 18.6 for women) and peaked in the sixth decade of life. After controlling for age, sex, and smoking and drinking habits, obesity (relative risk (RR), 2.93; 95% confidence interval (CI), 2.33-3.69, P<0.001), low high-density lipoprotein-cholesterol (RR, 1.87; 95% CI, 1.42-2.47; P<0.001), hypertriglyceridemia (RR, 2.49; 95% CI, 1.96-3.15; P<0.001), glucose intolerance (RR, 1.51; 95% CI, 1.09-2.10; P=0.013) and hypertension (RR, 1.63; 95% CI, 1.30-2.04; P<0.001) were predictive of fatty liver. In multivariate analysis including all variables, obesity (RR, 2.55; 95% CI, 1.93-3.38; P<0.001), hypertriglyceridemia (RR, 1.92; 95% CI, 1.41-2.62; P<0.001) and hypertension (RR, 1.31; 95% CI, 1.01-1.71; P=0.046) remained predictive. In fatty liver cases, body mass index and serum triglycerides, but not systolic or diastolic blood pressure, increased significantly and steadily up to the time of the diagnosis. Obesity, hypertriglyceridemia and, to a lesser extent, hypertension might serve as predictive variables for fatty liver. (author)

Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken

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Zhang, Yonghong; Liu, Zhen; Liu, Ranran; Wang, Jie; Zheng, Maiqing; Li, Qinghe; Cui, Huanxian; Zhao, Guiping; Wen, Jie

2018-01-01

Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF) diet and a methionine choline-deficient (MCD) diet. The results showed that the dwarf Jingxing-Huang (JXH) chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL) and local Beijing-You (BJY) breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism (ACACA, FASN, SCD, ACSL5, FADS2, FABP1, APOA4 and ME1). This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers. PMID:29642504

Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken.

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Zhang, Yonghong; Liu, Zhen; Liu, Ranran; Wang, Jie; Zheng, Maiqing; Li, Qinghe; Cui, Huanxian; Zhao, Guiping; Wen, Jie

2018-04-08

Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF) diet and a methionine choline-deficient (MCD) diet. The results showed that the dwarf Jingxing-Huang (JXH) chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL) and local Beijing-You (BJY) breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism ( ACACA , FASN , SCD , ACSL5 , FADS2 , FABP1 , APOA4 and ME1 ). This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers.

Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken

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Yonghong Zhang

2018-04-01

Full Text Available Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF diet and a methionine choline-deficient (MCD diet. The results showed that the dwarf Jingxing-Huang (JXH chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL and local Beijing-You (BJY breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism (ACACA, FASN, SCD, ACSL5, FADS2, FABP1, APOA4 and ME1. This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers.

Quantitative evaluation of 99mTc-GSA for fatty liver and ischemia-reperfusion injury in rats

International Nuclear Information System (INIS)

Kimoto, Mitsunori

1996-01-01

99m Tc-GSA (GSA) liver scintigraphy was performed in rats with fatty liver and ischemia-reperfusion injury to study the usefulness of GSA in evaluating these pathological processes. Fatty liver was produced by feeding rats a choline-deficient diet. The rats with fatty liver were divided into five groups according to the length of the diet (controls, two weeks, six weeks, 10 weeks, and 12 weeks). In the rats dieted for two weeks and six weeks, regional hepatic ischemia was also induced by clamping the left hepatic artery and the left portal vein for 10 minutes, then reperfusion was performed for 15 minutes. GSA was administered via the IVC. t 90 , or the time at which the liver time activity curve reached ninety percent of its peak value, was used as an index of GSA hepatic uptake, Ku and Kd, determined by two compartment analysis, were also used as indices. In rats of the fatty liver group, we confirmed microscopically that various degrees of fatty infiltration existed according to the diet period, and t 90 became significantly longer according to the severity of fatty infiltration. Ku and Kd also decreased according to the severity of fatty infiltration. In the rats with fatty infiltration and ischemia-reperfusion injury, t 90 also increased according to the severity of fatty infiltration, becoming longer than in the rats without ischemia-reperfusion injury. Quantitative analysis of GSA liver scintigraphy was useful for evaluating fatty liver and ischemia-reperfusion injury. (author)

Uridine prevents fenofibrate-induced fatty liver.

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Thuc T Le

Full Text Available Uridine, a pyrimidine nucleoside, can modulate liver lipid metabolism although its specific acting targets have not been identified. Using mice with fenofibrate-induced fatty liver as a model system, the effects of uridine on liver lipid metabolism are examined. At a daily dosage of 400 mg/kg, fenofibrate treatment causes reduction of liver NAD(+/NADH ratio, induces hyper-acetylation of peroxisomal bifunctional enzyme (ECHD and acyl-CoA oxidase 1 (ACOX1, and induces excessive accumulation of long chain fatty acids (LCFA and very long chain fatty acids (VLCFA. Uridine co-administration at a daily dosage of 400 mg/kg raises NAD(+/NADH ratio, inhibits fenofibrate-induced hyper-acetylation of ECHD, ACOX1, and reduces accumulation of LCFA and VLCFA. Our data indicates a therapeutic potential for uridine co-administration to prevent fenofibrate-induced fatty liver.

Fatty Liver Index and Lipid Accumulation Product Can Predict Metabolic Syndrome in Subjects without Fatty Liver Disease

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Yuan-Lung Cheng

2017-01-01

Full Text Available Background. Fatty liver index (FLI and lipid accumulation product (LAP are indexes originally designed to assess the risk of fatty liver and cardiovascular disease, respectively. Both indexes have been proven to be reliable markers of subsequent metabolic syndrome; however, their ability to predict metabolic syndrome in subjects without fatty liver disease has not been clarified. Methods. We enrolled consecutive subjects who received health check-up services at Taipei Veterans General Hospital from 2002 to 2009. Fatty liver disease was diagnosed by abdominal ultrasonography. The ability of the FLI and LAP to predict metabolic syndrome was assessed by analyzing the area under the receiver operating characteristic (AUROC curve. Results. Male sex was strongly associated with metabolic syndrome, and the LAP and FLI were better than other variables to predict metabolic syndrome among the 29,797 subjects. Both indexes were also better than other variables to detect metabolic syndrome in subjects without fatty liver disease (AUROC: 0.871 and 0.879, resp., and the predictive power was greater among women. Conclusion. Metabolic syndrome increases the cardiovascular disease risk. The FLI and LAP could be used to recognize the syndrome in both subjects with and without fatty liver disease who require lifestyle modifications and counseling.

Serum vaspin level as a predictive indicator in the amelioration of fatty liver and metabolic disturbance in patients with severe obesity after laparoscopic vertical banded gastroplasty.

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Wang, Yong; Yu, Zong-Fan; Cheng, Yun-Sheng; Jia, Ben-Li; Yu, Gang; Yin, Xiao-Qiang; Wang, Yang

2017-07-01

This study is all about predicting the value of serum vaspin level in the amelioration of fatty liver and metabolic disturbance in patients with severe obesity after laparoscopic vertical banded gastroplasty (LVBG). A total of 164 patients (from January 2012 to May 2015) with severe obesity were chosen and performed LVBG. Enzyme-linked immunosorbent assay was performed to detect the serum vaspin level. The patients were given a biochemical automatic analyzer to measure the biochemical indicators. Homeostasis model assessment (HOMA) helps in the calculation of fasting insulin level (FINS) and insulin resistance (IR). The changes in fatty liver were examined by computed tomography (CT). Receiver operating characteristic curve is used to increase the predictive value of serum vaspin level in the amelioration of liver function and disturbances in the metabolism. Weight, BMI, waist circumference, serum vaspin level, and triglyceride (TG) decreased, but CT value of liver increased at 4th, 7th, and 12th month after surgery. After the 7th and 12th month period of surgery, the alanine aminotransferase, aspartate aminotransferase, FINS, and HOMA-IR reduced in the patients (P fatty liver and metabolic disturbance. This study proves that the serum vaspin level serves as a predictive indicator in the amelioration of fatty liver and metabolic disturbance in patients with severe obesity after LVBG.

Quantitative characterization of fatty liver disease using x-ray scattering

International Nuclear Information System (INIS)

Elsharkawy, Wafaa B.; Elshemey, Wael M.

2013-01-01

Nonalcoholic fatty liver disease (NAFLD) is a dynamic condition in which fat abnormally accumulates within the hepatocytes. It is believed to be a marker of risk of later chronic liver diseases, such as liver cirrhosis and carcinoma. The fat content in liver biopsies determines its validity for liver transplantation. Transplantation of livers with severe NAFLD is associated with a high risk of primary non-function. Moreover, NAFLD is recognized as a clinically important feature that influences patient morbidity and mortality after hepatic resection. Unfortunately, there is a lack in a precise, reliable and reproducible method for quantification of NAFLD. This work suggests a method for the quantification of NAFLD. The method is based on the fact that fatty liver tissue would have a characteristic x-ray scattering profile with a relatively intense fat peak at a momentum transfer value of 1.1 nm −1 compared to a soft tissue peak at 1.6 nm −1 . The fat content in normal and fatty liver is plotted against three profile characterization parameters (ratio of peak intensities, ratio of area under peaks and ratio of area under fat peak to total profile area) for measured and Monte Carlo simulated x-ray scattering profiles. Results show a high linear dependence (R 2 >0.9) of the characterization parameters on the liver fat content with a reported high correlation coefficient (>0.9) between measured and simulated data. These results indicate that the current method probably offers reliable quantification of fatty liver disease. - Highlights: • A method for the quantification of NAFLD is suggested. • Fatty liver tissue has characteristic x-ray scattering profile. • Profile characterization parameters show differences between normal and fatty liver. • Monte Carlo simulated x-ray scattering profiles are compared to measured

Performance of transient elastography in diagnosis of nonalcoholic fatty liver disease

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ZHUANG Xiaofang

2017-12-01

Full Text Available ObjectiveTo investigate the value of transient elastography (TE in the diagnosis of nonalcoholic fatty liver disease (NAFLD. MethodsA total of 21 patients without fatty liver disease and 92 patients with NAFLD, who visited Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from June to December, 2016, were enrolled. Their general information was collected and body mass index (BMI was calculated. Routine blood test, liver function evaluation, and measurement of blood lipid, serum insulin, and alpha-fetoprotein were performed, and liver CT and FibroTouch were performed. The receiver operating characteristic (ROC curve was plotted with liver/spleen CT ratio as diagnostic criteria, and the ROC curve was used to evaluate the ability of controlled attenuation parameter (CAP to diagnose NAFLD. The area under the ROC curve (AUC was calculated, the Z test was used to evaluate diagnostic effectiveness, and Youden index was used to determine the optimal cut-off value. The t-test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between any two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. The chi-square test was used for comparison of categorical data between groups. ResultsThere were significant differences in age, alanine aminotransferase (ALT, aspartate aminotransferase (AST, serum insulin, fat attenuation, and liver stiffness measurement (LSM between the patients without fatty liver disease and those with varying degrees of NAFLD (all P＜0.05. The severe NAFLD group had a significantly lower mean age than the non-fatty liver disease group (P＜0.001. There was a significant difference in CAP

Evaluation of nonalcoholic fatty liver disease using magnetic resonance in obese children and adolescents.

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Benetolo, Patrícia O; Fernandes, Maria I M; Ciampo, Ieda R L Del; Elias-Junior, Jorge; Sawamura, Regina

2018-02-10

To determine the frequency of nonalcoholic fatty liver disease using nuclear magnetic resonance as a noninvasive method. This was a cross-sectional study conducted on 50 children and adolescents followed up at an outpatient obesity clinic. The subjects were submitted to physical examination, laboratory tests (transaminases, liver function tests, lipid profile, glycemia, and basal insulin) and abdominal nuclear magnetic resonance (calculation of hepatic, visceral, and subcutaneous fat). Nonalcoholic fatty liver disease was diagnosed in 14 (28%) participants, as a severe condition in eight (percent fat >18%), and as non-severe in four (percent fat from 9% to 18%). Fatty liver was associated with male gender, triglycerides, AST, ALT, AST/ALT ratio, and acanthosis nigricans. Homeostasis model assessment of insulin resistance and metabolic syndrome did not show an association with fatty liver. The frequency of nonalcoholic fatty liver disease in the present population of children and adolescents was lower than that reported in the international literature. It is suggested that nuclear magnetic resonance is an imaging exam that can be applied to children and adolescents, thus representing an effective noninvasive tool for the diagnosis of nonalcoholic fatty liver disease in this age range. However, further national multicenter studies with longitudinal design are needed for a better analysis of the correlation between nonalcoholic fatty liver disease and its risk factors, as well as its consequences. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

New Insights from Rodent Models of Fatty Liver Disease

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2011-01-01

Abstract Rodent models of fatty liver disease are essential research tools that provide a window into disease pathogenesis and a testing ground for prevention and treatment. Models come in many varieties involving dietary and genetic manipulations, and sometimes both. High-energy diets that induce obesity do not uniformly cause fatty liver disease; this has prompted close scrutiny of specific macronutrients and nutrient combinations to determine which have the greatest potential for hepatotoxicity. At the same time, diets that do not cause obesity or the metabolic syndrome but do cause severe steatohepatitis have been exploited to study factors important to progressive liver injury, including cell death, oxidative stress, and immune activation. Rodents with a genetic predisposition to overeating offer yet another model in which to explore the evolution of fatty liver disease. In some animals that overeat, steatohepatitis can develop even without resorting to a high-energy diet. Importantly, these models and others have been used to document that aerobic exercise can prevent or reduce fatty liver disease. This review focuses primarily on lessons learned about steatohepatitis from manipulations of diet and eating behavior. Numerous additional insights about hepatic lipid metabolism, which have been gained from genetically engineered mice, are also mentioned. Antioxid. Redox Signal. 15, 535–550. PMID:21126212

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

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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

Quantitative characterization of fatty liver disease using x-ray scattering

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Elsharkawy, Wafaa B.; Elshemey, Wael M.

2013-11-01

Nonalcoholic fatty liver disease (NAFLD) is a dynamic condition in which fat abnormally accumulates within the hepatocytes. It is believed to be a marker of risk of later chronic liver diseases, such as liver cirrhosis and carcinoma. The fat content in liver biopsies determines its validity for liver transplantation. Transplantation of livers with severe NAFLD is associated with a high risk of primary non-function. Moreover, NAFLD is recognized as a clinically important feature that influences patient morbidity and mortality after hepatic resection. Unfortunately, there is a lack in a precise, reliable and reproducible method for quantification of NAFLD. This work suggests a method for the quantification of NAFLD. The method is based on the fact that fatty liver tissue would have a characteristic x-ray scattering profile with a relatively intense fat peak at a momentum transfer value of 1.1 nm-1 compared to a soft tissue peak at 1.6 nm-1. The fat content in normal and fatty liver is plotted against three profile characterization parameters (ratio of peak intensities, ratio of area under peaks and ratio of area under fat peak to total profile area) for measured and Monte Carlo simulated x-ray scattering profiles. Results show a high linear dependence (R2>0.9) of the characterization parameters on the liver fat content with a reported high correlation coefficient (>0.9) between measured and simulated data. These results indicate that the current method probably offers reliable quantification of fatty liver disease.

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

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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.

Non-Alcoholic Fatty Liver Disease in HIV Infection.

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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.

Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease

Institute of Scientific and Technical Information of China (English)

Hiroshi Sakugawa; Fukunori Kinjo; Atsushi Saito; Tomofumi Nakayoshi; Kasen Kobashigawa; Tsuyoshi Yamashiro; Tatsuji Maeshiro; Satoru Miyagi; Joji Shiroma; Akiyo Toyama; Tomokuni Nakayoshi

2005-01-01

AIM: Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD), and progresses to the end stage of liver disease. Biochemical markers of liver fibrosis are strongly associated with the degree of histological liver fibrosis in patients with chronic liver disease.However, data are few on the usefulness of markers in NAFLD patients. The aim of this study was to identify better noninvasive predictors of hepatic fibrosis, with special focus on markers of liver fibrosis, type Ⅵ collagen 7S domain and hyaluronic acid.METHODS: One hundred and twelve patients with histologically proven NAFLD were studied.RESULTS: The histological stage of NAFLD correlated with several clinical and biochemical variables, the extent of hepatic fibrosis and the markers of liver fibrosis were relatively strong associated. The best cutoff values to detect NASH were assessed by using receiver operating characteristic analysis: type Ⅵ collagen 7S domain ≥5.0 ng/mL, hyaluronic acid ≥43 ng/mL. Both markers had a high positive predictive value: type Ⅵ collagen 7S domain, 86% and hyaluronic acid,92%. Diagnostic accuracies of these markers were evaluated to detect severe fibrosis. Both markers showed high negative predictive values: type Ⅵ collagen 7S domain (≥5.0 ng/mL),84% and hyaluronic acid (≥50 ng/mL), 78%, and were significantly and independently associated with the presence of NASH or severe fibrosis by logistic regression analysis.CONCLUSION: Both markers of liver fibrosis are useful in discriminating NASH from fatty liver alone or patients with severe fibrosis from patients with non-severe fibrosis.

[Causes and management of severe acute liver damage during pregnancy].

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Sepulveda-Martinez, Alvaro; Romero, Carlos; Juarez, Guido; Hasbun, Jorge; Parra-Cordero, Mauro

2015-05-01

Abnormalities in liver function tests appear in 3% of pregnancies. Severe acute liver damage can be an exclusive condition of pregnancy (dependent or independent of pre-eclampsia) or a concomitant disease. HELLP syndrome and acute fatty liver of pregnancy are the most severe liver diseases associated with pregnancy. Both appear during the third trimester and have a similar clinical presentation. Acute fatty liver may be associated with hypoglycemia and HELLP syndrome is closely linked with pre-eclampsia. Among concomitant conditions, fulminant acute hepatitis caused by medications or virus is the most severe disease. Its clinical presentation may be hyper-acute with neurological involvement and severe coagulation disorders. It has a high mortality and patients should be transplanted. Fulminant hepatic failure caused by acetaminophen overdose can be managed with n-acetyl cysteine. Because of the high fetal mortality rate, the gestational age at diagnosis is crucial.

CT appearance of focal fatty infiltration of the liver

International Nuclear Information System (INIS)

Halvorsen, R.A.; Korobkin, M.; Ram, P.C.; Thompson, W.M.

1982-01-01

Focal fatty infiltration of the liver is an entity that may be confused with liver metastasis on computed tomography (CT). The imaging results and medical records of 16 patients with CT appearance suggestive of focal fatty liver were reviewed, three of whom had the simultaneous presence of metastitic liver disease. Focal fatty liver often has a distinctive appearance with CT, usually with a nonspherical shape, absence of mass effect, and density close to water. Liver metastases are usually round or oval, and unless cystic or necrotic, they have CT attenuation values closer to normal liver parenchyma than water. A radionuclide liver scan almost always resolves any confusion about the differential diagnosis of focal fatty liver: a well defined focus of photon deficiency is due to neoplasm rather than focal fatty infiltration. Sonography sometimes helps to confirm the CT impression, but may be misleading if the diagnosis of focal or diffuse fatty infiltration is not suspected before the examination

Dietary modification dampens liver inflammation and fibrosis in obesity-related fatty liver disease.

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Larter, Claire Z; Yeh, Matthew M; Haigh, W Geoffrey; Van Rooyen, Derrick M; Brooling, John; Heydet, Deborah; Nolan, Christopher J; Teoh, Narci C; Farrell, Geoffrey C

2013-06-01

Alms1 mutant (foz/foz) mice develop hyperphagic obesity, diabetes, metabolic syndrome, and fatty liver (steatosis). High-fat (HF) feeding converts pathology from bland steatosis to nonalcoholic steatohepatitis (NASH) with fibrosis, which leads to cirrhosis in humans. We sought to establish how dietary composition contributes to NASH pathogenesis. foz/foz mice were fed HF diet or chow 24 weeks, or switched HF to chow after 12 weeks. Serum ALT, NAFLD activity score (NAS), fibrosis severity, neutrophil, macrophage and apoptosis immunohistochemistry, uncoupling protein (UCP)2, ATP, NF-κB activation/expression of chemokines/adhesion molecules/fibrogenic pathways were determined. HF intake upregulated liver fatty acid and cholesterol transporter, CD36. Dietary switch expanded adipose tissue and decreased hepatomegaly by lowering triglyceride, cholesterol ester, free cholesterol and diacylglyceride content of liver. There was no change in lipogenesis or fatty acid oxidation pathways; instead, CD36 was suppressed. These diet-induced changes in hepatic lipids improved NAS, reduced neutrophil infiltration, normalized UCP2 and increased ATP; this facilitated apoptosis with a change in macrophage phenotype favoring M2 cells. Dietary switch also abrogated NF-κB activation and chemokine/adhesion molecule expression, and arrested fibrosis by dampening stellate cell activation. Reversion to a physiological dietary composition after HF feeding in foz/foz mice alters body weight distribution but not obesity. This attenuates NASH severity and fibrotic progression by suppressing NF-κB activation and reducing neutrophil and macrophage activation. However, adipose inflammation persists and is associated with continuing apoptosis in the residual fatty liver disease. Taken together, these findings indicate that other measures, such as weight reduction, may be required to fully reverse obesity-related NASH. Copyright © 2013 The Obesity Society.

Detection of serum leptin levels in patients with viral hepatitis and fatty liver

International Nuclear Information System (INIS)

Sun Shuhong; Sun Bingmei; Niu Airong; Lan Cuixia

2007-01-01

In order to find out the correlations between serum leptin levels and viral hepatitis, the serum leptin levels in 167 patients with viral chronic hepatitis, 87 patients with fatty liver, and 80 control subjects were determined by radioimmunoassay. The liver function (ALT, AST), glucose(Glu) and total cholesterol(TC) in these patients were also measured. Compared with controls and patients with fatty liver, the levels of serum leptin in patients with viral hepatitis were significantly increased (P 0.05). The increase of serum leptin levels in the patients with viral hepatitis was correlated positively with the severity of liver inflammation. Therefore, the leptin can be regarded as an indicator to reflect the severity of liver inflammation. (authors)

Fatty infiltration of the liver: evaluation by proton spectroscopic imaging

International Nuclear Information System (INIS)

Heiken, J.P.; Lee, J.K.; Dixon, W.T.

1985-01-01

The reliability of proton spectroscopic imaging in evaluating fatty infiltration of the liver was investigated in 35 subjects (12 healthy volunteers and 23 patients with fatty livers). With this modified spin-echo technique, fatty liver could be separated from normal liver both visually and quantitatively. On the opposed image, normal liver had an intermediate signal intensity, greater than that of muscle, whereas fatty liver had a lower signal intensity, equal to or less than that of muscle. In normal livers, the lipid signal fraction was less than 10%, while in fatty livers it was greater than 10% and usually exceeded 20%. With this technique, nonuniform fatty infiltration of the liver can be differentiated from hepatic metastases, and the technique may prove useful in the differentiation of some hepatic disorders

Influence of obstructive sleep apnea on fatty liver disease: role of chronic intermittent hypoxia.

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Türkay, Cansel; Ozol, Duygu; Kasapoğlu, Benan; Kirbas, Ismail; Yıldırım, Zeki; Yiğitoğlu, Ramazan

2012-02-01

Currently the common pathogenetic mechanisms in nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) are gaining increased attention. The aim of this study is to find out the influence of chronic intermittent hypoxemia and OSA related parameters to the severity of NAFLD. We examined the liver functions tests and ultrasonographic data of liver as well as markers of OSA severity (apnea-hypopnea index [AHI], oxygen desaturation index, minimum oxygen saturation, percentage of time spent with S(pO(2)) hypoxia during sleep. The prevalence of NAFLD was higher in patients with severe OSA, suggesting a role for nocturnal hypoxemia in the pathogenesis of fatty liver disease.

Focal sparing around the gallbladder in fatty liver

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Chen, Kemin; Hiramatsu, Yoshihiro; Yunoki, Masanori; Hirano, Yoko

1989-01-01

In evaluating fatty liver with CT, the residual normal liver tissues without fat deposits are occasionally detected on CT as high attenuation regions, especially surrounding the gallbladder. This study examined the incidence of this phenomenon in terms of the diagnostic value of CT in fatty liver. Fifty-seven patients with fatty liver were examined with CT. The incidence of focal sparing area was the highest in the gallbladder bed (42/57, 74%), followed by the interlobar fissure or subcapsular area (13, 23%), quadrate lobe (8, 14%), caudate lobe (2, 4%), and right lobe (one, 1.8%). These CT appearances were of spot, band, ring, and the mixed type. In 38 patients, fatty liver was too moderate to be detected without CT attenuation numbers. Among them, 27 patients (71%) had focal sparing area surrounding the gallbladder. This CT appearance seemed to be of significance in preventing the missing of moderate fatty liver. (Namekawa, K)

Nonalcoholic fatty liver disease - A multisystem disease?

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Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470

Evaluation of usefulness of 99mTc-GSA liver scintigraphy on fatty liver in the rat

International Nuclear Information System (INIS)

Kimoto, Mitsunori; Akaki, Shiro; Kohno, Yoshihiro; Gohbara, Hideo; Sakae, Katsuyoshi; Nagaya, Isao; Takeda, Yoshihiro; Hiraki, Yoshio

1994-01-01

99m Tc-GSA is a new liver-imaging radiopharmaceutical which binds to the asialoglycoprotein receptors on the hepatocytes. We evaluated liver injury induced by fatty infiltration in the rats. Studies were performed in the Wistar rats under control conditions (6 cases), and with choline deficiency diet for 2, 4, 6, 10 and 12 weeks (6 cases respectively). 99m Tc-GSA was administered via the inferior vena cava. Immediately after injection, a dynamic imaging study was performed for 30 min. t 90 (the time at which the liver time-activity curve reached 90% of its peak), K u and K d (calculated by 2 compartment model) were used as parameters which reflect on asialoglycoprotein receptors on the hepatocytes. t 90 prolonged, and K u and K d decreased according to the severity of fatty infiltration. These results suggest that 99m Tc-GSA is useful for evaluating liver injury induced by fatty infiltration. (author)

Transient Elastography Role in the Diagnosis of Nonalcoholic Fatty Liver Disease

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Yu.M. Stepanov

2016-04-01

Full Text Available Non-alcoholic fatty liver disease includes hepatic steatosis, steatohepatitis and fibrosis, which can progress to cirrhosis. In view of the prevalence of this disease, the deterioration of the quality of life of patients, mortality from complications, the development of methods for accurate and timely assessment of the severity of fatty liver and progression of fibrosis are becoming of greater interest. Purpose. The study of diagnostic potential of transient elastography in patients with idiopathic transaminase elevations. Methods. In 52 patients (20 men and 32 women with idiopathic increased transaminases without signs of hepatic steatosis according to sonographic study, controlled attenuation parameter (CAP and liver stiffness measurements (LSM were performed using FibroScan with M probe. Exclusion criteria from the study were the presence of chronic viral, autoimmune hepatitis and alcohol abuse. Results. Forty one patients (78.8 % had fatty liver disease according to CAP. The analysis of the data of transient elastography demonstrated that 63.4 % had fibrosis F0–F1, 29.3 % — F1–F2 and in 7.3 % — F3. In terms of the CAP there were significant differences between the group with severe fibrosis (F3 and groups with minimal fibrosis (F0–F1 ((203.0 ± 5.1 vs. (243.0 ± 10.1, p < 0.05. The analysis of biochemical parameters demonstrated significant differences in terms of gamma-glutamyltransferase in the groups with severe fibrosis (F3 and minimal fibrosis ((40.2 ± 5.7 vs. (26.4 ± 3.7, p < 0.05. Thus, the results obtained in the study indicate that a significant proportion of patients with idiopathic transaminase elevations inflammation factor is fatty liver disease, which is not detected at routine ultrasound examination. In the group with more expressed fibrosis reduction of fat in the liver and increased activity gamma glutamyltransferase were determined, that indicated the cholestasis deterioration in the liver in these patients

Epicardial Adipose Tissue (EAT Thickness Is Associated with Cardiovascular and Liver Damage in Nonalcoholic Fatty Liver Disease.

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Anna Ludovica Fracanzani

Full Text Available Epicardial adipose tissue (EAT has been proposed as a cardiometabolic and hepatic fibrosis risk factor in patients with non alcoholic fatty liver disease (NAFLD. Aim of this study was to evaluate the role of EAT in NAFLD by analyzing 1 the association between EAT, the other metabolic parameters and the severity of steatosis 2 the relationship between cardiovascular (cIMT, cplaques, E/A, liver (presence of NASH and significant fibrosis damage and metabolic risk factors including EAT 3 the relationship between EAT and genetic factors strongly influencing liver steatosis.In a cross-sectional study, we considered 512 consecutive patients with NAFLD (confirmed by biopsy in 100. EAT, severity of steatosis, carotid intima-media thickness (cIMT and plaques were evaluated by ultrasonography and results analysed by multiple linear and logistic regression models. Variables independently associated with EAT (mm were female gender (p = 0.003, age (p = 0.001, BMI (p = 0.01, diastolic blood pressure (p = 0.009, steatosis grade 2 (p = 0.01 and 3 (p = 0.04, fatty liver index (p = 0.001 and statin use (p = 0.03. Variables independently associated with carotid IMT were age (p = 0.0001, hypertension (p = 0.009, diabetes (p = 0.04, smoking habits (p = 0.04 and fatty liver index (p = 0.02, with carotid plaques age (p = 0.0001, BMI (p = 0.03, EAT (p = 0.02, and hypertension (p = 0.02, and with E/A age (p = 0.0001, diabetes (p = 0.005, hypertension (p = 0.04 and fatty liver index (p = 0.004. In the 100 patients with available liver histology non alcoholic steatohepatitis (NASH was independently associated with EAT (p = 0.04 and diabetes (p = 0.054 while significant fibrosis with EAT (p = 0.02, diabetes (p = 0.01 and waist circumference (p = 0.05. No association between EAT and PNPLA3 and TM6SF2 polymorphisms was found.In patients with NAFLD, EAT is associated with the severity of liver and vascular damage besides with the known metabolic risk factors.

Analysis of fatty liver by CT values in obese children

International Nuclear Information System (INIS)

Naganuma, Yoshihiro; Tomizawa, Shuichi; Ikarashi, Kozo; Tohyama, Jun; Ozawa, Kanzi; Uchiyama, Makoto.

1996-01-01

Liver attenuation values were measured by CT in 97 (183 times) obese children with ages 3 to 18 years and a diagnosis of fatty liver was made in 42 subjects. Liver/spleen ration from CT measurements showed a significant negative correlation with the percentage of standard body weight, and with the systolic pressure. In children with fatty liver, systolic pressure and serum GOT, GPT, ChE, TC, TG, ApoB and insulin were significantly higher than those in children without fatty liver. After a low-calorie dietary regimen and exercise therapy, the liver/spleen ratio and GPT improved in all children. The diagnosis of fatty infiltration (fatty liver) was made with a liver/spleen ratio of less than 1.0 as determined by the number of measurements taken, a reasonable criterion for the diagnosis of fatty liver by CT in children. There were some children with elevated GPT who showed normal CT findings. This may be caused by overnutrition which was associated with fatty infiltration, since GPT decreased in all these children after treatment. The present study suggests that CT is a useful procedure in diagnosing fatty liver, and in monitoring and determining efficacy of treatment in obese children. (author)

GLCM algorithm image analysis of nonalcoholic fatty liver and focal fat sparing zone in the ultrasonography

International Nuclear Information System (INIS)

Cho, Jin Young; Ye, Soo Young

2017-01-01

There is a need for aggressive diagnosis and treatment in middle-aged and high-risk individuals who are more likely to progress from nonalcoholic fatty liver to hepatitis. In this study, nonalcoholic fatty liver was divided into severe, moderate, and severe, and classified by quantitative method using computer analysis of GLCM algorithm. The purpose of this study was to evaluate the characteristics of ultrasound images in the local fat avoidance region. Normal, mild, moderate, severe fatty liver, and focal fat sparing area, 80 cases, respectively. Among the parameters of the GLCM algorithm, the values of the Autocorrelation, Square of the deviation, Sum of averages and Sum of variances with high recognition rate of the liver ultrasound image were calculated. The average recognition rate of the GLCM algorithm was 97.5%. The result of local fat avoidance image analysis showed the most similar value to the normal parenchyma. Ultrasonography can be easily accessed by primary screening, but there may be differences in the accuracy of the test method or the correspondence of results depending on proficiency. GLCM algorithm was applied to quantitatively classify the degree of fatty liver. Local fat avoidance region was similar to normal parenchyma, so it could be predicted to be homogeneous liver parenchyma without fat deposition. We believe that GLCM computer image analysis will provide important information for differentiating not only fatty liver but also other lesions

GLCM algorithm image analysis of nonalcoholic fatty liver and focal fat sparing zone in the ultrasonography

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Cho, Jin Young [Dept. of Radiological Science, Graduate School of Catholic University of Pusan, Busan (Korea, Republic of); Ye, Soo Young [Dept. of Radiological Science, Catholic University of Pusan, Busan (Korea, Republic of)

2017-06-15

There is a need for aggressive diagnosis and treatment in middle-aged and high-risk individuals who are more likely to progress from nonalcoholic fatty liver to hepatitis. In this study, nonalcoholic fatty liver was divided into severe, moderate, and severe, and classified by quantitative method using computer analysis of GLCM algorithm. The purpose of this study was to evaluate the characteristics of ultrasound images in the local fat avoidance region. Normal, mild, moderate, severe fatty liver, and focal fat sparing area, 80 cases, respectively. Among the parameters of the GLCM algorithm, the values of the Autocorrelation, Square of the deviation, Sum of averages and Sum of variances with high recognition rate of the liver ultrasound image were calculated. The average recognition rate of the GLCM algorithm was 97.5%. The result of local fat avoidance image analysis showed the most similar value to the normal parenchyma. Ultrasonography can be easily accessed by primary screening, but there may be differences in the accuracy of the test method or the correspondence of results depending on proficiency. GLCM algorithm was applied to quantitatively classify the degree of fatty liver. Local fat avoidance region was similar to normal parenchyma, so it could be predicted to be homogeneous liver parenchyma without fat deposition. We believe that GLCM computer image analysis will provide important information for differentiating not only fatty liver but also other lesions.

Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.

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Lee, Yun-Hee; Kim, Sou Hyun; Kim, Sang-Nam; Kwon, Hyun-Jung; Kim, Jeong-Dong; Oh, Ji Youn; Jung, Young-Suk

2016-07-26

Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease.

Choline-Deficient-Diet-Induced Fatty Liver Is a Metastasis-Resistant Microenvironment.

Science.gov (United States)

Nakamura, Miki; Suetsugu, Atsushi; Hasegawa, Kosuke; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Hoffman, Robert M

2017-07-01

Fatty liver disease is increasing in the developed and developing world. Liver metastasis from malignant lymphoma in the fatty liver is poorly understood. In a previous report, we developed color-coded imaging of the tumor microenvironment (TME) of the murine EL4-RFP malignant lymphoma during metastasis, including the lung. In the present report, we investigated the potential and microenvironment of the fatty liver induced by a choline-deficient diet as a metastatic site in this mouse lymphoma model. C57BL/6-GFP transgenic mice were fed with a choline-deficient diet in order to establish a fatty liver model. EL4-RFP cells were injected in the spleen of normal mice and fatty-liver mice. Metastases in mice with fatty liver or normal liver were imaged with the Olympus SZX7 microscope and the Olympus FV1000 confocal microscope. Metastases of EL4-RFP were observed in the liver, ascites and bone marrow. Primary tumors were imaged in the spleen at the injection site. The fewest metastases were observed in the fatty liver. In addition, the fewest cancer-associated fibroblasts (CAFs) were observed in the fatty liver. The relative metastatic resistance of the fatty liver may be due to the reduced number of CAFs in the fatty livers. The mechanism of the effect of the choline-deficient diet is discussed. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Diagnostic methods of fatty liver disease; Diagnostik der Fettleber

Energy Technology Data Exchange (ETDEWEB)

Kukuk, Guido Matthias; Sprinkart, Alois Martin; Traeber, Frank [Radiologische Universitaetsklinik Bonn (Germany). FE MRT

2017-09-15

Fatty liver disease is defined as an abnormal accumulation of lipids into the cytoplasm of hepatocytes. Different kinds of fatty liver diseases are becoming the most important etiologies of end-stage liver disease in the western world. Because fatty liver is a theoretically reversible process, timely and accurate diagnosis is a prerequisite for potential therapeutic options. This work describes major diagnostic methods and discusses particular advantages and disadvantages of various techniques.

Fatty Acid–Regulated Transcription Factors in the Liver

Science.gov (United States)

Jump, Donald B.; Tripathy, Sasmita; Depner, Christopher M.

2014-01-01

Fatty acid regulation of hepatic gene transcription was first reported in the early 1990s. Several transcription factors have been identified as targets of fatty acid regulation. This regulation is achieved by direct fatty acid binding to the transcription factor or by indirect mechanisms where fatty acids regulate signaling pathways controlling the expression of transcription factors or the phosphorylation, ubiquitination, or proteolytic cleavage of the transcription factor. Although dietary fatty acids are well-established regulators of hepatic transcription factors, emerging evidence indicates that endogenously generated fatty acids are equally important in controlling transcription factors in the context of glucose and lipid homeostasis. Our first goal in this review is to provide an up-to-date examination of the molecular and metabolic bases of fatty acid regulation of key transcription factors controlling hepatic metabolism. Our second goal is to link these mechanisms to nonalcoholic fatty liver disease (NAFLD), a growing health concern in the obese population. PMID:23528177

Imaging patterns and focal lesions in fatty liver: a pictorial review.

