Amount Of Liver Fat Research Articles

Predicting of hepatic steatosis in living liver donor via CT liver attenuation index (LAI) and fibroscan controlled attenuation parameter (CAP) correlation with biopsy result

BackgroundThe most prevalent persistent parenchymatous liver alterations in healthy individuals are thought to be hepatic steatosis. The liver biopsy is the most crucial procedure for the identification and measurement of hepatic steatosis. By identifying the liver attenuation index (LAI) at CT image with fibroscan controlled attenuation parameter (CAP), hepatic steatosis can be evaluated without the risk of liver resection.ObjectiveUsing liver biopsy histological analysis as a reference standard, to examine the precision of the CT liver attenuation index (LAI) and fibroscan controlled attenuation parameter (CAP) for quantitative evaluation of macrovesicular steatosis in living related liver donors.MethodsIn this cross-sectional study, comparing the CT liver attenuation index & fibroscan controlled attenuation parameter with liver biopsy result for the detection of the steatosis in subject's candidate for liver living donors, 50 subjects were conducted at Ain Shams Specialized Hospital and other private hospitals over about 2 years.ResultsOur study reported that liver attenuation index of 9 is the cutoff value in post-contrast CT images with sensitivity 100% and specificity 80% that make it a very good method to exclude donor to have steatosis ≥ 15%, which mean that if donor had LAI index < 9, we can safely do proceed do liver biopsy. Our study reported that CAP measurement had an AUROC OF 0.780, for detecting steatosis ≥ 15%, with sensitivity is only 60% with specificity as CT LAI of 80%, our results consider low compared to other studies, that could be due to small number of donors in our study with steatosis ≥ 15% (five cases from 50 donors) unlike the other studies.ConclusionWhen used to estimate the amount of liver fat in liver donors, the examined CAP and CT indices worked equally. But according to multivariate analysis, the only factor strongly linked with hepatic steatosis in a living donors was the CT LAI index. We contend that the combination of CT LS attenuation index and CAP allows for the detection of the degree of hepatic steatosis and can be used as an option to liver biopsy, reserving liver biopsy for those with positive steatosis donors.

Predicting of Hepatic Steatosis in Living Liver Donor via CT Liver Attenuation Index (LAI) and Fibroscan Controlled Attenuation Parameter (CAP) Correlation with Biopsy Result

Abstract Background The most prevalent persistent parenchymatous liver alterations in healthy individuals are thought to be hepatic steatosis. The liver biopsy is the most crucial procedure for the identification and measurement of hepatic steatosis. By identifying the liver attenuation index (LAI) at an unenhanced CT image, hepatic steatosis can be evaluated without the risk of liver resection. Objective Using liver biopsy histological analysis as a reference standard, to examine the precision of the CT liver attenuation index (LAI) and fibroscan controlled attenuation parameter (CAP) for quantitative evaluation of macro vesicular steatosis in living related liver donors. Methods In this study comparing CT liver attenuation index &amp; fibroscan controlled attenuation parameter with liver pathology of steatosis in subject's candidate for liver living donors 50 subjects in each two study's correlation with biopsy results, conducted at Ain Shams Shams Specialized hospital and other Private hospitals over about 2 years. Results Our study reported that liver – spleen attenuation index of 9 is the cutoff value with sensitivity 100% and specificity 80% that make it a very good method to exclude donor to have steatosis ≥15%, which mean if donor had LS index &amp;lt; 9 we can safely do proceed do liver biopsy. Our study reported that CAP measurement had an AUROC OF 0.780, for detecting steatosis ≥ 15 %, with sensitivity is only 60% with specificity as CT LAI of 80%, which consider low compared to other study, that could be due to small number of donors in out study with steatosis ≥ 15 % (5 case from 50 donors) unlike the other studies. Conclusion When used to estimate the amount of liver fat in liver donors, the examined CAP and CT indices worked equally. But according to multivariate analysis, the only factor strongly linked with hepatic steatosis in alive donors was the CT L-S attenuation index. We contend that the combination of CT L-S attenuation index and CAP allows for the detection of the degree of hepatic steatosis and can be used as an option to liver biopsy, reserving liver biopsy for those with positive steatosis donors.

