Liver Fat Quantification Research Articles

Quantitative relationship between liver fat content and metabolic syndrome in obese children and adolescents.

Previous studies have shown a significant association between quantified liver fat content (LFC) and metabolic syndrome (MetS) in adults, but the nature of this association in obese paediatric populations is unclear. The aim of this study was to investigate the quantitative relationship of LFC to MetS and its individual components in obese children and adolescents. A population-based cross-sectional study. One hundred and eighty-nine Chinese obese paediatric subjects aged 5-16 years were enrolled. Measurements included MetS components, as defined by the Chinese-specific version of the International Diabetes Foundation MetS criteria (MetS-CHN2012), and LFC using proton magnetic resonance spectroscopy. LFC was significantly higher in subjects with MetS [median 9.7% (interquartile range 4.5-19.9%)] than without MetS [5.7% (2.0-12.8%)] (P < 0.01). LFC was also positively associated with the total number of MetS components (P for trend <0.01). In analyses adjusted for traditional risk factors, increasing levels of LFC were associated with a greater risk of MetS, hypertriglyceridaemia and low high-density lipoprotein cholesterol (P < 0.05 for all associations), but were not associated with risk of hyperglycaemia or hypertension. In obese Chinese paediatric patients, quantitative measures of LFC are positively associated with the risk of MetS, hypertriglyceridaemia and low high-density lipoprotein cholesterol, independent of traditional risk factors. These findings suggest that quantitatively measured LFC may be a clinically useful marker for identifying obese paediatric who are at increased risk of developing MetS and its components.

Simultaneous liver iron and fat measures by magnetic resonance imaging in patients with hyperferritinemia

Objective. Hyperferritinemia is frequent in chronic liver diseases of any cause, but the extent to which ferritin truly reflects iron stores is variable. In these patients, both liver iron and fat are found in variable amount and association. Liver biopsy is often required to quantify liver fat and iron, but sampling variability and invasiveness limit its use. We aimed to assess single breath-hold multiecho magnetic resonance imaging (MRI) for the simultaneous lipid and iron quantification in patients with hyperferritinemia. Material and methods. We compared MRI results for both iron and fat with their respective gold standards – liver iron concentration and computer-assisted image analysis for steatosis on biopsy. We prospectively studied 67 patients with hyperferritinemia and other 10 consecutive patients were used for validation. We estimated two linear calibration equations for the prediction of iron and fat based on MRI. The agreement between MRI and biopsy was evaluated. Results. MRI showed good performances in both the training and validation samples. MRI information was almost completely in line with that obtained from liver biopsy. Conclusion. Single breath-hold multiecho MRI is an accurate method to obtain a valuable measure of both liver iron and steatosis in patients with hyperferritinemia.

Reproducibility of MR-based liver fat quantification across field strength: Same-day comparison between 1.5T and 3T in obese subjects.

To examine the reproducibility of quantitative magnetic resonance (MR) methods to estimate hepatic proton density fat-fraction (PDFF) at different magnetic field strengths. This Health Insurance Portability and Accountability Act (HIPAA)-compliant study was approved by the Institutional Review Board. Following informed consent, 25 severely obese subjects (mean body mass index [BMI]: 45 ± 4, range: 38-53 kg/m(2) ) were scanned at 1.5T and 3T on the same day. Two confounder-corrected multiecho chemical shift-encoded gradient-echo-based imaging methods were acquired to estimate PDFF over the entire liver: 3D complex-based (MRI-C) and 2D magnitude-based (MRI-M) MRI. Single-voxel MR spectroscopy (MRS) was performed in the right liver lobe. Using linear regression, pairwise comparisons of estimated PDFF were made between methods (MRI-C, MRI-M, MRS) at each field strength and for each method across field strengths. 1.5T vs. 3T regression analyses for MRI-C, MRI-M, and MRS PDFF measurements yielded R(2) values of 0.99, 0.97, and 0.90, respectively. The best-fit line was near unity (slope(m) = 1, intercept(b) = 0), indicating excellent agreement for each case: MRI-C (m = 0.92 [0.87, 0.99], b = 1.4 [0.7, 1.8]); MRI-M (m = 1.0 [0.90, 1.08], b = -1.4 [-2.4, -0.5]); MRS (m = 0.98 [0.82, 1.15], b = 1.2 [-0.2, 3.0]). Comparing MRI-C and MRI-M yielded an R(2) = 0.98 (m = 1.1 [1.02, 1.16], b = -1.8 [-2.8, -1.1]) at 1.5T, and R(2) = 0.99 (m = 0.98 [0.93, 1.03], b = 1.2 [0.7, 1.7]) at 3T. This study demonstrates that PDFF estimation is reproducible across field strengths and across two confounder-corrected MR-based methods.

Ultrasound hepatic/renal ratio and hepatic attenuation rate for quantifying liver fat content.