Science.gov (United States)

Venkatesh, Sudhakar K; Hennedige, Tiffany; Johnson, Geoffrey B; Hough, David M; Fletcher, Joel G

2017-05-01

Non-alcoholic fatty liver disease is the most common cause of chronic liver disease and affects nearly one-third of US population. With the increasing trend of obesity in the population, associated fatty change in the liver will be a common feature observed in imaging studies. Fatty liver causes changes in liver parenchyma appearance on imaging modalities including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) and may affect the imaging characteristics of focal liver lesions (FLLs). The imaging characteristics of FLLs were classically described in a non-fatty liver. In addition, focal fatty change and focal fat sparing may also simulate FLLs. Knowledge of characteristic patterns of fatty change in the liver (diffuse, geographical, focal, subcapsular, and perivascular) and their impact on the detection and characterization of FLL is therefore important. In general, fatty change may improve detection of FLLs on MRI using fat suppression sequences, but may reduce sensitivity on a single-phase (portal venous) CT and conventional ultrasound. In patients with fatty liver, MRI is generally superior to ultrasound and CT for detection and characterization of FLL. In this pictorial essay, we describe the imaging patterns of fatty change in the liver and its effect on detection and characterization of FLLs on ultrasound, CT, MRI, and PET.

Ischemia-reperfusion injury in rat fatty liver: role of nutritional status.

Science.gov (United States)

Caraceni, P; Nardo, B; Domenicali, M; Turi, P; Vici, M; Simoncini, M; De Maria, N; Trevisani, F; Van Thiel, D H; Derenzini, M; Cavallari, A; Bernardi, M

1999-04-01

Fatty livers are more sensitive to the deleterious effects of ischemia-reperfusion than normal livers. Nutritional status greatly modulates this injury in normal livers, but its role in the specific setting of fatty liver is unknown. This study aimed to determine the effect of nutritional status on warm ischemia-reperfusion injury in rat fatty livers. Fed and fasted rats with normal or fatty liver induced by a choline deficient diet underwent 1 hour of lobar ischemia and reperfusion. Rat survival was determined for 7 days. Serum transaminases, liver histology and cell ultrastructure were assessed before and after ischemia, and at 30 minutes, 2 hours, 8 hours, and 24 hours after reperfusion. Survival was also determined in fatty fasted rats supplemented with glucose before surgery. The preischemic hepatic glycogen was measured in all groups. Whereas survival was similar in fasted and fed rats with normal liver (90% vs. 100%), fasting dramatically reduced survival in rats with fatty liver (14% vs. 64%, P nutritional repletion procedure may be part of a treatment strategy aimed to prevent ischemia-reperfusion injury in fatty livers.

Risk for development of severe liver disease in lean patients with nonalcoholic fatty liver disease: A long-term follow-up study.

Science.gov (United States)

Hagström, Hannes; Nasr, Patrik; Ekstedt, Mattias; Hammar, Ulf; Stål, Per; Hultcrantz, Rolf; Kechagias, Stergios

2018-01-01

Most patients with nonalcoholic fatty liver disease (NAFLD) are overweight or obese. However, a significant proportion of patients have a normal body mass index (BMI), denoted as lean NAFLD. The long-term prognosis of lean NAFLD is unclear. We conducted a cohort study of 646 patients with biopsy-proven NAFLD. Patients were defined as lean (BMI lean and nonlean NAFLD. Lean NAFLD was seen in 19% of patients, while 52% were overweight and 29% were obese. Patients with lean NAFLD were older, had lower transaminases, lower stages of fibrosis, and lower prevalence of nonalcoholic steatohepatitis at baseline compared to patients with a higher BMI. During a mean follow-up of 19.9 years (range 0.4-40 years) representing 12,631 person years and compared to patients who were overweight, patients with lean NAFLD had no increased risk for overall mortality (hazard ratio 1.06; P =  0.73) while an increased risk for development of severe liver disease was found (hazard ratio 2.69; P =  0.007). Conclusion : Although patients with lean NAFLD have lower stages of fibrosis, they are at higher risk for development of severe liver disease compared to patients with NAFLD and a higher BMI, independent of available confounders. ( Hepatology Communications 2018;2:48-57).

Pharmacological Approaches for Nonalcoholic Fatty Liver Disease

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Ionică Floriana Elvira

2016-09-01

Full Text Available Background and aims: Nonalcoholic fatty liver disease (NAFDL is a multifactorial condition with a wide spectrum of histological severities, from asymptomatic hepatic steatosis to nonalcoholic steatohepatitis (NASH with or without fibrosis. NAFLD is highly common and potentially serious in children and adolescents and affects approximately one third of the general population. It is closely associated with obesity, insulin resistance and dyslipidemia. NASH is a histological diagnosis and has a great significance because it can progress to cirrhosis, liver failure, and hepatocellular carcinoma (HCC, and is associated with both increased cardiovascular and liver related mortality. The purpose of this review is to summarize the evidence for current potential therapies of NAFLD.

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

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Azadeh Nabizadeh Haghighi

2016-03-01

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

Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan

Science.gov (United States)

Sakitani, Kosuke; Enooku, Kenichiro; Kubo, Hirokazu; Tanaka, Akifumi; Arai, Hisakatsu; Kawazu, Shoji; Koike, Kazuhiko

2017-01-01

Objective The leading cause of liver injuries in diabetes mellitus may be associated with fatty liver. We aimed to elucidate the relationship between fatty liver and diabetes characteristics. Methods Retrospectively, 970 patients with diabetes were analysed. Fatty liver was diagnosed when the liver/spleen Hounsfield unit ratio by computed tomography was below 0.9. Clinical diabetes characteristics were compared between patients with and without fatty liver. Results Of 970 patients (717 male and 253 female; mean age 64.4 years), 175 males (24.4%) and 60 females (23.7%) had fatty liver. None of the 28 patients with type 1 diabetes had fatty liver. In male patients with type 2 diabetes, age, visceral adipose tissue (VAT), albumin, alanine amino-transferase (ALT), and triglycerides were independently associated with fatty liver. In females, age and bilirubin were associated with fatty liver. Conclusions Fatty liver is associated with type 2 diabetes characteristics, including younger age and elevated VAT, albumin, ALT, and triglycerides in males and younger age and elevated bilirubin levels in females. PMID:28553763

Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan.

Science.gov (United States)

Sakitani, Kosuke; Enooku, Kenichiro; Kubo, Hirokazu; Tanaka, Akifumi; Arai, Hisakatsu; Kawazu, Shoji; Koike, Kazuhiko

2017-06-01

Objective The leading cause of liver injuries in diabetes mellitus may be associated with fatty liver. We aimed to elucidate the relationship between fatty liver and diabetes characteristics. Methods Retrospectively, 970 patients with diabetes were analysed. Fatty liver was diagnosed when the liver/spleen Hounsfield unit ratio by computed tomography was below 0.9. Clinical diabetes characteristics were compared between patients with and without fatty liver. Results Of 970 patients (717 male and 253 female; mean age 64.4 years), 175 males (24.4%) and 60 females (23.7%) had fatty liver. None of the 28 patients with type 1 diabetes had fatty liver. In male patients with type 2 diabetes, age, visceral adipose tissue (VAT), albumin, alanine amino-transferase (ALT), and triglycerides were independently associated with fatty liver. In females, age and bilirubin were associated with fatty liver. Conclusions Fatty liver is associated with type 2 diabetes characteristics, including younger age and elevated VAT, albumin, ALT, and triglycerides in males and younger age and elevated bilirubin levels in females.

Effects of Ramadan fasting on plasma free fatty acids in patients with non-alcoholic fatty liver disease

Directory of Open Access Journals (Sweden)

Seyed Mostafa Arabi

2016-09-01

Full Text Available Introduction: Nonalcoholic fatty liver disease (NAFLD is a global disease which its prevalence is about 10-35%. Several factors are involved in the pathogenesis of the disease. The present study was conducted to evaluate the effect of fasting during Ramadan on plasma free fatty acids in patients with NAFLD.Methods: This cross-sectional study was performed during the month of Ramadan in June-July, 2014 (Islamic year: 1435 with 50 patients who were living in Mashhad, Iran. The participants were recruited from 18-65 years old patients. The inclusion criteria were 1 patients with NAFLD that diagnosed fatty liver by ultrasonography and 2 being at least 10 hours fasting. Levels of plasma free fatty acids (Palmitic, Elaidic and Oleic fatty acid were analyzed in blood sample of all patients by gas chromatography apparatus equipped with a flame ionization detector (GC-FID.Result: results indicated that there was no significant changes were observed in plasma levels of Palmitic, Elaidic and Oleic fatty acids in overweight patients (BMI 25-30 , but plasma levels of Elaidic acid significantly increased in obese patients (P

Study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings

International Nuclear Information System (INIS)

Yang, Jeong Hwa

2006-01-01

The study obtained the following conclusions by making a comparative study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings. I surveyed the value of abdominal ultrasound in 400 patients without clinical symptoms at C Health Clinic Center, Seoul. Compare with blood pressure was high (systolic/diastolic) in 7.5%/4.5% on persons who were diagnosed fatty liver. At the time of the diagnosis, Total cholesterol level was increased in fatty liver patients, HDL-cholesterol level was high in fatty liver patients. And Trigryceride level was increased in fatty liver persons, LDL-cholesterol was high in fatty liver persons. SGOT level was increased in 5.5% on patients who were diagnosed fatty liver, 0% on persons who were normal and SGPT level was high in 29.5% on people who were diagnosed fatty liver, 0% on patients who were diagnosed normal

Study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings

Energy Technology Data Exchange (ETDEWEB)

Yang, Jeong Hwa [Cheju Halla College, Cheju (Korea, Republic of)

2006-03-15

The study obtained the following conclusions by making a comparative study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings. I surveyed the value of abdominal ultrasound in 400 patients without clinical symptoms at C Health Clinic Center, Seoul. Compare with blood pressure was high (systolic/diastolic) in 7.5%/4.5% on persons who were diagnosed fatty liver. At the time of the diagnosis, Total cholesterol level was increased in fatty liver patients, HDL-cholesterol level was high in fatty liver patients. And Trigryceride level was increased in fatty liver persons, LDL-cholesterol was high in fatty liver persons. SGOT level was increased in 5.5% on patients who were diagnosed fatty liver, 0% on persons who were normal and SGPT level was high in 29.5% on people who were diagnosed fatty liver, 0% on patients who were diagnosed normal.

Quantitative evaluation of fatty liver by computed tomography in rabbits

International Nuclear Information System (INIS)

Kawata, R.; Sakata, K.; Kunieda, T.; Saji, S.; Doi, H.; Nozawa, Y.

1984-01-01

Biochemical, histologic, and computed tomographic (CT) examinations of the liver were performed in 32 rabbits in which fatty liver was induced by prolonged intravenous fat infusion. In two groups of rabbits, in which 2 and 4 g/kg/day of fat emulsion was administered, respectively, posttreatment reduction in CT value of mild degree was observed. In the group that received 8 g/kg/day of fat emulsion, posttreatment change in CT value was sufficient for a diagnosis of fatty liver of moderate degree. Reduction in CT value in fatty liver might be due largely to accumulation of triglyceride and cholesterol in the liver cells. Significant correlation was found between changes in CT value of the liver and degrees of histological fat accumulation in the liver cells. Consecutive measurement of CT values of the liver during prolonged intravenous hyperalimentation is a nonagressive method of diagnosing fatty liver

Long-term prognosis of fatty liver: risk of chronic liver disease and death

DEFF Research Database (Denmark)

Dam-Larsen, S.; Franzmann, M.; Andersen, I.B.

2004-01-01

BACKGROUND AND AIMS: Fatty liver is a common histological finding in human liver biopsy specimens. It affects 10-24% of the general population and is believed to be a marker of risk of later chronic liver disease. The present study examined the risk of development of cirrhotic liver disease...... and the risk of death in a cohort diagnosed with pure fatty liver without inflammation. METHODS: A total of 215 patients who had a liver biopsy performed during the period 1976-1987 were included in the study. The population consisted of 109 non-alcoholic and 106 alcoholic fatty liver patients. Median follow...... up time was 16.7 (0.2-21.9) years in the non-alcoholic and 9.2 (0.6-23.1) years in the alcoholic group. Systematic data collection was carried out by review of all medical records. All members of the study cohort were linked through their unique personal identification number to the National Registry...

Fatty liver and drugs: the two sides of the same coin.

Science.gov (United States)

Miele, L; Liguori, A; Marrone, G; Biolato, M; Araneo, C; Vaccaro, F G; Gasbarrini, A; Grieco, A

2017-03-01

Drug-induced liver injury (DILI) is a common and underestimated cause of liver disease. Several drugs and other xenobiotics can be the cause of different clinicopathologic patterns of liver disease. Steatosis and steatohepatitis are rare but well-documented types of DILI. Over the past decades commonly used drugs like amiodarone, tamoxifen, irinotecan, methotrexate, valproic acid and glucocorticoids have been recognized to be associated with steatosis. Even though the pathophysiological pathways are still only partially understood, inhibition of mitochondrial beta-oxidation, reduced very low-density lipoprotein secretion, insulin resistance induction and increased de novo synthesis or increased liver uptake of fatty acids are considered the main pathogenic mechanisms through which drugs can lead to hepatic steatosis. On the other hand, fatty liver itself is a very common clinical condition, and there is a growing awareness of the potential risk factors for DILI due to the underlying metabolic condition itself.

The association of vitamin D deficiency with non-alcoholic fatty liver disease

OpenAIRE

Küçükazman, Metin; Ata, Naim; Dal, Kürşat; Yeniova, Abdullah Özgür; Kefeli, Ayşe; Basyigit, Sebahat; Aktas, Bora; Akin, Kadir Okhan; Ağladioğlu, Kadir; Üre, Öznur Sari; Topal, Firdes; Nazligül, Yaşar; Beyan, Esin; Ertugrul, Derun Taner

2014-01-01

OBJECTIVE: Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease. METHODS: We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease. RESULTS: The non-alcoholic fatty liver ...

Fatty liver diagnostic from medical examination to analyze the accuracy between the abdominal ultrasonography and liver hounsfield units

International Nuclear Information System (INIS)

Oh, Wang Kyun; Kim, Sang Hyun

2017-01-01

In abdominal Ultrasonography, the fatty liver is diagnosed through hepatic parenchymal echo increased parenchymal density and unclear blood vessel boundary, and according to many studies, abdominal Ultrasonography has 60 ∼ 90% of sensitivity and 84 ∼ 95% of specificity in diagnosis of fatty liver, but the result of Ultrasonography is dependent on operators, so there can be difference among operators, and quantitative measurement of fatty infiltration is impossible. Among examinees who same day received abdominal Ultrasonography and chest computed tomography (CT), patients who were diagnosed with a fatty liver in the Ultrasonography were measured with liver Hounsfield Units (HU) of chest CT imaging to analyze the accuracy of the fatty liver diagnosis. Among 720 subject examinees, those who were diagnosed with a fatty liver through abdominal Ultrasonography by family physicians were 448, which is 62.2%. The result of Liver HU measurement in the chest CT imaging of those who were diagnosed with a fatty liver showed that 175 out of 720 had the measured value of less than 40 HU, which is 24.3%, and 173 were included to the 175 among 448 who were diagnosed through Ultrasonography, so 98.9% corresponded. This indicates that the operators' subjective ability has a great impact on diagnosis of lesion in Ultrasonography diagnosis of a fatty liver, and that in check up chest CT, under 40 HU in the measurement of Liver HU can be used for reference materials in diagnosis of a fatty liver

Fatty liver diagnostic from medical examination to analyze the accuracy between the abdominal ultrasonography and liver hounsfield units

Energy Technology Data Exchange (ETDEWEB)

Oh, Wang Kyun [Dept. of Radiology, Cheongju Medical Center, Cheongju (Korea, Republic of); Kim, Sang Hyun [Dept. of Radiological Science, Shinhan University, Uijeongbu (Korea, Republic of)

2017-06-15

In abdominal Ultrasonography, the fatty liver is diagnosed through hepatic parenchymal echo increased parenchymal density and unclear blood vessel boundary, and according to many studies, abdominal Ultrasonography has 60 ∼ 90% of sensitivity and 84 ∼ 95% of specificity in diagnosis of fatty liver, but the result of Ultrasonography is dependent on operators, so there can be difference among operators, and quantitative measurement of fatty infiltration is impossible. Among examinees who same day received abdominal Ultrasonography and chest computed tomography (CT), patients who were diagnosed with a fatty liver in the Ultrasonography were measured with liver Hounsfield Units (HU) of chest CT imaging to analyze the accuracy of the fatty liver diagnosis. Among 720 subject examinees, those who were diagnosed with a fatty liver through abdominal Ultrasonography by family physicians were 448, which is 62.2%. The result of Liver HU measurement in the chest CT imaging of those who were diagnosed with a fatty liver showed that 175 out of 720 had the measured value of less than 40 HU, which is 24.3%, and 173 were included to the 175 among 448 who were diagnosed through Ultrasonography, so 98.9% corresponded. This indicates that the operators' subjective ability has a great impact on diagnosis of lesion in Ultrasonography diagnosis of a fatty liver, and that in check up chest CT, under 40 HU in the measurement of Liver HU can be used for reference materials in diagnosis of a fatty liver.

Impact of liver fibrosis and fatty liver on T1rho measurements: A prospective study

International Nuclear Information System (INIS)

Xie, Shuang Shuang; Li, Qing; Cheng, Yue; Shen, Wen; Zhang, Yu; Zhuo, Zhi Zheng; Zhao, Guiming

2017-01-01

To investigate the liver T1rho values for detecting fibrosis, and the potential impact of fatty liver on T1rho measurements. This study included 18 healthy subjects, 18 patients with fatty liver, and 18 patients with liver fibrosis, who underwent T1rho MRI and mDIXON collections. Liver T1rho, proton density fat fraction (PDFF) and T2* values were measured and compared among the three groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the T1rho values for detecting liver fibrosis. Liver T1rho values were correlated with PDFF, T2* values and clinical data. Liver T1rho and PDFF values were significantly different (p 0.05). T1rho MRI is useful for noninvasive detection of liver fibrosis, and may not be affected with the presence of fatty liver

Functional pitch of a liver: fatty liver disease diagnosis with photoacoustic spectrum analysis

Science.gov (United States)

Xu, Guan; Meng, Zhuoxian; Lin, Jiandie; Carson, Paul; Wang, Xueding

2014-03-01

To provide more information for classification and assessment of biological tissues, photoacoustic spectrum analysis (PASA) moves beyond the quantification of the intensities of the photoacoustic (PA) signals by the use of the frequency-domain power distribution, namely power spectrum, of broadband PA signals. The method of PASA quantifies the linear-fit to the power spectrum of the PA signals from a biological tissue with 3 parameters, including intercept, midband-fit and slope. Intercept and midband-fit reflect the total optical absorption of the tissues whereas slope reflects the heterogeneity of the tissue structure. Taking advantage of the optical absorption contrasts contributed by lipid and blood at 1200 and 532 nm, respectively and the heterogeneous tissue microstructure in fatty liver due to the lipid infiltration, we investigate the capability of PASA in identifying histological changes of fatty livers in mouse model. 6 and 9 pairs of normal and fatty liver tissues from rat models were examined by ex vivo experiment with a conventional rotational PA measurement system. One pair of rat models with normal and fatty livers was examined non-invasively and in situ with our recently developed ultrasound and PA parallel imaging system. The results support our hypotheses that the spectrum analysis of PA signals can provide quantitative measures of the differences between the normal and fatty liver tissues and that part of the PA power spectrum can suffice for characterization of microstructures in biological tissues. Experimental results also indicate that the vibrational absorption peak of lipid at 1200nm could facilitate fatty liver diagnosis.

Nonalcoholic Fatty Liver Disease Treatment

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M Sadeghian

2014-04-01

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

Impact of liver fibrosis and fatty liver on T1rho measurements: A prospective study

Energy Technology Data Exchange (ETDEWEB)

Xie, Shuang Shuang; Li, Qing; Cheng, Yue; Shen, Wen [Dept. of Radiology, Tianjin First Center Hospital, Tianjin (China); Zhang, Yu; Zhuo, Zhi Zheng [Clinical Science, Philips Healthcare, Beijing (China); Zhao, Guiming [Dept. of Hepatology, Tianjin Second People' s Hospital, Tianjin (China)

2017-11-15

To investigate the liver T1rho values for detecting fibrosis, and the potential impact of fatty liver on T1rho measurements. This study included 18 healthy subjects, 18 patients with fatty liver, and 18 patients with liver fibrosis, who underwent T1rho MRI and mDIXON collections. Liver T1rho, proton density fat fraction (PDFF) and T2* values were measured and compared among the three groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the T1rho values for detecting liver fibrosis. Liver T1rho values were correlated with PDFF, T2* values and clinical data. Liver T1rho and PDFF values were significantly different (p < 0.001), whereas the T2* (p = 0.766) values were similar, among the three groups. Mean liver T1rho values in the fibrotic group (52.6 ± 6.8 ms) were significantly higher than those of healthy subjects (44.9 ± 2.8 ms, p < 0.001) and fatty liver group (45.0 ± 3.5 ms, p < 0.001). Mean liver T1rho values were similar between healthy subjects and fatty liver group (p = 0.999). PDFF values in the fatty liver group (16.07 ± 10.59%) were significantly higher than those of healthy subjects (1.43 ± 1.36%, p < 0.001) and fibrosis group (1.07 ± 1.06%, p < 0.001). PDFF values were similar in healthy subjects and fibrosis group (p = 0.984). Mean T1rho values performed well to detect fibrosis at a threshold of 49.5 ms (area under the ROC curve, 0.855), had a moderate correlation with liver stiffness (r = 0.671, p = 0.012), and no correlation with PDFF, T2* values, subject age, or body mass index (p > 0.05). T1rho MRI is useful for noninvasive detection of liver fibrosis, and may not be affected with the presence of fatty liver.

Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan

OpenAIRE

Sakitani, Kosuke; Enooku, Kenichiro; Kubo, Hirokazu; Tanaka, Akifumi; Arai, Hisakatsu; Kawazu, Shoji; Koike, Kazuhiko

2017-01-01

Objective The leading cause of liver injuries in diabetes mellitus may be associated with fatty liver. We aimed to elucidate the relationship between fatty liver and diabetes characteristics. Methods Retrospectively, 970 patients with diabetes were analysed. Fatty liver was diagnosed when the liver/spleen Hounsfield unit ratio by computed tomography was below 0.9. Clinical diabetes characteristics were compared between patients with and without fatty liver. Results Of 970 patients (717 male a...

CT evaluation of the bile ducts in patients with fatty liver

International Nuclear Information System (INIS)

Quint, L.E.; Glazer, G.M.

1984-01-01

Computed tomographic (CT) evaluation of the bile ducts in the fatty liver can be difficult, since hepatic attenuation decreases with increased triglyceride content, and liver parenchyma may become isodense with bile. Forty-seven patients with fatty infiltration of the liver were retrospectively identified. In 7 of these patients, attenuation of liver and bile differed by less than 10 HU. In 2 patients, dilated intrahepatic ducts were invisible using CT, because bile was isodense with fatty liver parenchyma. Thus, the fatty liver presents a potential pitfall in CT evaluation of the bile ducts. For maximal accuracy scans should be obtained both before and after administration of intravenous urographic contrast material

Computed tomography in the diagnosis of fatty liver

International Nuclear Information System (INIS)

Yajima, Yoshiaki; Narui, Takashi; Ishii, Motoyasu; Abe, Ryuzo; Ohtsuki, Masao

1982-01-01

Fifty-three histologically proved cases of various diffuse liver disease were studied for their computed tomography numbers (CTN). The machine used was Ohio Nuclear's Delta Scanner 50FS type and CTN was expressed by the Hounsfield unit (H). Mean CTN in each group was as follows: 66.6 +- 2.6 H in normal control (N), 63.3 +- 6.0 H in chronic hepatitis (CH), 61.8 +- 7.0 H in liver cirrhosis (LC), and 44.4 +- 10.6 H in fatty infiltration (FI). There were no significant differences among them except FI group. As N group were all above 60 H and CH and LC groups were all above 50 H, CTN below 60 H suggests chronic liver disease or fatty infiltration and CTN below 50 H strongly suggests fatty infiltration. In eleven cases where total lipid content of the liver could be biochemically determined by the sulfo-phospho-vanillin reagent, a relation of total lipid content to CTN was studied. As a result, a significant correlation existed between them (r = -0.89; p < 0.001). If the diagnostic criterion of fatty liver was set at total lipid content above 100 mg/g wet liver, CT criterion was estimated at CTN below 48 H from the regression formula. (author)

Computed tomography in the diagnosis of fatty liver

International Nuclear Information System (INIS)

Yajima, Yoshiaki; Narui, Takashi; Ishii, Motoyasu; Abe, Ryuzo; Ohtsuki, Masao

1981-01-01

Fifty-three histologically proved cases of various diffuse liver diseases were studied on their computed tomography numbers (CTN). The machine used was the Ohio Nuclear's Delta Scanner 50 FS type and CTN was expressed by the Hounsfield unit (H). The mean was 66.6 +- 2.6 H for normal control (N), 63.3 +- 6.0 H for chronic hepatitis (CH), 61.8 +- 7.0 H for liver cirrhosis (LC), 44.4 +- 10.6 H for fatty infiltration (FI). There were no significant differences among them except FI group. As N group were all above 60 H and CH and LC groups were all above 50 H, CTN below 60 H could suggest chronic liver disease or fatty infiltration and CTN below 50 H could strongly suggest fatty infiltration. In eleven cases where total lipid content of the liver could be biochemically determined by the sulfophospho-vanillin reagent, a relation of total lipid content to CTN was studied. As a result, a significant correlation existed between them (r = -0.89; p < 0.001). If the diagnostic criterion for the fatty liver was set at total lipid content above 100 mg/g wet liver, CT criterion was estimated at CTN below 48 H from the regression formula. (author)

Fatty infiltration of the liver in severely burned pediatric patients : Autopsy findings and clinical implications

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Barret, JP; Jeschke, MG; Herndon, DN

2001-01-01

Background. Trauma induces hypermetabolic responses that are characterized by the mobilization of all available substrates. The marked increase of peripheral lipolysis after a burn can lead to the development of fatty liver, which has been associated with immunodepression and increased mortality.

The effectiveness of metformin in patients with metabolic syndrome and nonalcoholic fatty liver disease

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S A Butrova

2008-06-01

Full Text Available The mechanism of action of metformin is realized through activation of cAMP-dependent protein kinase, leading to a decrease hepatic glucose production as well as to decrease the synthesis of triglycerides and an increase in fat oxidation. Several studies have demonstrated the positive effect of the drug in non-alcoholic fatty liver disease, manifested in reducing the activity of enzymes, reducing the size of the liver and insulin resistance. The aim of our study was to evaluate the effectiveness of metformin in patients with metabolic syndrome and nonalcoholic fatty liver disease. The study found that the use Siofor 850 mg 2 times a day in conjunction with a reduced-calorie nutrition in patients with metabolic syndrome and nonalcoholic fatty liver disease leads to a significant reduction in insulin resistance associated with decreased activity of transaminases, improvement of metabolic parameters. The therapy Siofor majority of patients (60% with metabolic syndrome and nonalcoholic fatty liver disease achieved a clinically significant weight loss and improved body composition. Application Siofor improves lifestyle changes in obese patients with non-alcoholic liver disease dirovoy and metabolic disorders.

Effect of Telmisartan or Losartan for Treatment of Nonalcoholic Fatty Liver Disease: Fatty Liver Protection Trial by Telmisartan or Losartan Study (FANTASY

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Takumi Hirata

2013-01-01

Full Text Available Aim. This study compared the effects of telmisartan and losartan on nonalcoholic fatty liver disease (NAFLD and biochemical markers of insulin resistance in hypertensive NAFLD patients with type 2 diabetes mellitus. Methods. This was a randomized, open-label, parallel-group comparison of therapy with telmisartan or losartan. Nineteen hypertensive NAFLD patients with type 2 diabetes were randomly assigned to receive telmisartan at a dose of 20 mg once a day (n=12 or losartan at a dose of 50 mg once a day (n=7 for 12 months. Body fat area as determined by CT scanning and hepatic fat content based on the liver-to-spleen (L/S ratio, as well as several parameters of glycemic and lipid metabolism, were compared before and after 12 months. Results. The telmisartan group showed a significant decline in serum free fatty acid (FFA level (from 0.87±0.26 to 0.59±0.22 mEq/L (mean ± SD, P=0.005 and a significant increase in L/S ratio (P=0.049 evaluated by CT scan, while these parameters were not changed in the losartan group. Conclusion. Although there was no significant difference in improvement in liver enzymes with telmisartan and losartan treatment in hypertensive NAFLD patients with type 2 diabetes after 12 months, it is suggested that telmisartan may exert beneficial effects by improving fatty liver.

Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats

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Fisher, Craig D.; Lickteig, Andrew J.; Augustine, Lisa M.; Oude Elferink, Ronald P. J.; Besselsen, David G.; Erickson, Robert P.; Cherrington, Nathan J.

2009-01-01

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diagnoses ranging from simple fatty liver (SFL), to non-alcoholic steatohepatitis (NASH). This study aimed to determine the effect of moderate and severe NAFLD on hepatic transporter expression and function in vivo. Rats were fed a

Non-alcoholic fatty liver disease: An expanded review

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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

CT quantitative diagnosis in fatty liver. An experimental study

International Nuclear Information System (INIS)

Zhao Hong; Li Binxiang; Zhang Lizhong; Liang Jianfang

1997-01-01

Purpose: To evaluate the relation between liver fat content and CT value in animal experiment for the diagnosis and treatment of fatty liver in clinical practice. Materials and methods: Fatty liver model was established in 30 Wistar rats (experimental group), 5 rats was used as the control group. The 5 rats of the control group and 5 rats randomly chosen from experimental group at the first, second, third, and the fourth weekends, were measured for the CT number of total liver. Three pieces of liver specimen from each rats were removed from left, central and right lobes for histologic examination. The ratio of liver fat content to liver volume (Vv value) was measured by microscopic image pattern analyzer. Results: Significant linear negative correlation (r = -0.950, t = 12.90, P<0.001) was found between CT and Vv values. Conclusion: Using CT monitoring, the degree and amount of liver fat could be assessed and liver biopsy obviated in the diagnosis and follow up during treatment of fatty liver

Subclassification of fatty liver by its pathogenesis: cIEFing is believing.

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Byrne, Frances L; Hoehn, Kyle L

2016-05-01

Fatty liver, also termed hepatic steatosis or fatty liver disease, is a condition characterized by excess fat accumulation in the liver. Common causes of fatty liver include obesity, ageing, medications, genetic disorders, viral hepatitis, excess alcohol or toxins. This diversity in pathogenesis is matched by an equally diverse spectrum of consequences, whereby some individuals remain asymptomatic yet others progress through a series of inflammatory, fibrotic and metabolic disorders that can lead to liver failure, cancer or diabetes. Current treatment approaches for fatty liver do not differ by disease aetiology and primarily involve weight loss strategies or management of co-morbidities. In a recent paper published in this journal, Urasaki et al used capillary isoelectric focusing (cIEF) to create profiles of protein post-translational modifications that distinguish four different models of fatty liver in mice. Importantly, this new cIEF approach has the potential to provide rapid individualized diagnosis of fatty liver pathogenesis that may enable more accurate and personalized treatment strategies. Further testing and optimization of cIEF as a diagnostic screening tool in humans is warranted. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression

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Reue, K.; Rehnmark, S.; Cohen, R.D.; Leete, T.H.; Doolittle, M.H. [West Los Angeles VA Medical Center, CA (United States). Lipid Research Lab.]|[Univ. of California, Los Angeles, CA (United States). Dept. of Medicine; Giometti, C.S.; Mishler, K. [Argonne National Lab., IL (United States); Slavin, B.G. [Univ. of Southern California, Los Angeles, CA (United States)

1997-07-01

Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and these droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.

NON-ALCOHOLIC FATTY LIVER DISEASE IN CHILDREN

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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

Antioxidant dietary approach in treatment of fatty liver: New insights and updates.

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Ferramosca, Alessandra; Di Giacomo, Mariangela; Zara, Vincenzo

2017-06-21

Non-alcoholic fatty liver disease (NAFLD) is a common clinicopathological condition, encompassing a range of conditions caused by lipid deposition within liver cells. To date, no approved drugs are available for the treatment of NAFLD, despite the fact that it represents a serious and growing clinical problem in the Western world. Identification of the molecular mechanisms leading to NAFLD-related fat accumulation, mitochondrial dysfunction and oxidative balance impairment facilitates the development of specific interventions aimed at preventing the progression of hepatic steatosis. In this review, we focus our attention on the role of dysfunctions in mitochondrial bioenergetics in the pathogenesis of fatty liver. Major data from the literature about the mitochondrial targeting of some antioxidant molecules as a potential treatment for hepatic steatosis are described and critically analysed. There is ample evidence of the positive effects of several classes of antioxidants, such as polyphenols ( i.e ., resveratrol, quercetin, coumestrol, anthocyanins, epigallocatechin gallate and curcumin), carotenoids ( i.e ., lycopene, astaxanthin and fucoxanthin) and glucosinolates ( i.e ., glucoraphanin, sulforaphane, sinigrin and allyl-isothiocyanate), on the reversion of fatty liver. Although the mechanism of action is not yet fully elucidated, in some cases an indirect interaction with mitochondrial metabolism is expected. We believe that such knowledge will eventually translate into the development of novel therapeutic approaches for fatty liver.

ACOUSTIC RADIATION FORCE IMPULSE IS EQUIVALENT TO LIVER BIOPSY TO EVALUATE LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C AND NONALCOHOLIC FATTY LIVER DISEASE

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Juliana Ayres de Alencar Arrais GUERRA

2015-09-01

Full Text Available BackgroundLiver biopsy is recommended as the gold standard method for assessing the stage of liver fibrosis in patients with chronic liver disease. However, it is invasive, with potential risks and complications. Elastography is an ultrasound technique that provides information of changes in the liver tissue, evaluating tissue elasticity and acoustic radiation force impulse is one of the available techniques.ObjectiveThe main objective of this study was to evaluate the sensitivity and specificity of acoustic radiation force impulse comparing to liver biopsy to evaluate fibrosis in patients with chronic hepatitis C virus and nonalcoholic fatty liver disease.MethodsTwenty four patients were included, everyone underwent liver biopsy and acoustic radiation force impulse, and the results were compared with values described in the literature by several authors.ResultsIn the population of patients with chronic hepatitis C, our data were better correlated with data published by Carmen Fierbinteanu-Braticevici et al., with an accuracy of 82.4%, sensitivity of 71.4% and specificity of 90%. For nonalcoholic fatty liver disease, our data were better correlated with data published by Masato Yoneda et al., with an accuracy of 85.7%, sensitivity 80% and specificity of 100%.ConclusionAcoustic radiation force impulse is a method with good accuracy to distinguish initial fibrosis from advanced fibrosis in hepatitis C virus and nonalcoholic fatty liver disease and can replace biopsy in most cases.

CT values of fatty liver due to L-asparaginase administration

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Muraki, Kotaro; Kubo, Kazuaki; Hamamoto, Kazuko; Ueda, Kazuhiro; Kashiwado, Kozo; Ito, Katsuhide (Hiroshima Red Cross Hospital (Japan))

1984-02-01

Chemotherapy involving L-asparaginase was performed on a 9-year-old female child with malignant lymphoma, and a 3-year-old male child and a 14-year-old female child with acute lymphatic leukemia, and the course of L-asparaginase-induced fatty liver was followed up primarily by CT findings. In all 3 cases, L-asparaginase administration caused a marked fatty liver characterized by a diffuse cold area of the liver and a decrease in the value of the liver (liver/spleen<1) on CT. Hypoproteinemia, hypofibrinogenemia and elevations of GOT and GPT were simultaneously observed, but marked anemia, pancreatitis, decreased glucose tolerance and central nervous disorder did not occur. Recovery of fatty liver was slower in CT findings than in blood biochemistry, taking about 4 weeks.