Starvation in Mice Induces Liver Damage Associated with Autophagy.

Anorexia nervosa (AN) induces organ dysfunction caused by malnutrition, including liver damage leading to a rise in transaminases due to hepatocyte damage. The underlying pathophysiology of starvation-induced liver damage is poorly understood. We investigate the effect of a 25% body weight reduction on murine livers in a mouse model and examine possible underlying mechanisms of starvation-induced liver damage. Female mice received a restricted amount of food with access to running wheels until a 25% weight reduction was achieved. This weight reduction was maintained for two weeks to mimic chronic starvation. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured spectrophotometrically. Liver fat content was analyzed using an Oil Red O stain, and liver glycogen was determined using a Periodic acid-Schiff (PAS) stain. Immunohistochemical stains were used to investigate macrophages, proliferation, apoptosis, and autophagy. Starvation led to an elevation of AST and ALT values, a decreased amount of liver fat, and reduced glycogen deposits. The density of F4/80+ macrophage numbers as well as proliferating KI67+ cells were decreased by starvation, while apoptosis was not altered. This was paralleled by an increase in autophagy-related protein staining. Increased transaminase values suggest the presence of liver damage in the examined livers of starved mice. The observed starvation-induced liver damage may be attributed to increased autophagy. Whether other mechanisms play an additional role in starvation-induced liver damage remains to be investigated.

Liver fat as risk factor of hepatic and cardiometabolic diseases.

Non-alcoholic fatty liver disease (NAFLD) is a disorder characterized by excessive accumulation of fat in the liver that can progress to liver inflammation (non-alcoholic steatohepatitis [NASH]), liver fibrosis, and cirrhosis. Although most efforts for drug development are focusing on the treatment of the latest stages of NAFLD, where significant fibrosis and NASH are present, findings from studies suggest that the amount of liver fat may be an important independent risk factor and/or predictor of development and progression of NAFLD and metabolic diseases. In this review, we first describe the current tools available for quantification of liver fat in humans and then present the clinical and pathophysiological evidence that link liver fat with NAFLD progression as well as with cardiometabolic diseases. Finally, we discuss current pharmacological and non-pharmacological approaches to reduce liver fat and present open questions that have to be addressed in future studies.

Quantitative Prediction of Steatosis in Patients with Non-Alcoholic Fatty Liver by Means of Hepatic MicroRNAs Present in Serum and Correlating with Hepatic Fat.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease worldwide, but a reliable non-invasive method to quantify liver steatosis in primary healthcare is not available. Circulating microRNAs have been proposed as biomarkers of severe/advanced NAFLD (steatohepatitis and fibrosis). However, the use of circulating miRNAs to quantitatively assess the % of liver fat in suspected NAFLD patients has not been investigated. We performed global miRNA sequencing in two sets of samples: human livers from organ donors (n = 20), and human sera from biopsy-proven NAFLD patients (n = 23), both with a wide range of steatosis quantified in their liver biopsies. Partial least squares (PLS) regression combined with recursive feature elimination (RFE) was used to select miRNAs associated with steatosis. Moreover, regression models with only 2 or 3 miRNAs, with high biological relevance, were built. Comprehensive microRNA sequencing of liver and serum samples resulted in two sets of abundantly expressed miRNAs (418 in liver and 351 in serum). Pearson correlation analyses indicated that 18% of miRNAs in liver and 14.5% in serum were significantly associated with the amount of liver fat. PLS-RFE models demonstrated that 50 was the number of miRNAs providing the lowest error in both liver and serum models predicting steatosis. Comparison of the two miRNA subsets showed 19 coincident miRNAs that were ranked according to biological significance (guide/passenger strand, relative abundance in liver and serum, number of predicted lipid metabolism target genes, correlation significance, etc.). Among them, miR-10a-5p, miR-98-5p, miR-19a-3p, miR-30e-5p, miR-32-5p and miR-145-5p showed the highest biological relevance. PLS regression models with serum levels of 2–3 of these miRNAs predicted the % of liver fat with errors <5%.