Alcoholic fatty liver is enhanced in CYP2A5 knockout mice: The role of the PPARα-FGF21 axis

International Nuclear Information System (INIS)

Chen, Xue; Ward, Stephen C.; Cederbaum, Arthur I.; Xiong, Huabao; Lu, Yongke

2017-01-01

Background & aims: Cytochrome P450 2A5 (CYP2A5) is induced by ethanol, and the ethanol induction of CYP2A5 is regulated by nuclear factor-erythroid 2-related factor 2 (NRF2). Cyp2a5 knockout (Cyp2a5 −/− ) mice develop more severe alcoholic fatty liver than Cyp2a5 +/+ mice. Fibroblast growth factor 21 (FGF21), a PPARα-regulated liver hormone, is involved in hepatic lipid metabolism. Alcoholic and non-alcoholic fatty liver are enhanced in Pparα knockout (Pparα −/− ) mice. This study investigates the relationship between the PPARα-FGF21 axis and the enhanced alcoholic fatty liver in Cyp2a5 −/− mice. Methods: Mice were fed the Lieber-Decarli ethanol diet to induce alcoholic fatty liver. Results: More severe alcoholic fatty liver disease was developed in Cyp2a5 −/− mice than in Cyp2a5 +/+ mice. Basal FGF21 levels were higher in Cyp2a5 −/− mice than in Cyp2a5 +/+ mice, but ethanol did not further increase the elevated FGF21 levels in Cyp2a5 −/− mice while FGF21 was induced by ethanol in Cyp2a5 +/+ mice. Basal levels of serum FGF21 were lower in Pparα −/− mice than in Pparα +/+ mice; ethanol induced FGF21 in Pparα +/+ mice but not in Pparα −/− mice, whereas ethanol induced hypertriglyceridemia in Pparα −/− mice but not in Pparα +/+ mice. Administration of recombinant FGF21 normalized serum FGF21 and triglyceride in Pparα −/− mice. Alcoholic fatty liver was enhanced in liver-specific Fgf21 knockout mice. Pparα and Cyp2a5 double knockout (Pparα −/− /Cyp2a5 −/− ) mice developed more severe alcoholic fatty liver than Pparα +/+ /Cyp2a5 −/− mice. Conclusions: These results suggest that CYP2A5 protects against the development of alcoholic fatty liver disease, and the PPARα-FGF21 axis contributes to the protective effects of CYP2A5 on alcoholic fatty liver disease.

Assessment of US score and CT number for diagnosis of fatty liver

International Nuclear Information System (INIS)

Ogasawara, Tetsuo; Tanda, Shigeru; Lim, Insu; Oota, Keisuke; Taima, Tadashi

1987-01-01

The author evaluates US and CT for diagnosis of fatty liver in 70 cases with fatty change of the liver. We tried to score the US findings of the fatty change, i.e., ''bright liver pattern'', ''liver-kidney contrast'', ''vascular blurring'', ''deep attenuation'', and the usefulness of the scoring was examined. Comparing with CT number, US score was more sensitive, but had no significant correlation with the amount of the fat in the liver and with the abnormality of the liver function tests. The results indicate that US should be used as a primary screening examination, and for the further evaluation of the fatty change of the liver, CT should be carried out. (author)

Preoperative detection of colorectal liver metastases in fatty liver: MDCT or MRI?

International Nuclear Information System (INIS)

Kulemann, Vanessa; Schima, Wolfgang; Tamandl, Dietmar; Kaczirek, Klaus; Gruenberger, Thomas; Wrba, Friedrich; Weber, Michael; Ba-Ssalamah, Ahmed

2011-01-01

Objective: To compare the diagnostic value of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the preoperative detection of colorectal liver metastases in diffuse fatty infiltration of the liver, associated with neoadjuvant chemotherapy. Materials and methods: Twenty preoperative tri-phasic MDCT (4-64-row, Siemens) and dynamic contrast-enhanced MRI (1.5 T or 3.0 T, Siemens) examinations of patients with colorectal cancer and liver metastases in diffuse steatosis were retrospectively evaluated. All patients underwent surgical resection for liver metastases (time interval 1-60 days). The amount of fatty infiltration of the liver was determined histopathologically by semi-quantitative percent-wise estimation and ranged from 25 to 75%. Results: Overall, 51 metastases were found by histopathology of the resected liver segments/lobes. The size of the metastases ranged from 0.4 to 13 cm, with 18 (35%) being up to 1 cm in diameter. In the overall rating, MDCT detected 33/51 lesions (65%), and MRI 45/51 (88%). For lesions up to 1 cm, MDCT detected only 2/18 (11%) and MRI 12/18 (66%). One false positive lesion was detected by MDCT. Statistical analysis showed that MRI is markedly superior to MDCT, with a statistically significant difference (p 1 cm. Conclusion: For the detection of colorectal liver metastases after neoadjuvant chemotherapy and consecutive diffuse fatty infiltration of the liver, MRI is superior to MDCT, especially for the detection of small lesions.

Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice.

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Xia, Bo; Cai, Guo He; Yang, Hao; Wang, Shu Pei; Mitchell, Grant A; Wu, Jiang Wei

2017-12-01

Fatty liver is a major health problem worldwide. People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver. In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association. We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age. To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created. Surprisingly, liver HSL deficiency did not influence liver fat content, suggesting that fatty liver in HSL deficiency is not liver autonomous. Given the importance of adipose tissue in systemic triglyceride metabolism, we created adipose-specific HSL knockout mice and found that adipose HSL deficiency, to a similar extent as systemic HSL deficiency, causes age-dependent fatty liver in mice. Mechanistic study revealed that deficiency of HSL in adipose tissue caused inflammatory macrophage infiltrates, progressive lipodystrophy, abnormal adipokine secretion and systemic insulin resistance. These changes in adipose tissue were associated with a constellation of changes in liver: low levels of fatty acid oxidation, of very low density lipoprotein secretion and of triglyceride hydrolase activity, each favoring the development of hepatic steatosis. In conclusion, HSL-deficient mice revealed a complex interorgan interaction between adipose tissue and liver: the role of HSL in the liver is minimal but adipose tissue deficiency of HSL can cause age-dependent hepatic steatosis. Adipose tissue is a potential target for treating the hepatic steatosis of HSL deficiency.

Dietary intake of ain-93 standard diet induces Fatty liver with altered hepatic fatty acid profile in Wistar rats.

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Farias Santos, Juliana; Suruagy Amaral, Monique; Lima Oliveira, Suzana; Porto Barbosa, Júnia; Rego Cabral, Cyro; Sofia Melo, Ingrid; Bezerra Bueno, Nassib; Duarte Freitas, Johnatan; Goulart Sant'ana, Antônio; Rocha Ataíde, Terezinha

2015-05-01

There are several standard diets for animals used in scientific research, usually conceived by scientific institutions. The AIN-93 diet is widely used, but there are some reports of fatty liver in Wistar rats fed this diet. We aimed to evaluate the hepatic repercussions of the AIN-93 diet intake in Wistar rats. Forty newly-weaned 21-day-old male Wistar rats were fed either the AIN-93 diet or a commercial diet for either 1 month or 4 months. Weight gain, serum biochemistry, hepatic histology, and hepatic fatty acid profile were analyzed. Hepatic steatosis was observed, especially in the group fed the AIN-93 diet. Serum blood glucose, absolute and relative liver weight and hepatic levels of oleic, palmitoleic, stearic, and palmitic fatty acids were related to the observed steatosis, while lipidogram and serum markers of liver function and injury were not. AIN-93 diet induced acute hepatic steatosis in Wistar rats, which may compromise its use as a standard diet for experimental studies with rodents. The hepatic fatty acid profile was associated with steatosis, with possible implications for disease prognosis. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

The association of vitamin D deficiency with non-alcoholic fatty liver disease

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Metin Küçükazman

2014-08-01

Full Text Available OBJECTIVE: Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease. METHODS: We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease. RESULTS: The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005, uric acid (p = 0.001, aspartate aminotransferase (p<0.001, alanine aminotransferase (p<0.001, γ-glutamyltransferase (p<0.0001, alkaline phosphatase (p = 0.028, HbA1c (p<0.001, ferritin (p<0.001, insulin (p = 0.016, C-peptide (p = 0.001, HOMA-IR (p = 0.003, total cholesterol (p = 0.001, triglyceride (p = 0.001 and white blood cell (p = 0.04 levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OHD levels (12.3±8.9 ng/dl, p<0.001 compared with those of the control group (20±13.6 ng/dl. CONCLUSIONS: In this study, we found lower serum 25(OHD levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed.

Biphasic effect of alcohol intake on the development of fatty liver disease.

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Takahashi, Hirokazu; Ono, Masafumi; Hyogo, Hideyuki; Tsuji, Chika; Kitajima, Yoichiro; Ono, Naofumi; Eguchi, Takahisa; Fujimoto, Kazuma; Chayama, Kazuaki; Saibara, Toshiji; Anzai, Keizo; Eguchi, Yuichiro

2015-11-01

Fatty liver is an important clinical feature not only in alcoholic and non-alcoholic fatty liver diseases, but in other chronic liver diseases as well. Our aim was to elucidate the effect and relationship between habitual alcohol intake and obesity in the development of fatty liver disease. We enrolled 8,029 subjects undergoing abdominal ultrasonography with general medical examinations, and analyzed the factors associated with fatty liver based on daily alcohol intake, body mass index (BMI), and waist circumference. For fatty liver, BMI, waist circumference, total cholesterol, triglycerides, and fasting plasma glucose were significant and independent risk factors. Heavy alcohol intake (50 g/day) was a significant risk factor for fatty liver in women (odds ratio [OR], 3.35). Analysis based on the presence or absence of obesity revealed that moderate alcohol intake was a significant negative risk factor for fatty liver in both male and female obese (BMI ≥25 kg/m(2)) subjects (OR, 0.74 for non-obese and 0.39 for obese patients, respectively). Heavy alcohol intake was also a significant negative risk factor in obese males (0.62). In contrast, heavy alcohol intake was a risk factor in non-obese males (OR, 1.29) and in all females (OR, 2.22 for non-obese and 6.6 for obese patients, respectively). The influence of alcohol intake on fatty liver differed depending on the level of alcohol consumption, gender, and the presence of obesity, and showed biphasic effects.

Correlation of Body Mass Index and Serum Parameters With Ultrasonographic Grade of Fatty Change in Non-alcoholic Fatty Liver Disease.

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Abangah, Ghobad; Yousefi, Atefeh; Asadollahi, Rouhangiz; Veisani, Yousef; Rahimifar, Paria; Alizadeh, Sajjad

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease in the western population and expanding disease in the world. Pathological changes in fatty liver are like alcohol liver damage, which can lead to end-stage liver disease. The prevalence of NAFLD in obese or overweight people is higher than general population, and it seems that people with high Body Mass Index (BMI) or abnormality in some laboratory tests are more susceptible for severe fatty liver and high grade of NAFLD in ultrasonography (U.S). This study aimed to evaluate the correlation of BMI and laboratory tests with NAFLD in ultrasonography. During a multi-step process, we selected two-hundred and thirteen cases from four hundred and eighteen patients with NAFLD. Laboratory tests performed included: ALT, AST, FBS, Triglyceride and cholesterol levels, hepatitis B surface antigen, hepatitis C antibody, ceruloplasmin, serum iron, TIBC, transferrin saturation, ferritin, AMA, ANA, ANTI LKM1, serum protein electrophoresis, TSH, anti TTG (IgA). BMI and ultrasonography for 213 patients were performed, and then data was analyzed. These parameters and grades of ultrasonography were compared with the values obtained using one way ANOVA. An ordinal logistic regression model was used to estimate the probability of ultrasonography grade. The Statistical Package for the Social Science program (SPSS, version 16.0) was used for data analysis. Two-hundred and thirteen cases including 140 male and 73 female, were studied. In general, 72.3% of patients were overweight and obese. Post-hoc tests showed that only BMI (P < 0.001) and TG (P < 0.011) among variables had statistically significant associations with ultrasonography grade (USG), and ordinal logistic regression model showed that BMI and AST were the best predictors. Our results suggest that in patients with NAFLD, BMI and TG are most effective factors in severity of fatty liver disease and ultrasonography grade (USG). On the other hand, BMI as a

CT values of fatty liver due to L-asparaginase administration

International Nuclear Information System (INIS)

Muraki, Kotaro; Kubo, Kazuaki; Hamamoto, Kazuko; Ueda, Kazuhiro; Kashiwado, Kozo; Ito, Katsuhide

1984-01-01

Chemotherapy involving L-asparaginase was performed on a 9-year-old female child with malignant lymphoma, and a 3-year-old male child and a 14-year-old female child with acute lymphatic leukemia, and the course of L-asparaginase-induced fatty liver was followed up primarily by CT findings. In all 3 cases, L-asparaginase administration caused a marked fatty liver characterized by a diffuse cold area of the liver and a decrease in the value of the liver (liver/spleen<1) on CT. Hypoproteinemia, hypofibrinogenemia and elevations of GOT and GPT were simultaneously observed, but marked anemia, pancreatitis, decreased glucose tolerance and central nervous disorder did not occur. Recovery of fatty liver was slower in CT findings than in blood biochemistry, taking about 4 weeks. (Chiba, N.)

Ultrasonographic diagnosis of fatty liver and relations with body index, serum lipid, and serum triglyceride

International Nuclear Information System (INIS)

Jang, Young Deog; Lee, S. H.; Lee, H. K.; Kim, D. H.; Kwon, K. H.; Kim, K. C.

1989-01-01

Hepatic fatty infiltration appears as an area of increased echogenicity. And many factors concerned to fatty infiltration. With 65 cases of fatty liver and 42 cases of normal group, we analyzed fatty liver with grading and attempt to find relations between grade of fatty liver and levels of body index, serum triglyceride, and serum lipid. And compared fatty liver with normal control group. Patients with fatty liver are higher percentage of supra-normal value in body index, serum lipid, and serum triglyceride than normal control group. As fatty infiltration progressed, serum lipid, serum trig-lyceride and body index are also increased. Conclusively ultrasonographic examination of liver with serum triglyceride, serum lipid, and body index are simple method, useful follow-up examination of fatty liver, and preventive routine check-up of chronic liver disease

Role of dietary fatty acids in liver injury caused by vinyl chloride metabolites in mice

Energy Technology Data Exchange (ETDEWEB)

Anders, Lisanne C [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Yeo, Heegook; Kaelin, Brenna R; Lang, Anna L; Bushau, Adrienne M; Douglas, Amanda N [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Cave, Matt [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Hepatobiology and Toxicology Program, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Diabetes and Obesity Center, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Robley Rex Louisville VAMC, Louisville, KY 40206 (United States); Arteel, Gavin E [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Hepatobiology and Toxicology Program, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); McClain, Craig J [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Hepatobiology and Toxicology Program, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Diabetes and Obesity Center, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Robley Rex Louisville VAMC, Louisville, KY 40206 (United States); and others

2016-11-15

Background: Vinyl chloride (VC) causes toxicant-associated steatohepatitis at high exposure levels. Recent work by this group suggests that underlying liver disease may predispose the liver to VC hepatotoxicity at lower exposure levels. The most common form of underlying liver disease in the developed world is non-alcoholic fatty liver disease (NAFLD). It is well-known that the type of dietary fat can play an important role in the pathogenesis of NAFLD. However, whether the combination of dietary fat and VC/metabolites promotes liver injury has not been studied. Methods: Mice were administered chloroethanol (CE - a VC metabolite) or vehicle once, 10 weeks after being fed diets rich in saturated fatty acids (HSFA), rich in poly-unsaturated fatty acids (HPUFA), or the respective low-fat control diets (LSFA; LPUFA). Results: In control mice, chloroethanol caused no detectable liver injury, as determined by plasma transaminases and histologic indices of damage. In HSFA-fed mice, chloroethanol increased HSFA-induced liver damage, steatosis, infiltrating inflammatory cells, hepatic expression of proinflammatory cytokines, and markers of endoplasmic reticulum (ER) stress. Moreover, markers of inflammasome activation were increased, while markers of inflammasome inhibition were downregulated. In mice fed HPUFA all of these effects were significantly attenuated. Conclusions: Chloroethanol promotes inflammatory liver injury caused by dietary fatty acids. This effect is far more exacerbated with saturated fat, versus poly-unsaturated fat; and strongly correlates with a robust activation of the NLRP3 inflammasome in the saturated fed animals only. Taken together these data support the hypothesis that environmental toxicant exposure can exacerbate the severity of NAFLD/NASH. - Highlights: • CE promotes inflammatory liver injury caused by dietary fatty acids. • This effect is stronger with saturated than with unsaturated fatty acids. • Damage caused by saturated fat and CE

Role of dietary fatty acids in liver injury caused by vinyl chloride metabolites in mice

International Nuclear Information System (INIS)

Anders, Lisanne C; Yeo, Heegook; Kaelin, Brenna R; Lang, Anna L; Bushau, Adrienne M; Douglas, Amanda N; Cave, Matt; Arteel, Gavin E; McClain, Craig J

2016-01-01

Background: Vinyl chloride (VC) causes toxicant-associated steatohepatitis at high exposure levels. Recent work by this group suggests that underlying liver disease may predispose the liver to VC hepatotoxicity at lower exposure levels. The most common form of underlying liver disease in the developed world is non-alcoholic fatty liver disease (NAFLD). It is well-known that the type of dietary fat can play an important role in the pathogenesis of NAFLD. However, whether the combination of dietary fat and VC/metabolites promotes liver injury has not been studied. Methods: Mice were administered chloroethanol (CE - a VC metabolite) or vehicle once, 10 weeks after being fed diets rich in saturated fatty acids (HSFA), rich in poly-unsaturated fatty acids (HPUFA), or the respective low-fat control diets (LSFA; LPUFA). Results: In control mice, chloroethanol caused no detectable liver injury, as determined by plasma transaminases and histologic indices of damage. In HSFA-fed mice, chloroethanol increased HSFA-induced liver damage, steatosis, infiltrating inflammatory cells, hepatic expression of proinflammatory cytokines, and markers of endoplasmic reticulum (ER) stress. Moreover, markers of inflammasome activation were increased, while markers of inflammasome inhibition were downregulated. In mice fed HPUFA all of these effects were significantly attenuated. Conclusions: Chloroethanol promotes inflammatory liver injury caused by dietary fatty acids. This effect is far more exacerbated with saturated fat, versus poly-unsaturated fat; and strongly correlates with a robust activation of the NLRP3 inflammasome in the saturated fed animals only. Taken together these data support the hypothesis that environmental toxicant exposure can exacerbate the severity of NAFLD/NASH. - Highlights: • CE promotes inflammatory liver injury caused by dietary fatty acids. • This effect is stronger with saturated than with unsaturated fatty acids. • Damage caused by saturated fat and CE

Experimental study on quantitative evaluation of fatty liver by computed tomography

International Nuclear Information System (INIS)

Kunieda, Tokuro; Kawata, Ryo; Hayashi, Koki; Nishiwaki, Tsutomu; Kunieda, Katsuyuki; Saji, Shigetoyo; Sakata, Kazuki

1984-01-01

Biochemical, histological and CT examinations of the liver were perfiormed in 32 rabbits on significance of measuring CT values in the diagnosis of fatty liver. In 2 groups of rabbits, in which 2g/kg/day and 4g/kg/day of fat emulsion were adminstered intravenously for 4 weeks respectively, post-treatment reduction in CT value of light dergree was observed. In a group, in which 8g/kg/day were given, there was a sufficient reduction in CT value for giving diagnosis of fatty liver of moderate degree. Significant correlation was found between changes in CT value of the liver on the one hand and contents of triglyceride, total cholesterol and cholesterol ester in the liver on the other hand, while there was no significant correlation between changes in CT value and contents of phospholipid, protein and water. Significcant correlation was found between changes in CT value of the liver and degress of histological fat accumulation in the liver cells. It has been evidenced experimentally that prolonged administration of fat emulsion may cause fatty liver, and that measurement of CT values of the liver is a non-aggressive method of diagnosing fatty liver. (author)

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

Case Report: Acute Fatty Liver Of Pregnancy In A 30-year Old ...

African Journals Online (AJOL)

Acute fatty liver of pregnancy is an uncommon, potentially fatal disorder that usually occurs in the third trimester of pregnancy or in the early post partum. We present here a 30-year-old Nigerian primigravida with acute fatty liver of pregnancy. She was successfully managed and discharged. Keywords: Acute fatty liver of ...

MR and magnetisation transfer imaging in cirrhotic and fatty livers

International Nuclear Information System (INIS)

Alanen, A.; Komu, M.; Leino, R.; Toikkanen, S.

1998-01-01

Purpose: To determine whether low-field MR fat/water separation and magnetisation transfer (MT) techniques are useful in studying the livers of patients with parenchymal liver diseases in vivo. Material and Methods: MR and MT imaging of the liver in 33 patients (14 with primary biliary cirrhosis, 15 with alcohol-induced liver disease, and 4 with fatty liver) was performed by means of the fat/water separation technique at 0.1 T. The relaxation time T1 and the MT contrast (MTC) parameter of liver and spleen tissue were measured, and the relative proton density fat content N(%) and MTC of the liver were calculated from the separate fat and water images. The value of N(%) was also compared with the percentage of fatty hepatocytes at histology. Results: The relaxation rate R1 of liver measured from the magnitude image, and the difference in the value of MTC measured form the water image compared with the one measured from the fat and water magnitude image, both depended linearly on the value of N(%). The value of N(%) correlated significantly with the percentage of the fatty hepatocytes. In in vivo fatty tissue, fat infiltration increased both the observed relaxation rate R1 and the measured magnetisation ratio (the steady state magnetisation M s divided by the equilibrium magnetisation M o , M s /M o ) and consequently decreased the MT efficiency measured in a magnitude MR image. The amount of liver fibrosis did not correlate with the value of MTC measured after fat separation. Conclusion: Our results in studying fatty livers with MR imaging and the MT method show that the fat/water separation gives more reliable parametric results. Characterisation of liver cirrhosis by means of the MTC parameter is not reliable, even after fat separation. (orig.)

Fatty liver: prospective comparative study with sonography and CT

International Nuclear Information System (INIS)

Kim, Sung Jin; Kim, Y. M.; Kim, W. S.; Choi, B. I.; Lee, J. S.; Han, C. K.; Kim, C. W.

1990-01-01

To identify the reasonable criteria in detection of the degree of Fatty liver, we prospectively evaluated sonograms and CT scans in 33 Patients With bright liver on sonography. On sonograms, we analyzed the echogenicity of the liver, acoustic attenuation, and visualization of the portal vein and the diaphragm, Each criterion was scored from 0 to 2. CT criterion for fatty liver was assessed by the attenuation difference between the liver and the spleen on nonocontrast CT scans, The average sonographic grade for CT Grade I was 1.3, Grade II was 2.1,and Grade III was 2.8. The accurate detection rate of each sonographic grade was as follows, Grade

Acute fatty liver of pregnancy. CT scan imaging in 4 cases

International Nuclear Information System (INIS)

Coche, G.; Moran, V.; Schmitt, M.; Boillot, A.; Miguet, J.P.; Hadni-Bresson, S.; Weill, F.S.

1987-01-01

Acute fatty liver of pregnancy is a disease of the third trimester, generally considered to be rare and to have a grave prognosis. Histologically the characteristic fine droplet steatosis usually produces distinct vacuolization. Successful treatment depends on accurate diagnosis and early delivery. Computed tomography is of value in the diagnosis of fatty liver through liver and spleen attenuation value measurements. We reviewed 4 cases of acute fatty liver of pregnancy. Computed tomography was performed in two cases and was very helpful in the diagnosis of this condition [fr

Diffuse fatty infiltration of the liver: Pitfalls in computed tomography diagnosis

International Nuclear Information System (INIS)

Loh, Y.H.; Dunn, G.D.

1997-01-01

The presence of a fatty liver often complicates the interpretation of abdominal computed tomography (CT). Abnormalities in or adjacent to the liver, including dilated bile ducts, liver masses and subphrenic collections, may be masked by the fatty liver. Furthermore, normal structures may simulate pathological conditions. Five cases are presented to illustrate some of these diagnostic pitfalls. (authors)

Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of nonalcoholic fatty liver disease

Science.gov (United States)

Obesity is often associated with a cluster of increased health risks collectively known as "Metabolic Syndrome" (MS). MS is often accompanied by development of fatty liver. Sometimes fatty liver results in damage leading to reduced liver function, and need for a transplant. This condition is known...

Lipocalin-2 in Fructose-Induced Fatty Liver Disease

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Jessica Lambertz

2017-11-01

Full Text Available The intake of excess dietary fructose most often leads to non-alcoholic fatty liver disease (NAFLD. Fructose is metabolized mainly in the liver and its chronic consumption results in lipogenic gene expression in this organ. However, precisely how fructose is involved in NAFLD progression is still not fully understood, limiting therapy. Lipocalin-2 (LCN2 is a small secreted transport protein that binds to fatty acids, phospholipids, steroids, retinol, and pheromones. LCN2 regulates lipid and energy metabolism in obesity and is upregulated in response to insulin. We previously discovered that LCN2 has a hepatoprotective effect during hepatic insult, and that its upregulation is a marker of liver damage and inflammation. To investigate if LCN2 has impact on the metabolism of fructose and thereby arising liver damage, we fed wild type and Lcn2−/− mice for 4 or 8 weeks on diets that were enriched in fructose either by adding this sugar to the drinking water (30% w/v, or by feeding a chow containing 60% (w/w fructose. Body weight and daily intake of food and water of these mice was then measured. Fat content in liver sections was visualized using Oil Red O stain, and expression levels of genes involved in fat and sugar metabolism were measured by qRT-PCR and Western blot analysis. We found that fructose-induced steatosis and liver damage was more prominent in female than in male mice, but that the most severe hepatic damage occurred in female mice lacking LCN2. Unexpectedly, consumption of elevated fructose did not induce de novo lipogenesis or fat accumulation. We conclude that LCN2 acts in a lipid-independent manner to protect the liver against fructose-induced damage.

Focal fatty infiltration of the liver: demonstration by magnetic resonance imaging

International Nuclear Information System (INIS)

Wenker, J.C.; Baker, M.K.; Ellis, J.H.; Glant, M.D.

1984-01-01

Focal fatty infiltration of the liver is a recently recognized yet poorly understood entity, which has become more apparent since the onset of widespread computed tomographic (CT) scanning. Recent reports have suggested that magnetic resonance imaging (MRI) may not be sensitive in the evaluation of diffuse fatty liver. A case is presented in which MRI was as sensitive as CT and sonography in the demonstration of focal fatty change within the liver

Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver.

Directory of Open Access Journals (Sweden)

Marta Moya

Full Text Available Triglyceride accumulation in nonalcoholic fatty liver (NAFL results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2 however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB. Moreover, Foxa1 represses the fatty acid transporter protein FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing peroxisomal fatty acid β-oxidation and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolic pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance.

Moro orange juice prevents fatty liver in mice.

Science.gov (United States)

Salamone, Federico; Li Volti, Giovanni; Titta, Lucilla; Puzzo, Lidia; Barbagallo, Ignazio; La Delia, Francesco; Zelber-Sagi, Shira; Malaguarnera, Michele; Pelicci, Pier Giuseppe; Giorgio, Marco; Galvano, Fabio

2012-08-07

To establish if the juice of Moro, an anthocyanin-rich orange, may improve liver damage in mice with diet-induced obesity. Eight-week-old mice were fed a high-fat diet (HFD) and were administrated water or Moro juice for 12 wk. Liver morphology, gene expression of lipid transcription factors, and metabolic enzymes were assessed. Mice fed HFD displayed increased body weight, insulin resistance and dyslipidemia. Moro juice administration limited body weight gain, enhanced insulin sensitivity, and decreased serum triglycerides and total cholesterol. Mice fed HFD showed liver steatosis associated with ballooning. Dietary Moro juice markedly improved liver steatosis by inducing the expression of peroxisome proliferator-activated receptor-α and its target gene acylCoA-oxidase, a key enzyme of lipid oxidation. Consistently, Moro juice consumption suppressed the expression of liver X receptor-α and its target gene fatty acid synthase, and restored liver glycerol-3-phosphate acyltransferase 1 activity. Moro juice counteracts liver steatogenesis in mice with diet-induced obesity and thus may represent a promising dietary option for the prevention of fatty liver.

Comparison of Serum Ferritin and Vitamin D in Association with the Severity of Nonalcoholic Fatty Liver Disease in Korean Adults

Directory of Open Access Journals (Sweden)

Dong Wook Jeong

2014-12-01

Full Text Available BackgroundIncreased serum ferritin and decreased vitamin D levels associated with nonalcoholic fatty liver disease (NAFLD. However, their association with the severity of NAFLD has not been fully evaluated. The aim of this study was to compare the association of serum ferritin and 25(OHD3 levels with the severity of ultrasonographically detected NAFLD (US-NAFLD and hepatic steatosis defined by fatty liver index (FLI in Korean adults.MethodsA cross-sectional analysis of clinical and anthropometric data, including serum ferritin and 25(OHD3, from men (n=295 and women (n=263 who underwent a routine health check-up in 2012.ResultsIn men, with an increase in the quartile of serum ferritin level, the incidences of subjects with metabolic syndrome (P=0.002, US-NAFLD (P=0.041, and FLI ≥60 (P=0.010 were significantly elevated. In women, the incidence of subjects with US-NAFLD was also significantly elevated with increases in the serum ferritin quartile (P=0.012. Regarding 25(OHD3, no statistical differences were observed among the different quartiles in either gender. Serum ferritin level significantly increased as the severity of US-NAFLD increased (P<0.001; however, no significant differences in 25(OHD3 level were observed in men. No significant differences in either serum ferritin or 25(OHD3 level were observed among women with different levels of severity of US-NAFLD.ConclusionIncreased serum ferritin level showed a closer association with severity of NAFLD compared with level of serum vitamin D, suggesting that serum ferritin level may be a better marker than vitamin D level for predicting the severity of US-NAFLD and hepatic steatosis in a clinical setting.

Kefir improves fatty liver syndrome by inhibiting the lipogenesis pathway in leptin-deficient ob/ob knockout mice.

Science.gov (United States)

Chen, H-L; Tung, Y-T; Tsai, C-L; Lai, C-W; Lai, Z-L; Tsai, H-C; Lin, Y-L; Wang, C-H; Chen, C-M

2014-09-01

Fatty liver disease is commonly associated with obesity, insulin resistance and diabetes. Severe fatty liver is sometimes accompanied by steatohepatitis and may lead to the development of hepatocellular carcinoma. At present, there is no effective treatment for non-alcoholic fatty liver disease (NAFLD); thus, recent investigations have focused on developing effective therapeutics to treat this condition. This study aimed to evaluate the effects of kefir on the hepatic lipid metabolism of ob/ob mice, which are commonly used to model fatty liver disease. In this study, we used leptin receptor-deficient ob/ob mice as an animal disease model of NAFLD. Six-week-old ob/ob mice were orally administered the dairy product kefir (140 mg kg(-1) of body weight (BW) per day) for 4 weeks. The data demonstrated that kefir improved fatty liver syndrome on BW, energy expenditure and basal metabolic rate by inhibiting serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities (Pkefir administration also significantly reduced the macrovesicular fat quantity in liver tissue. In addition, kefir markedly decreased the expression of the genes sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) (Pkefir improves NAFLD on BW, energy expenditure and basal metabolic rate by inhibiting the lipogenesis pathway and that kefir may have the potential for clinical application to the prevention or treatment of NAFLD.

Endocrine causes of nonalcoholic fatty liver disease.

Science.gov (United States)

Marino, Laura; Jornayvaz, François R

2015-10-21

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

Effects of Fatty Liver Induced by Excess Orotic Acid on B-Group Vitamin Concentrations of Liver, Blood, and Urine in Rats.

Science.gov (United States)

Shibata, Katsumi; Morita, Nobuya; Kawamura, Tomoyo; Tsuji, Ai; Fukuwatari, Tsutomu

2015-01-01

Fatty liver is caused when rats are given orotic acid of the pyrimidine base in large quantities. The lack of B-group vitamins suppresses the biosynthesis of fatty acids. We investigated how orotic acid-induced fatty liver affects the concentrations of liver, blood, and urine B-group vitamins in rats. The vitamin B6 and B12 concentrations of liver, blood, and urine were not affected by orotic acid-induced fatty liver. Vitamin B2 was measured only in the urine, but was unchanged. The liver, blood, and urine concentrations of niacin and its metabolites fell dramatically. Niacin and its metabolites in the liver, blood, and urine were affected as expected. Although the concentrations of vitamin B1, pantothenic acid, folate, and biotin in liver and blood were decreased by orotic acid-induced fatty liver, these urinary excretion amounts showed a specific pattern toward increase. Generally, as for the typical urinary excretion of B-group vitamins, these are excreted when the body is saturated. However, the ability to sustain vitamin B1, pantothenic acid, folate, and biotin decreased in fatty liver, which is hypothesized as a specific phenomenon. This metabolic response might occur to prevent an abnormally increased biosynthesis of fatty acids by orotic acid.

Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity

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Massart, Julie; Begriche, Karima; Moreau, Caroline; Fromenty, Bernard

2017-01-01

Background Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. Aim The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity. For this purpose, we performed a data-mining analysis using different queries including drug-induced liver injury (or DILI), drug-induced hepatotoxicity, fatty liver, nonalcoholic fatty liver disease (or NAFLD), steatosis and obesity. The main data from the collected articles are reported in this review and when available, some pathophysiological hypotheses are put forward. Relevance for patients Drugs that could pose a potential risk in obese patients include compounds belonging to different pharmacological classes such as acetaminophen, halothane, methotrexate, rosiglitazone, stavudine and tamoxifen. For some of these drugs, experimental investigations in obese rodents confirmed the clinical observations and unveiled different pathophysiological mechanisms which could explain why these pharmaceuticals are particularly hepatotoxic in obesity and NAFLD. Other drugs such as pentoxifylline, phenobarbital and omeprazole might also pose a risk but more investigations are required to determine whether this risk is significant or not. Because obese people often take several drugs for the treatment of different obesity-related diseases such as type 2 diabetes, hyperlipidemia and coronary heart disease, it is urgent to identify the main pharmaceuticals that can cause acute hepatitis on a fatty liver background or induce NAFLD worsening

Nodular focal fatty infiltration of the liver: CT appearance

International Nuclear Information System (INIS)

Baker, M.E.; Silverman, P.M.

1985-01-01

Focal fatty infiltration of the liver is a well recognized entity generally characterized by a nonspherical, low-density area without significant mass effect. CT usually distinguishes this from focal liver processes such as abscess or metastasis by its sharply marginated, geographic pattern and lack of mass effect on hepatic and portal veins. Recently, the authors formed a CT scan of the liver in one patient in whom fatty infiltration appeared nodular or rounded. The clinical presentation and radiographic and pathologic features form the basis of this report

The nutritional geometry of liver disease including non-alcoholic fatty liver disease.

Science.gov (United States)

Simpson, Stephen J; Raubenheimer, David; Cogger, Victoria C; Macia, Laurence; Solon-Biet, Samantha M; Le Couteur, David G; George, Jacob

2018-02-01

Nutrition has a profound effect on chronic liver disease, especially non-alcoholic fatty liver disease (NAFLD). Most observational studies and clinical trials have focussed on the effects of total energy intake, or the intake of individual macronutrients and certain micronutrients, such as vitamin D, on liver disease. Although these studies have shown the importance of nutrition on hepatic outcomes, there is not yet any unifying framework for understanding the relationship between diet and liver disease. The Geometric Framework for Nutrition (GFN) is an innovative model for designing nutritional experiments or interpreting nutritional data that can determine the effects of nutrients and their interactions on animal behaviour and phenotypes. Recently the GFN has provided insights into the relationship between dietary energy and macronutrients on obesity and ageing in mammals including humans. Mouse studies using the GFN have disentangled the effects of macronutrients on fatty liver and the gut microbiome. The GFN is likely to play a significant role in disentangling the effects of nutrients on liver disease, especially NAFLD, in humans. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Curcumin improves alcoholic fatty liver by inhibiting fatty acid biosynthesis.

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Guo, Chang; Ma, Jingfan; Zhong, Qionghong; Zhao, Mengyuan; Hu, Tianxing; Chen, Tong; Qiu, Longxin; Wen, Longping

2017-08-01

Alcoholic fatty liver is a threat to human health. It has been long known that abstinence from alcohol is the most effective therapy, other effective therapies are not available for the treatment in humans. Curcumin has a great potential for anti-oxidation and anti-inflammation, but the effect on metabolic reconstruction remains little known. Here we performed metabolomic analysis by gas chromatography/mass spectrometry and explored ethanol pathogenic insight as well as curcumin action pattern. We identified seventy-one metabolites in mouse liver. Carbohydrates and lipids were characteristic categories. Pathway analysis results revealed that ethanol-induced pathways including biosynthesis of unsaturated fatty acids, fatty acid biosynthesis and pentose and glucuronate interconversions were suppressed by curcumin. Additionally, ethanol enhanced galactose metabolism and pentose phosphate pathway. Glyoxylate and dicarboxylate metabolism and pyruvate metabolism were inhibited in mice fed ethanol diet plus curcumin. Stearic acid, oleic acid and linoleic acid were disease biomarkers and therapical biomarkers. These results reflect the landscape of hepatic metabolism regulation. Our findings illustrate ethanol pathological pathway and metabolic mechanism of curcumin therapy. Copyright © 2017. Published by Elsevier Inc.

Psoriasis and Nonalcoholic Fatty Liver Disease.

Science.gov (United States)

Carrascosa, J M; Bonanad, C; Dauden, E; Botella, R; Olveira-Martín, A

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the West. The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis. The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance, a common finding in diseases associated with psoriasis. NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis, in particular if they show signs of metabolic syndrome and require systemic treatment. Concomitant psoriasis and NAFLD and the likelihood of synergy between them place limitations on general recommendations and treatment for these patients given the potential for liver toxicity. As hepatotoxic risk is associated with some of the conventional drugs used in this setting (e.g., acitretin, methotrexate, and ciclosporin), patients prescribed these treatments should be monitored as appropriate. Anti-tumor necrosis factor agents hold the promise of potential benefits based on their effects on the inflammatory process and improving peripheral insulin resistance. However, cases of liver toxicity have also been reported in relation to these biologics. No evidence has emerged to suggest that anti-p40 or anti-interleukin 17 agents provide benefits or have adverse effects. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Focal fatty infiltra- tion and focal fatty sparing of the liver

African Journals Online (AJOL)

Enrique

Department of Radiology. Nelson Mandela School of Health Sciences. Durban. Fig. 1a. Unenhanced CT of the liver in case 1 demonstrates multiple focal low density regions in both lobes of the liver. Region of interest 1 over the fatty left lobe measured 10 HU while region of interest 2 over the right lobe measure 40 HU in.

Computed tomographic demonstration of rapid changes in fatty infiltration of the liver

International Nuclear Information System (INIS)

Bashist, B.; Hecht, H.L.; Harely, W.D.

1982-01-01

Two alcoholic patients in whom computed tomography (CT) demonstrated reversal of fatty infiltration of the liver are described. The rapid reversibility of fatty infiltration can be useful in monitoring alcoholics with fatty livers. Focal fatty infiltration can mimic focal hepatic lesions and repeat scans can be utilized to assess changes in CT attenuation values when this condition is suspected

Protective effect of bicyclol on tetracycline-induced fatty liver in mice

International Nuclear Information System (INIS)

Yu, Hong-Yan; Wang, Bao-Lian; Zhao, Jing; Yao, Xiao-Min; Gu, Yu; Li, Yan

2009-01-01

Peroxisome proliferators-activated receptor α (PPARα) and oxidative stress are two important pathological factors in non-alcoholic fatty liver disease (NAFLD). Tetracycline-induced fatty liver was partly due to the disturbance of mitochondrial fatty acids β-oxidation regulated by PPARα. Bicyclol was found to protect against high fat diet-induced fatty liver through modulating PPARα and clearing reactive oxygen species (ROS). The present study was performed to further investigate the effect of bicyclol on tetracycline-induced fatty liver and related mechanism in mice. Bicyclol (75, 150, 300 mg/kg) was given orally three times in two consecutive days. Tetracycline (200 mg/kg) was injected intraperitoneally 1 h after the last administration of bicyclol. Oxidative stress, mitochondrial function, PPARα and its target genes were evaluated by biochemical and RT-PCR analysis. The activity of CYP4A was assessed by liquid chromatography/mass spectrometry (LC/MS) method. Bicyclol significantly protected against tetracycline-induced fatty liver by reducing the accumulation of hepatic lipids and elevation of serum aminotransferase. In addition, bicyclol remarkably alleviated the over-production of thiobarbituric acid-reactive substance. The reduced activity of mitochondrial respiratory chain (MRC) complexes I and IV and mitochondrial permeability transition (MPT) were also improved by bicyclol. Furthermore, bicyclol inhibited the decrease of PPARα expression and its target genes, including long-chain acyl CoA dehydrogenase (LCAD), acetyl CoA oxidase (AOX) and CYP4A at mRNA and enzyme activity level. Bicyclol protected against tetracycline-induced fatty liver mainly through modulating the disturbance of PPARα pathway and ameliorating mitochondrial function.

Prevalence of non alcoholic fatty liver disease in patients with metabolic syndrome

International Nuclear Information System (INIS)

Iftikhar, R.; Kamran, S.M.

2015-01-01

To determine frequency of Non Alcoholic fatty liver disease in patients with Metabolic Syndrome (MetS). Study Design: Cross sectional study. Place and Duration of Study: Department of medicine, CMH Okara, Jan 2013 to July 2013. Patients and Methods: We included 491 adult males, diagnosed with metabolic syndrome (MetS), presenting in outpatient department for routine review. MetS was diagnosed as per the International Diabetes Federation (IDF) proposed criteria of 2004. Detailed history and examination of each individual was done and data entered in pre designed performa. Brightness and posterior attenuation on ultrasound abdomen were considered indices for fatty liver disease in presence of elevated ALT, negative hepatitis serology and absence of alcohol intake. All the data was analyzed using SPSS version 16. p value of less than 0.05 was considered statistically significant. Results: Out of 491 participants with MetS, 222 (45.2%) had fatty liver disease. Mean BMI in patients with metabolic syndrome was 26.1 (± .89) and mean BMI in fatty liver patients was 27.3 (± 0.67). Out of total 5 components of Mets, patients with fatty liver disease had 3.24 (± 0.25) components, as compared to 2.1 (± 0.34) in whole of study group. Conclusion: A large number of patients with metabolic syndrome have fatty liver disease. Fatty liver disease is more frequent in patients who are overweight and those having multiple risk factors of metabolic syndrome. (author)

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.

The study on fatty infiltration of the liver with the use of CT scan

International Nuclear Information System (INIS)

Yamawaki, Tadaharu; Hirofuji, Hideo; Yatomi, Akira; Kawabe, Masami; Sugie, Hajime

1981-01-01

On the basis of experience thus far, it is said that the diagnosis of fatty liver is comparatively difficult. It has been reported that the diagnosis of fatty liver can be done by its decreased attenuation number on CT scan among diffuse liver diseases. We investigated 80 cases of which attenuation number revealed below 35 Hn (Hounsfield units). Analysis of correlations between eight variables (T. Cholesterol, β-lipoprotein, Triglyceride, HDL Cholesterol, Cholinesterase, Obsity index, BSP and the degree of fatty infiltration of the liver specimen) and mean attenuation number of the liver were investigated and highly significant correlation was found only between the degree of fatty infiltration of the liver and the mean attenuation number of the liver (r = -0.746, p < 0.01). Therefore, it is concluded that CT scan is an epochmaking morphological examination of fatty liver. (author)

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

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Benan Kasapoglu

2016-01-01

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

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

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Hannele Yki-Järvinen

2015-11-01

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

Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease.

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Mendoza, Michael; Caltharp, Shelley; Song, Ming; Collin, Lindsay; Konomi, Juna V; McClain, Craig J; Vos, Miriam B

2017-07-01

Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.

[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

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.

SIRT7 Represses Myc Activity to Suppress ER Stress and Prevent Fatty Liver Disease

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Jiyung Shin

2013-11-01

Full Text Available Nonalcoholic fatty liver disease is the most common chronic liver disorder in developed countries. Its pathogenesis is poorly understood, and therapeutic options are limited. Here, we show that SIRT7, an NAD+-dependent H3K18Ac deacetylase, functions at chromatin to suppress ER stress and prevent the development of fatty liver disease. SIRT7 is induced upon ER stress and is stabilized at the promoters of ribosomal proteins through its interaction with the transcription factor Myc to silence gene expression and to relieve ER stress. SIRT7-deficient mice develop chronic hepatosteatosis resembling human fatty liver disease. Myc inactivation or pharmacological suppression of ER stress alleviates fatty liver caused by SIRT7 deficiency. Importantly, SIRT7 suppresses ER stress and reverts the fatty liver disease in diet-induced obese mice. Our study identifies SIRT7 as a cofactor of Myc for transcriptional repression and delineates a druggable regulatory branch of the ER stress response that prevents and reverts fatty liver disease.

Ultrasound image texture processing for evaluating fatty liver in peripartal dairy cows

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Amin, Viren R.; Bobe, Gerd; Young, Jerry; Ametaj, Burim; Beitz, Donald

2001-07-01

The objective of this work is to characterize the liver ultrasound texture as it changes in diffuse disease of fatty liver. This technology could allow non-invasive diagnosis of fatty liver, a major metabolic disorder in early lactation dairy cows. More than 100 liver biopsies were taken from fourteen dairy cows, as a part of the USDA-funded study for effects of glucagon on prevention and treatment of fatty liver. Up to nine liver biopsies were taken from each cow during peripartal period of seven weeks and total lipid content was determined chemically. Just before each liver biopsy was taken, ultrasonic B-mode images were digitally captured using a 3.5 or 5 MHz transducer. Effort was made to capture images that were non-blurred, void of large blood vessels and multiple echoes, and of consistent texture. From each image, a region-of-interest of size 100-by-100 pixels was processed. Texture parameters were calculated using algorithms such as first and second order statistics, 2D Fourier transformation, co-occurrence matrix, and gradient analysis. Many cows had normal liver (3% to 6% total lipid) and a few had developed fatty liver with total lipid up to 15%. The selected texture parameters showed consistent change with changing lipid content and could potentially be used to diagnose early fatty liver non-invasively. The approach of texture analysis algorithms and initial results on their potential in evaluating total lipid percentage is presented here.

Evaluation of the Effect of Exercise on Nonalcoholic Fatty Liver By Sonography

International Nuclear Information System (INIS)

Kim, Kyoung Yeon; Lim, Hyun Soo

2012-01-01

Nonalcoholic fatty liver disease (NAFLD) is accumulation state of fat in liver cells without excessive alcohol intake, and it has been studied that is closely related to obesity. The purpose of this study is to identify risk factors for NAFLD and may prevent or to manage risk factors. This study was in progress for six months (2011 May 1 to October 31), of the 83 people who underwent abdominal ultrasound 11 people eventually were selected. Research results was as follows : First, the decreased body weight and body mass index (BMI), and the second, a decrease of the deepening of fatty liver in ultrasound diagnosis, and the third, steady movement reduces the deepening of fatty liver regardless of calories. Thus, the implication of this research is that long-term exercise programs have positive effects in the treatment of fatty liver.

Evaluation of the Effect of Exercise on Nonalcoholic Fatty Liver By Sonography

Energy Technology Data Exchange (ETDEWEB)

Kim, Kyoung Yeon [Dept. of Radiology, Anseong Hanju Clinic, Anseong (Korea, Republic of); Lim, Hyun Soo [Dept. of Biomedical Engineering, Chungnam University, Daejeon (Korea, Republic of)

2012-03-15

Nonalcoholic fatty liver disease (NAFLD) is accumulation state of fat in liver cells without excessive alcohol intake, and it has been studied that is closely related to obesity. The purpose of this study is to identify risk factors for NAFLD and may prevent or to manage risk factors. This study was in progress for six months (2011 May 1 to October 31), of the 83 people who underwent abdominal ultrasound 11 people eventually were selected. Research results was as follows : First, the decreased body weight and body mass index (BMI), and the second, a decrease of the deepening of fatty liver in ultrasound diagnosis, and the third, steady movement reduces the deepening of fatty liver regardless of calories. Thus, the implication of this research is that long-term exercise programs have positive effects in the treatment of fatty liver.

Final results of a long-term, clinical follow-up in fatty liver patients

DEFF Research Database (Denmark)

Dam-Larsen, Sanne; Becker, Ulrik; Franzmann, Maria-Benedicte

2009-01-01

OBJECTIVE: There is increasing focus on non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to conduct a long-term clinical follow-up of patients with biopsy-confirmed fatty liver without inflammation or significant fibrosis (pure fatty liver), to analyse for potential risk....... All admissions, discharge diagnoses and causes of death during follow-up were collected. All surviving patients were invited to a clinical follow-up. RESULTS: The follow-up period was 20.4 and 21.0 years, respectively, for the NAFLD and alcoholic fatty liver disease (AFLD) groups. Two NAFLD patients...... of death. Patients with AFLD died primarily from cirrhosis and other alcohol-related disorders, whereas in patients with NAFLD the main causes of death were cardiovascular disease and cancer. CONCLUSIONS: For patients with pure non-alcoholic fatty liver, survival was good and independent...

Studies on the hepatic hemodynamics of the patients with fatty liver by hepatic blood flow mapping

International Nuclear Information System (INIS)

Kubo, Shuichi; Okajima, Tugio; Yamazaki, Yasurou

1991-01-01

To investigate intrahepatic hemodynamics of the patients with fatty liver, the time to reach maximal enhancement (PT) of every 3 x 3 pixel was depicted by a gray scale throughout an area of maximal horizontal slice of CT of the liver to obtain blood flow mapping of the liver, and compared with those of normal, chronic hepatitis and cirrhosis. Mottles of deep gray, light gray or black pixels were distributed throughout the liver slice of fatty liver. Although the mean PT of a ROI of fatty liver was longer than normal and shorter than that of cirrhosis and the same as that of chronic hepatitis, the map of fatty liver was different from that of chronic hepatitis. When the distribution of PT was expressed by their histogram, it was known that PT of fatty liver had a wider range than that of chronic hepatitis. The range was the same as that of cirrhosis. In one case of fatty liver, the deep gray pixels was increased when fatty infiltration of the liver was improved. It was concluded that the intrahepatic blood flow of fatty liver was impaired in a way not similar to chronic hepatitis or liver cirrhosis, which could be clearly seen by hepatic blood flow mapping, and which seemed to be reversible with the improvement of fatty liver. (author)

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...

Comparative study of clinicopathological states and imaging diagnosis in patients with fatty liver

International Nuclear Information System (INIS)

Ariga, Hisayuki; Arakawa, Yasuyuki; Miyamoto, Masatoshi

1985-01-01

The authors clarified the characteristics of the clinicopathological states of 74 patients with the fatty liver classified by the etiology, simultaneously evaluating clinically the usefulness of imaging diagnosis with ultrasound and CT by the comparison of pathohistological findings(the rate of fat occupation in the liver). It was confirmed that, although the outcome of ultrasonic diagnosis was inferior to that of CT in the diagnostic capacity, the so-called bright liver finding was obtained, provided that the accumulation of fat in the liver was over Grade III (40 - 60 %), and that clinical diagnosis for fatty liver was possible. With CT, on the other hand, there was negative correlation between the degree of fat accumulation in the liver vs. the liver CT level and the CT ratio of the liver/spleen. Particularly, the CT ratio of the liver/spleen in this disease was 0.80 ± 0.18, indicating a significantly lower level as compared with 1.13 ± 0.13 in the control (p < 0.001). It is therefore suggested that, in patients in whom accumulation of fat in the liver is comparatively a lower level of Grade II (20 - 40 %), diagnosis for fatty liver by CT may be possible at a considerably high probability. Since these imaging diagnostic methods have been highly evaluated as non-invasive and convenient screening means of the fatty liver, it is important to establish the diagnostic criteria for graphic quantification of the fatty liver. (author)

Current management of non-alcoholic fatty liver disease

OpenAIRE

LISBOA, QUELSON COELHO; COSTA, SILVIA MARINHO FEROLLA; COUTO, CLÁUDIA ALVES

2016-01-01

SUMMARY Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic accumulation of lipid in patients who do not consume alcohol in amounts generally considered harmful to the liver. NAFLD is becoming a major liver disease in Eastern countries and it is related to insulin resistance and metabolic syndrome. Treatment has focused on improving insulin sensitivity, protecting the liver from oxidative stress, decreasing obesity and improving diabetes mellitus, dyslipidemia, hepatic infla...

Unusual fatty metamorphosis observed in diffuse liver metastases of stage 4S neuroblastoma

Energy Technology Data Exchange (ETDEWEB)

Tazoe, Jun; Okuyama, Chio; Nishimura, Tsunehiko [Kyoto Prefectural University of Medicine, Department of Radiology, Graduate School of Medical Science, Kyoto City (Japan); Iehara, Tomoko; Hosoi, Hajime [Kyoto Prefectural University of Medicine, Department of Paediatrics, Graduate School of Medical Science, Kyoto City (Japan)

2010-05-15

We report a case of stage 4S neuroblastoma in which CT showed diffuse liver metastases containing a geographical fatty area in the periportal region. MRI showed this abnormality to correspond to an area with an unusual pattern of fatty change. {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy demonstrated increased accumulation throughout the liver, except for the region showing fatty change. To the best of our knowledge, this is the first report of liver metastases from neuroblastoma with geographical fatty infiltration. (orig.)

Unusual fatty metamorphosis observed in diffuse liver metastases of stage 4S neuroblastoma

International Nuclear Information System (INIS)

Tazoe, Jun; Okuyama, Chio; Nishimura, Tsunehiko; Iehara, Tomoko; Hosoi, Hajime

2010-01-01

We report a case of stage 4S neuroblastoma in which CT showed diffuse liver metastases containing a geographical fatty area in the periportal region. MRI showed this abnormality to correspond to an area with an unusual pattern of fatty change. 123 I-metaiodobenzylguanidine (MIBG) scintigraphy demonstrated increased accumulation throughout the liver, except for the region showing fatty change. To the best of our knowledge, this is the first report of liver metastases from neuroblastoma with geographical fatty infiltration. (orig.)

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 th......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...

Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys.

Science.gov (United States)

Wattacheril, Julia; Lavine, Joel E; Chalasani, Naga P; Guo, Xiuqing; Kwon, Soonil; Schwimmer, Jeffrey; Molleston, Jean P; Loomba, Rohit; Brunt, Elizabeth M; Chen, Yii-Der Ida; Goodarzi, Mark O; Taylor, Kent D; Yates, Katherine P; Tonascia, James; Rotter, Jerome I

2017-11-01

To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7 -07 ). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9 -07 ). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular classification of fatty liver by high-throughput profiling of protein post-translational modifications.

Science.gov (United States)

Urasaki, Yasuyo; Fiscus, Ronald R; Le, Thuc T

2016-04-01

We describe an alternative approach to classifying fatty liver by profiling protein post-translational modifications (PTMs) with high-throughput capillary isoelectric focusing (cIEF) immunoassays. Four strains of mice were studied, with fatty livers induced by different causes, such as ageing, genetic mutation, acute drug usage, and high-fat diet. Nutrient-sensitive PTMs of a panel of 12 liver metabolic and signalling proteins were simultaneously evaluated with cIEF immunoassays, using nanograms of total cellular protein per assay. Changes to liver protein acetylation, phosphorylation, and O-N-acetylglucosamine glycosylation were quantified and compared between normal and diseased states. Fatty liver tissues could be distinguished from one another by distinctive protein PTM profiles. Fatty liver is currently classified by morphological assessment of lipid droplets, without identifying the underlying molecular causes. In contrast, high-throughput profiling of protein PTMs has the potential to provide molecular classification of fatty liver. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Fatty liver disease in Sudan is not alcohol related | Nail | Sudan ...

African Journals Online (AJOL)

Background: The finding of fatty liver disease (FLD) has generally been assumed to be a consequence of ethanol ingestion. However, non- alcoholic fatty liver disease (NAFLD) was identified as a specific entity. Although FLD is generally nonprogressive or only slowly progressive, cirrhosis and HCC can develop.

ω-3 Fatty acids reverse lipotoxity through induction of autophagy in nonalcoholic fatty liver disease.

Science.gov (United States)

Chen, Yi; Xu, Chengfu; Yan, Tianlian; Yu, Chaohui; Li, Youming

2015-01-01

The aim of this study was to evaluate the effect of ω-3 fatty acids on nonalcoholic fatty liver disease concerning hepatocyte lipid accumulation as well as apoptosis induced by free fatty acids (FFAs) and to explore the underlying mechanism involving autophagy. Hepatocytes were incubated with a mixture of free fatty acids (FFAs) to mimic in vitro lipotoxicity in the pathogenesis of nonalcoholic fatty liver disease, presented by lipid accumulation and cellular apoptosis. Chemical inhibitor or inducer of autophagy and genetic deficit cells, as well as ω-3 fatty acids were used as intervention. The autophagic role of ω-3 fatty acids was investigated using Western blot and immunofluorescence. The underlying mechanism of ω-3 fatty acids involving autophagy was preliminarily explored by quantitative real-time polymerase chain reaction and Western blot. FFAs induce lipid accumulation and apoptosis in hepatocytes. Inhibition or genetic defect of autophagy increases lipid accumulation induced by FFA, whereas induction acts inversely. ω-3 Fatty acids reduced lipid accumulation and inhibited apoptosis induced by FFA. ω-3 Fatty acids induced autophagy by downregulating stearoyl-CoA desaturase 1 expression in hepatocytes. ω-3 Fatty acids exert protective effects on hepatocytes against lipotoxicity through induction of autophagy, as demonstrated by inhibition of lipid accumulation and apoptosis. Copyright © 2015 Elsevier Inc. All rights reserved.

EX VIVO STUDY OF QUANTITATIVE ULTRASOUND PARAMETERS IN FATTY RABBIT LIVERS

Science.gov (United States)

Ghoshal, Goutam; Lavarello, Roberto J.; Kemmerer, Jeremy P.; Miller, Rita J.; Oelze, Michael L.

2012-01-01

Nonalcoholic fatty liver disease (NAFLD) affects more than 30% of Americans, and with increasing problems of obesity in the United States, NAFLD is poised to become an even more serious medical concern. At present, accurate classification of steatosis (fatty liver) represents a significant challenge. In this study, the use of high-frequency (8 to 25 MHz) quantitative ultrasound (QUS) imaging to quantify fatty liver was explored. QUS is an imaging technique that can be used to quantify properties of tissue giving rise to scattered ultrasound. The changes in the ultrasound properties of livers in rabbits undergoing atherogenic diets of varying durations were investigated using QUS. Rabbits were placed on a special fatty diet for 0, 3, or 6 weeks. The fattiness of the livers was quantified by estimating the total lipid content of the livers. Ultrasonic properties, such as speed of sound, attenuation, and backscatter coefficients, were estimated in ex vivo rabbit liver samples from animals that had been on the diet for varying periods. Two QUS parameters were estimated based on the backscatter coefficient: effective scatterer diameter (ESD) and effective acoustic concentration (EAC), using a spherical Gaussian scattering model. Two parameters were estimated based on the backscattered envelope statistics (the k parameter and the μ parameter) according to the homodyned K distribution. The speed of sound decreased from 1574 to 1565 m/s and the attenuation coefficient increased from 0.71 to 1.27 dB/cm/MHz, respectively, with increasing fat content in the liver. The ESD decreased from 31 to 17 μm and the EAC increased from 38 to 63 dB/cm3 with increasing fat content in the liver. A significant increase in the μ parameter from 0.18 to 0.93 scatterers/mm3 was observed with increasing fat content in the liver samples. The results of this study indicate that QUS parameters are sensitive to fat content in the liver. PMID:23062376

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.

Reversible fatty infiltration of the liver

International Nuclear Information System (INIS)

Bostel, F.; Hauger, W.

1987-01-01

Case studies show that acute pancreatitis occurring independently or combined with a preceding abuse of alcohol may be the cause of fatty infiltration of the liver. These fat areas can evolve in a very short time and provoke in the case of focal incidence diagnostic problems of differentiation against abscesses of metastases. Due to this fact and because of the rapid reversibility of the fatty infiltration under therapy, the safest method to clarify the situation consists of short-term CT controls. (orig.) [de

Serum paraoxonase-1 as biomarker for improved diagnosis of fatty liver in dairy cows.

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Farid, Ayman Samir; Honkawa, Kazuyuki; Fath, Eman Mohamed; Nonaka, Nariaki; Horii, Yoichiro

2013-04-11

Fatty liver is a major metabolic disorder in dairy cows and is believed to result in major economic losses in dairy farming due to decreased health status, reproductive performance and fertility. Currently, the definitive means for diagnosing fatty liver is determining the fat content of hepatic tissue by liver biopsy, which is an invasive and costly procedure, making it poorly suited to dairy farms. Therefore, the key aim of this study was to investigate the measurement of serum paraoxonase-1 (PON1), an enzyme exclusively synthesized by the liver, as a sensitive noninvasive biomarker for diagnosis of fatty liver in dairy cows. A comparative cohort study using serum specimens from Holstein-Friesian dairy cows (46 healthy and 46 fatty liver cases) was conducted. Serum PON1 (paraoxonase, lactonase and arylesterase) activity and other biochemical and hematological parameters were measured. We found that serum PON1 activity was lower (Pratio (+LR), negative likelihood ratio (-LR), diagnostic odd ratio (DOR) and overall diagnostic accuracy in diagnosing fatty liver. The present results indicate that addition of serum PON1 activity measurement to the biochemical profile could improve the diagnosis of fatty liver in dairy cows, which would have a considerable clinical impact and lead to greater profitability in the dairy industry.

Fatty liver disease--a practical guide for GPs.

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Iser, David; Ryan, Marno

2013-07-01

Non-alcoholic fatty liver disease (NAFLD), encompassing both simple steatosis and non-alcoholic steato-hepatitis (NASH), is the most common cause of liver disease in Australia. Non-alcoholic fatty liver disease needs to be considered in the context of the metabolic syndrome, as cardiovascular disease will account for much of the mortality associated with NAFLD. To provide an approach to the identification of NAFLD in general practice, the distinction between simple steatosis and NASH, and the management of these two conditions. Non-alcoholic steato-hepatitis is more common in the presence of diabetes, obesity, older age and increased inflammation, and is more likely to progress to cirrhosis. Cirrhosis may be complicated by hepatocellular carcinoma or liver failure. Hepatocellular carcinoma has also been described in NASH without cirrhosis. Assessment and treatment of features of the metabolic syndrome may reduce associated cardiovascular mortality. Numerous agents have been evaluated, but weight loss remains the only effective treatment for NAFLD.

Radiologic evaluation of nonalcoholic fatty liver disease

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Lee, Seung Soo; Park, Seong Ho

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is a frequent cause of chronic liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH)-related liver cirrhosis. Although liver biopsy is still the gold standard for the diagnosis of NAFLD, especially for the diagnosis of NASH, imaging methods have been increasingly accepted as noninvasive alternatives to liver biopsy. Ultrasonography is a well-established and cost-effective imaging technique for the diagnosis of hepatic steatosis, especially for screening a large population at risk of NAFLD. Ultrasonography has a reasonable accuracy in detecting moderate-to-severe hepatic steatosis although it is less accurate for detecting mild hepatic steatosis, operator-dependent, and rather qualitative. Computed tomography is not appropriate for general population assessment of hepatic steatosis given its inaccuracy in detecting mild hepatic steatosis and potential radiation hazard. However, computed tomography may be effective in specific clinical situations, such as evaluation of donor candidates for hepatic transplantation. Magnetic resonance spectroscopy and magnetic resonance imaging are now regarded as the most accurate practical methods of measuring liver fat in clinical practice, especially for longitudinal follow-up of patients with NAFLD. Ultrasound elastography and magnetic resonance elastography are increasingly used to evaluate the degree of liver fibrosis in patients with NAFLD and to differentiate NASH from simple steatosis. This article will review current imaging methods used to evaluate hepatic steatosis, including the diagnostic accuracy, limitations, and practical applicability of each method. It will also briefly describe the potential role of elastography techniques in the evaluation of patients with NAFLD. PMID:24966609

Ultrasonographic diagnosis of fatty liver in preoperative evaluation of living liver donor candidates: Histologic correlation

International Nuclear Information System (INIS)

Kim, Seong Hyun; Lee, Won Jae; Lim, Hyo Keun; Kim, Soo Ah; Kim, Seung Hoon; Lee, Soon Jin; Lim, Jae Hoon

2003-01-01

To analyze the correlation between the ultrasonographic (US) grading system of fatty liver (FL) and histologic grading system in living liver donor candidates and to investigate the clinical significance of this qualitative US grading system in the selection of living donor candidates. For a recent 21-month period, ninety three living donor candidates who underwent both preoperative US and parenchymal biopsy of the liver were consecutively selected. FL was ultrasonographically graded using the well-known three-Point grading system (ie, mild, moderate and severe degrees) whereas histologic grade of FL was divided into minimal ( 60%) degrees depending upon the percentages of each of macrovesicular, microvesicular and total fat-containing hepatocytes. US grade and histologic grade of FL in each patient were retrospectively correlated according to the US and pathologic records in their databases. Statistical analysis was conducted with the chi-square test and linear by linear association. US findings included the normal liver, mild FL, and moderate FL in 63, 23 and 7 patients, respectively. Analyzed with the total fat content, 38 of 63 patients (60%) whose US finding was normal proved to have FL of various histologic grades. Meanwhile, US grade of FL correlated well with the histologic grade in 16 (53%) of 30 patients who showed mild or moderate FL on US, and in the remaining patients, US grade was more commonly underestimated compared to the histologic grade. All patients with moderate FL on US Proved to have either moderate or severe FL at histology. US grade statistically correlated well with the histologic grade classified by either the total or macrovesicular fat contents (p<.001) while a poor correlation was seen when histologic grade using the microvesicular fat content was used. The well-known qualitative US grading system of fatty liver seems to show a relatively good correlation with the histologic grade, but it has a tendency to underestimate compared to the

Role of 3-Hydroxy Fatty Acid-Induced Hepatic Lipotoxicity in Acute Fatty Liver of Pregnancy

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Sathish Kumar Natarajan

2018-01-01

Full Text Available Acute fatty liver of pregnancy (AFLP, a catastrophic illness for both the mother and the unborn offspring, develops in the last trimester of pregnancy with significant maternal and perinatal mortality. AFLP is also recognized as an obstetric and medical emergency. Maternal AFLP is highly associated with a fetal homozygous mutation (1528G>C in the gene that encodes for mitochondrial long-chain hydroxy acyl-CoA dehydrogenase (LCHAD. The mutation in LCHAD results in the accumulation of 3-hydroxy fatty acids, such as 3-hydroxy myristic acid, 3-hydroxy palmitic acid and 3-hydroxy dicarboxylic acid in the placenta, which are then shunted to the maternal circulation leading to the development of acute liver injury observed in patients with AFLP. In this review, we will discuss the mechanistic role of increased 3-hydroxy fatty acid in causing lipotoxicity to the liver and in inducing oxidative stress, mitochondrial dysfunction and hepatocyte lipoapoptosis. Further, we also review the role of 3-hydroxy fatty acids in causing placental damage, pancreatic islet β-cell glucolipotoxicity, brain damage, and retinal epithelial cells lipoapoptosis in patients with LCHAD deficiency.

Role of 3-Hydroxy Fatty Acid-Induced Hepatic Lipotoxicity in Acute Fatty Liver of Pregnancy

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Ibdah, Jamal A.

2018-01-01

Acute fatty liver of pregnancy (AFLP), a catastrophic illness for both the mother and the unborn offspring, develops in the last trimester of pregnancy with significant maternal and perinatal mortality. AFLP is also recognized as an obstetric and medical emergency. Maternal AFLP is highly associated with a fetal homozygous mutation (1528G>C) in the gene that encodes for mitochondrial long-chain hydroxy acyl-CoA dehydrogenase (LCHAD). The mutation in LCHAD results in the accumulation of 3-hydroxy fatty acids, such as 3-hydroxy myristic acid, 3-hydroxy palmitic acid and 3-hydroxy dicarboxylic acid in the placenta, which are then shunted to the maternal circulation leading to the development of acute liver injury observed in patients with AFLP. In this review, we will discuss the mechanistic role of increased 3-hydroxy fatty acid in causing lipotoxicity to the liver and in inducing oxidative stress, mitochondrial dysfunction and hepatocyte lipoapoptosis. Further, we also review the role of 3-hydroxy fatty acids in causing placental damage, pancreatic islet β-cell glucolipotoxicity, brain damage, and retinal epithelial cells lipoapoptosis in patients with LCHAD deficiency. PMID:29361796

SREBP-1c overactivates ROS-mediated hepatic NF-κB inflammatory pathway in dairy cows with fatty liver.

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Li, Xinwei; Huang, Weikun; Gu, Jingmin; Du, Xiliang; Lei, Lin; Yuan, Xue; Sun, Guoquan; Wang, Zhe; Li, Xiaobing; Liu, Guowen

2015-10-01

Dairy cows with fatty liver are characterized by hepatic lipid accumulation and a severe inflammatory response. Sterol receptor element binding protein-1c (SREBP-1c) and nuclear factor κB (NF-κB) are components of the main pathways for controlling triglyceride (TG) accumulation and inflammatory levels, respectively. A previous study demonstrated that hepatic inflammatory levels are positively correlated with hepatic TG content. We therefore speculated that SREBP-1c might play an important role in the overactivation of the hepatic NF-κB inflammatory pathway in cows with fatty liver. Compared with healthy cows, cows with fatty liver exhibited severe hepatic injury and high blood concentrations of the inflammatory cytokines TNF-α, IL-6 and IL-1β. Hepatic SREBP-1c-mediated lipid synthesis and the NF-κB inflammatory pathway were both overinduced in cows with fatty liver. In vitro, treatment with non-esterified fatty acids (NEFA) further increased SREBP-1c expression and NF-κB pathway activation, which then promoted TG and inflammatory cytokine synthesis. SREBP-1c overexpression overactivated the NF-κB inflammatory pathway in hepatocytes by increasing ROS content and not through TLR4. Furthermore, SREBP-1c silencing decreased ROS content and further attenuated the activation of the NEFA-induced NF-κB pathway, thereby decreasing TNF-α, IL-6 and IL-1β synthesis. SREBP-1c-overexpressing mice exhibited hepatic steatosis and an overinduced hepatic NF-κB pathway. Taken together, these results indicate that SREBP-1c enhances the NEFA-induced overactivation of the NF-κB inflammatory pathway by increasing ROS in cow hepatocytes, thereby further increasing hepatic inflammatory injury in cows with fatty liver. Copyright © 2015. Published by Elsevier Inc.

Bicyclol attenuates tetracycline-induced fatty liver associated with inhibition of hepatic ER stress and apoptosis in mice.

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Yao, Xiao-Min; Li, Yue; Li, Hong-Wei; Cheng, Xiao-Yan; Lin, Ai-Bin; Qu, Jun-Ge

2016-01-01

Endoplasmic reticulum (ER) stress is known to be involved in the development of several metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). Tetracycline can cause hepatic steatosis, and ER stress may be involved in tetracycline-induced fatty liver. Our previous study showed that bicyclol has been proven to protect against tetracycline-induced fatty liver in mice, and ER stress may also be involved in bicyclol's hepatoprotective effect. Therefore, this study was performed to investigate the underlying mechanisms associated with ER stress and apoptosis, by which bicyclol attenuated tetracycline-induced fatty liver in mice. Bicyclol (300 mg/kg) was given to mice by gavage 3 times. Tetracycline (200 mg/kg, intraperitoneally) was injected at 1 h after the last dose of bicyclol. At 6 h and 24 h after single dose of tetracycline injection, serum ALT, AST, TG, CHO and hepatic histopathological examinations were performed to evaluate liver injuries. Hepatic steatosis was assessed by the accumulation of hepatic TG and CHO. Moreover, hepatic apoptosis and ER stress related markers were determined by TUNEL, real-time PCR, and western blot. As a result, bicyclol significantly protected against tetracycline-induced fatty liver as evidenced by the decrease of elevated serum transaminases and hepatic triglyceride, and the attenuation of histopathological changes in mice. In addition, bicyclol remarkably alleviated hepatic apoptosis and the gene expression of caspase-3, and increased the gene expression of XIAP. The gene expressions of ER stress-related markers, including CHOP, GRP78, IRE-1α, and ATF6, which were downregulated by bicyclol pretreatment in tetracycline-injected mice. These results suggested that bicyclol protected tetracycline-induced fatty liver partly due to its ability of anti-apoptosis associated with ER stress.

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

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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.

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

The Role of Tumor Necrosis Factor- alpha and Resistin in Nonalcoholic Fatty Liver Disease

International Nuclear Information System (INIS)

Alkady, M.M.

2011-01-01

Nonalcoholic fatty liver disease (NAFLD) represents one of the most common liver diseases. It is strongly associated with obesity and insulin resistance and is thought to be a part of the metabolic syndrome. It can progress from simple fatty liver to steatohepatitis, cirrhosis and liver failure. Adipocytokines, synthesized in adipose tissue, are involved in the pathophysiology of many acute and chronic liver diseases. The aim of this study was to investigate the role of Tumor Necrosis Factor-alpha (TNF-alpha) and resistin in the pathogenesis of NAFLD and their correlation to the severity of the disease. Serum concentration of TNF-alpha and resistin were measured in 20 patients with NAFLD and 20 healthy controls with ELISA method. The results of this study revealed that serum levels of both adipokines were significantly elevated in NAFLD patients than controls (P<0.01). Moreover, they were significantly higher in patients with nonalcoholic steatohepatitis than in patients with simple fatty liver. There was a significant positive correlation between TNF-alpha, resistin and each of AST, ALT and HOMA. Similarly, the results showed a significant positive correlation between the two studied adipokines, TNF-alpha and resistin (P<0.001). We conclude that TNF-alpha and resistin have a role in the pathogenesis of NAFLD and they may be promising markers for the progressin to steatohepatitis and inhibition of their activities by drugs may be a new approach for the treatment of NAFLD

Low Birthweight Increases the Likelihood of Severe Steatosis in Pediatric Non-Alcoholic Fatty Liver Disease.

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Bugianesi, Elisabetta; Bizzarri, Carla; Rosso, Chiara; Mosca, Antonella; Panera, Nadia; Veraldi, Silvio; Dotta, Andrea; Giannone, Germana; Raponi, Massimiliano; Cappa, Marco; Alisi, Anna; Nobili, Valerio

2017-08-01

Small for gestational age (SGA) is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD). Our aim was to investigate the correlation of birthweight with the severity of liver damage in a large cohort of children with NAFLD. Two hundred and eighty-eight consecutive Caucasian Italian overweight/obese children with biopsy-proven NAFLD were included in the study. We examined the relative association of each histological feature of NAFLD with metabolic alterations, insulin-resistance, I148M polymorphism in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, and birthweight relative to gestational age. In the whole NAFLD cohort, 12.2% of patients were SGA, 62.8% appropriate for gestational age (AGA), and 25% large for gestational age (LGA). SGA children had a higher prevalence of severe steatosis (69%) and severe portal inflammation (14%) compared with the AGA and LGA groups. Notably, severe steatosis (>66%) was decreasing from SGA to AGA and LGA, whereas the prevalence of moderate steatosis (33-66%) was similar in three groups. The prevalence of type 1 NAFLD is higher in the LGA group with respect to the other two groups (25% vs.5.2% vs.9.4%), whereas the SGA group shows a higher prevalence of overlap type (85.8%) with respect to the LGA group (51.4%) but not compared with the AGA group (75%). At multivariable regression analysis, SGA at birth increased fourfold the likelihood of severe steatosis (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.43-10.9, P=0.008) and threefold the likelihood of NAFLD Activity Score (NAS)≥5 (OR 2.98, 95% CI 1.06-8.33, P=0.037) independently of homeostasis model assessment of insulin resistance and PNPLA3 genotype. The PNPLA3-CC wild-type genotype was the strongest independent predictor of the absence of significant fibrosis (OR 0.26, 95% CI 0.13-0.52, P=<0.001). In children with NAFLD, the risk of severe steatosis is increased by SGA at birth, independent of and in addition to other

Genetic background in nonalcoholic fatty liver disease: A comprehensive review

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Macaluso, Fabio Salvatore; Maida, Marcello; Petta, Salvatore

2015-01-01

In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease. PMID:26494964

NON-ALCOHOLIC FATTY LIVER DISEASE AT OUR INSTITUTE

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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.