EPA/DHA and linseed oil have different effects on liver and adipose tissue in rats fed with a high-fat diet

The incidence of cardiovascular diseases and metabolic disorders has increased worldwide. Clinical and experimental research has shown that the consumption of ω-3 FAs can be beneficial to metabolism in several ways, as they can act on metabolic pathways. Our objective was to evaluate the effect of treatment with linseed oil, a vegetable oil rich in alpha-linolenic acid, and EPA and DHA in different proportions (3:1 EPA:DHA, and 1:3 EPA:DHA), on the metabolic disorders induced by a high-fat diet (20 % lipids) in rats for 2 weeks, after 18 weeks of consumption of a high-fat diet. In 18 weeks, the high-fat diet increased blood glucose, systolic blood pressure, triglyceride concentration in the liver and adipose tissue, and impaired insulin sensibility without interfering in the weight of the animals. All treatments were effective in reducing the deposition of hepatic type III collagen, the proportion of ω-6/ω-3 in the liver and WAT (white adipose tissue), the proportion of area/number of adipocytes, and the gene expression of the ACC, FAS, and CPT1 enzymes. In addition, treatment with EPA and DHA reduced blood glucose, serum TNF-α concentration, amount of liver fat, degree of microsteatosis and type I collagen deposition in the liver, deposition of type I and III collagen in TA, gene expression of the transcription factor SREBP-1c, and increased hepatic binucleation. EPA in major proportion was more effective in reducing the area of adipocytes, hepatic triglyceride concentration, PPAR-α expression, and WAT fat weight. DHA in a major proportion reduced the concentration of MCP1 in WAT. LO treatment did not have any isolated effects. We concluded that EPA and DHA were more effective in treating metabolic damage than treatment with LO, leading to a more favorable metabolic profile.

Psoas muscle area and paraspinal muscle fat in children and young adults with or without obesity and fatty liver.

BackgroundLittle is known about the muscle condition in children with obesity.ObjectivesTo investigate the effect of obesity and fatty liver on muscle area and muscle fat in children and young adults.Materials and methodsWe evaluated consecutive liver fat quantification MRIs in children and young adults between June 2015 and April 2019. We obtained hepatic fat and paraspinal muscle fat at mid L2 from the fat map, psoas muscle area (PMA) at mid L3, and z-score of PMA. The patient’s age, height and weight at the time of the MRI were recorded. Body mass index (BMI) z-score was also calculated. Spearman correlation and partial correlation analyses were performed. Univariate and multivariate regression analyses were also performed using significant variables.ResultsA total of 132 patients (97 male) were included with a median age of 13.0 years (interquartile range 11–16 years). The median BMI was 23.7 kg/m2 (interquartile range 21.2–27.7 kg/m2). The weight, BMI, liver fat, and z-score of PMA were all higher in male patients than they were in female patients. The amount of liver fat had no correlation with muscle fat or PMA z-score after adjusting BMI. However, the BMI z-score was positively correlated with the PMA z-score (ρ = 0.432, p<0.001) even after adjusting for liver fat. On regression analyses, the BMI z-score had linear positive relationship with PMA z-score (β = 0.289, p<0.001) and muscle fat (β = 0.218, p = 0.016).ConclusionsMale children and young adults have greater PMA than do female children and young adults. Obesity is associated with higher PMA and paraspinal muscle fat. However, liver fat is not related with the muscle condition in children and young adults.

Test-Retest Reliability of the Assessment of Fatty Liver Disease Using Low-Dose Computed Tomography in Cardiac Patients.