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

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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.

Validity criteria for the diagnosis of fatty liver by M probe-based controlled attenuation parameter.

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Wong, Vincent Wai-Sun; Petta, Salvatore; Hiriart, Jean-Baptiste; Cammà, Calogero; Wong, Grace Lai-Hung; Marra, Fabio; Vergniol, Julien; Chan, Anthony Wing-Hung; Tuttolomondo, Antonino; Merrouche, Wassil; Chan, Henry Lik-Yuen; Le Bail, Brigitte; Arena, Umberto; Craxì, Antonio; de Lédinghen, Victor

2017-09-01

Controlled attenuation parameter (CAP) can be performed together with liver stiffness measurement (LSM) by transient elastography (TE) and is often used to diagnose fatty liver. We aimed to define the validity criteria of CAP. CAP was measured by the M probe prior to liver biopsy in 754 consecutive patients with different liver diseases at three centers in Europe and Hong Kong (derivation cohort, n=340; validation cohort, n=414; 101 chronic hepatitis B, 154 chronic hepatitis C, 349 non-alcoholic fatty liver disease, 37 autoimmune hepatitis, 49 cholestatic liver disease, 64 others; 277 F3-4; age 52±14; body mass index 27.2±5.3kg/m 2 ). The primary outcome was the diagnosis of fatty liver, defined as steatosis involving ≥5% of hepatocytes. The area under the receiver-operating characteristics curve (AUROC) for CAP diagnosis of fatty liver was 0.85 (95% CI 0.82-0.88). The interquartile range (IQR) of CAP had a negative correlation with CAP (r=-0.32, psteatosis was lower among patients with body mass index ≥30kg/m 2 and F3-4 fibrosis. The validity of CAP for the diagnosis of fatty liver is lower if the IQR of CAP is ≥40dB/m. Lay summary: Controlled attenuation parameter (CAP) is measured by transient elastography (TE) for the detection of fatty liver. In this large study, using liver biopsy as a reference, we show that the variability of CAP measurements based on its interquartile range can reflect the accuracy of fatty liver diagnosis. In contrast, other clinical factors such as adiposity and liver enzyme levels do not affect the performance of CAP. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts.

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Ma, Jiantao; Fox, Caroline S; Jacques, Paul F; Speliotes, Elizabeth K; Hoffmann, Udo; Smith, Caren E; Saltzman, Edward; McKeown, Nicola M

2015-08-01

Non-alcoholic fatty liver disease affects ∼30% of US adults, yet the role of sugar-sweetened beverages and diet soda on these diseases remains unknown. We examined the cross-sectional association between intake of sugar-sweetened beverages or diet soda and fatty liver disease in participants of the Framingham Offspring and Third Generation cohorts. Fatty liver disease was defined using liver attenuation measurements generated from computed tomography in 2634 participants. Alanine transaminase concentration, a crude marker of fatty liver disease, was measured in 5908 participants. Sugar-sweetened beverage and diet soda intake were estimated using a food frequency questionnaire. Participants were categorized as either non-consumers or consumers (3 categories: 1 serving/month to sugar-sweetened beverages or diet soda. After adjustment for age, sex, smoking status, Framingham cohort, energy intake, alcohol, dietary fiber, fat (% energy), protein (% energy), diet soda intake, and body mass index, the odds ratios of fatty liver disease were 1, 1.16 (0.88, 1.54), 1.32 (0.93, 1.86), and 1.61 (1.04, 2.49) across sugar-sweetened beverage consumption categories (p trend=0.04). Sugar-sweetened beverage consumption was also positively associated with alanine transaminase levels (p trend=0.007). We observed no significant association between diet soda intake and measures of fatty liver disease. In conclusion, we observed that regular sugar-sweetened beverage consumption was associated with greater risk of fatty liver disease, particularly in overweight and obese individuals, whereas diet soda intake was not associated with measures of fatty liver disease. Copyright © 2015 European Association for the Study of the Liver. All rights reserved.

AMPK Re-Activation Suppresses Hepatic Steatosis but its Downregulation Does Not Promote Fatty Liver Development.

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Boudaba, Nadia; Marion, Allison; Huet, Camille; Pierre, Rémi; Viollet, Benoit; Foretz, Marc

2018-02-01

Nonalcoholic fatty liver disease is a highly prevalent component of disorders associated with disrupted energy homeostasis. Although dysregulation of the energy sensor AMP-activated protein kinase (AMPK) is viewed as a pathogenic factor in the development of fatty liver its role has not been directly demonstrated. Unexpectedly, we show here that liver-specific AMPK KO mice display normal hepatic lipid homeostasis and are not prone to fatty liver development, indicating that the decreases in AMPK activity associated with hepatic steatosis may be a consequence, rather than a cause, of changes in hepatic metabolism. In contrast, we found that pharmacological re-activation of downregulated AMPK in fatty liver is sufficient to normalize hepatic lipid content. Mechanistically, AMPK activation reduces hepatic triglyceride content both by inhibiting lipid synthesis and by stimulating fatty acid oxidation in an LKB1-dependent manner, through a transcription-independent mechanism. Furthermore, the effect of the antidiabetic drug metformin on lipogenesis inhibition and fatty acid oxidation stimulation was enhanced by combination treatment with small-molecule AMPK activators in primary hepatocytes from mice and humans. Overall, these results demonstrate that AMPK downregulation is not a triggering factor in fatty liver development but in contrast, establish the therapeutic impact of pharmacological AMPK re-activation in the treatment of fatty liver disease. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

The Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease

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Sanjoy Roychowdhury

2018-06-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is the leading cause of chronic liver disease, with prevalence increasing in parallel with the rising incidence in obesity. Believed to be a “multiple-hit” disease, several factors contribute to NAFLD initiation and progression. Of these, the gut microbiome is gaining interest as a significant factor in NAFLD prevalence. In this paper, we provide an in-depth review of the progression of NAFLD, discussing the mechanistic modes of hepatocyte injury and the potential role for manipulation of the gut microbiome as a therapeutic strategy in the prevention and treatment of NAFLD.

The Correlation of Sonographic Finding of Fatty Liver with Hematologic Examination and Body Fat Percentage

International Nuclear Information System (INIS)

Cheon, Hae Kyung; Lee, Tae Yong; Kim, Young Ran

2009-01-01

Ultrasonography has been used as a basic examination of a medical check up for prevention and diagnostics of diseases. Even the person who has no particular subjective symptoms can have a variety of diseases. Especially fatty liver is found in many cases. In this study, we tested 3582 persons who are in between the ages of 15 to 81 and observed that 1390 persons had fatty liver while 2192 persons are normal. We classified the grade of fatty liver and compared their life styles with the results of liver function test and BMI. The results are as follows. Ratio of the subjects who had a fatty liver is 38.8%. Male and female ratio was 46.2% and 24.2%. On the correlation among the fatty liver, the body mass index and the body fat, the average value of body mass index and body fat were significantly higher in the group of the fatty liver than in those of the normal liver. The influence of the related factor and the correlation on the fatty liver was shown that it was more related with the order of age, body mass index, triglyceride, ALT, body fat, sex, HDL-Cholesterol, LDL-Cholesterol, and GGT. The result of the ultrasonography carried out for the purpose of regular health check up indicates that even the 38.8% of those who was diagnosed as normal condition could have the fatty liver and have possibility of other diseases. Therefore, if there are any troubles related to liver function and lipid through hematologic examination or when practicing follow-up study with ultrasonography concerning the correlation relation between the body fat and dietary preference, alcohol consumption and exercise, the ultrasonography is definitely useful for prevention and treatment of diseases.

The Correlation of Sonographic Finding of Fatty Liver with Hematologic Examination and Body Fat Percentage

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Cheon, Hae Kyung [Dept. of Radiology, Sun General Hospital, Daejeon (Korea, Republic of); Lee, Tae Yong; Kim, Young Ran [Dept. of Preventive Medicine and Public Health College of Midicin, Chungnam National University, Daejeon (Korea, Republic of)

2009-12-15

Ultrasonography has been used as a basic examination of a medical check up for prevention and diagnostics of diseases. Even the person who has no particular subjective symptoms can have a variety of diseases. Especially fatty liver is found in many cases. In this study, we tested 3582 persons who are in between the ages of 15 to 81 and observed that 1390 persons had fatty liver while 2192 persons are normal. We classified the grade of fatty liver and compared their life styles with the results of liver function test and BMI. The results are as follows. Ratio of the subjects who had a fatty liver is 38.8%. Male and female ratio was 46.2% and 24.2%. On the correlation among the fatty liver, the body mass index and the body fat, the average value of body mass index and body fat were significantly higher in the group of the fatty liver than in those of the normal liver. The influence of the related factor and the correlation on the fatty liver was shown that it was more related with the order of age, body mass index, triglyceride, ALT, body fat, sex, HDL-Cholesterol, LDL-Cholesterol, and GGT. The result of the ultrasonography carried out for the purpose of regular health check up indicates that even the 38.8% of those who was diagnosed as normal condition could have the fatty liver and have possibility of other diseases. Therefore, if there are any troubles related to liver function and lipid through hematologic examination or when practicing follow-up study with ultrasonography concerning the correlation relation between the body fat and dietary preference, alcohol consumption and exercise, the ultrasonography is definitely useful for prevention and treatment of diseases.

Diet-induced metabolic hamster model of nonalcoholic fatty liver disease

Directory of Open Access Journals (Sweden)

Bhathena J

2011-06-01

Full Text Available Jasmine Bhathena, Arun Kulamarva, Christopher Martoni, Aleksandra Malgorzata Urbanska, Meenakshi Malhotra, Arghya Paul, Satya PrakashBiomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Québec, CanadaBackground: Obesity, hypercholesterolemia, elevated triglycerides, and type 2 diabetes are major risk factors for metabolic syndrome. Hamsters, unlike rats or mice, respond well to diet-induced obesity, increase body mass and adiposity on group housing, and increase food intake due to social confrontation-induced stress. They have a cardiovascular and hepatic system similar to that of humans, and can thus be a useful model for human pathophysiology.Methods: Experiments were planned to develop a diet-induced Bio F1B Golden Syrian hamster model of dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hamsters were fed a normal control diet, a high-fat/high-cholesterol diet, a high-fat/high-cholesterol/methionine-deficient/choline-devoid diet, and a high-fat/high-cholesterol/choline-deficient diet. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, atherogenic index, and body weight were quantified biweekly. Fat deposition in the liver was observed and assessed following lipid staining with hematoxylin and eosin and with oil red O.Results: In this study, we established a diet-induced Bio F1B Golden Syrian hamster model for studying dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hyperlipidemia and elevated serum glucose concentrations were induced using this diet. Atherogenic index was elevated, increasing the risk for a cardiovascular event. Histological analysis of liver specimens at the end of four weeks showed increased fat deposition in the liver of animals fed

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

Association of nonalcoholic fatty liver disease with low bone mass in postmenopausal women.

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Moon, Seong-Su; Lee, Young-Sil; Kim, Sung Woo

2012-10-01

Osteoporosis is a disease associated with insulin resistant states such as central obesity, diabetes, and metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is also increased in such conditions. However, little is known about whether osteoporosis and nonalcoholic fatty liver disease are etiologically related to each other or not. We examined whether bone mineral density (BMD) is associated with NAFLD in pre- and postmenopausal women. Four hundred eighty-one female subjects (216 premenopausal and 265 postmenopausal) were enrolled. Lumbar BMD was measured using dual-energy X-ray absorptiometry. Liver ultrasonography was done to check the severity of fatty liver. We excluded subjects with a secondary cause of liver disease. Blood pressure, lipid profile, fasting plasma glucose, alanine aminotransferase (ALT), aspartate aminotransferase, and body mass index were measured in every subject. Mean lumbar BMD was lower in subjects with NAFLD than those without NAFLD in postmenopausal women (0.98 ± 0.01 vs. 1.01 ± 0.02 g/cm², P = 0.046). Multiple correlation analysis revealed a significant association between mean lumbar BMD and NAFLD in postmenopausal subjects after adjusting for age, body mass index, ALT, smoking status, and alcohol consumption (β coefficient -0.066, 95% CI -0.105 to -0.027, P = 0.001). Even after adjusting the presence of metabolic syndrome, the significance was maintained (β coefficient -0.043, 95% CI -0.082 to -0.004, P = 0.031). Lumbar BMD is related with NAFLD in postmenopausal females. We suggest that postmenopausal women with NAFLD may have a higher risk of osteoporosis than those without.

Xenon-133 hepatic retention ratio: A useful index for fatty liver quantification

International Nuclear Information System (INIS)

Yeh, S.H.; Wu, L.C.; Wang, S.J.; Lin, H.C.; Liu, R.S.; Lee, S.D.; Wu, J.C.

1989-01-01

Xenon-133 hepatic retention ratio was developed for quantifying fatty liver. Data were acquired in frame mode in the hepatic region and both lung bases for 5 min after rebreathing 20 mCi of gaseous 133 Xe and for another 5 min during washout. Static [ 99m Tc]sulfur colloid liver imaging was performed with the patient in the identical position immediately after the ventilation study and data were stored for liver localization. A hepatic time-activity curve corrected for background activity was generated. The 133Xe retention ratio was derived by dividing the activity at 3.5 min after washout by the peak activity. The data of 16 controls and 20 patients with fatty liver were analyzed. The retention ratio (mean +/- s.d.) was greatly increased in patients with fatty infiltration (0.43 +/- 0.20 vs. 0.04 +/- 0.08 in controls, p less than 0.001). There was a strong positive correlation between the 133 Xe retention ratios and percentage of fat on biopsy as assessed by the amount of the liver tissue occupied by fat globules on H ampersand E stained sections. The 133 Xe hepatic retention ratio is a simple, accurate and clinically useful index of detecting, quantifying and managing fatty infiltration of the liver

Aspects of the regulation of long-chain fatty acid oxidation in bovine liver

International Nuclear Information System (INIS)

Jesse, B.W.; Emery, R.S.; Thomas, J.W.

1986-01-01

Factors involved in regulation of bovine hepatic fatty acid oxidation were examined using liver slices. Fatty acid oxidation was measured as the conversion of l-[ 14 C] palmitate to 14 CO 2 and total [ 14 C] acid-soluble metabolites. Extended (5 to 7 d) fasting of Holstein cows had relatively little effect on palmitate oxidation to acid-soluble metabolites by liver slices, although oxidation to CO 2 was decreased. Feeding a restricted roughage, high concentrate ration to lactating cows resulted in inhibition of palmitate oxidation. Insulin, glucose, and acetate inhibited palmitate oxidation by bovine liver slices. The authors suggest the regulation of bovine hepatic fatty acid oxidation may be less dependent on hormonally induced alterations in enzyme activity as observed in rat liver and more dependent upon action of rumen fermentation products or their metabolites on enzyme systems involved in fatty acid oxidation

Fatty liver disease and lifestyle in youngsters: diet, food intake frequency, exercise, sleep shortage and fashion.

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Trovato, Francesca M; Martines, Giuseppe Fabio; Brischetto, Daniela; Catalano, Daniela; Musumeci, Giuseppe; Trovato, Guglielmo M

2016-03-01

Fatty liver is associated with alcohol habits and/or overweight/obesity. We challenged several lifestyle features associated with fatty liver and, particularly, with non-alcoholic fatty liver disease (NAFLD). Among them, sleep shortage as a result of nightlife habits and a preference for plus-size fashion were assessed. The latter consists of fashionable plus-sized clothing for actual individuals' size and reflects a frequent attitude of some social or age groups, conceivably indicating more global and widespread trend and behaviour. We studied a group of 708 non-diabetic youngsters, 458 women and 250 men, 21.72 ± 3.71 years old (range 15-35 years), referred for minor digestive ailments for clinical assessment, ultrasound detection of fatty liver and nutritional counselling. Details of personal history regarding lifestyle, food intake frequency and alcohol intake, dietary and physical exercise profile, sleep duration and clothing preferences were recorded. The prevalence of NAFLD in this cohort of youngsters is 67/708 (9.4%). Even if it is quantitatively very low in both groups, the average alcohol intake, always below 20 g/day, is greater in NAFLD subjects (5.83 ± 4.32 g) vs. subjects with normal liver (2.02 ± 3.20 g). The number of meals/day and adherence to a Mediterranean diet profile are smaller in NAFLD subjects. By multiple regression, BMI, sedentary life, plus-sized clothing for their actual size, sleep shortage and lower frequency of daily food intake are associated with the presence of NAFLD. Onset and continuation of fatty liver disease, beyond food and exercise quantity and quality, with their effects on obesity, may also be associated with other aspects of lifestyle. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chronic Uridine Administration Induces Fatty Liver and Pre-Diabetic Conditions in Mice.

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Yasuyo Urasaki

Full Text Available Uridine is a pyrimidine nucleoside that exerts restorative functions in tissues under stress. Short-term co-administration of uridine with multiple unrelated drugs prevents drug-induced liver lipid accumulation. Uridine has the ability to modulate liver metabolism; however, the precise mechanism has not been delineated. In this study, long-term effects of uridine on liver metabolism were examined in both HepG2 cell cultures and C57BL/6J mice. We report that uridine administration was associated with O-GlcNAc modification of FOXO1, increased gluconeogenesis, reduced insulin signaling activity, and reduced expression of a liver-specific fatty acid binding protein FABP1. Long-term uridine feeding induced systemic glucose intolerance and severe liver lipid accumulation in mice. Our findings suggest that the therapeutic potentials of uridine should be designed for short-term acute administration.

Pediatric Non-Alcoholic Fatty Liver Disease

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Haley Bush

2017-06-01

Full Text Available Abstract: With the increase in the prevalence of obesity, non-alcoholic fatty liver disease (NAFLD has become among the leading causes of chronic liver disease in the pediatric age group. Once believed to be a “two-hit process”, it is now clear that the actual pathophysiology of NAFLD is complex and involves multiple pathways. Moreover, NAFLD is not always benign, and patients with non-alcoholic steatohepatitis (NASH are at increased risk of developing advanced stages of liver disease. It has also been shown that NAFLD is not only a liver disease, but is also associated with multiple extrahepatic manifestations, including cardiovascular diseases, type 2 diabetes, and low bone mineral density. Although the data is scarce in the pediatric population, some studies have suggested that long-term mortality and the requirement of liver transplantation will continue to increase in patients with NAFLD. More studies are needed to better understand the natural history of NAFLD, especially in the pediatric age group.

Fatty acid biosynthesis VII. Substrate control of chain-length of products synthesised by rat liver fatty acid synthetase

DEFF Research Database (Denmark)

Hansen, Heinz Johs. Max; Carey, E.M.; Dils, R.

1970-01-01

- 1. Gas-liquid and paper chromatography have been used to determine the chain-lengths of fatty acids synthesised by purified rat liver fatty acid synthetase from [1-14C]acetyl-CoA, [1,3-14C2]malonyl-CoA and from [1-14C]acetyl-CoA plus partially purified rat liver acetyl-CoA carboxylase. - 2....... A wide range (C4:0–C18:0) of fatty acids was synthesised and the proportions were modified by substrate concentrations in the same manner as for purified rabbit mammary gland fatty acid synthetase. - 3. The relative amount of radioactivity incorporated from added acetyl-CoA and malonyl-CoA depended...... of long-chain fatty acids was synthesised from carboxylated acetyl-CoA than from added malonyl-CoA. - 5. It is suggested that acetyl-CoA carboxylase may carboxylate acetate bound to fatty acid synthetase....

Comparison of fatty liver index with noninvasive methods for steatosis detection and quantification

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Zelber-Sagi, Shira; Webb, Muriel; Assy, Nimer; Blendis, Laurie; Yeshua, Hanny; Leshno, Moshe; Ratziu, Vlad; Halpern, Zamir; Oren, Ran; Santo, Erwin

2013-01-01

AIM: To compare noninvasive methods presently used for steatosis detection and quantification in nonalcoholic fatty liver disease (NAFLD). METHODS: Cross-sectional study of subjects from the general population, a subgroup from the First Israeli National Health Survey, without excessive alcohol consumption or viral hepatitis. All subjects underwent anthropometric measurements and fasting blood tests. Evaluation of liver fat was performed using four noninvasive methods: the SteatoTest; the fatty liver index (FLI); regular abdominal ultrasound (AUS); and the hepatorenal ultrasound index (HRI). Two of the noninvasive methods have been validated vs liver biopsy and were considered as the reference methods: the HRI, the ratio between the median brightness level of the liver and right kidney cortex; and the SteatoTest, a biochemical surrogate marker of liver steatosis. The FLI is calculated by an algorithm based on triglycerides, body mass index, γ-glutamyl-transpeptidase and waist circumference, that has been validated only vs AUS. FLI fatty liver. RESULTS: Three hundred and thirty-eight volunteers met the inclusion and exclusion criteria and had valid tests. The prevalence rate of NAFLD was 31.1% according to AUS. The FLI was very strongly correlated with SteatoTest (r = 0.91, P fatty liver by SteatoTest (≥ S2) and by FLI (≥ 60) was 0.74, which represented good agreement. The sensitivity of FLI vs SteatoTest was 85.5%, specificity 92.6%, positive predictive value (PPV) 74.7%, and negative predictive value (NPV) 96.1%. Most subjects (84.2%) with FLI fatty liver by HRI (≥ 1.5) and by FLI (≥ 60) was 0.43, which represented only moderate agreement. The sensitivity of FLI vs HRI was 56.3%, specificity 86.5%, PPV 57.0%, and NPV 86.1%. The diagnostic accuracy of FLI for steatosis > 5%, as predicted by SteatoTest, yielded an area under the receiver operating characteristic curve (AUROC) of 0.97 (95% CI: 0.95-0.98). The diagnostic accuracy of FLI for steatosis > 5%, as

Nondiffuse fatty infiltration of the liver: Does the uptake of iron-oxide increase or decrease at SPIO-enhanced MR imaging?

International Nuclear Information System (INIS)

Onoda, Hideko; Ito, Katsuyoshi; Tanabe, Masahiro; Shimizu, Ayame; Matsunaga, Naofumi

2011-01-01

Purpose: To clarify whether the uptake of SPIO increases or decreases in areas of fatty change compared with surrounding areas of nonfatty change at SPIO-enhanced MR imaging. Materials and methods: Approval for this retrospective study was obtained from our institutional review board. This study included 14 patients with nondiffuse fatty infiltration of the liver who underwent SPIO-enhanced MR imaging. Additionally, 30 patients without nondiffuse fatty infiltration of the liver were also evaluated. Results: Among 14 patients, areas of fatty change showed relatively high signal intensity in 7 patents, indicating decreased uptake of SPIO in areas of fatty change. In these 7 patients, 4 had mild cirrhosis and 3 did not have cirrhosis. The mean percentage of signal intensity loss (42%) of fatty areas was significantly lower (p < 0.007) than that of adjacent areas of nonfatty change (52%). In the remaining 7 of 14 patients, areas of fatty change showed relatively low signal intensity, indicating increased uptake of SPIO in areas of fatty change. Among these 7 patients, 6 had advanced cirrhosis. The mean percentage of signal intensity loss (47%) of fatty areas was significantly higher (p < 0.008) than that of adjacent areas of nonfatty change (31%). Conclusion: The uptake of SPIO generally decreased in areas of fatty change compared with normal liver parenchyma at SPIO-enhanced MR imaging. However, in patients with advanced cirrhosis, areas of fatty change shows relatively low signal intensity because the uptake of SPIO in surrounding areas of nonfatty change severely decreased probably due to liver fibrosis.

Anti-fatty liver effects of oils from Zingiber officinale and Curcuma longa on ethanol-induced fatty liver in rats.

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Nwozo, Sarah Onyenibe; Osunmadewa, Damilola Adeola; Oyinloye, Babatunji Emmanuel

2014-01-01

The present study is aimed at evaluating the protective effects of oils from Zingiber officinale (ginger) and Curcuma longa (turmeric) on acute ethanol-induced fatty liver in male Wistar rats. Ferric reducing antioxidant power activity and oxygen radical absorbance capacity of the oils were evaluated ex vivo. Rats were pretreated for 28 d with standard drug (Livolin Forte) and oils from Z. officinale and C. longa before they were exposed to 45% ethanol (4.8 g/kg) to induce acute fatty liver. Histological changes were observed and the degree of protection was measured by using biochemical parameters such as alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities. Serum triglyceride (TG) level, total cholesterol (TC) level and the effects of both oils on reduced gluthatione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) levels were estimated. Oils from Z. officinale and C. longa at a dose of 200 mg/kg showed hepatoprotection by decreasing the activities of serum enzymes, serum TG, serum TC and hepatic MDA, while they significantly restored the level of GSH as well as GST and SOD activities. Histological examination of rats tissues was related to the obtained results. From the results it may be concluded that oils from Z. officinale and C. longa (200 mg/kg) exhibited hepatoprotective activity in acute ethanol-induced fatty liver and Z. officinale oil was identified to have better effects than C. longa oil.

The gut microbiota of nonalcoholic fatty liver disease: current methods and their interpretation

NARCIS (Netherlands)

van Best, Niels; Jansen, Peter L.; Rensen, Sander S.

2015-01-01

The role of intestinal bacteria in the pathogenesis of nonalcoholic fatty liver disease is increasingly acknowledged. Recently developed microbial profiling techniques are beginning to shed light on the nature of gut microbiota alterations in nonalcoholic fatty liver disease. In this review, we

Sulfur Amino Acids in Diet-induced Fatty Liver: A New Perspective Based on Recent Findings

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John I. Toohey

2014-06-01

Full Text Available The relationship of sulfur amino acids to diet-induced fatty liver was established 80 years ago, with cystine promoting the condition and methionine preventing it. This relationship has renewed importance today because diet-induced fatty liver is relevant to the current epidemics of obesity, non-alcoholic fatty liver disease, metabolic syndrome, and type 2 diabetes. Two recent papers provide the first evidence linking sulfane sulfur to diet-induced fatty liver opening a new perspective on the problem. This review summarizes the early data on sulfur amino acids in fatty liver and correlates that data with current knowledge of sulfur metabolism. Evidence is reviewed showing that the lipotropic effect of methionine may be mediated by sulfane sulfur and that the hepatosteatogenic effect of cystine may be related to the removal of sulfane sulfur by cysteine catabolites. Possible preventive and therapeutic strategies are discussed.

Nonalcoholic Fatty Liver Disease: Prevalence, Influence on Age and Sex, and Relationship with Metabolic Syndrome and Insulin Resistance

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Hui-Yun Cheng

2013-12-01

Conclusion: Fatty liver can be considered as the hepatic consequence of metabolic syndrome, specifically IR. There is a high prevalence of metabolic syndrome and fatty liver among the elderly population. Metabolic disorders are closely related to fatty liver; moreover, fatty liver appears to be a good predictor for the clustering of risk factors for metabolic syndrome.

Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

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Oliveira C.P.M.S.

2006-01-01

Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

Impact of variations in fatty liver on sonographic detection of focal hepatic lesions originally identified by CT

OpenAIRE

Wu, Size; Tu, Rong; Nan, Ruixia; Liu, Guangqing; Cui, Xiaojing; Liang, Xian

2015-01-01

Purpose: The aim of this study was to investigate the influence of variations in fatty liver on the ultrasonographic detection of focal liver lesions. Methods: A total of 229 patients with varying degrees of fatty liver and focal liver lesions and 200 patients with focal liver lesions but no fatty liver were randomly selected for inclusion in groups I and II, respectively. Findings of focal liver lesions identified on computed tomography were taken as the reference, and findings on ultrasonog...

Clinical course of nonalcoholic fatty liver disease: an assessment of severity, progression, and outcomes

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Simeone JC

2017-12-01

Full Text Available Jason C Simeone,1 Jay P Bae,2 Byron J Hoogwerf,3 Qian Li,1 Axel Haupt,3 Ayad K Ali,4 Marilyn K Boardman,3 Beth L Nordstrom1 1Real-world Evidence, Evidera, Waltham, MA, USA; 2Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 3Lily Diabetes, Eli Lilly and Company, Indianapolis, IN, USA; 4Global Patient Safety, Eli Lilly and Company, Indianapolis, IN, USA Purpose: To identify the characteristics and initial disease severity of patients with nonalcoholic fatty liver disease (NAFLD and assess incidence and risk factors for disease progression in a retrospective study.Methods: Patients ≥18 years of age without alcoholism or other liver diseases (eg, hepatitis B/C were selected from Geisinger Health System electronic medical record data from 2004 to 2015. Initial disease stage was stratified into uncomplicated NAFLD, advanced fibrosis, cirrhosis, hepatocellular carcinoma (HCC, and liver transplant using clinical biomarkers, diagnosis, and procedure codes. Disease progression was defined as stage progression or death and analyzed via Kaplan–Meier plots and multistate models.Results: In the NAFLD cohort (N=18,754, 61.5% were women, 39.0% had type 2 diabetes mellitus (T2DM, and the mean body mass index was 38.2±10.2 kg/m2. At index, 69.9% had uncomplicated NAFLD, 11.7% had advanced fibrosis, and 17.8% had cirrhosis. Of 18,718 patients assessed for progression, 17.3% progressed (11.0% had stage progression, 6.3% died without evidence of stage progression during follow-up (median=842 days. Among subgroups, 12.3% of those without diabetes mellitus progressed vs 24.7% of those with T2DM. One-year mortality increased from 0.5% in uncomplicated NAFLD to 22.7% in HCC. After liver transplant, mortality decreased to 5.6% per year.Conclusions: In 2.3 years of follow-up, approximately 17% of patients progressed or died without evidence of stage progression. T2DM was associated with approximately twice the risk of

Correlation between Abdominal Fat Amount and Fatty Liver, using Liver to Kidney Echo Ratio on Ultrasound

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Park, Yanhg Shin; Lee, Chang Hee; Choi, Kyung Mook; Lee, Jong Mee; Choi, Jae Woong; Kim, Kyeong Ah; Park, Cheol Min [Korea University Guro Hospital, Korea University College of Medicine, Seoul (Korea, Republic of)

2012-08-15

It has been generally recognized that fatty liver can often be seen in the obese population. This study was conducted in order to evaluate the association between fatty liver and abdominal fat volume. A total of 105 patients who visited our obesity clinic in the recent three years underwent fat CT scans and abdominal US. Attenuation difference between liver and spleen on CT was considered as a reference standard for the diagnosis of fatty liver. On US, the echogenicity of the liver parenchyma was measured in three different regions of interest (ROI) close to the adjacent right kidney in the same slice, avoiding vessels, bile duct, and calcification. Similar measurements were performed in the right renal cortex. The mean values were calculated automatically on the histogram of the ROI using the PACS program. The hepatorenal echogenicity ratio (HER; mean hepatic echogenicity/ mean renal echogenicity) was then calculated. Abdominal fat volume was measured using a 3 mm slice CT scan at the L4/5 level and was calculated automatically using a workstation. Abdominal fat was classified according to total fat (TF), visceral fat (VF), and subcutaneous fat (SF). We used Pearson's bivariate correlation method for assessment of the correlation between HER and TF, VF, and SF, respectively. Significant correlation was observed between HER and abdominal fat (TF, VF, and SF). HER showed significant correlation with VF and TF (r = 0.491 and 0.402, respectively; p = 0.000). The correlation between HER and SF (r = 0.255, p = 0.009) was less significant than for VF or TF. Fat measurement (HER) by hepatic ultrasound correlated well with the amount of abdominal fat. In particular, the VF was found to show a stronger association with fatty liver than SF.

Correlation between Abdominal Fat Amount and Fatty Liver, using Liver to Kidney Echo Ratio on Ultrasound

International Nuclear Information System (INIS)

Park, Yanhg Shin; Lee, Chang Hee; Choi, Kyung Mook; Lee, Jong Mee; Choi, Jae Woong; Kim, Kyeong Ah; Park, Cheol Min

2012-01-01

It has been generally recognized that fatty liver can often be seen in the obese population. This study was conducted in order to evaluate the association between fatty liver and abdominal fat volume. A total of 105 patients who visited our obesity clinic in the recent three years underwent fat CT scans and abdominal US. Attenuation difference between liver and spleen on CT was considered as a reference standard for the diagnosis of fatty liver. On US, the echogenicity of the liver parenchyma was measured in three different regions of interest (ROI) close to the adjacent right kidney in the same slice, avoiding vessels, bile duct, and calcification. Similar measurements were performed in the right renal cortex. The mean values were calculated automatically on the histogram of the ROI using the PACS program. The hepatorenal echogenicity ratio (HER; mean hepatic echogenicity/ mean renal echogenicity) was then calculated. Abdominal fat volume was measured using a 3 mm slice CT scan at the L4/5 level and was calculated automatically using a workstation. Abdominal fat was classified according to total fat (TF), visceral fat (VF), and subcutaneous fat (SF). We used Pearson's bivariate correlation method for assessment of the correlation between HER and TF, VF, and SF, respectively. Significant correlation was observed between HER and abdominal fat (TF, VF, and SF). HER showed significant correlation with VF and TF (r = 0.491 and 0.402, respectively; p = 0.000). The correlation between HER and SF (r = 0.255, p = 0.009) was less significant than for VF or TF. Fat measurement (HER) by hepatic ultrasound correlated well with the amount of abdominal fat. In particular, the VF was found to show a stronger association with fatty liver than SF.

Initial study of quantitative analysis of fatty liver by 1H-MR spectroscopy imaging

International Nuclear Information System (INIS)

Liang Changhong; Liu Yubao; Zhang Zhonglin; Xie Shufei; Wang Qiushi

2007-01-01

Objective: To investigate the feasibility of 1 H-MR spectroscopy ( 1 H-MRS) imaging to quantitatively detect fatty liver. Methods: Twenty patients with fatty liver and 11 healthy volunteers underwent plain CT scan, conventional MR imaging and 1 H-MRS analysis. The blood lipid and liver function were tested on the same day as the MR examination. 1 H-MRS sequence measured the peaks of H 2 O and lipid, and the areas under the peaks. The relative contents of the lipid compound were calculated, and compared with the results of CT scan and liver function tests. Results: The CT values of the normal group and the fatty liver group were (59 ± 9) HU and (24 ± 11) HU respectively. On 1 H-MRS a protruding high H 2 O peak and a flat low lipid peak were observed in the normal group, while the protruding high H 2 O peak and a high lipid peak appeared in the fatty liver group. The values of lipid peak in the normal group and the fatty liver group were (0.05 ± 0.01) x l0 5 , (0.70 ± 0.24) x l0 5 respectively (t=4.32, P 5 , (1.85 ± 0.47) x l0 5 respectively (t=1.26, P>0.05), the areas under the lipid peak were (1.36 ± 0.73) x 10 9 , (2.35 ± 1.15) x 10 9 respectively (t=5.21, P 2 O peak were (4.33 ± 1.28) x 10 11 , (3.55 ± 0.94) x 10 11 respectively (t=2.04, P>0.05). Conclusion: 1 H-MRS imaging is feasible to quantitatively detect liver fat and is a non-invasive method for detecting early fatty liver. (authors)

Molecular pathways in non-alcoholic fatty liver disease

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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

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...

Increased circulating zonulin in children with biopsy-proven nonalcoholic fatty liver disease.

Science.gov (United States)

Pacifico, Lucia; Bonci, Enea; Marandola, Lidia; Romaggioli, Sara; Bascetta, Stefano; Chiesa, Claudio

2014-12-07

To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD). A case-control study was performed. Cases were 40 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (HFF ≥ 5%), and confirmed by liver biopsy with ≥ 5% of hepatocytes containing macrovesicular fat. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1) with the cases on age, gender, pubertal stage and as closely as possible on body mass index- standard deviation score. All participants underwent clinical examination, laboratory tests including zonulin, inflammatory and metabolic parameters, and MRI for measurement of HFF and visceral adipose tissue. Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD [median (interquartile range), 4.23 (3.18-5.89) vs 3.31 (2.05-4.63), P zonulin concentrations increased significantly with the severity of steatosis and the Spearman's coefficient revealed a positive correlation between zonulin values and steatosis (r = 0.372, P zonulin and lobular inflammation (P = 0.23), ballooning (P = 0.10), fibrosis score (P = 0.18), or presence of nonalcoholic steatohepatitis (P = 0.17). Within the entire study population, zonulin levels were positively associated with gamma-glutamyl transferase, 2-h insulin, HFF, and negatively associated with whole-body insulin sensitivity index (WBISI), after adjustment for age, gender and pubertal status. When the associations were restricted to the group of NAFLD patients, 2-h insulin, hepatic fat, and WBISI retained statistical significance. Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of

Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty liver disease

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Jiang, Pengtao [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101 (China); University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049 (China); Huang, Zhen [Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021 (China); Zhao, Hong, E-mail: zhaohong9@sina.com [Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021 (China); Wei, Taotao, E-mail: weitt@moon.ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101 (China)

2013-04-19

Highlights: •Free fatty acids exposure induces elevated autophagy. •H{sub 2}O{sub 2} inhibits autophagic flux through impairing the fusion between autophagosomes and lysosomes. •Inhibition of autophagy potentiates H{sub 2}O{sub 2}-induced cell death. -- Abstract: Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, but the pathogenesis of NAFLD is not fully clear. The aim of this study was to determine whether autophagy plays a role in the pathogenesis of NAFLD. We found that the levels of autophagy were elevated in hepatoma cells upon exposure to free fatty acids, as confirmed by the increase in the number of autophagosomes. However, exposure of hepatoma cells to H{sub 2}O{sub 2} and TNF-α, two typical “second hit” factors, increased the initiation of autophagy but inhibited the autophagic flux. The inhibition of autophagy sensitized cells to pro-apoptotic stimuli. Taken together, our results suggest that autophagy acts as a protective mechanism in the pathogenesis of NAFLD and that impairment of autophagy might induce more severe lesions of the liver. These findings will be a benefit to the understanding of the pathogenesis of NAFLD and might suggest a strategy for the prevention and cure of NAFLD.