Non-alcoholic fatty liver disease (NAFLD) is a common disorder that is associated with the risk of cardiovascular diseases. Therefore, its prevalence is high in patients with coronary artery disease. In myocardial perfusion imaging (MPI), low-dose computed tomography (CT) scans are used for attenuation correction in separate stress and rest studies. Here, the test–retest reliability of CT-based quantification of NAFLD was evaluated using these two CT scans. The study population consisted of 261 patients (156 men and 105 women, age 66 ± 10 years). Quantification of liver fat content was based on the radiodensity of the liver in Hounsfield units as well as in relation to corresponding values of the spleen. NAFLD was observed in 47 subjects (18%). CT quantification has good test–retest reliability in assessing NAFLD, with concordance correlation coefficient (CCC) ranging from 0.512 to 0.923, intraclass correlation coefficient (ICC) ranging from 0.513 to 0.923, and coefficient of variation ranging from 3.1 to 7.0%. Regarding the liver to spleen ratio, CCC for non-NAFLD patients and NAFLD patients was 0.552 and 0.911, respectively. For non-NAFLD patients ICC was 0.553 and NAFLD patients it was 0.913. The coefficient of variation for non-NAFLD and NAFLD patients was 4.9% and 3.1%, respectively. Our results suggest that low-dose CT is a feasible and well repeatable method but amount of liver fat contributes to repeatability. In NAFLD patients CCC and ICC were high reflecting excellent reliability, whereas in non-NAFLD patients test-retest reliability was moderate. Assessment of liver fat content can be used as additional information in studies where a CT scan has been done for other medical reasons, such as for low-dose attenuation correction CT along with MPI.

Dairy Fat Intake, Plasma Pentadecanoic Acid, and Plasma Iso-heptadecanoic Acid Are Inversely Associated With Liver Fat in Children.

We sought to evaluate the relevance of pediatric dairy fat recommendations for children at risk for nonalcoholic fatty liver disease (NAFLD) by studying the association between dairy fat intake and the amount of liver fat. The effects of dairy fat may be mediated by odd chain fatty acids (OCFA), such as pentadecanoic acid (C15:0), and monomethyl branched chain fatty acids (BCFA), such as iso-heptadecanoic acid (iso-C17:0). Therefore, we also evaluated the association between plasma levels of OCFA and BCFA with the amount of liver fat. Observational, cross-sectional, community-based sample of 237 children ages 8 to 17. Dairy fat intake was assessed by 3 24-hour dietary recalls. Plasma fatty acids were measured by gas chromatography-mass spectrometry. Main outcome was hepatic steatosis measured by whole liver magnetic resonance imaging proton density fat fraction (MRI-PDFF). Median dairy fat intake was 10.6 grams/day (range 0.0--44.5 g/day). Median liver MRI-PDFF was 4.5% (range 0.9%-45.1%). Dairy fat intake was inversely correlated with liver MRI-PDFF (r = -0.162; P = .012). In multivariable log linear regression, plasma C15:0 and iso-C17:0 were inverse predictors of liver MRI-PDFF (B = -0.247, P = 0.048; and B = -0.234, P = 0.009). Dairy fat intake, plasma C15:0, and plasma iso-C17:0 were inversely correlated with hepatic steatosis in children. These hypothesis-generating findings should be tested through clinical trials to better inform dietary guidelines.

Cereal bar sweetened with stevia leaves reduces fatty liver in diabetic rats

Diabetes mellitus and hepatic steatosis are diseases of great epidemiological impact and have been associated with increased consumption of sugary foods and drinks. The objective of this work was to evaluate the effect of food supplementation with cereal bars sweetened with Stevia rebaudiana leaves pretreated with ethanol (SLPE) on the metabolic control of streptozotocininduced diabetic rats. Two cereal bar formulations were developed: one sweetened with SLPE, and the other sweetened with sucrose. The cereal bars were added to the standard ration for rodents (125g:1000g) and offered ad libitum to diabetic animals for 30 days. Important physiological parameters were recorded during and at the end of this period for metabolic control (body weight, food intake, glycemia, fructosamine, triglycerides, cholesterol, AST, ALT, liver fat and glucose tolerance). The diet supplemented with cereal bars sweetened with SLPE significantly reduced the amount of liver fat in diabetic rats, suggesting the potential of cereal bars sweetened with SLPE to act as a functional food for diabetic patients.

MRI-determined liver fat correlates with risk of metabolic syndrome in patients with nonalcoholic fatty liver disease.

Little is known about that the relationship between hepatic fat content (HFC) and metabolic syndrome (MetS). We aimed to determine whether HFC correlated with MetS in patients with nonalcoholic fatty liver disease (NAFLD). HFC was measured by MRI-determined proton density fat fraction (MRI-PDFF) for 131 suspected NAFLD subjects. Patients with NAFLD defined as MRI-PDFF ≥5% were stratified into two groups based on whether they were above or below the median MRI-PDFF value; the MRI-PDFF value for the control group was <5%. The primary outcome was the presence of MetS. Logistic regression models were used to obtain the associations between the severity of liver fat and MetS, and the corresponding odds ratios (ORs) and 95% confidence intervals (CIs) were recorded. Compared to NAFLD patients with low-HFC (n = 48) and the control group (n = 35), NAFLD patients with high-HFC (n = 48) had significantly greater prevalence of central obesity, hypertension, hyperglycemia, and hypertriglyceridemia (all P < 0.05). NAFLD patients with high-HFC had a higher prevalence of MetS than NAFLD patients with low-HFC (79.2% vs. 56.2%, P < 0.05). The multivariate-adjusted OR for the prevalence of MetS comparing NAFLD patient with low-HFC and high-HFC to the control group were 4.56 (95% CI: 0.54-38.79, P = 0.165) and 22.91 (95% CI: 1.80-292.21, P = 0.016), respectively (Ptrend = 0.014). Increased hepatic fat quantitatively measured by MRI-PDFF had a significant dose-relationship with the presence of MetS, and the amount of liver fat may affect cardiovascular risk.

The amount of liver fat predicts mortality and development of type 2 diabetes in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a risk factor for development of type 2 diabetes mellitus (T2DM). We aimed to evaluate whether conventional histological grading of steatosis and accurate quantification of fat content in liver biopsies using stereological point counting (SPC) can predict mortality and future development of T2DM in NAFLD patients. 129 patients with biopsy proven NAFLD, enrolled between 1988 and 1992, were re-evaluated on two occasions, after 13.7 (±1.5) and 23.2 (±6.8) years. In patients accepting to undergo the procedure, repeat liver biopsies were performed on each follow-up and were evaluated with conventional histopathological methodology and SPC. Of the 106 patients without T2DM at baseline, 66 (62%) developed T2DM during a mean follow-up of 23.2 (± 6.8) years. Steatosis grade and liver fat measured with SPC independently (adjusted for age, BMI, fibrosis stage) predicted development of T2DM with an aHR of 1.60 per grade and 1.03 for each SPC percentage increase respectively. Overall mortality and development of T2DM was more common in patients with grade 3 steatosis compared to lower grades of steatosis. Liver fat measured with SPC was significant for overall mortality (aHR 1.04). In patients that underwent repeat biopsy, reduction in liver fat measured with SPC was associated with decreased risk of developing T2DM (aHR 0.91 for each SPC percentage decrease). Steatosis grade and liver fat measured with SPC predict mortality and the risk of developing T2DM in NAFLD. Reduction in liver fat decreases the risk of developing T2DM.

Dynamics of fluorine-18-fluorodeoxyglucose uptake in the liver and its correlation with hepatic fat content and BMI.