Deregulation of fatty acid metabolism and cannabinoid receptors in liver of morbidly obese women with non-alcoholic fatty liver disease

OpenAIRE

Berlanga Bustos, Alba

2015-01-01

Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH), with the latter being more frequently progressive. Due to lipid accumulation in the human liver seems to be a crucial mechanism in the NAFLD pathogenesis, an improved understanding of the underlying mechanisms leading to the initial hepatic lipid accumulation could be of great interest for controlling the progression of NAFLD. It has also been repor...

Development of coaxial ultrasonic probe for fatty liver diagnostic system using ultrasonic velocity change

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Hori, Makoto; Yokota, Daiki; Aotani, Yuhei; Kumagai, Yuta; Wada, Kenji; Matsunaka, Toshiyuki; Morikawa, Hiroyasu; Horinaka, Hiromichi

2017-07-01

A diagnostic system for fatty liver at an early stage is needed because fatty liver is linked to metabolic syndrome. We have already proposed a fatty liver diagnosis method based on the temperature coefficient of ultrasonic velocity. In this study, we fabricated a coaxial ultrasonic probe by integrating two kinds of transducers for warming and signal detection. The diagnosis system equipped with the coaxial probe was applied to tissue-mimicking phantoms including the fat area. The fat content rates corresponding to the set rates of the phantoms were estimated by the ultrasonic velocity-change method.

Human germline hedgehog pathway mutations predispose to fatty liver.

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Guillen-Sacoto, Maria J; Martinez, Ariel F; Abe, Yu; Kruszka, Paul; Weiss, Karin; Everson, Joshua L; Bataller, Ramon; Kleiner, David E; Ward, Jerrold M; Sulik, Kathleen K; Lipinski, Robert J; Solomon, Benjamin D; Muenke, Maximilian

2017-10-01

Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations that affect this pathway. Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD. A combined mouse model of Hh signaling attenuation (Gli2 heterozygous null: Gli2 +/- ) and diet-induced NAFLD was used to examine aspects of NAFLD and hepatic gene expression profiles, including molecular markers of hepatic fibrosis and inflammation. Patients with HPE had a higher prevalence of liver steatosis compared to the general population, independent of obesity. Exposure of Gli2 +/- mice to fatty liver-inducing diets resulted in increased liver steatosis compared to wild-type mice. Similar to humans, this effect was independent of obesity in the mutant mice and was associated with decreased expression of pro-fibrotic and pro-inflammatory genes, and increased expression of PPARγ, a potent anti-fibrogenic and anti-inflammatory regulator. Interestingly, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2 +/- mice exposed to a high-fat diet. Our results indicate that germline mutations disrupting Hh signaling promotes liver steatosis, independent of obesity, with reduced fibrosis. While Hh signaling inhibition has been associated with a better NAFLD prognosis, further studies are required to evaluate the long-term effects of mutations affecting this pathway. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess fat deposition in the liver predominantly due to high calorie intake and a sedentary lifestyle. NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease.

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Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández-Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan

Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

A STUDY OF CLINICAL, BIOCHEMICAL AND SONOLOGICAL PROFILE OF NON-ALCOHOLIC FATTY LIVER DISEASE IN TYPE 2 DIABETES PATIENTS

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Ganga Prasad Uppalapati

2017-11-01

Full Text Available BACKGROUND The Prevalence of Diabetes is increasing worldwide and is expected to affect 57 million adults in India by 2025. Virtually, the entire spectrum of liver disease is seen in patients with type 2 diabetes. This includes NAFLD, NASH and cirrhosis. Nearly, 70- 80% of the diabetic subjects have been reported to have hepatic fat accumulation, referred to as NAFLD (Non Alcoholic Fatty Liver Disease. There are not enough studies done on hepatic status of diabetic patients in our country. Hence, this study aims to describe the hepatic profile of type 2 diabetic patients. The aim of the study is to assess the clinical, biochemical and sonological profile of fatty liver in type 2 diabetes patients. MATERIALS AND METHODS Type 2 diabetes patients who are attending medical OPD (n=118 were taken as subjects. They underwent liver function tests, blood glucose levels and assessed by ultrasound examination of abdomen. Their diabetic duration and treatment history was also recorded. RESULTS Age wise and sex wise comparison of the liver function tests did not reveal any significant difference. Comparing mean blood glucose between those with or without fatty liver did not reveal any significant difference. There was no clinically significant difference between liver enzyme parameters among patients with fatty liver and those without fatty liver (as assessed by ultrasonogram. Significant number of females developed fatty liver disease as compared to males. Obesity was found to have a significant association with fatty liver disease. Only 6 patients among 60 patients of those with normal or underweight showed fatty liver change as compared to 44 patients. Among 58 patients of those with overweight or obese patients showed fatty liver change (assessed by ultrasonogram. CONCLUSION Obese persons are at greater risk of developing NAFLD. Females have high risk of developing fatty liver disease when compared to males. No significant correlation was found between

Therapeutic Mechanisms of Bile Acids and Nor-Ursodeoxycholic Acid in Non-Alcoholic Fatty Liver Disease.

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Steinacher, Daniel; Claudel, Thierry; Trauner, Michael

2017-01-01

Non-alcoholic fatty liver disease is one of the most rapidly rising clinical problems in the 21st century. So far no effective drug treatment has been established to cure this disease. Bile acids (BAs) have a variety of signaling properties, which can be used therapeutically for modulating hepatic metabolism and inflammation. A side-chain shorted derivative of ursodeoxycholic acid (UDCA) is 24 nor-ursodeoxycholic acid (NorUDCA) and it represents a new class of drugs for treatment of liver diseases. NorUDCA has unique biochemical and therapeutic properties, since it is relatively resistant to conjugation with glycine or taurine compared to UDCA. NorUDCA undergoes cholehepatic shunting, resulting in ductular targeting, bicarbonate-rich hypercholeresis, and cholangiocyte protection. Furthermore, it showed anti-fibrotic, anti-inflammatory, and anti-lipotoxic properties in several animal models. As such, NorUDCA is a promising new approach in the treatment of cholestatic and metabolic liver diseases. This review is a summary of current BA-based therapeutic approaches in the treatment of the fatty liver disease. © 2017 S. Karger AG, Basel.

Ultrasonographic Quantification of Fat Content in Fatty Liver Phantoms

International Nuclear Information System (INIS)

Kim, Il Young; Kim, Pyo Nyun; Joo, Gyung Soo; Kim, Ho Jung; Kim, Young Beom; Lee, Byoung Ho

1995-01-01

Assuming that the fat content of certain tissue might be quantified by measurirrg the ultrasound echo level, we analyzed the ultrasound histograms obtained from the fatty liver phantoms that contained various amount of fat. Various amount of margarine(Mazola. Cliff wood. USA) was mixed with 2% of agarin solution state to produce fatty liver phantoms that contained 5, 10, 20, 30 and 40% of fat. We obtained ultrasound histogram from each fatty liver phantom in gel state. We used 2% agar gel as a control. The ultrasound histograms from the control phantom showed gradual increase in echo level as the depth from the surface increased. The echo level from the phantom that contained 5% of fat showed gradual increase and subsequent decrease with the peak echo level at the depth of 3cm. The echo levels from the phantoms that contained more in 5% of fat gradually decreased as the depth from the surface increased; the change becoming more pronounced as the fat content of the phantom increased. The echo levels measured at the depth of 1cm were 9.3(control), 29.6(5%phantom), 3l.3 (10% phantom), 26.3 (20% phantom), l8.8 (30% phantom), and l6dB (40% phantom). Fat content of fatty phantoms can not be quantified by measuring only echo level. Simultaneous measurement of attenuation of ultrasound, which is not easy to do and not done in this study, is prerequisite to quantify fat content

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

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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.

Focus on Therapeutic Strategies of Nonalcoholic Fatty Liver Disease

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Marilena Durazzo

2012-01-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease in the Western world (it affects 30% of the general adult population. The NAFLD encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH, defined by steatosis, hepatocellular damage, and lobular inflammation in individuals without significant alcohol consumption and negative viral, congenital, and autoimmune liver disease markers. Currently, NAFLD is considered an emerging epidemic in light of the dramatic increase in obesity rates. With the progressive nature of NASH and its rising prevalence there is a significant need for a specific and targeted treatments since to date there has not been any validated therapies for NAFLD other than weight loss, which is well known to have a poor long-term success rate. In recent years, visceral adipose tissue has taken an important role in NAFLD pathogenesis, and current therapeutic approaches aim at reducing visceral obesity and free fatty acid overflow to the liver. This paper is focused on the treatments used for NAFLD and the potential new therapy.

[Effects of three Wenyang Jianpi Tang on cell proliferation and apoptosis of nonalcoholic fatty liver cells].

Science.gov (United States)

Yang, Jia-Yao; Tao, Dong-Qing; Liu, Song; Zhang, Shu; Ma, Wei; Shi, Zhao-Hong

2017-04-01

To investigate the effects of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang on the cell proliferation and apoptosis of nonalcoholic fatty liver cells through the nonalcoholic fatty liver cell model established by inducing L02 cells with oleic acid. Different concentrations of oleic acid were added into L02 cells to induce the nonalcoholic fatty liver cell model. Oil red O staining was used to observe fatty droplets of fatty liver cells. Automatic biochemical analyzer was used to detect the levels of aspartic transaminase(AST), alanine aminotransferase(ALT), total cholesterol(TC), and triglyceride(TG) in the cell supernatants. There were five groups, namely normal group, model group, model and Sijunzi Tang group, model and Lizhong Tang group, and model and Fuzi Lizhong Tang group. The cell proliferation and apoptosis of the five groups were detected by MTT colorimetry test and flow cytometer. The expressions of PCNA, cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax and Bcl-2 proteins of the five groups were detected by Western blot. The oil red O staining results showed that the optimum concentration of oleic acid that was used to induce nonalcoholic fatty liver cell models was 80 mg•L-1. The levels of AST, ALT, TC and TG in the nonalcoholic fatty liver cell supernatants were higher than that in normal liver cell supernatants(PTang, Lizhong Tang and Fuzi Lizhong Tang could effectively promote the cell proliferation, and inhibit the cellular apoptosis of nonalcoholic fatty liver cells(PTang showed the best effect. Western blot results showed that Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could down-regulate the expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9 and Bax proteins, and up-regulate the expressions of PCNA and Bcl-2 proteins of nonalcoholic fatty liver cells. And Fuzi Lizhong Tang showed the best effect. In conclusion, all of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could effectively promote the cell

Nine-year incident diabetes is predicted by fatty liver indices: the French D.E.S.I.R. study

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Vol Sylviane

2010-06-01

Full Text Available Abstract Background Fatty liver is known to be linked with insulin resistance, alcohol intake, diabetes and obesity. Biopsy and even scan-assessed fatty liver are not always feasible in clinical practice. This report evaluates the predictive ability of two recently published markers of fatty liver: the Fatty Liver Index (FLI and the NAFLD fatty liver score (NAFLD-FLS, for 9-year incident diabetes, in the French general-population cohort: Data from an Epidemiological Study on the Insulin Resistance syndrome (D.E.S.I.R. Methods At baseline, there were 1861 men and 1950 women, non-diabetic, aged 30 to 65 years. Over the follow-up, 203 incident diabetes cases (140 men, 63 women were identified by diabetes-treatment or fasting plasma glucose ≥ 7.0 mmol/l. The FLI includes: BMI, waist circumference, triglycerides and gamma glutamyl transferase, and the NAFLD-FLS: the metabolic syndrome, diabetes, insulin, alanine aminotransferase, and asparate aminotransferase. Logistic regression was used to determine the odds ratios for incident diabetes associated with categories of the fatty liver indices. Results In comparison to those with a FLI Conclusions These fatty liver indexes are simple clinical tools for evaluating the extent of liver fat and they are predictive of incident diabetes. Physicians should screen for diabetes in patients with fatty liver.

Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice

International Nuclear Information System (INIS)

Gao, Jialin; Zhang, Yao; Yu, Cui; Tan, Fengbiao; Wang, Lizhuo

2016-01-01

Sidt2 is a newly discovered lysosomal membrane protein that is closely related to glucose metabolism. In the present study, we found that Sidt2 is also closely related to lipid metabolism. Gradual increases in serum triglyceride (TG) and free fatty acid, as well as elevated aspartate transaminase and alanine transaminase levels were observed in Sidt2"−"/"− mice fed a normal diet from the age of 3 months, suggesting the presence of lipid metabolism disorders and impaired liver function in these mice. In the liver slices of 6-month-old Sidt2"−"/"− mice, there were obvious fat degeneration and inflammatory changes. Almost all of the liver cells demonstrated different levels of lipid droplet accumulation and cell swelling, and some of the cells demonstrated balloon-like changes. Infiltration of inflammatory cells was observed in the portal area and hepatic lobule. Electron microscopy showed that macrophages tended to be attached to the endothelial cells, and a large number of lipid droplets were present in the liver cells. Oil red O staining showed that there were significantly increased number of deep straining particles in the liver cells of Sidt2"−"/"− mice, and the TG content in liver tissue was also significantly increased. Detection of key genes and proteins related to fat synthesis showed that mRNA and protein levels of the SREBP1c in the liver of Sidt2"−"/"− mice were significantly elevated, and the downstream genes acetyl-CoA carboxylase, fatty acid synthase, and mitochondrial glycerol 3-phosphate acyltransferase were significantly upregulated. In addition, there was severe endoplasmic reticulum stress (ERS) in the liver of Sidt2"−"/"− mice, which had significantly increased levels of markers specific for unfolded protein response activation, Grp78 and CHOP, as well as significant elevation of downstream p-PERK, p-eIF2a, p-IRE1a, along with ER damage. These results suggest that Sidt2"−"/"− mice had spontaneous nonalcoholic fatty liver

Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice

Energy Technology Data Exchange (ETDEWEB)

Gao, Jialin [Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical College, Wuhu, 241002 (China); Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Zhang, Yao [Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Department of Biochemistry and Molecular Biology, Wannan Medical Collage, Wuhu, 241002 (China); Yu, Cui [Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical College, Wuhu, 241002 (China); Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Tan, Fengbiao [Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Department of Biochemistry and Molecular Biology, Wannan Medical Collage, Wuhu, 241002 (China); Wang, Lizhuo, E-mail: 19277924@qq.com [Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001 (China); Department of Biochemistry and Molecular Biology, Wannan Medical Collage, Wuhu, 241002 (China)

2016-08-05

Sidt2 is a newly discovered lysosomal membrane protein that is closely related to glucose metabolism. In the present study, we found that Sidt2 is also closely related to lipid metabolism. Gradual increases in serum triglyceride (TG) and free fatty acid, as well as elevated aspartate transaminase and alanine transaminase levels were observed in Sidt2{sup −/−} mice fed a normal diet from the age of 3 months, suggesting the presence of lipid metabolism disorders and impaired liver function in these mice. In the liver slices of 6-month-old Sidt2{sup −/−} mice, there were obvious fat degeneration and inflammatory changes. Almost all of the liver cells demonstrated different levels of lipid droplet accumulation and cell swelling, and some of the cells demonstrated balloon-like changes. Infiltration of inflammatory cells was observed in the portal area and hepatic lobule. Electron microscopy showed that macrophages tended to be attached to the endothelial cells, and a large number of lipid droplets were present in the liver cells. Oil red O staining showed that there were significantly increased number of deep straining particles in the liver cells of Sidt2{sup −/−} mice, and the TG content in liver tissue was also significantly increased. Detection of key genes and proteins related to fat synthesis showed that mRNA and protein levels of the SREBP1c in the liver of Sidt2{sup −/−} mice were significantly elevated, and the downstream genes acetyl-CoA carboxylase, fatty acid synthase, and mitochondrial glycerol 3-phosphate acyltransferase were significantly upregulated. In addition, there was severe endoplasmic reticulum stress (ERS) in the liver of Sidt2{sup −/−} mice, which had significantly increased levels of markers specific for unfolded protein response activation, Grp78 and CHOP, as well as significant elevation of downstream p-PERK, p-eIF2a, p-IRE1a, along with ER damage. These results suggest that Sidt2{sup −/−} mice had spontaneous

The Role of Lipid and Lipoprotein Metabolism in Non‐Alcoholic Fatty Liver Disease

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Francesco Massimo Perla

2017-06-01

Full Text Available Due to the epidemic of obesity across the world, nonalcoholic fatty liver disease (NAFLD has become one of the most prevalent chronic liver disorders in children and adolescents. NAFLD comprises 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 NAFLD and may progress to nonalcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. The mechanism of the liver injury in NAFLD is currently thought to be a “multiple-hit process” where the first “hit” is an increase in liver fat, followed by multiple additional factors that trigger the inflammatory activity. At the onset of disease, NAFLD is characterized by hepatic triglyceride accumulation and insulin resistance. Liver fat accumulation is associated with increased lipotoxicity from high levels of free fatty acids, free cholesterol and other lipid metabolites. As a consequence, mitochondrial dysfunction with oxidative stress and production of reactive oxygen species and endoplasmic reticulum stress-associated mechanisms, are activated. The present review focuses on the relationship between intra-cellular lipid accumulation and insulin resistance, as well as on lipid and lipoprotein metabolism in NAFLD.

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)

Fat content, fatty acid pattern and iron content in livers of turkeys with hepatic lipidosis.

Science.gov (United States)

Visscher, Christian; Middendorf, Lea; Günther, Ronald; Engels, Alexandra; Leibfacher, Christof; Möhle, Henrik; Düngelhoef, Kristian; Weier, Stefan; Haider, Wolfram; Radko, Dimitri

2017-05-30

The so-called "hepatic lipidosis" in turkeys is an acute progressive disease associated with a high mortality rate in a very short time. Dead animals show a massive fatty degeneration of the liver. The cause is still unclear. Previous findings suggest that there may be parallels to human non-alcoholic fatty liver disease. The object of the study was to examine the changes in the fat contents, the fatty acid composition and the iron content in livers of animals, which have died from hepatic lipidosis. The conspicuous livers (n = 85) were collected from 20 flocks where the phenomenon of massive increased animal losses accompanied by marked macroscopically visible pathological liver steatosis suddenly occurred. For comparison and as a reference, livers (n = 16) of two healthy flocks were taken. Healthy and diseased flocks were fed identical diets concerning official nutrient recommendations and were operating under standardized, comparable conventional conditions. Compared to livers of healthy animals, in the livers of turkeys died from hepatic lipidosis there were found massively increased fat levels (130 ± 33.2 vs. 324 ± 101 g/kg dry matter-DM). In all fatty livers, different fatty acids concentrations were present in significantly increased concentrations compared to controls (palmitic acid: 104 g/kg DM, +345%; palmitoleic acid: 18.0 g/kg DM, + 570%; oleic acid: 115 g/kg DM, +437%). Fatty acids concentrations relevant for liver metabolism and inflammation were significantly reduced (arachidonic acid: 2.92 g/kg DM, -66.6%; eicosapentaenoic acid: 0.141 g/kg DM, -78.3%; docosahexaenoic acid: 0.227 g/kg DM, -90.4%). The ratio of certain fatty acids to one another between control and case livers changed analogously to liver diseases in humans (e.g.: C18:0/C16:0 - 0.913 against 0.311; C16:1n7/C16:0 - 0.090 against 0.165; C18:1/C18:0 - 0.938 against 4.03). The iron content in the liver tissue also increased massively (271 ± 51.5 vs 712 ± 214 mg/kg DM). The hepatic

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

An investigation of the prevalence rate of fatty liver disease among people undergoing physical examination in Tangshan, China

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MENG Yulin

2017-12-01

Full Text Available ObjectiveTo investigate the prevalence rate of fatty liver disease among people undergoing physical examination in Tangshan, China, and to provide a reasonable basis for the prevention and treatment of fatty liver disease. MethodsThe clinical data of 12 808 individuals who underwent physical examination in Tangshan from March 2014 to February 2016 were collected, and among these individuals, 3540 had fatty liver disease. The data including age, sex, body mass index (BMI, fasting plasma glucose (FPG, total cholesterol (TC, triglyceride (TG, low-density lipoprotein cholesterol (LDL-C, and liver ultrasound findings were analyzed. The t-test was used for comparison of continuous data between groups and the chi-square test was used for comparison of categorical data between groups. Results Of all 7151 male individuals who underwent physical examination, 2750 (38.46% had fatty liver disease, and of all 5657 female individuals, 790 (13.96% had fatty liver disease; there was a significant difference in the prevalence rate of fatty liver disease between male and female individuals (χ2=947.25, P＜0.01. There was a significant difference in the detection rate of fatty liver disease between male and female individuals in each age group of 18-29, 30-39, 40-49, and ≥50 years (χ2=337.58, 474.06, 449.38, and 12.86, all P＜0.01. There was a significant difference in the detection rate of fatty liver disease between male or female individuals with different BMIs ［obese (BMI ≥28, overweight (24≤BMI＜28, and normal (BMI＜24］ (χ2=1104.01 and 500.23, both P＜0.01. In the three groups of obese (BMI ≥28, overweight (24≤BMI＜28, and normal (BMI＜24 individuals who underwent physical examination, there was a significant difference in the detection rate of fatty liver disease between male and female individuals in each group (χ2=71.24, 87.97, and 323.84, all P＜0.01. Male and female individuals with obesity (BMI ≥28 and overweight (24�

Nonalcoholic Fatty Liver Disease: Focus on Lipoprotein and Lipid Deregulation

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Klementina Fon Tacer

2011-01-01

Full Text Available Obesity with associated comorbidities is currently a worldwide epidemic and among the most challenging health conditions in the 21st century. A major metabolic consequence of obesity is insulin resistance which underlies the pathogenesis of the metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD is the hepatic manifestation of obesity and metabolic syndrome. It comprises a disease spectrum ranging from simple steatosis (fatty liver, through nonalcoholic steatohepatitis (NASH to fibrosis, and ultimately liver cirrhosis. Abnormality in lipid and lipoprotein metabolism accompanied by chronic inflammation is the central pathway for the development of metabolic syndrome-related diseases, such as atherosclerosis, cardiovascular disease (CVD, and NAFLD. This paper focuses on pathogenic aspect of lipid and lipoprotein metabolism in NAFLD and the relevant mouse models of this complex multifactorial disease.

Nonalcoholic Fatty Liver Disease: Noninvasive Methods of Diagnosing Hepatic Steatosis

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AlShaalan, Rasha; Aljiffry, Murad; Al-Busafi, Said; Metrakos, Peter; Hassanain, Mazen

2015-01-01

Hepatic steatosis is the buildup of lipids within hepatocytes. It is the simplest stage in nonalcoholic fatty liver disease (NAFLD). It occurs in approximately 30% of the general population and as much as 90% of the obese population in the United States. It may progress to nonalcoholic steatohepatitis, which is a state of hepatocellular inflammation and damage in response to the accumulated fat. Liver biopsy remains the gold standard tool to diagnose and stage NAFLD. However, it comes with the risk of complications ranging from simple pain to life-threatening bleeding. It is also associated with sampling error. For these reasons, a variety of noninvasive radiological markers, including ultrasound, computed tomography, magnetic resonance spectroscopy, and the controlled attenuation parameter using transient elastography and Xenon-133 scan have been proposed to increase our ability to diagnose NAFLD, hence avoiding liver biopsy. The aim of this review is to discuss the utility and accuracy of using available noninvasive diagnostic modalities for fatty liver in NAFLD. PMID:25843191

Coffee and non-alcoholic fatty liver disease: brewing evidence for hepatoprotection?

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Chen, Shaohua; Teoh, Narci C; Chitturi, Shiv; Farrell, Geoffrey C

2014-03-01

Coffee is one of the most popular beverages in the world. Several studies consistently show that coffee drinkers with chronic liver disease have a reduced risk of cirrhosis and a lower incidence of hepatocellular carcinoma regardless of primary etiology. With the increasing prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide, there is renewed interest in the effect of coffee intake on NAFLD severity and positive clinical outcomes. This review gives an overview of growing epidemiological and clinical evidence which indicate that coffee consumption reduces severity of NAFLD. These studies vary in methodology, and potential confounding factors have not always been completely excluded. However, it does appear that coffee, and particular components other than caffeine, reduce NAFLD prevalence and inflammation of non-alcoholic steatohepatitis. Several possible mechanisms underlying coffee's hepatoprotective effects in NAFLD include antioxidative, anti-inflammatory, and antifibrotic effects, while a chemopreventive effect against hepatocarcinogenesis seems likely. The so-far limited data supporting such effects will be discussed, and the need for further study is highlighted. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Assessment of Liver Viscoelasticity for the Diagnosis of Early Stage Fatty Liver Disease Using Transient Elastography

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Remenieras, Jean-Pierre; Dejobert, Maelle; Bastard, Cécile; Miette, Véronique; Perarnau, Jean-Marc; Patat, Frédéric

Nonalcoholic fatty liver disease (NAFLD) is characterized by accumulation of fat within the Liver. The main objective of this work is (1) to evaluate the feasibility of measuring in vivo in the liver the shear wave phase velocity dispersion cs(ω) between 20 Hz and 90 Hz using vibration-controlled transient elastography (VCTE); (2) to estimate through the rheological Kelvin-Voigt model the shear elastic μ and shear viscosity η modulus; (3) to correlate the evolution of these viscoelastic parameters on two patients at Tours Hospital with the hepatic fat percentage measured with T1-weighted gradient-echo in-and out-phase MRI sequence. For the first volunteer who has 2% of fat in the liver, we obtained μ = 1233 ± 133 Pa and η = 0.5 ± 0.4 Pa.s. For the patient with 22% of fat, we measure μ = 964 ± 91 Pa and η = 1.77 ± 0.3 Pa.s. In conclusion, this novel method showed to be sensitive in characterizing the visco-elastic properties of fatty liver.

Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level.

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Sookoian, Silvia; Castaño, Gustavo O; Scian, Romina; Fernández Gianotti, Tomas; Dopazo, Hernán; Rohr, Cristian; Gaj, Graciela; San Martino, Julio; Sevic, Ina; Flichman, Diego; Pirola, Carlos J

2016-02-01

Extensive epidemiologic studies have shown that cardiovascular disease and the metabolic syndrome (MetS) are associated with serum concentrations of liver enzymes; however, fundamental characteristics of this relation are currently unknown. We aimed to explore the role of liver aminotransferases in nonalcoholic fatty liver disease (NAFLD) and MetS. Liver gene- and protein-expression changes of aminotransferases, including their corresponding isoforms, were evaluated in a case-control study of patients with NAFLD (n = 42), which was proven through a biopsy (control subjects: n = 10). We also carried out a serum targeted metabolite profiling to the glycolysis, gluconeogenesis, and Krebs cycle (n = 48) and an exploration by the next-generation sequencing of aminotransferase genes (n = 96). An in vitro study to provide a biological explanation of changes in the transcriptional level and enzymatic activity of aminotransferases was included. Fatty liver was associated with a deregulated liver expression of aminotransferases, which was unrelated to the disease severity. Metabolite profiling showed that serum aminotransferase concentrations are a signature of liver metabolic perturbations, particularly at the amino acid metabolism and Krebs cycle level. A significant and positive association between systolic hypertension and liver expression levels of glutamic-oxaloacetic transaminase 2 (GOT2) messenger RNA (Spearman R = 0.42, P = 0.03) was observed. The rs6993 located in the 3' untranslated region of the GOT2 locus was significantly associated with features of the MetS, including arterial hypertension [P = 0.028; OR: 2.285 (95% CI: 1.024, 5.09); adjusted by NAFLD severity] and plasma lipid concentrations. In the context of an abnormal hepatic triglyceride accumulation, circulating aminotransferases rise as a consequence of the need for increased reactions of transamination to cope with the liver metabolic derangement that is associated with greater gluconeogenesis and

High coffee intake is associated with lower grade nonalcoholic fatty liver disease: the role of peripheral antioxidant activity.

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Gutiérrez-Grobe, Ylse; Chávez-Tapia, Norberto; Sánchez-Valle, Vicente; Gavilanes-Espinar, Juan Gabriel; Ponciano-Rodríguez, Guadalupe; Uribe, Misael; Méndez-Sánchez, Nahum

2012-01-01

Some phytochemicals present in coffee have a potential antioxidant role which seems to protect the human body against cardiovascular diseases, liver disease and malignancies. Nonalcoholic fatty liver disease is a common disease with limited therapeutic options. This study investigated the antioxidant effect of coffee by measuring antioxidant enzymes and lipid peroxidation markers in patients with nonalcoholic fatty liver disease. We performed a case-control study at the University Hospital, Mexico City. Anthropometric, metabolic, dietary and biochemical variables of all patients were determined and compared. The presence of nonalcoholic fatty liver disease was established by ultrasonography. All patients completed a dietary questionnaire in order to determine their of coffee consumption. Catalase, superoxide dismutase and thiobarbituric acid reactive substances were measured in all of the patients. Seventy-three subjects with and 57 without nonalcoholic fatty liver disease were included. Patients with nonalcoholic fatty liver disease had significantly higher body mass index, blood glucose, homeostasis model of assessment-insulin resistance and insulin values in comparison to patients without nonalcoholic fatty liver disease. On the one hand, there was a significant difference in coffee intake between the groups (p coffee has a protective effect against nonalcoholic fatty liver disease however there was no significant difference in the antioxidant variables analyzed.

Fat content, fatty acid pattern and iron content in livers of turkeys with hepatic lipidosis

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Visscher, Christian; Middendorf, Lea; G?nther, Ronald; Engels, Alexandra; Leibfacher, Christof; M?hle, Henrik; D?ngelhoef, Kristian; Weier, Stefan; Haider, Wolfram; Radko, Dimitri

2017-01-01

Background The so-called ?hepatic lipidosis? in turkeys is an acute progressive disease associated with a high mortality rate in a very short time. Dead animals show a massive fatty degeneration of the liver. The cause is still unclear. Previous findings suggest that there may be parallels to human non-alcoholic fatty liver disease. The object of the study was to examine the changes in the fat contents, the fatty acid composition and the iron content in livers of animals, which have died from...

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

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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

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

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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

Gender and racial differences in nonalcoholic fatty liver disease.

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Pan, Jen-Jung; Fallon, Michael B

2014-05-27

Due to the worldwide epidemic of obesity, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of elevated liver enzymes. NAFLD represents a spectrum of liver injury ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which may progress to advanced fibrosis and cirrhosis. Individuals with NAFLD, especially those with metabolic syndrome, have higher overall mortality, cardiovascular mortality, and liver-related mortality compared with the general population. According to the population-based studies, NAFLD and NASH are more prevalent in males and in Hispanics. Both the gender and racial ethnic differences in NAFLD and NASH are likely attributed to interaction between environmental, behavioral, and genetic factors. Using genome-wide association studies, several genetic variants have been identified to be associated with NAFLD/NASH. However, these variants account for only a small amount of variation in hepatic steatosis among ethnic groups and may serve as modifiers of the natural history of NAFLD. Alternatively, these variants may not be the causative variants but simply markers representing a larger body of genetic variations. In this article, we provide a concise review of the gender and racial differences in the prevalence of NAFLD and NASH in adults. We also discuss the possible mechanisms for these disparities.

Sex impact on the quality of fatty liver and its genetic determinism in mule ducks.

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Marie-Etancelin, C; Retailleau, B; Alinier, A; Vitezica, Z G

2015-09-01

Recent changes to French regulations now allow farmers to produce "foie gras" from both male and female mule ducks. The aim of this study was to assess the quality of female fatty liver and to compare, from a phenotypic and genetic point of view, liver quality in males and females. A total of 914 mule ducks (591 males and 323 females), hatched in a single pedigree batch, were reared until 86 d of age and then force-fed for 12 d, before being slaughtered. Carcasses and livers were weighed and liver quality was assessed by grading the extent of liver veining and measuring the liver melting rate, either after sterilization of 60 g of liver or pasteurization of 180 g of liver. Sexual dimorphism was observed in favor of males, with a difference of approximately 10% in carcass and liver weights and up to 54% for the liver melting rate. Moreover, one-third of female livers showed moderate to high veining, whereas this was not the case for male livers. The fatty livers of female mule ducks are, therefore, of poorer quality and could not be transformed into a product with the appellation "100% fatty liver." According to sex and parental line, heritability values ranged from 0.12 ± 0.05 to 0.18 ± 0.07 for fatty liver weight and from 0.09 ± 0.05 to 0.18 ± 0.05 for the 2 melting rate traits. The genetic correlations between the fatty liver weight and both melting rates were high (greater than +0.80) in the Muscovy population, whereas in the Pekin population, the liver weight and melting rates were less strongly correlated (estimates ranging from +0.36 ± 0.30 to +0.45 ± 0.28). Selection for lower liver melting rates without reducing the liver weight would, therefore, be easier to achieve in the Pekin population. Finally, as the 2 melting rate measurements are highly correlated (0.91 and over 0.95 for phenotypic and genetic correlations, respectively), we suggest using the easiest method, that is, sterilization of 60 g of liver.

Ablation of systemic SIRT1 activity promotes nonalcoholic fatty liver disease by affecting liver-mesenteric adipose tissue fatty acid mobilization

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The incidence of nonalcoholic fatty liver disease (NAFLD) is escalating paralleled with obesity rates in both adults and children. Mammalian sirtuin 1 (SIRT1), a highly conserved NAD+-dependent protein deacetylase, has been identified as a metabolic regulator of lipid homeostasis and a potential tar...

Prevalence and features of fatty liver detected by physical examination in Guangzhou

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Liao, Xian-Hua; Cao, Xu; Liu, Jie; Xie, Xiao-Hua; Sun, Yan-Hong; Zhong, Bi-Hui

2013-01-01

AIM: To investigate the prevalence of fatty liver discovered upon physical examination of Chinese patients and determine the associated clinical characteristics. METHODS: A total of 3433 consecutive patients who received physical examinations at the Huangpu Division of the First Affiliated Hospital at Sun Yat-sen University in Guangzhou, China from June 2010 to December 2010 were retrospectively enrolled in the study. Results of biochemical tests, abdominal ultrasound, electrocardiography, and chest X-ray were collected. The diagnosis of fatty liver was made if a patient met any two of the three following ultrasonic criteria: (1) liver and kidney echo discrepancy and presence of an increased liver echogenicity (bright); (2) unclear intrahepatic duct structure; and (3) liver far field echo decay. RESULTS: The study population consisted of 2201 males and 1232 females, with a mean age of 37.4 ± 12.8 years. When all 3433 patients were considered, the overall prevalence of hyperlipidemia was 38.1%, of fatty liver was 26.0%, of increased alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels was 11.9%, of gallstone was 11.4%, of hyperglycemia was 7.3%, of hypertension was 7.1%, and of hyperuricemia was 6.2%. Of the 2605 patients who completed the abdominal ultrasonography exam, 677 (26.0%) were diagnosed with fatty liver and the prevalence was higher in males (32.5% vs females: 15.3%, P 50-year-old did not reach statistical significance. Only 430 of the patients diagnosed with fatty liver had complete information; among those, increased ALT and/or AST levels were detected in only 30%, with all disturbances being mild or moderate. In these 430 patients, the overall prevalence of hypertriglyceridemia was 31.4%, of mixed type hyperlipidemia was 20.9%, of hypercholesterolemia was 12.3%, of hyperglycemia was 17.6%, of hypertension was 16.0%, of hyperuricemia was 15.3%, and of gallstone was 14.4%. Again, the prevalences of hypertriglyceridemia and

Promiscuous activity of the LXR antagonist GSK2033 in a mouse model of fatty liver disease

International Nuclear Information System (INIS)

Griffett, Kristine; Burris, Thomas P.

2016-01-01

The liver X receptor (LXR) functions as a receptor for oxysterols and plays a critical role in the regulation of glucose and lipid metabolism. We recently described a synthetic LXR inverse agonist that displayed efficacy in treatment of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD). This compound, SR9238, was designed to display liver specificity so as to avoid potential detrimental effects on reverse cholesterol transport in peripheral tissues. Here, we examined the effects of a LXR antagonist/inverse agonist, GSK2033, which displays systemic exposure. Although GSK2033 performed as expected in cell-based models as a LXR inverse agonist, it displayed unexpected activity in the mouse NAFLD model. The expression of lipogenic enzyme genes such as fatty acid synthase and sterol regulatory binding protein 1c were induced rather than suppressed and no effect on hepatic steatosis was found. Further characterization of the specificity of GSK2033 revealed that it displayed a significant degree of promiscuity, targeting a number of other nuclear receptors that could clearly alter hepatic gene expression. - Highlights: • The LXR antagonist GSK2033 suppresses the expression of lipogenic genes FASN and SREBF1 in HepG2 cells. • GSK2033 exhibits sufficient exposure to perform animal experiments targeting the liver. • GSK2033 has fails to suppress hepatic Fasn and Srebf1 expression in an animal model of non-alcoholic fatty liver disease. • GSK2033 may regulate the activity of several nuclear receptors.