The aim of this study was to explore the rate of elimination of fluorine-18-fluorodeoxyglucose (F-FDG) from the liver and assess the impact of hepatic fat and obesity on F-FDG clearance in early and delayed PET scans. We hypothesized that an increase in liver fat may cause a decline in hepatic F-FDG elimination with potential consequences as measured by dual time-point F-FDG PET/CT imaging. A total of 32 patients from the Cardiovascular Molecular Calcification Assessed by F-NaF PET/CT (CAMONA) clinical trial (17 males, 15 females; mean age: 47.2 years, range: 23-69 years, mean BMI: 27.2 kg/m) were enrolled and underwent F-FDG PET/CT 90 and 180 min after tracer injection. Global mean standardized uptake value (SUVmean) (i.e. the average of SUVmean in segmented liver slices) and average maximum standardized uptake value (SUVmax) (i.e. the average of the SUVmax values recorded in same slices) were calculated for semiquantification of liver F-FDG uptake at both time-points. Percentage difference in global SUVmean and average SUVmax were also calculated to yield respective retention indices (RImean and RImax). Changes in global SUVmean, average SUVmax, RImean, and RImax from 90 to 180 min were correlated with BMI and liver fat content as measured by CT Hounsfield units. There was a 12.2±3.5 percent reduction in global liver SUVmean and a 4.1±5.8 percent reduction in average SUVmax at 180 min scan as compared with the 90 min time-point. RImean and RImax were inversely correlated with liver fat content and positively correlated with BMI. We observed a time-dependent decrease in global hepatic SUVmean and average SUVmax, which was affected by the amount of liver fat. Patients with higher BMI and hepatic fat content tended to retain F-FDG.

Glucagon-like peptide 1 (GLP-1) drives postprandial hyperinsulinemic hypoglycemia in pregnant women with a history of Roux-en-Y gastric bypass operation

BackgroundThe influential role of incretin hormones on glucose metabolism in patients with a history of Roux-en-Y gastric bypass (RYGB) has been investigated thoroughly, but there has been little examination of the effect of incretins and ectopic lipids on altered glucose profiles, especially severe hypoglycemia in pregnant women with RYGB. MethodsIn this prospective clinical study, an oral glucose tolerance test (OGTT), an intravenous glucose tolerance test (IVGTT), and continuous glucose monitoring (CGM) were conducted in 25 women with RYGB during pregnancy, 19 of normal weight (NW) and 19 with obesity (OB) between the 24th and the 28th weeks of pregnancy, and 3 to 6 months post-partum. Post-partum, the ectopic lipid content in the liver, heart, and skeletal muscle was analyzed using 1H-magnetic resonance spectroscopy (1H-MRS). ResultsRYGB patients presented with major fluctuations in glucose profiles, including a high occurrence of postprandial hyperglycemic spikes and hypoglycemic events during the day, as well as a high risk of hypoglycemic periods during the night (2.9 ± 1.1% vs. 0.1 ± 0.2% in the OB and vs. 0.8 ± 0.6% in the NW groups, p < 0.001). During the extended OGTT, RYGB patients presented with exaggerated expression of GLP-1, which was the main driver of the exaggerated risk of postprandial hypoglycemia in a time-lagged correlation analysis. Basal and dynamic GLP-1 levels were not related to insulin sensitivity, insulin secretion, or beta cell function and did not differ between pregnant women with and without GDM. A lower amount of liver fat (2.34 ± 5.22% vs.5.68 ± 4.42%, p = 0.015), which was positively related to insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR: rho = 0.61, p = 0.002) and beta-cell function (insulinogenic index: rho = 0.65, p = 0.001), was observed in the RYGB group after delivery in comparison to the OB group. ConclusionGLP-1 is mainly involved in the regulation of postprandial glucose metabolism and therefore especially in the development of postprandial hypoglycemia in pregnant RYGB patients, who are characterized by major alterations in glucose profiles, and thus in long-term regulation, multiple organ-related mechanisms, such as the lipid content in the liver, must be involved.

Dietary Intervention in Clinical Improvement of Nonalcoholic Fatty Liver Patients

Nonalcoholic fatty liver disease (NAFLD) is related to lifestyle practices including dietary intake and sedentary lifestyle. The common treatment is directed towards weight loss, which is usually difficult to be achieved or maintained. Therefore, a nutritional intervention program aiming at improving the metabolic health not only focusing on weight loss was conducted. Total of 110 patients referred to the hepatology outpatient clinic in the Main Alexandria University Hospital were selected based on ultrasound examination. Data about dietary intake, habits, and practices, and lifestyle practices were collected. Body composition measurements, laboratory investigations, clinical examination and measuring liver fat by ultrasound were assessed. A Mediterranean diet reduced in total carbohydrates, very low in refined sugars, rich in vegetables, moderate in fruits and low fat dairy, with more incorporation of fish, legumes, olive oil, nuts and seeds; was used for 12 weeks and different exercise advices were provided to patients. A significant reduction in the amount of liver fat, together with improvement in lipid profile, liver enzymes, blood pressure, fasting blood glucose and waist circumference were reported. The criteria of metabolic syndrome and gastrointestinal tract symptoms were improved among the majority of patients, with moderate reduction in body weight 5-6%. Liver fat content estimated by ultrasound was associated with the amount of dietary fat and carbohydrate intake, eating meals at irregular times, and unhealthy cooking methods. Nutrition intervention with Mediterranean diet has significant positive impact on metabolic health of NAFLD patients.

Liver fat is related to cardiovascular risk factors and subclinical vascular disease: the Rotterdam Study.

Increasing evidence suggests involvement of the amount of liver fat in the development of cardiovascular disease. We investigated the relation of liver fat with cardiovascular risk factors and subclinical vascular disease in the general population. Between 2003 and 2006, 2351 persons from the population-based Rotterdam Study (mean age 69.6 ± 6.7 years, 47.2% males) underwent non-enhanced computed tomography. We measured the mean liver attenuation value in Hounsfield units and quantified the following markers of subclinical vascular disease: epicardial fat volume and volumes of coronary (CAC), aortic (AAC), extracranial (ECAC), and intracranial carotid calcification (ICAC). Using linear regression, we investigated associations between traditional cardiovascular risk factors and mean liver attenuation. We also investigated relations of mean liver attenuation with markers of subclinical vascular disease, adjusting for cardiovascular risk factors. We found strong associations of waist circumference, diastolic blood pressure, and diabetes with lower mean liver attenuation [multivariable-adjusted beta per unit increase in waist circumference: -2.54 (95% CI: -3.10; -1.99); diastolic blood pressure: -0.52 (95% CI: -0.88; -0.17); and the presence of diabetes: -21.91 (95% CI: -31.76; -12.06)]. Moreover, we found that larger mean liver attenuation values were associated with smaller volumes of epicardial fat and CAC, independent of cardiovascular risk factors [beta per 1-SD increase in mean liver attenuation value: -0.05 (95% CI: -0.08; -0.02) and -0.05 (95% CI: -0.10; -0.01), respectively]. Larger amounts of liver fat are related to larger volumes of epicardial fat and CAC, independent of traditional cardiovascular risk factors, providing important novel insights into the role of liver fat as a marker of vascular disease.

Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a major risk factor leading to chronic liver disease and type 2 diabetes. Here we chart liver metabolic activity and functionality in NAFLD by integrating global transcriptomic data, from human liver biopsies, and metabolic flux data, measured across the human splanchnic vascular bed, within a genome-scale model of human metabolism. We show that an increased amount of liver fat induces mitochondrial metabolism, lipolysis, glyceroneogenesis and a switch from lactate to glycerol as substrate for gluconeogenesis, indicating an intricate balance of exacerbated opposite metabolic processes in glycemic regulation. These changes were associated with reduced metabolic adaptability on a network level in the sense that liver fat accumulation puts increasing demands on the liver to adaptively regulate metabolic responses to maintain basic liver functions. We propose that failure to meet excessive metabolic challenges coupled with reduced metabolic adaptability may lead to a vicious pathogenic cycle leading to the co-morbidities of NAFLD.