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

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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.

Metabolic profiling of fatty liver in young and middle‐aged adults: Cross‐sectional and prospective analyses of the Young Finns Study

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Würtz, Peter; Suomela, Emmi; Lehtovirta, Miia; Kangas, Antti J.; Jula, Antti; Mikkilä, Vera; Viikari, Jorma S.A.; Juonala, Markus; Rönnemaa, Tapani; Hutri‐Kähönen, Nina; Kähönen, Mika; Lehtimäki, Terho; Soininen, Pasi; Ala‐Korpela, Mika; Raitakari, Olli T.

2016-01-01

Nonalcoholic fatty liver is associated with obesity‐related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis‐related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty‐eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population‐based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34‐49 years (19% prevalence). Cross‐sectional associations as well as 4‐year and 10‐year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P fatty acids including omega‐6 (OR = 0.37, 0.32‐0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P fatty liver diagnosis. Conclusion: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults. (Hepatology 2017;65:491‐500). PMID:27775848

Connection Between Non-Alcoholic Fatty Liver Disease and Diabetes Mellitus

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Oprea-Călin Gabriela

2014-06-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is the commonest liver condition in the world, accounting for 20-30% of the adult population, and encompasses a spectrum of liver disorders characterized by fat accumulation within the liver, associated or not with varying degrees of hepatic inflammation and liver fibrosis through to cirrhosis. The prevalence of NAFLD increases significantly in the presence of obesity (60-80% and type 2 diabetes (60%. NAFLD is associated with metabolic disorders (type 2 diabetes, obesity and hyperlipidemia grouped together as the metabolic syndrome (MetS. It is now regarded as the hepatic manifestation of this syndrome and is closely linked to insulin resistance (IR.The presence of NAFLD predicts the development of type 2 diabetes independent of established risk factors. NAFLD patients should therefore be screened for diabetes, including by the Oral Glucose Tolerance Test (OGTT if there any abnormalities of fasting blood glucose (FBG and given appropriate lifestyle advice. Early diagnosis with the institution of lifestyle measures could help prevent or retard the onset of these metabolic disorders. Type 2 diabetes causes more severe non-alcoholic steatohepatitis (NASH, and patients with diabetes have an increased risk for cirrhosis and the development of hepatocellular carcinoma (HCC

Nonalcoholic fatty liver disease and polycystic ovary syndrome

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Vassilatou, Evangeline

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD. PMID:25024594

Nonalcoholic fatty liver disease and polycystic ovary syndrome.

Science.gov (United States)

Vassilatou, Evangeline

2014-07-14

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD.

Fimasartan Ameliorates Nonalcoholic Fatty Liver Disease through PPARδ Regulation in Hyperlipidemic and Hypertensive Conditions

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Yong-Jik Lee

2017-01-01

Full Text Available To investigate the effects of fimasartan on nonalcoholic fatty liver disease in hyperlipidemic and hypertensive conditions, the levels of biomarkers related to fatty acid metabolism were determined in HepG2 and differentiated 3T3-L1 cells treated by high fatty acid and liver and visceral fat tissue samples of spontaneously hypertensive rats (SHRs given high-fat diet. In HepG2 cells and liver tissues, fimasartan was shown to increase the protein levels of peroxisome proliferator-activated receptor delta (PPARδ, phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK, phosphorylated acetyl-CoA carboxylase (p-ACC, malonyl-CoA decarboxylase (MCD, medium chain acyl-CoA dehydrogenase (MCAD, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α, and it led to a decrease in the protein levels of 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSDH1, fatty acid synthase (FAS, and tumor necrosis factor-alpha (TNF-α. Fimasartan decreased lipid contents in HepG2 and differentiated 3T3-L1 cells and liver tissues. In addition, fimasartan increased the adiponectin level in visceral fat tissues. The antiadipogenic effects of fimasartan were offset by PPARδ antagonist (GSK0660. Consequently, fimasartan ameliorates nonalcoholic fatty liver disease mainly through the activation of oxidative metabolism represented by PPARδ-AMPK-PGC-1α pathway.

Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease

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Guanliang Chen

2016-08-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin.

Changes of α-glycerophosphate dehydrogenase activity in fatty liver of rats by amino acid imbalance

International Nuclear Information System (INIS)

Ogura, Masaji; Katsunuma, Eiichi; Akabane, Tomoko; Ogawa, Seiichi

1976-01-01

The previous study on the lipogenesis in the fatty livers of rats, which was induced by feeding the diet with imbalanced amino acid, revealed that the induction of this type of fatty livers was due mainly to the acceleration of triglyceride synthesis by the increase in both synthesis and esterification of fatty acid in the livers. Although many studies have been carried out on the dietary control of α-glycerophosphate dehydrogenase activity in rat livers, the enzyme change in amino acid imbalance has not been reported. In the present study, in order to elucidate the difference in the supply of glycerol moiety of triglyceride due to the imbalance, the change of the α-glycerophosphate dehydrogenase activity in livers was investigated. The experimental diets were 8% casein basal diet and basal + 0.3% DL-methionine imbalanced diet. 5 rats of each group were killed after 0.5 and 10 days on the diet, and the analysis of the lipid content in the livers and the determination of the α-glycerophosphate dehydrogenase activity were carried out. The linear response of the enzyme activity to time and protein concentration was obtained. The development of fatty livers was observed in the imbalanced diet group in the feeding period of 10 days. It was found that the specific activity of the imbalanced diet group increased significantly in 5 and 10 days as compared with that of the basal diet group. The elevation in the enzyme activity may suggest that the supply of α-glycerophosphate for triglyceride synthesis is also increased in this type of fatty livers. (Kako, I.)

PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid -Hydroxylase (CYP4 Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease

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James P. Hardwick

2009-01-01

Full Text Available Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis, due to a decrease in mitochondria -oxidation with an increase in both peroxisomal -oxidation, and microsomal -oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs. How steatosis increases PPAR activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid -oxidation and -oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA, monounsaturated (MUFA, or saturated (SFA may be determined by the interplay of PPARs and HNF4 with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the -oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPAR. Although numerous studies have suggested the role ethanol-inducible CYP2E1 in contributing to increased oxidative stress, Cyp2e1-null mice still develop steatohepatitis with a dramatic increase in CYP4A gene expression. This strongly implies that CYP4A fatty acid -hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium-chain fatty acid (MCFA CYP4A and long-chain fatty acid (LCFA CYP4F -hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to

Ethanol and liver: Recent insights into the mechanisms of ethanol-induced fatty liver

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Liu, Jinyao

2014-01-01

Alcoholic fatty liver disease (AFLD), a potentially pathologic condition, can progress to steatohepatitis, fibrosis, and cirrhosis, leading to an increased probability of hepatic failure and death. Alcohol induces fatty liver by increasing the ratio of reduced form of nicotinamide adenine dinucleotide to oxidized form of nicotinamide adenine dinucleotide in hepatocytes; increasing hepatic sterol regulatory element-binding protein (SREBP)-1, plasminogen activator inhibitor (PAI)-1, and early growth response-1 activity; and decreasing hepatic peroxisome proliferator-activated receptor-α activity. Alcohol activates the innate immune system and induces an imbalance of the immune response, which is followed by activated Kupffer cell-derived tumor necrosis factor (TNF)-α overproduction, which is in turn responsible for the changes in the hepatic SREBP-1 and PAI-1 activity. Alcohol abuse promotes the migration of bone marrow-derived cells (BMDCs) to the liver and then reprograms TNF-α expression from BMDCs. Chronic alcohol intake triggers the sympathetic hyperactivity-activated hepatic stellate cell (HSC) feedback loop that in turn activates the HSCs, resulting in HSC-derived TNF-α overproduction. Carvedilol may block this feedback loop by suppressing sympathetic activity, which attenuates the progression of AFLD. Clinical studies evaluating combination therapy of carvedilol with a TNF-α inhibitor to treat patients with AFLD are warranted to prevent the development of alcoholic liver disease. PMID:25356030

Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD).

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Notarnicola, Maria; Caruso, Maria Gabriella; Tutino, Valeria; Bonfiglio, Caterina; Cozzolongo, Raffaele; Giannuzzi, Vito; De Nunzio, Valentina; De Leonardis, Giampiero; Abbrescia, Daniela I; Franco, Isabella; Intini, Vincenza; Mirizzi, Antonella; Osella, Alberto R

2017-08-23

The lipidomic profiling of erythrocyte membranes is expected to provide a peculiar scenario at molecular level of metabolic and nutritional pathways which may influence the lipid balance and the adaptation and homeostasis of the organism. Considering that lipid accumulation in the cell is important in promoting tissue inflammation, the purpose of this study is to analyze the fatty acid profile in red blood cell membranes of patients with Non-Alcoholic Fatty Liver Disease (NAFLD), in order to identify and validate membrane profiles possibly associated with the degree of hepatic damage. This work presents data obtained at baseline from 101 subjects that participated to a nutritional trial (registration number: NCT02347696) enrolling consecutive subjects with NAFLD. Diagnosis of liver steatosis was performed by using vibration-controlled elastography implemented on FibroScan. Fatty acids, extracted from phospholipids of erythrocyte membranes, were quantified by gas chromatography method. The subjects with severe NAFLD showed a significant decrease of the ratio of stearic acid to oleic acid (saturation index, SI) compared to controls, 1.281 ± 0.31 vs 1.5 ± 0.29, respectively. Low levels of SI in red blood cell membranes, inversely associated with degree of liver damage, suggest that an impairment of circulating cell membrane structure can reflect modifications that take place in the liver. Subjects with severe NAFLDalso showed higher levels of elongase 5 enzymatic activity, evaluated as vaccenic acid to palmitoleic acid ratio. Starting from these evidences, our findings show the importance of lipidomic approach in the diagnosis and the staging of NAFLD.

Added fructose as a principal driver of non-alcoholic fatty liver disease: a public health crisis

OpenAIRE

DiNicolantonio, James J; Subramonian, Ashwin M; O’Keefe, James H

2017-01-01

Fatty liver disease affects up to one out of every two adults in the western world. Data from animal and human studies implicate added sugars (eg, sucrose and high-fructose corn syrup) in the development of fatty liver disease and its consequences. Added fructose in particular, as a component of added sugars, may pose the greatest risk for fatty liver disease. Considering that there is no requirement for added sugars in the diet, dietary guidelines should recommend reducing the intake of adde...

Xe-133 accumulation in fatty liver: hepatic uptake and washout correlated with pulmonary and mesenteric retention

International Nuclear Information System (INIS)

Samuels, L.D.

1980-01-01

Xe-133 uptake in patients with fatty livers is described and compared with uptake and retention in lungs, blood and mesenteric fat and with normal hepatic uptake. In the absence of obstructive lung disease or excessive obesity, Xe-133 uptake and retention is a valuable means of screening patients for the presence of fatty liver. Although non-specific for the etiology of fatty liver, the test is an effective and non-invasive method of detection which merits further application. (author)

Audio-Visual Aid in Teaching "Fatty Liver"

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Dash, Sambit; Kamath, Ullas; Rao, Guruprasad; Prakash, Jay; Mishra, Snigdha

2016-01-01

Use of audio visual tools to aid in medical education is ever on a rise. Our study intends to find the efficacy of a video prepared on "fatty liver," a topic that is often a challenge for pre-clinical teachers, in enhancing cognitive processing and ultimately learning. We prepared a video presentation of 11:36 min, incorporating various…

Enhanced expression of Nrf2 in mice attenuates the fatty liver produced by a methionine- and choline-deficient diet

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Zhang, Yu-Kun Jennifer; Yeager, Ronnie L.; Tanaka, Yuji; Klaassen, Curtis D.

2010-01-01

Oxidative stress has been proposed as an important promoter of the progression of fatty liver diseases. The current study investigates the potential functions of the Nrf2-Keap1 signaling pathway, an important hepatic oxidative stress sensor, in a rodent fatty liver model. Mice with no (Nrf2-null), normal (wild type, WT), and enhanced (Keap1 knockdown, K1-kd) expression of Nrf2 were fed a methionine- and choline-deficient (MCD) diet or a control diet for 5 days. Compared to WT mice, the MCD diet-caused hepatosteatosis was more severe in the Nrf2-null mice and less in the K1-kd mice. The Nrf2-null mice had lower hepatic glutathione and exhibited more lipid peroxidation, whereas the K1-kd mice had the highest amount of glutathione in the liver and developed the least lipid peroxidation among the three genotypes fed the MCD diet. The Nrf2 signaling pathway was activated by the MCD diet, and the Nrf2-targeted cytoprotective genes Nqo1 and Gstα1/2 were induced in WT and even more in K1-kd mice. In addition, Nrf2-null mice on both control and MCD diets exhibited altered expression profiles of fatty acid metabolism genes, indicating Nrf2 may influence lipid metabolism in liver. For example, mRNA levels of long chain fatty acid translocase CD36 and the endocrine hormone Fgf21 were higher in livers of Nrf2-null mice and lower in the K1-kd mice than WT mice fed the MCD diet. Taken together, these observations indicate that Nrf2 could decelerate the onset of fatty livers caused by the MCD diet by increasing hepatic antioxidant and detoxification capabilities.

Imaging evaluation of non-alcoholic fatty liver disease: focused on quantification

Science.gov (United States)

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) has been an emerging major health problem, and the most common cause of chronic liver disease in Western countries. Traditionally, liver biopsy has been gold standard method for quantification of hepatic steatosis. However, its invasive nature with potential complication as well as measurement variability are major problem. Thus, various imaging studies have been used for evaluation of hepatic steatosis. Ultrasonography provides fairly good accuracy to detect moderate-to-severe degree hepatic steatosis, but limited accuracy for mild steatosis. Operator-dependency and subjective/qualitative nature of examination are another major drawbacks of ultrasonography. Computed tomography can be considered as an unsuitable imaging modality for evaluation of NAFLD due to potential risk of radiation exposure and limited accuracy in detecting mild steatosis. Both magnetic resonance spectroscopy and magnetic resonance imaging using chemical shift technique provide highly accurate and reproducible diagnostic performance for evaluating NAFLD, and therefore, have been used in many clinical trials as a non-invasive reference of standard method. PMID:28994271

Nutrition: a promising route for prevention and management of obesity-related nonalcoholic fatty liver disease.

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Tarantino, Giovanni

2014-11-01

When dealing with the treatment of obesity-linked illnesses - in particular nonalcoholic fatty liver disease - beyond diet, various nutritional ingredients are reported to be useful as silymarin, spirulina, choline, folic acid, methionine and vitamin E, all of them showing promising but not definite results. An emerging field of study is represented by prebiotics/probiotics and restoration of normal gut flora, which could play a fundamental role diet and various its components. It is noteworthy to point out that both improving or reducing the severity of nonalcoholic fatty liver disease bear a positive consequence on evolution of atherosclerosis and its cardiovascular-associated disease, such as coronary artery disease, even though the involved immunologic mechanisms are gaining greater credit in the most recent literature, without excluding the role of nutrition in modulating the acquired immunity in this condition.

Nonalcoholic fatty liver disease in Japanese patients with severe obesity who received laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) in comparison to non-Japanese patients

International Nuclear Information System (INIS)

Kakizaki, Satoru; Takizawa, Daichi; Yamazaki, Yuichi; Nakajima, Yuka; Ichikawa, Takeshi; Sato, Ken; Takagi, Hitoshi; Mori, Masatomo; Kasama, Kazunori

2008-01-01

The number of patients with morbid obesity is increasing worldwide. However, the prevalence of morbid obesity is still low in Japan, and therefore few systematic investigations of liver dysfunction in this population have so far been carried out. This study aimed to investigate the clinical characteristics in severe obese Japanese patients undergoing laparoscopic Roux-en-Y gastric bypass surgery (LRYGB). Eighty-four patients with severe obesity, including 61 Japanese and 23 non-Japanese patients, were analyzed. The mean body mass index (BMI) was 43.7±7.8 kg/m 2 , and there was no difference between Japanese and non-Japanese patients. Nonalcoholic fatty liver disease (NAFLD) was observed in 45/59 (76.2%) of the Japanese patients. Although there were no differences in the BMI and body weight, serum alanine aminotransferase (ALT) was higher in Japanese patients in comparison to non-Japanese patients (P<0.05). The indices for insulin resistance were significantly higher in the Japanese patients in comparison to non-Japanese patients (P<0.01). The liver/spleen computed tomography (CT) ratios were lower in Japanese patients (P<0.05). The laboratory data and BMI significantly improved at 1 year after LRYGB in both groups. Racial difference may exist difference may exist in NAFLD in patients with severe obesity. When the BMI is similar, liver dysfunction among Japanese patients with severe obesity tends to be higher than in non-Japanese patients. Japanese patients with severe obesity must therefore reduce their body weight to a greater degree in comparison to non-Japanese patients with the same BMI. LRYGB can achieve effective weight control and lower ALT levels in Japanese patients with severe obesity. (author)

Role of scintigraphy in focally abnormal sonograms of fatty livers

International Nuclear Information System (INIS)

Lisbona, R.; Mishkin, S.; Derbekyan, V.; Novales-Diaz, J.A.; Roy, A.; Sanders, L.

1988-01-01

Fatty infiltration of the liver may cause a range of focal abnormalities on hepatic sonography which may simulate hepatic nodular lesions. Discrete deposits of fat or islands of normal tissue which are uninvolved by fatty infiltration may stand out as potential space-occupying lesions on the sonograms. Twelve patients with such focally abnormal ultrasound images were referred for liver scintigraphy with 133 Xe and /sup 99m/Tc colloidal SPECT studies to clarify the issue. These examinations helped identify, in nine of 12 patients, the innocent nature of the sonographic abnormalities which were simply related to the fat deposition process. Further, [/sup 99m/Tc]RBC scans defined the additional pathologic process in three patients in whom actual space-occupying lesions were indeed present in the liver. Scintigraphy has an important role to play in the understanding of focal hepatic ultrasound abnormalities particularly in unsuspected hepatic steatosis

Role of scintigraphy in focally abnormal sonograms of fatty livers

Energy Technology Data Exchange (ETDEWEB)

Lisbona, R.; Mishkin, S.; Derbekyan, V.; Novales-Diaz, J.A.; Roy, A.; Sanders, L.

1988-06-01

Fatty infiltration of the liver may cause a range of focal abnormalities on hepatic sonography which may simulate hepatic nodular lesions. Discrete deposits of fat or islands of normal tissue which are uninvolved by fatty infiltration may stand out as potential space-occupying lesions on the sonograms. Twelve patients with such focally abnormal ultrasound images were referred for liver scintigraphy with /sup 133/Xe and /sup 99m/Tc colloidal SPECT studies to clarify the issue. These examinations helped identify, in nine of 12 patients, the innocent nature of the sonographic abnormalities which were simply related to the fat deposition process. Further, (/sup 99m/Tc)RBC scans defined the additional pathologic process in three patients in whom actual space-occupying lesions were indeed present in the liver. Scintigraphy has an important role to play in the understanding of focal hepatic ultrasound abnormalities particularly in unsuspected hepatic steatosis.

Clinical epidemiology and disease burden of nonalcoholic fatty liver disease

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Perumpail, Brandon J; Khan, Muhammad Ali; Yoo, Eric R; Cholankeril, George; Kim, Donghee; Ahmed, Aijaz

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis. PMID:29307986

Alternation of plasma fatty acids composition and desaturase activities in children with liver steatosis.

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Man-Chin Hua

Full Text Available The aim of this study was to investigate changes in plasma fatty acids proportions and estimated desaturase activities for variable grading of liver steatosis in children.In total, 111 schoolchildren (aged 8-18 years were included in the analysis from March 2015 to August 2016. Anthropometric evaluation, liver ultrasound examination and scoring for nonalcoholic fatty liver disease (NAFLD score = 0-6, and biochemical and plasma fatty acids analysis were performed. We compared the composition ratio of fatty acids between children with high-grade liver steatosis (NAFLD score = 4-6, low-grade liver steatosis (NAFLD score = 1-3, and healthy controls (NAFLD score = 0. In addition, correlation coefficients (r between NAFLD score, metabolic variables, and estimated activity of desaturase indices (stearoyl-coenzyme A desaturase-1 (SCD1, delta-5 and delta-6 desaturase were calculated.Compared with healthy controls, children with liver steatosis showed a higher proportion of monounsaturated fatty acids (21.16 ± 2.81% vs. 19.68 ± 2.71%, p = 0.024. In addition, children with high- grade liver steatosis exhibited higher proportions of palmitic acid (C16:0, palmitoleic acid (C16:1n-7, dihomo-γ-linolenic acid (C20:3n-6, adrenic acid (C22:4n-6, and docosapentaenoic acid (C22:5n-6; and lower proportions of eicosapentaenoic acid (C20:5n-3 (P< 0.05. In all subjects, the NAFLD score was positively correlated with body mass index (BMI (kg/m2 (r = 0.696, homeostasis model of assessment ratio-index (HOMA-IR (r = 0.510, SCD1(16 (r = 0.273, and the delta-6 index (r = 0.494; and inversely associated with the delta-5 index (r = -0.443.Our current data suggested that children with liver steatosis was highly associated with obesity, and insulin resistance. In addition, increased endogenous lipogenesis through altered desaturase activity may contribute to the progression of liver steatosis in children.

In vivo (1)H-MRS hepatic lipid profiling in nonalcoholic fatty liver disease: an animal study at 9.4 T.

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Lee, Yunjung; Jee, Hee-Jung; Noh, Hyungjoon; Kang, Geun-Hyung; Park, Juyeun; Cho, Janggeun; Cho, Jee-Hyun; Ahn, Sangdoo; Lee, Chulhyun; Kim, Ok-Hee; Oh, Byung-Chul; Kim, Hyeonjin

2013-09-01

The applicability of the in vivo proton magnetic resonance spectroscopy hepatic lipid profiling (MR-HLP) technique in nonalcoholic fatty liver disease was investigated. Using magnetic resonance spectroscopy, the relative fractions of diunsaturated (fdi), monounsaturated (fmono), and saturated (fsat) fatty acids as well as total hepatic lipid content were estimated in the livers of 8 control and 23 CCl4-treated rats at 9.4 T. The mean steatosis, necrosis, inflammation, and fibrosis scores of the treated group were all significantly higher than those of the control group (P steatosis and fibrosis are positively correlated with fmono and negatively correlated with fdi. Both necrosis and inflammation, however, were not correlated with any of the MR-HLP parameters. Hepatic lipid composition appears to be changed in association with the severity of steatosis and fibrosis in nonalcoholic fatty liver disease, and these changes can be depicted in vivo by using the MR-HLP method at 9.4 T. Thus, while it may not likely be that MR-HLP helps differentiate between steatohepatitis in its early stages and simple steatosis, these findings altogether are in support of potential applicability of in vivo MR-HLP at high field in nonalcoholic fatty liver disease. Copyright © 2012 Wiley Periodicals, Inc.

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

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Eun Sung Choi

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

Total lipids and fatty acid profile in the liver of wild and farmed catla catla fish

Energy Technology Data Exchange (ETDEWEB)

Hassan, M.; Shaihid chatha, S. A.; Tahira, I.; Hussain, B.

2010-07-01

This experimental work was aimed to study the moisture content, total lipids and fatty acid profile in the liver of wild and farmed freshwater major carp Catla catla of three different weight categories designated as W{sub 1} (601-900g), W{sub 2} (901- 1200)g and W{sub 3} (1201-1500g). Seven fish specimens of each of the three weight categories of wild and farmed Catla catla were obtained from Trimu Head, Jhang and Fish Hatchery, Satiana Road and Faisalabad, respectively. The fish were dissected to remove the liver and after weighing, liver samples were prepared and subjected to chemical analysis. Wild Catla catla liver had a significantly (p <0.05) higher moisture content as compared to the farmed species. Farmed Catla catla deposited significantly (p < 0.05) higher lipid contents in liver. Proportions of saturated fatty acids varied irregularly in the lipids of the liver from both wild and farmed Catla catla. Saturated fatty acids C12:0, C14:0, C16:0, C18:0, C20:0 and C22:0 were identified with considerable percentages in the liver of Catla catla from both habitats and monounsaturated fatty acid C18:1 was found in considerable amounts in the liver of both major carp. Polyunsaturated fatty acids such as C18:3 (n-6) and C20: 2 (n-6) were detected in the liver of the wild fish of W{sub 2} and W{sub 3} and was similar in the W{sub 3} weight category of the farmed species. (Author) 22 refs.

Effects of transcutaneous electrical stimulation of lower limb muscles on experimental fatty liver.

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El-Kafoury, Bataa M; Seif, Ansam A; El-Aziz Abd El-Hady, Enas A; El-Sebaiee, Ahmed E

2016-03-01

Although the beneficial effects of exercise on fatty liver have been described, a previous study conducted at our department showed that transcutaneous electrical muscle stimulation (TEMS) of lower abdominal muscles aggravated fatty liver. The present study aims to evaluate the ability of TEMS of the lower limb muscles to improve fatty liver infiltration. Thirty male Wistar rats were randomly allocated into three groups: control; fructose-fed (F), fed fructose-enriched diet for 6weeks; and fructose-fed with transcutaneous electrical muscle stimulation (F+TEMS), fed fructose-enriched diet for 6weeks and lower limb muscles subjected to TEMS during the last 3weeks of feeding, five sessions/week. Body weight, length, body mass index (BMI), and abdominal and lower limb circumferences were all recorded. Fasting blood glucose, serum insulin, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, serum albumin, high density lipoprotein cholesterol (HDL-C), triglyceride (TG), and total cholesterol (TC) levels were measured. LDL cholesterol (LDL-C) and the atherogenic index (AI) were calculated. Absolute and relative hepatic weights as well as histological examination of the liver were assessed. Final body weight, abdominal and lower limb circumferences, absolute liver weight, homoeostasis model assessment (HOMA) score, and TG, LDL-C, AI, serum ALT, and AST levels were all significantly reduced in the (F+TEMS) group compared to the (F) group. There was a significant increase in GPx and HDL-C levels, HDL/LDL ratio, and total protein and serum albumin content in (F+TEMS) rats compared to (F) rats. Histologically, hepatic tissue from (F+TEMS) rats had minimal steatotic changes that were restricted to zone 1 and less marked inflammatory cell infiltration compared to (F) rats. TEMS was able to reverse steatosis, hyperglycaemia, insulin resistance, dyslipidaemia, and fatty liver caused by fructose feeding. The study confirmed that the variation in

Omega-3 fatty acid deficiency selectively up-regulates delta6-desaturase expression and activity indices in rat liver: prevention by normalization of omega-3 fatty acid status.

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Hofacer, Rylon; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Magrisso, I Jack; Benoit, Stephen C; McNamara, Robert K

2011-09-01

This study investigated the effects of perinatal dietary omega-3 (n-3) fatty acid depletion and subsequent repletion on the expression of genes that regulate long-chain (LC) polyunsaturated fatty acid biosynthesis in rat liver and brain. It was hypothesized that chronic n-3 fatty acid deficiency would increase liver Fads1 and Fads2 messenger RNA (mRNA) expression/activity and that n-3 fatty acid repletion would normalize this response. Adult rats fed the n-3-free diet during perinatal development exhibited significantly lower erythrocyte, liver, and frontal cortex LCn-3 fatty acid composition and reciprocal elevations in LC omega-6 (n-6) fatty acid composition compared with controls (CONs) and repleted rats. Liver Fads2, but not Fads1, Elovl2, or Elovl5, mRNA expression was significantly greater in n-3-deficient (DEF) rats compared with CONs and was partially normalized in repleted rats. The liver 18:3n-6/18:2n-6 ratio, an index of delta6-desturase activity, was significantly greater in DEF rats compared with CON and repleted rats and was positively correlated with Fads2 mRNA expression among all rats. The liver 18:3n-6/18:2n-6 ratio, but not Fads2 mRNA expression, was also positively correlated with erythrocyte and frontal cortex LCn-6 fatty acid compositions. Neither Fads1 or Fads2 mRNA expression was altered in brain cortex of DEF rats. These results confirm previous findings that liver, but not brain, delta6-desaturase expression and activity indices are negatively regulated by dietary n-3 fatty acids. Copyright © 2011 Elsevier Inc. All rights reserved.

Correlation of secretory phospholipase-A2 activity and fatty acids in cerebrospinal fluid with liver enzymes tests

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Sepideh Ghodoosifar

2016-02-01

Full Text Available Introduction: The aim was to determine whether secretory phospholipase-A2 (sPLA2 activity and fatty acids in cerebrospinal fluid (CSF are correlated with liver enzymes tests. Methods: CSF and serum samples were collected from 49 patients (age 18-65 as part of routine diagnostic testing. Along with serum liver enzymes aspartate aminotransferase (AST, alanine aminotransferase (ALT and alkaline phosphatase (ALP, the fatty acid composition of CSF was measured by gas liquid chromatography. CSF enzyme activities of sPLA2 were measured using the standard assay with diheptanoyl thio-phosphatidylcholin as substrate. Results: The saturated fatty acids (SFAs including palmitic acid and stearic acid were positively, and the unsaturated fatty acids including oleic acid and linoleic acid were negatively correlated with liver enzymes tests. In regression analysis with adjustment for body mass index (BMI, the elevated liver enzymes tests were positively associated with activity of sPLA2 (β > 0.31, P 0.38, P < 0.010 and negatively with total monounsaturated fatty acids (MUFAs (β < -0.40, P < 0.001 contents of CSF. Conclusion: CSF activity of sPLA2 and fatty acids may be linked to peripheral markers of liver function, suggesting an indirect impact of central fatty acids on hepatocytes function and metabolism.

Detection of liver metastases in cancer patients with geographic fatty infiltration of the liver: the added value of contrast-enhanced sonography

International Nuclear Information System (INIS)

Bartolotta, Tommaso Vincenzo; Taibbi, Adele; Picone, Dario; Anastasi, Andrea; Midiri, Massimo; Lagalla, Roberto

2017-01-01

The aim of this study is to assess the role of contrast-enhanced ultrasonography (CEUS) in the detection of liver metastases in cancer patients with geographic liver fatty deposition on greyscale ultrasonography (US). Thirty-seven consecutive cancer patients (24 women and 13 men; age, 33 to 80 years; mean, 58.1 years) with geographic liver fatty deposition, but without any detectable focal liver lesion on greyscale US, underwent sulphur hexafluoride-enhanced US. Two readers reported by consensus the presence, size, and location of any detected lesion. All patients underwent magnetic resonance imaging (MRI) as a confirmatory study. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy were calculated. Seven focal liver lesions (size, 4 to 10 mm; mean, 6.1 mm) were detected in 4/37 patients (10.8%): four metastases (size, 5 to 10 mm; mean, 6.7 mm) were detected both by CEUS and MRI, with one hemangioma and two cysts (size range, 4 to 6 mm; mean, 5.3 mm) detected by MRI only. In 1/37 patients (2.7%), CEUS misdiagnosed geographic fatty change as three metastases. In 32/37 patients (86.5%), no lesions were detected. Sensitivity, specificity, PPV, NPV, and accuracy of CEUS were 100% (95% confidence Interval [CI], 1.000 to 1.000), 97.1% (95% CI, 0.914 to 1.027), 75%, 100%, and 97.3%, respectively. No statistically significant differences were found between CEUS and MRI in the detection of focal liver lesions (P=0.480), whereas both of them performed better than baseline US (P<0.001). CEUS improves the detection of liver metastases in cancer patients with geographic liver fatty deposition on greyscale US

Detection of liver metastases in cancer patients with geographic fatty infiltration of the liver: the added value of contrast-enhanced sonography

Energy Technology Data Exchange (ETDEWEB)

Bartolotta, Tommaso Vincenzo; Taibbi, Adele; Picone, Dario; Anastasi, Andrea; Midiri, Massimo; Lagalla, Roberto [Dept. of Radiology-Di.Bi.Med., University of Palermo, Palermo (Italy)

2017-04-15

The aim of this study is to assess the role of contrast-enhanced ultrasonography (CEUS) in the detection of liver metastases in cancer patients with geographic liver fatty deposition on greyscale ultrasonography (US). Thirty-seven consecutive cancer patients (24 women and 13 men; age, 33 to 80 years; mean, 58.1 years) with geographic liver fatty deposition, but without any detectable focal liver lesion on greyscale US, underwent sulphur hexafluoride-enhanced US. Two readers reported by consensus the presence, size, and location of any detected lesion. All patients underwent magnetic resonance imaging (MRI) as a confirmatory study. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy were calculated. Seven focal liver lesions (size, 4 to 10 mm; mean, 6.1 mm) were detected in 4/37 patients (10.8%): four metastases (size, 5 to 10 mm; mean, 6.7 mm) were detected both by CEUS and MRI, with one hemangioma and two cysts (size range, 4 to 6 mm; mean, 5.3 mm) detected by MRI only. In 1/37 patients (2.7%), CEUS misdiagnosed geographic fatty change as three metastases. In 32/37 patients (86.5%), no lesions were detected. Sensitivity, specificity, PPV, NPV, and accuracy of CEUS were 100% (95% confidence Interval [CI], 1.000 to 1.000), 97.1% (95% CI, 0.914 to 1.027), 75%, 100%, and 97.3%, respectively. No statistically significant differences were found between CEUS and MRI in the detection of focal liver lesions (P=0.480), whereas both of them performed better than baseline US (P<0.001). CEUS improves the detection of liver metastases in cancer patients with geographic liver fatty deposition on greyscale US.

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

Secondhand tobacco exposure is associated with nonalcoholic fatty liver disease in children

International Nuclear Information System (INIS)

Lin, Connie; Rountree, Carl B.; Methratta, Sosamma; LaRusso, Salvatore; Kunselman, Allen R.; Spanier, Adam J.

2014-01-01

Background: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in children in the United States, and prevalence rates are rising. Smoking is associated with NAFLD, but the association of secondhand smoke exposure with NAFLD is unknown. Aims: To investigate the association of secondhand tobacco exposure with NAFLD in children. Methods: We surveyed parents/guardians of 304 children aged 3–12 years who had received an abdominal ultrasound at Penn State Hershey Medical Center. The survey addressed demographics, medical history, secondhand tobacco exposure, activity level, screen viewing time and other environmental exposures. A pediatric radiologist and sonographer reviewed the ultrasounds to grade the presence of bight liver compatible with NAFLD. We conducted logistic regression analysis to assess the association of secondhand tobacco exposure and NAFLD. Results: 54% of eligible potential participants responded to the survey. Fatty liver was present in 3% of the children. Increasing child age was associated with increased odds of NAFLD (OR 1.63 95% CI 1.1, 2.4). Reported child obesity was associated with increased odds of NAFLD (OR 44.5 95% CI 5.3, 371.7). The rate of NAFLD was higher in the smoke exposed group (6.7% vs. 1.7%). For every extra pack per day smoked at home, the odds of a child having NAFLD increased 1.8 times (AOR 1.8, 95% CI 1.2, 2.8), and any exposure increased a child's odds of NAFLD four-fold (AOR 4.0, 95% CI 1.02, 15.8). Conclusion: We found an association of secondhand smoke exposure and NAFLD in children. This may represent an area for future prevention efforts. - Highlights: • We evaluated the relation of tobacco exposure with nonalcoholic fatty liver disease. • Tobacco smoke exposure was associated with nonalcoholic fatty liver disease. • Tobacco smoke exposure may be an addressable risk factor

Secondhand tobacco exposure is associated with nonalcoholic fatty liver disease in children

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Lin, Connie [College of Medicine, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Rountree, Carl B. [Department of Pediatrics, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Department of Pediatrics, Bon Secour St. Mary' s Hospital, 5801 Bremo Rd, Richmond, VA 23226 (United States); Methratta, Sosamma [Department of Pediatrics, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Department of Radiology, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); LaRusso, Salvatore [Department of Radiology, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Kunselman, Allen R. [Department of Public Health Sciences, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Spanier, Adam J., E-mail: aspanier@hmc.psu.edu [Department of Pediatrics, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States); Department of Public Health Sciences, Penn State University Hershey Medical Center, 500 University Drive, PO Box 850, Hershey, PA 17033-0850 (United States)

2014-07-15

Background: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in children in the United States, and prevalence rates are rising. Smoking is associated with NAFLD, but the association of secondhand smoke exposure with NAFLD is unknown. Aims: To investigate the association of secondhand tobacco exposure with NAFLD in children. Methods: We surveyed parents/guardians of 304 children aged 3–12 years who had received an abdominal ultrasound at Penn State Hershey Medical Center. The survey addressed demographics, medical history, secondhand tobacco exposure, activity level, screen viewing time and other environmental exposures. A pediatric radiologist and sonographer reviewed the ultrasounds to grade the presence of bight liver compatible with NAFLD. We conducted logistic regression analysis to assess the association of secondhand tobacco exposure and NAFLD. Results: 54% of eligible potential participants responded to the survey. Fatty liver was present in 3% of the children. Increasing child age was associated with increased odds of NAFLD (OR 1.63 95% CI 1.1, 2.4). Reported child obesity was associated with increased odds of NAFLD (OR 44.5 95% CI 5.3, 371.7). The rate of NAFLD was higher in the smoke exposed group (6.7% vs. 1.7%). For every extra pack per day smoked at home, the odds of a child having NAFLD increased 1.8 times (AOR 1.8, 95% CI 1.2, 2.8), and any exposure increased a child's odds of NAFLD four-fold (AOR 4.0, 95% CI 1.02, 15.8). Conclusion: We found an association of secondhand smoke exposure and NAFLD in children. This may represent an area for future prevention efforts. - Highlights: • We evaluated the relation of tobacco exposure with nonalcoholic fatty liver disease. • Tobacco smoke exposure was associated with nonalcoholic fatty liver disease. • Tobacco smoke exposure may be an addressable risk factor.

Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease.

Science.gov (United States)

Kowdley, Kris V; Belt, Patricia; Wilson, Laura A; Yeh, Matthew M; Neuschwander-Tetri, Brent A; Chalasani, Naga; Sanyal, Arun J; Nelson, James E

2012-01-01

Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P 1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P 1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033). A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis. Copyright © 2011 American Association for the Study of Liver Diseases.

Interactions between fatty acid synthesis, oxidation, and esterification in the production of triglyceride-rich lipoproteins by the liver.

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Fukuda, N; Ontko, J A

1984-08-01

In a series of experiments with male rat livers perfused with or without 5-tetradecyloxy-2-furoic acid (TOFA) in the presence and absence of oleate, the relationships between fatty acid synthesis, oxidation, and esterification from newly synthesized and exogenous fatty acid substrates have been examined. When livers from fed rats were perfused without exogenous fatty acid substrate, 20% of the triglyceride secreted was derived from de novo fatty acid synthesis. Addition of TOFA caused immediate and nearly complete inhibition of fatty acid synthesis, measured by incorporation of 3H2O into fatty acids. Concurrently, ketone body production increased 140% and triglyceride secretion decreased 84%. These marked reciprocal alterations in fatty acid synthesis and oxidation in the liver almost completely abolished the production of very low density lipoproteins (VLDL). Cholesterol synthesis was also depressed by TOFA, suggesting that this drug also inhibited lipid synthesis at a site other than acetyl-CoA carboxylase. When livers from fed rats were supplied with a continuous infusion of [1-14C]oleate as exogenous substrate, similar proportions, about 45-47%, of both ketone bodies and triglyceride in the perfusate were derived from the infused [1-14C]oleate. The production of ketone bodies was markedly increased by TOFA; the secretion of triglyceride and cholesterol were decreased. Altered conversion of [1-14C]oleate into these products occurred in parallel. While TOFA decreased esterification of oleate into triglyceride, incorporation of [1-14C]oleate into liver phospholipid was increased, indicating that TOFA also affected glycerolipid synthesis at the stage of diglyceride processing. The decreased secretion of triglyceride and cholesterol following TOFA treatment was localized almost exclusively in VLDL. The specific activities of 3H and of 14C fatty acids in triglyceride of the perfusate were greater than those of liver triglyceride, indicating preferential secretion of

Increased Nitroxidative Stress Promotes Mitochondrial Dysfunction in Alcoholic and Nonalcoholic Fatty Liver Disease

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Byoung-Joon Song

2013-01-01

Full Text Available Increased nitroxidative stress causes mitochondrial dysfunctions through oxidative modifications of mitochondrial DNA, lipids, and proteins. Persistent mitochondrial dysfunction sensitizes the target cells/organs to other pathological risk factors and thus ultimately contributes to the development of more severe disease states in alcoholic and nonalcoholic fatty liver disease. The incidences of nonalcoholic fatty liver disease continuously increase due to high prevalence of metabolic syndrome including hyperlipidemia, hypercholesterolemia, obesity, insulin resistance, and diabetes. Many mitochondrial proteins including the enzymes involved in fat oxidation and energy supply could be oxidatively modified (including S-nitrosylation/nitration under increased nitroxidative stress and thus inactivated, leading to increased fat accumulation and ATP depletion. To demonstrate the underlying mechanism(s of mitochondrial dysfunction, we employed a redox proteomics approach using biotin-N-maleimide (biotin-NM as a sensitive biotin-switch probe to identify oxidized Cys residues of mitochondrial proteins in the experimental models of alcoholic and acute liver disease. The aims of this paper are to briefly describe the mechanisms, functional consequences, and detection methods of mitochondrial dysfunction. We also describe advantages and limitations of the Cys-targeted redox proteomics method with alternative approaches. Finally, we discuss various applications of this method in studying oxidatively modified mitochondrial proteins in extrahepatic tissues or different subcellular organelles and translational research.

Analysis of hepatic gene expression during fatty liver change due to chronic ethanol administration in mice

International Nuclear Information System (INIS)

Yin, H.-Q.; Je, Young-Tae; Kim, Mingoo; Kim, Ju-Han; Kong, Gu; Kang, Kyung-Sun; Kim, Hyung-Lae; Yoon, Byung-IL; Lee, Mi-Ock; Lee, Byung-Hoon

2009-01-01

Chronic consumption of ethanol can cause cumulative liver damage that can ultimately lead to cirrhosis. To explore the mechanisms of alcoholic steatosis, we investigated the global intrahepatic gene expression profiles of livers from mice administered alcohol. Ethanol was administered by feeding the standard Lieber-DeCarli diet, of which 36% (high dose) and 3.6% (low dose) of the total calories were supplied from ethanol for 1, 2, or 4 weeks. Histopathological evaluation of the liver samples revealed fatty changes and punctate necrosis in the high-dose group and ballooning degeneration in the low-dose group. In total, 292 genes were identified as ethanol responsive, and several of these differed significantly in expression compared to those of control mice (two-way ANOVA; p < 0.05). Specifically, the expression levels of genes involved in hepatic lipid transport and metabolism were examined. An overall net increase in gene expression was observed for genes involved in (i) glucose transport and glycolysis, (ii) fatty acid influx and de novo synthesis, (iii) fatty acid esterification to triglycerides, and (iv) cholesterol transport, de novo cholesterol synthesis, and bile acid synthesis. Collectively, these data provide useful information concerning the global gene expression changes that occur due to alcohol intake and provide important insights into the comprehensive mechanisms of chronic alcoholic steatosis

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 ...

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

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Gemma Aragonès

2016-04-01

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

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

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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.

Inverse association between hepatitis B virus infection and fatty liver disease: a large-scale study in populations seeking for check-up.

Directory of Open Access Journals (Sweden)

Yuan-Lung Cheng

Full Text Available BACKGROUND: Although many studies have attempted to clarify the association between hepatitis B virus (HBV infection and fatty liver disease, no prior studies have emphasized the relationship of HBV and fatty liver regarding different demographics of age and body mass index (BMI. AIM: To investigate the correlation of HBV and fatty liver in the different demographics of age and BMI. METHODS: We enrolled consecutive subjects who had received health check-up services at the Taipei Veterans General Hospital from 2002 to 2009 and ultrasonography was used to diagnose fatty liver according to the practice guidelines of the American Gastroenterological Association. RESULTS: Among the 33,439 subjects enrolled in this study, fatty liver was diagnosed in 43.9% of the population and 38.9% of patients with chronic HBV infection. Multivariate analysis showed that BMI, age, waist circumference, systolic blood pressure, fasting glucose, cholesterol, alanine aminotransferase (ALT levels, and platelet counts were positively associated, while hepatitis B surface antigen (HBsAg positivity was inversely associated with fatty liver, especially for subjects with BMI>22.4 kg/m(2 and age>50 years. On the contrary, HBV infection was positively correlated with the presence of elevated serum ALT levels in subjects with fatty liver disease regardless of their age and BMI. CONCLUSIONS: Metabolic factors are important determinants for the prevalence of fatty liver. Patients with HBV infection were inversely associated with fatty liver disease than the general population, especially in older and obese patients. Furthermore, metabolic factors and HBV infection were associated with elevated serum ALT levels in fatty liver disease.

Identification of protective components that prevent the exacerbation of goose fatty liver: Characterization, expression and regulation of adiponectin receptors.

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Geng, Tuoyu; Yang, Biao; Li, Fuyuan; Xia, Lili; Wang, Qianqian; Zhao, Xing; Gong, Daoqing

2016-01-01

Fat accumulation in the liver is a natural process in goose, which prepares goose for long-distance migration. In contrast to mammalian fatty liver that usually progresses into an irreversible status, steatohepatitis, goose fatty liver can return to normal without obvious pathological damage, suggesting a protective system exists in goose liver. This study was to identify the components of this system. We first focused on goose adiponectin receptor 1 and 2 (Adipor1/2) as they have ceramidase activity, and can cleave ceramide, a group of proinflammatory signaling lipid species. Quantitative analysis indicated that tumor necrosis factor alpha (Tnfα), a key proinflammatory cytokine, was down-regulated in goose fatty liver by overfeeding. This inhibition of Tnfα was accompanied with reduced adiponectin and increased Adipor1/2 in the adipose tissues and in the livers of the overfed geese, respectively. To investigate the regulation of goose Adipor2 in the context of fatty liver, we treated goose primary hepatocytes with fatty liver associated factors. Data indicated that Adipor2 was upregulated by glucose and oleate but not palmitate. Its expression was even suppressed by high level of insulin. The regulation of Adipor1 by these factors was quite similar to that of Adipor2 except that glucose did not induce Adipor1. Together, these findings suggest the upregulation of Adipor1/2 may, at least partially, contribute to the inhibition of inflammation in goose fatty liver, and the expression of Adipor1/2 can be regulated by fatty liver-associated factors. Copyright © 2016 Elsevier Inc. All rights reserved.

Procoagulant imbalance in patients with non-alcoholic fatty liver disease.

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Tripodi, Armando; Fracanzani, Anna L; Primignani, Massimo; Chantarangkul, Veena; Clerici, Marigrazia; Mannucci, Pier Mannuccio; Peyvandi, Flora; Bertelli, Cristina; Valenti, Luca; Fargion, Silvia

2014-07-01

Non-alcoholic fatty liver disease (NAFLD) is characterized by increased risk of cardiovascular events and liver-fibrosis. Both could be explained by a procoagulant-imbalance that was surmised but never directly demonstrated. We investigated 113 patients with varying histological liver damage [steatosis (n=32), steatohepatitis (n=51), metabolic-cirrhosis (n=30)], 54 with alcoholic/viral-cirrhosis and 179 controls. Plasma was evaluated for levels of pro- and anti-coagulants, and for thrombin-generation assessed as endogenous-thrombin-potential (ETP) with and without thrombomodulin or Protac® as protein C activators. The procoagulant-imbalance was defined as ETP-ratio (with-to-without thrombomodulin) or as Protac®-induced-coagulation-inhibition (PICI%). High ETP-ratios or low PICI% indicate resistance to thrombomodulin or Protac® and hence a procoagulant-imbalance. ETP-ratio increased from controls [0.57 (0.11-0.89)] to steatosis [0.72 (0.33-0.86)] and metabolic-cirrhosis [0.80 (0.57-0.95)], (pimbalance detected as ETP-ratio greater or PICI% lower than the median value of controls tended to have a higher risk of metabolic-syndrome, higher intima-media thickness, fibrosis, steatosis or lobular inflammation, all considered clinical manifestations of NAFLD. NAFLD is characterized by a procoagulant-imbalance progressing from the less severe (steatosis) to the most severe form of the disease (metabolic-cirrhosis). This imbalance appears to result from increased factor VIII and reduced protein C and might play a role in the risk of cardiovascular events and liver-fibrosis commonly observed in NAFLD. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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

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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.

Fatty acid-binding protein in liver and small intestine of the preruminant calf

International Nuclear Information System (INIS)

Jenkins, K.J.

1986-01-01

Cytosol obtained from differential centrifugation of homogenates from liver and small intestine mucosa was incubated with 1-[ 14 C] oleic acid or 1-[ 14 C] palmitic acid and filtered through Sephadex G-75. Elution profiles for both tissues showed radioactivity in two main peaks, the first corresponding to binding of fatty acid to high molecular weight proteins and the second to a protein fraction with a molecular weight of approximately 12,000 daltons. The low molecular weight fraction had high fatty acid-binding activity, which was greater for oleic than palmitic acid. The findings demonstrate the presence of fatty acid-binding protein in liver and intestinal mucosa of the preruminant calf

Digital liver biopsy: Bio-imaging of fatty liver for translational and clinical research.

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Mancini, Marcello; Summers, Paul; Faita, Francesco; Brunetto, Maurizia R; Callea, Francesco; De Nicola, Andrea; Di Lascio, Nicole; Farinati, Fabio; Gastaldelli, Amalia; Gridelli, Bruno; Mirabelli, Peppino; Neri, Emanuele; Salvadori, Piero A; Rebelos, Eleni; Tiribelli, Claudio; Valenti, Luca; Salvatore, Marco; Bonino, Ferruccio

2018-02-27

The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a "digital biopsy" for in vivo study of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines (Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure) discussed criteria, methods and guidelines for facilitating the requisite application of data collection. This manuscript provides a multi-Author review of the issue with special focus on fatty liver.

T1-weighted dual-echo MRI for fat quantification in pediatric nonalcoholic fatty liver disease.

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Pacifico, Lucia; Martino, Michele Di; Catalano, Carlo; Panebianco, Valeria; Bezzi, Mario; Anania, Caterina; Chiesa, Claudio

2011-07-07

To determine in obese children with nonalcoholic fatty liver disease (NAFLD) the accuracy of magnetic resonance imaging (MRI) in assessing liver fat concentration. A case-control study was performed. Cases were 25 obese children with biopsy-proven NAFLD. Controls were 25 obese children matched for age and gender, without NAFLD at ultrasonography and with normal levels of aminotransferases and insulin. Hepatic fat fraction (HFF) by MRI was obtained using a modification of the Dixon method. HFF ranged from 2% to 44% [mean, 19.0% (95% CI, 15.1-27.4)] in children with NAFLD, while in the controls this value ranged from 0.08% to 4.69% [2.0% (1.3-2.5), P steatosis (r = 0.883, P steatosis, the mean HFF was 8.7% (95% CI, 6.0-11.6) for mild, 21.6% (15.3-27.0) for moderate, and 39.7% (34.4-45.0) for severe fatty liver infiltration. With a cutoff of 4.85%, HFF had a sensitivity of 95.8% for the diagnosis of histological steatosis ≥ 5%. All control children had HFF lower than 4.85%; thus, the specificity was 100%. After 12 mo, children with weight loss displayed a significant decrease in HFF. MRI is an accurate methodology for liver fat quantification in pediatric NAFLD.

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

Brain and liver fatty acid composition changes upon consumption of Lactobacillus rhamnosus LA68.

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Ivanovic, Nevena; Minic, Rajna; Djuricic, Ivana; Dimitrijevic, Ljiljana; Sobajic, Sladjana; Zivkovic, Irena; Djordjevic, Brizita

2015-02-01

Recent reports suggest that the metabolic activity of the enteric microbiota may influence the fatty acid composition of the host tissue. There are many studies dealing with the influence of lactobacilli on various pathological conditions, and some of the effects are strain-specific. This study was designed to test the effects of a particular Lactobacillus strain, Lactobacillus rhamnosus LA68 on fatty acid composition of the liver and the brain of C57BL/6 mice in the absence of an underlying pathological condition. Female mice were supplemented with live L. rhamnosus LA68 bacteria for the duration of 1 month. Serum biochemistry was analyzed and liver and brain fatty acid composition was assessed by gas-liquid chromatography. Significant changes in liver and brain fatty acid composition were detected. In the liver tissue we detected an increase in palmitoleic acid (p = 0.038), while in the brain compartment we found an increase in palmitic (p = 0.042), stearic (p = 0.017), arachidonic acid (p = 0.009) and docosahexaenoic acid (p = 0.004) for control versus experimental group. These results show discrete changes caused by LA68 strain consumption. Even short duration of administration of LA68 influences the fatty acid composition of the host which adds to the existing knowledge about Lactobacillus host interaction, and adds to the growing knowledge of metabolic intervention possibilities.

Systematic review of bariatric surgery liver biopsies clarifies the natural history of liver disease in patients with severe obesity.

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Bedossa, Pierre; Tordjman, Joan; Aron-Wisnewsky, Judith; Poitou, Christine; Oppert, Jean-Michel; Torcivia, Adriana; Bouillot, Jean-Luc; Paradis, Valerie; Ratziu, Vlad; Clément, Karine

2017-09-01

Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of morbid obesity, but its severity varies greatly and thus there is a strong need to better define its natural history in these patients. Liver biopsies were systematically performed in 798 consecutive patients with severe obesity undergoing bariatric surgery. Histology was compared with clinical, biological, anthropometrical and body composition characteristics. Patients with presumably normal liver (n=179, 22%) were significantly younger at bariatric surgery than patients with NAFLD (37.0 vs 44.4 years, pliver reported the onset of obesity at a significantly younger age than those with NAFLD (14.8 vs 20.0 year, pliver disease severity (presumably normal liver: 1.00, steatosis: 1.21, non-alcoholic steatohepatitis (NASH): 1.34, pliver: 50%, steatosis: 49.1%, NASH: 47.4%, pliver disease but only in female patients (presumably normal liver: 8543 picolitres, steatosis: 9156 picolitres, NASH: 9996 picolitres). These results suggest that young adults are more prone to store fat in subcutaneous tissue and reach the threshold of bariatric surgery indication before their liver is damaged. A shift of fat storage from subcutaneous to visceral adipose tissue compartment is associated with liver damages. Liver might also be targeted by subcutaneous hypertrophic adipocytes in females since hypertrophic adipocytes are more exposed to lipolysis and to the production of inflammatory mediators. 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/.

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease.

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Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan

Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Accurate Identification of Fatty Liver Disease in Data Warehouse Utilizing Natural Language Processing.

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Redman, Joseph S; Natarajan, Yamini; Hou, Jason K; Wang, Jingqi; Hanif, Muzammil; Feng, Hua; Kramer, Jennifer R; Desiderio, Roxanne; Xu, Hua; El-Serag, Hashem B; Kanwal, Fasiha

2017-10-01

Natural language processing is a powerful technique of machine learning capable of maximizing data extraction from complex electronic medical records. We utilized this technique to develop algorithms capable of "reading" full-text radiology reports to accurately identify the presence of fatty liver disease. Abdominal ultrasound, computerized tomography, and magnetic resonance imaging reports were retrieved from the Veterans Affairs Corporate Data Warehouse from a random national sample of 652 patients. Radiographic fatty liver disease was determined by manual review by two physicians and verified with an expert radiologist. A split validation method was utilized for algorithm development. For all three imaging modalities, the algorithms could identify fatty liver disease with >90% recall and precision, with F-measures >90%. These algorithms could be used to rapidly screen patient records to establish a large cohort to facilitate epidemiological and clinical studies and examine the clinic course and outcomes of patients with radiographic hepatic steatosis.

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

DEFF Research Database (Denmark)

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

2016-01-01

BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with few therapeutic options. RSV prevents the development of steatosis in a number of experimental fatty liver (NAFL) models but the preventive or therapeutic effects on experimental NASH.......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...... are not yet clarified, and clinical results on NAFLD are ambiguous. Thus, we aimed to compare the RSV-mediated preventive and therapeutic effects on experimental NAFL and NASH. METHODS: 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...

[Balneotherapeutics of non-alcoholic fatty liver disease with the use of the Essentuki-type drinking mineral waters].

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

2012-01-01

The objective of the present work was to estimate the effectiveness of combined spa-and-resort treatment with the use of the Essentuki-type drinking mineral waters for the patients presenting with non-alcoholic fatty liver disease. A total of 40 patients presening with non-alcoholic fatty liver disease (NOFLD) were available for the examination. The study has demonstrated positive dynamics of clinical symptoms and results of liver functional tests, characteristics of intrahepatic dynamics, lipid metabolism, antioxidant hemostais, and the hormonal status of the patients with non-alcoholic fatty liver disease. The intake of the Essentuki-type drinking mineral waters promoted normalization of adiponectin and leptin levels in conjunction with the reduction in the degree of insulin resistance, i.e., the key pathogenetic factors responsible for hepatic steatosis and non-alcoholic steatohepatitis. It is concluded that the Essentuki-type drinking mineral waters may be recommended for the inclusion in the combined treatment and prevention of the progression of non-alcoholic fatty liver disease.

In vivo 19F-MRS observation of 5-FU metabolism in fatty liver induced by choline-deficient diet

International Nuclear Information System (INIS)

Otsuka, Hideki; Harada, Masafumi; Nishitani, Hiromu; Koga, Keiko.

1996-01-01

Using 19 F-MRS, 5-FU metabolism was investigated in rat fatty liver. Fatty liver was induced by choline-deficient diet (CD diet). This study showed differences in 5-FU metabolism between normal and fatty liver. After laparotomy, a surface coil was placed directly on the liver surface. Spectra were continuously obtained after injection of 5-FU 100 mg/kg body weight via a catheter inserted into femoral vein. We made MRI and 1 H-MRS study to examine the lipid accumulation. Histological study was also performed using HE (hematoxylin-eosin) and oil red stain. The livers of rats fed a CD diet showed very high intensity on T 1 -WI. 1 H-MRS was very useful in deteminating the fat content because the fat ratio demonstrated by 1 H-MRS is well correlated to histological findings. In 19 F-MRS, we recognized the following four peaks: 5-FU, FBAL, Fnct (fluoronucleotide) and FUPA. The decrease of 5-FU was not very apparent, but compared to the normal liver, the formation of Fnct increased and the formation of FBAL was suppressed in fatty liver. The rats fed a CD diet for four weeks showed a higher Fnct peak and lower FBAL peak compared with the results of rats fed a CD diet for two weeks. In a CD diet group, liver cell degeneration and necrotic changes were observed histologically. It is reported that cell degeneration is followed by cell proliferation in fatty liver induced by a choline deficient diet, and the high Fnct peak found in our study may reflect this phenomenon. The high Fnct peak on 19 F-MRS may correspond to recovering reaction from liver injury like fatty liver. (author)

Recent insights into the biological functions of liver fatty acid binding protein 1

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Wang, GuQi; Bonkovsky, Herbert L.; de Lemos, Andrew; Burczynski, Frank J.

2015-01-01

Over four decades have passed since liver fatty acid binding protein (FABP)1 was first isolated. There are few protein families for which most of the complete tertiary structures, binding properties, and tissue occurrences are described in such detail and yet new functions are being uncovered for this protein. FABP1 is known to be critical for fatty acid uptake and intracellular transport and also has an important role in regulating lipid metabolism and cellular signaling pathways. FABP1 is an important endogenous cytoprotectant, minimizing hepatocyte oxidative damage and interfering with ischemia-reperfusion and other hepatic injuries. The protein may be targeted for metabolic activation through the cross-talk among many transcriptional factors and their activating ligands. Deficiency or malfunction of FABP1 has been reported in several diseases. FABP1 also influences cell proliferation during liver regeneration and may be considered as a prognostic factor for hepatic surgery. FABP1 binds and modulates the action of many molecules such as fatty acids, heme, and other metalloporphyrins. The ability to bind heme is another cytoprotective property and one that deserves closer investigation. The role of FABP1 in substrate availability and in protection from oxidative stress suggests that FABP1 plays a pivotal role during intracellular bacterial/viral infections by reducing inflammation and the adverse effects of starvation (energy deficiency). PMID:26443794

Scintigraphic appearance of focal fatty infiltration of the liver using single-photon emission computed tomography

International Nuclear Information System (INIS)

Kudo, M.; Hirasa, M.; Ibuki, Y.

1984-01-01

Fatty infiltration of the liver had been considered to assume a uniform distribution until quite recently. However, the development of X-ray computed tomography (XCT) and the ultrasound (US) has proven that fatty infiltration of the liver may sometimes assume a nonuniform distribution (focal fatty infiltration (FFI)). This investigation was undertaken to evaluate the scintigraphic appearance of FFI using single-photon emission computed tomography (SPECT) with a GE Maxicamera 400T. Radionuclide images including SPECT were evaluated in 12 cases with FFI which were diagnosed by XCT and US. Most of them were histrogically confirmed to be positive fatty infiltration in the liver. The results were as follows. The fatty infiltrated area was visualized as a hot spot in one case, a defect in 2 cases, a low uptake in one case and a normal uptake in 8 cases. Radionuclide imaging of FFI shows a large variety of findings and it suggests that Kupffer cell function varies with the causes or stage of fatty infiltration. And one can understand the pathological state of FFI from a viewpoint of Kupffer cell function only by radionuclide imaging including SPECT, which is very useful to compare the images with XCT images

Metabolic adaptations in models of fatty liver disease : Of mice and math

NARCIS (Netherlands)

Hijmans, Brenda

2017-01-01

The increasing incidence of overweight is accompanied by a plethora of medical symptoms together called the metabolic syndrome. Non-alcoholic fatty liver disease, characterized by persistent storage of lipids in the liver, is regarded as the hepatic component of the metabolic syndrome. An imbalance

Nutritional Management of Insulin Resistance in Nonalcoholic Fatty Liver Disease (NAFLD

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Judith Wylie-Rosett

2013-10-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is an emerging global health concern. It is the most common form of chronic liver disease in Western countries, affecting both adults and children. NAFLD encompasses a broad spectrum of fatty liver disease, ranging from simple steatosis (NAFL to nonalcoholic steatohepatitis (NASH, and is strongly associated with obesity, insulin resistance, and dyslipidemia. First-line therapy for NAFLD includes weight loss achieved through diet and physical activity. However, there is a lack of evidenced-based dietary recommendations. The American Diabetes Association’s (ADA recommendations that aim to reduce the risk of diabetes and cardiovascular disease may also be applicable to the NAFLD population. The objectives of this review are to: (1 provide an overview of NAFLD in the context of insulin resistance, and (2 provide a rationale for applying relevant aspects of the ADA recommendations to the nutritional management of NAFLD.

Multidisciplinary Pharmacotherapeutic Options for Nonalcoholic Fatty Liver Disease

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Kei Nakajima

2012-01-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1 inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.

Animal experimental studies on the influence of fatty infiltration of the liver on tissue relaxation times and signal changes in MRT

International Nuclear Information System (INIS)

Kreft, B.; Stark, D.; Schild, H.

1995-01-01

Using a spectrometer (n=60) in vitro and MRT imaging (n=8) in vivo, we studied the influence of fatty changes of liver cells on the relaxation times of the liver (two animal models of fatty liver disease/orotic acid, L-ethionine). Induction of fatty degeneration of the liver by means of an orotic acid diet resulted in pure deposition of fat in the liver without any histological or serological proof of inflammatory changes. Although accumulation of triglyceride in the liver reduced the T 1 relaxation time only relatively slightly (-15%), there was good correlation (r=0.88) between fat content and T 1 . There was also good correlation (r=0.92) between T 2 and histological fat content. Inflammatory changes besides fatty deposition were seen both serologically and histologically in the L-ethionine model, so that the fatty content did not correlate with T 1 . In-vivo MRT imaging showed that spin-echo sequences are inappropriate for diagnosing fatty infiltration of the liver despite the relaxation time changes produced by the fatty deposition. On the other hand, chemical-shift imaging sequences are very sensitive to identify fatty deposits, and are also independent of any additionally existing inflammatory changes. (orig.) [de

High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery.

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Xanthakos, Stavra A; Jenkins, Todd M; Kleiner, David E; Boyce, Tawny W; Mourya, Reena; Karns, Rebekah; Brandt, Mary L; Harmon, Carroll M; Helmrath, Michael A; Michalsky, Marc P; Courcoulas, Anita P; Zeller, Meg H; Inge, Thomas H

2015-09-01

Little is known about the prevalence of nonalcoholic fatty liver disease (NAFLD) among severely obese adolescents or factors that determine its development. We investigated the prevalence of NAFLD in a multicenter cohort of adolescents undergoing bariatric surgery and the factors associated with it. We enrolled 242 adolescents undergoing bariatric surgery between March 2007 and February 2012 at 5 tertiary care centers into a multicenter, prospective observational cohort study. Intraoperative core liver biopsies were collected from 165 subjects; 17 were excluded because of insufficient liver tissue or use of hepatotoxic medications, so 148 remained in the study (mean age, 16.8 ± 1.6 years; median body mass index = 52 kg/m(2)). Liver tissues were analyzed by histology using validated criteria. Hepatic gene expression was analyzed in 67 samples. NAFLD was present in 59% of this predominantly female (72%), white (68%), non-Hispanic (91%) cohort. Of subjects with NAFLD, 24% had borderline and 10% had definite nonalcoholic steatohepatitis (NASH). Mild fibrosis (stage 2 or lower) was observed in 18% of liver biopsies and stage 3 was observed in 0.7%, but cirrhosis was not detected. Dyslipidemia was present in 78% of subjects, hypertension in 44%, and diabetes in 14%. More severe NAFLD was associated with increasing levels of alanine aminotransferase, fasting glucose level, hypertension (each P adolescents undergoing bariatric surgery in this cohort had NAFLD, yet the prevalence of severe or fibrotic NASH was low. Increasing severity of NAFLD was associated with level of alanine aminotransferase and cardiometabolic risk factors, but not body mass index. Based on gene expression analysis, borderline and definite NASH were associated with abnormal immune function, intestinal cholesterol absorption, and lipid metabolism. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Nonalcoholic fatty liver in patients with Laron syndrome and GH gene deletion - preliminary report.

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Laron, Zvi; Ginsberg, Shira; Webb, Muriel

2008-10-01

There is little information on the relationship between growth hormone/insulin-like growth factor-I (GH/IGF-I) deficiency or IGF-I treatment on nonalcoholic fatty liver disease (NAFLD) a disorder linked to obesity and insulin resistance. To find out whether the markedly obese patients with Laron syndrome (LS) and GH gene deletion have fatty livers. We studied 11 untreated adult patients with LS (5M, 6F), five girls with LS treated by IGF-I and five adult patients with GH gene deletion (3M, 3F), four previously treated by hGH in childhood. Fatty liver was quantitatively evaluated by ultrasonography using a phase array US system (HITACHI 6500, Japan). Body adiposity was determined by DEXA, and insulin resistance was estimated by HOMA-IR using the fasting serum glucose and insulin values. Six out of 11 adult patients with LS, two out of the five IGF-I treated girls with LS and three out of five adult hGH gene deletion patients were found to have NAFLD (nonalcoholic fatty liver disease). NAFLD is a frequent complication in untreated and treated congenital IGF-I deficiency. No correlation between NAFLD and age, sex, degree of obesity, blood lipids, or degree of insulin resistance was observed.

Assessment of the fatty liver index as an indicator of hepatic steatosis for predicting incident diabetes independently of insulin resistance in a Korean population.

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Jung, C H; Lee, W J; Hwang, J Y; Yu, J H; Shin, M S; Lee, M J; Jang, J E; Leem, J; Park, J-Y; Kim, H-K

2013-04-01

Fatty liver disease, especially non-alcoholic fatty liver disease, is considered to be the hepatic manifestation of the metabolic syndrome, both closely associated with insulin resistance. Furthermore, fatty liver disease assessed by ultrasonography is known to be a predictor of the development of Type 2 diabetes mellitus. However, it remains unclear whether fatty liver disease plays a role in the pathogenesis of Type 2 diabetes independently of insulin resistance. In this study, we investigated whether fatty liver disease assessed by the fatty liver index can predict the development of Type 2 diabetes independently of systemic insulin resistance. We examined the clinical and laboratory data of 7860 subjects without diabetes who underwent general routine health evaluations at the Asan Medical Center in 2007 and had returned for follow-up examinations in 2011. Fatty liver index was calculated using an equation that considers serum triglyceride levels, γ-glutamyltransferase, waist circumference and BMI. During a 4-year period, 457 incident diabetes cases (5.8%) were identified. The odds ratios for the development of Type 2 diabetes were significantly higher in the group with a fatty liver index ≥ 60 (fatty liver index-positive) than in the group with a fatty liver index hepatic steatosis is valuable in identifying subjects at high risk for Type 2 diabetes. In addition, fatty liver disease itself contributes to the development of Type 2 diabetes independently of systemic insulin resistance. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease.

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Davide Povero

Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy.Choline Deficient L-Amino Acid (CDAA and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens.We observed statistically significant differences in the level of extracellular vesicles (EVs in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p<0.05, fibrosis (r2 = 0.66, p<0.05 and pathological angiogenesis (r2 = 0.71, p<0.05. Extensive characterization of blood EVs identified both microparticles (MPs and exosomes (EXO present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192--two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver.These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD.

Non-alcoholic fatty liver disease in obese persons with diabetes

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Tomašević Ratko

2007-01-01

Full Text Available Background. Obesity, diabetes and different lipid metabolic disorders are the most frequent risk factors for nonalcoholic fatty liver disease, presented with a high variability in clinical and histological findings. Case report. We presented a case of 37-year-old male, suffering from type 2 diabetes mellitus, grade III obesity (BMI 45 kg/m2 and multiple metabolic disorders. Abdominal ultrasound revealed hepatomegaly during the last six months. Laboratory diagnostics showed increased serum transaminase levels. Serologic markers for viral hepatitis B and C were negative. The patient denied significant alcohol consumption. Liver biopsy and pathohistologic finding revealed macro- (III grade and microvesicular (I grade fatty degeneration, as well as mixed-cell portal infiltration with moderate liver fibrosis, corresponding to the typical presentation of NASH (Non Alcoholic Steatohepatitis. Conclusion. NASH treatment options include the reduction of body mass and an adequate antidiabetic and dislipidemia treatment. The aim of all therapeutic measures was to stop the progression of the disease, to prevent the progression of fibrosis and the development of of cirrhosis. .

Emerging roles of the RB/E2F pathway in fatty liver disease and cancer

NARCIS (Netherlands)

Matondo, R.B.

2018-01-01

Liver cancer in humans is ranked number five concerning cancer related deaths accounted worldwide. Many risk factors related to liver cancer have been identified including hepatitis virus infection, exposure to mycotoxins, and fatty liver disease. These risk factors predispose livers to develop

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

International Nuclear Information System (INIS)

Kim, Seok-Joo; Lee, Sun-Mee

2012-01-01

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

Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

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Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

2016-09-01

Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet-Induced Nonalcoholic Fatty Liver Disease in Mice.

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Kim, Sung-Bae; Kang, Ok-Hwa; Lee, Young-Seob; Han, Sin-Hee; Ahn, Young-Sup; Cha, Seon-Woo; Seo, Yun-Soo; Kong, Ryong; Kwon, Dong-Yeul

2016-01-01

Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC) is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD)-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment), MCD diet (MCD diet only), MCD + silymarin (SIL) 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent against NAFLD.

Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet-Induced Nonalcoholic Fatty Liver Disease in Mice.

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Sung-Bae Kim

Full Text Available Nonalcoholic fatty liver disease (NAFLD, the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment, MCD diet (MCD diet only, MCD + silymarin (SIL 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent

[Progress in research of the mechanisms related with the hepatic steatosis in the nonalcoholic fatty liver disease].

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Shi, Li-Juan; Song, Guang-Yao

2013-12-01

With the increased morbidity of Nonalcoholic fatty liver disease, the pathogenesis of which has become one of the focuses for researchers. Many details need to be clarified. The hepatic steatosis has been taken as the clinical pathological characters and the "golden standard of diagnosis" for the nonalcoholic fatty liver disease. More and more studies have shown that the hepatic steatosis (mainly as triglycerides) is the consequence of hepatic lipid metabolism disequilibrium. Generally, the related metabolism pathways including lipid input, lipid uptake, de novo lipogenesis, fatty acid oxidation, fatty acid reesterification, and lipid secretion etc. In this review, we focused on the progress of some key enzymes involved in these pathways in order to clarify the possible molecular mechanisms and the effective targets so that to broad our vision about the prevention and treatment of non-alcoholic fatty liver disease.

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

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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.

An Overview of Dietary Interventions and Strategies to Optimize the Management of Non-Alcoholic Fatty Liver Disease

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Brandon J. Perumpail

2017-10-01

Full Text Available Aim: To investigate the efficacy of lifestyle adjustment strategies as a preventive measure and/or treatment of obesity-related non-alcoholic fatty liver disease in adults. Method: A systematic review of literature through 1 July 2017 on the PubMed Database was performed. A comprehensive search was conducted using key terms, such as non-alcoholic fatty liver disease (NAFLD, combined with lifestyle intervention, diet, and exercise. All of the articles and studies obtained from the search were reviewed. Redundant literature was excluded. Results: Several types of dietary compositions and exercise techniques were identified. Most studies concluded and recommended reduction in the intake of saturated and trans fatty acids, carbohydrates, and animal-based protein, and increased intake of polyunsaturated fatty acids (PUFAs, monounsaturated fatty acids (MUFAs, plant-based proteins, antioxidants, and other nutrients was recommended. The Mediterranean and Paleo diet both seem to be promising schemes for NAFLD patients to follow. Exercise was also encouraged, but the type of exercise did not affect its efficacy as a NAFLD treatment when the duration is consistent. Conclusions: Although these different dietary strategies and exercise regimens can be adopted to treat NAFLD, current literature on the topic is limited in scope. Further research should be conducted to truly elucidate which lifestyle adjustments individually, and in combination, may facilitate patients with obesity-related NAFLD.

An Overview of Dietary Interventions and Strategies to Optimize the Management of Non-Alcoholic Fatty Liver Disease.