Adipokines, cytokines and body fat stores in hepatitis C virus liver steatosis.

To identify patients with or without liver steatosis and its severity in treatment-naïve patients affected by hepatitis C virus (HCV) infection. We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body (by densitometry), hormones [insulin, homeostatic model assessment (HOMA)], adipokines (resistin, adiponectin, leptin), and cytokines (tumor necrosis factor α, interleukin-6). Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunk fat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin. Steatosis in HCV infection is common (67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines.

Abstract 19405: Association of Deep and Superficial Abdominal Subcutaneous Tissue With Hepatic Fat Content

Introduction: The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically during the past decades, affecting 50-75 % of the obese subjects. Visceral adipose tissue (VAT) is regarded to be an important factor in the pathogenesis of NAFLD. Subcutaneous adipose tissue (SAT) is separated by the fascia superficialis into the deep SAT (dSAT) and superficial SAT (sSAT). It has been suggested that dSAT is related to an increased risk for obesity related complications, whereas sSAT has a more favorable profile. The aim of this study was to investigate the association of superficial and deep subcutaneous adipose tissue with hepatic steatosis. Methods: We recruited a subcohort of the Nijmegen Biomedical Study, a large population based cohort, including 133 subjects, BMI &gt; 27 kg/m 2 , aged 55-81 years. Abdominal magnetic resonance imaging was performed at level L4-L5 to measure VAT, dSAT and sSAT volumes. The amount of liver fat was quantified by MR spectroscopy. Results: Men had significantly higher volumes of VAT and lower volumes of sSAT compared with women. No differences in volumes of dSAT were observed. In univariate analysis, the VAT volume was found to be correlated with hepatic steasosis (r = 0.339; p &lt;0.001), while no significant correlation was found between total SAT, sSAT or dSAT with hepatic steatosis. After adjustment for age, alcohol use and sex, VAT was still positively correlated with hepatic steatosis with a standardized β of 0,276 (p=0.007), and sSAT, but not total SAT or dSAT, was negatively correlated with hepatic steatosis with a standardized β of -0,363 (p=0.033). Conclusions: VAT as measured by MRI is positively correlated with hepatic steatosis, in contrast to sSAT which is negatively correlated after adjustment for age, alcohol use and sex. We found no significant correlation between total SAT or dSAT and hepatic steatosis.

Abstract 19220: Hepatic Steatosis is Independently Associated With an Increased Vascular Stiffness in Overweight Subjects

Introduction: The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically during the past decades, affecting 50-75 % of the obese subjects. Subjects with NAFLD have an increased risk of cardiovascular diseases. We investigated whether an increase in hepatic steatosis is independently associated with an increase in vascular stiffness. Methods: We recruited a subcohort of the Nijmegen Biomedical Study, a large population based cohort, including 112 subjects, BMI &gt; 27 kg/m2, aged 55-81 years. The amount of liver fat was quantified by MR spectroscopy. Arterial stiffness was assessed by measurement of the carotid-femoral pulse wave velocity (PWV). The association between the hepatic steatosis and vascular stiffness was investigated by linear regression analysis with and without adjustment for the conventional cardiovascular risk factors. Results: In univariate analysis, hepatic steasosis was found to be correlated with PWV (r = 0.267; p = 0.005). After adjustment for age, sex, heart rate, alcohol use, and BMI still a significant positive association was present with a standardized beta of 0,298 (p=0.004). Even after adjustment for conventional cardiovascular risk factors including mean arterial pressure, blood pressure lowering and anti-diabetic drugs, hepatic steatosis remained independently associated with PWV ( standardized beta 0.269, p = 0.019). Conclusions: In a group of overweight subjects hepatic steatosis is associated with arterial stiffness. This association is independent of blood pressure, use of antihypertensives and the other traditional cardiovascular risk factors.