To establish and validate a simple quantitative assessment method for nonalcoholic fatty liver disease (NAFLD) based on a combination of the ultrasound hepatic/renal ratio and hepatic attenuation rate. A total of 170 subjects were enrolled in this study. All subjects were examined by ultrasound and (1)H-magnetic resonance spectroscopy ((1)H-MRS) on the same day. The ultrasound hepatic/renal echo-intensity ratio and ultrasound hepatic echo-intensity attenuation rate were obtained from ordinary ultrasound images using the MATLAB program. Correlation analysis revealed that the ultrasound hepatic/renal ratio and hepatic echo-intensity attenuation rate were significantly correlated with (1)H-MRS liver fat content (ultrasound hepatic/renal ratio: r = 0.952, P = 0.000; hepatic echo-intensity attenuation r = 0.850, P = 0.000). The equation for predicting liver fat content by ultrasound (quantitative ultrasound model) is: liver fat content (%) = 61.519 × ultrasound hepatic/renal ratio + 167.701 × hepatic echo-intensity attenuation rate -26.736. Spearman correlation analysis revealed that the liver fat content ratio of the quantitative ultrasound model was positively correlated with serum alanine aminotransferase, aspartate aminotransferase, and triglyceride, but negatively correlated with high density lipoprotein cholesterol. Receiver operating characteristic curve analysis revealed that the optimal point for diagnosing fatty liver was 9.15% in the quantitative ultrasound model. Furthermore, in the quantitative ultrasound model, fatty liver diagnostic sensitivity and specificity were 94.7% and 100.0%, respectively, showing that the quantitative ultrasound model was better than conventional ultrasound methods or the combined ultrasound hepatic/renal ratio and hepatic echo-intensity attenuation rate. If the (1)H-MRS liver fat content had a value < 15%, the sensitivity and specificity of the ultrasound quantitative model would be 81.4% and 100%, which still shows that using the model is better than the other methods. The quantitative ultrasound model is a simple, low-cost, and sensitive tool that can accurately assess hepatic fat content in clinical practice. It provides an easy and effective parameter for the early diagnosis of mild hepatic steatosis and evaluation of the efficacy of NAFLD treatment.

MR quantification of total liver fat in patients with impaired glucose tolerance and healthy subjects.

ObjectiveTo explore the correlations between liver fat content and clinical index in patients with impaired glucose tolerance (IGT) and healthy subjects.Materials and Methods56 subjects were enrolled and each of them underwent upper-abdominal MRI examination that involved a T1 VIBE Dixon sequence. 14 was clinically diagnosed with IGT (collectively as IGT group ) while 42 showed normal glucose tolerance,(collectively as NGT group). NGT group was further divided into NGTFat (BMI≥25, 18 subjects) and NGTLean (BMI<25, 24 subjects). The total liver fat contents was measured and compared with clinical findings and laboratory results in order to determine statistical correlations between these parameters. Differences among IGT, NGTFat and NGTLean groups were evaluated.ResultsFor all the subjects, fat volume fractions (FVFs) ranged from 4.2% to 24.2%, positive correlations was observed with BMI, waist hip ratio(WHR), low density lipoprotein(LDL), fasting plasma insulin(FPI), homeostasis model assessment insulin resistance (HOMA-IR) and homeostasis model assessment β(HOMAβ). FVFs of IGT group (p = 0.004) and NGTFat group (p = 0.006) were significantly higher than those of NGTLean group.ConclusionsPeople with higher BMI, WHR and LDL levels tend to have higher liver fat content. Patients with BMI≥25 are more likely to develop IGT. Patients with higher FVF showed higher resistance to insulin, thus obtained a higher risk of developing type 2 diabetes mellitus.

Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study.

There is no licensed treatment for non-alcoholic fatty liver disease (NAFLD), a condition that increases risk of chronic liver disease, type 2 diabetes and cardiovascular disease. We tested whether 15-18 months treatment with docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA) (Omacor/Lovaza) (4 g/day) decreased liver fat and improved two histologically-validated liver fibrosis biomarker scores (primary outcomes). Patients with NAFLD were randomised in a double blind placebo-controlled trial [DHA+EPA(n=51), placebo(n=52)]. We quantified liver fat percentage (%) by magnetic resonance spectroscopy in three liver zones. We measured liver fibrosis using two validated scores. We tested adherence to the intervention (Omacor group) and contamination (with DHA and EPA) (placebo group) by measuring erythrocyte percentage DHA and EPA enrichment (gas chromatography). We undertook multivariable linear regression to test effects of: a) DHA+EPA treatment (ITT analyses) and b) erythrocyte DHA and EPA enrichment (secondary analysis). Median (IQR) baseline and end of study liver fat% were 21.7 (19.3) and 19.7 (18.0) (placebo), and 23.0 (36.2) and 16.3 (22.0), (DHA+EPA). In the fully adjusted regression model there was a trend towards improvement in liver fat% with DHA+EPA treatment (β=-3.64 (95%CI -8.0,0.8); p=0.1) but there was evidence of contamination in the placebo group and variable adherence to the intervention in the Omacor group. Further regression analysis showed that DHA enrichment was independently associated with a decrease in liver fat% (for each 1% enrichment, β=-1.70 (95%CI -2.9,-0.5); p=0.007). No improvement in the fibrosis scores occurred. Conclusion. Erythrocyte DHA enrichment with DHA+EPA treatment is linearly associated with decreased liver fat%. Substantial decreases in liver fat% can be achieved with high percentage erythrocyte DHA enrichment in NAFLD. (Hepatology 2014;).

Associations between nonalcoholic fatty liver disease and subclinical atherosclerosis in middle-aged adults: The Coronary Artery Risk Development in Young Adults Study

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is an obesity-related condition associated with cardiovascular mortality. Yet, whether or not NAFLD is independently related to atherosclerosis is unclear. In a population-based cross-sectional sample of middle-aged adults free from liver or heart disease, we tested the hypothesis that NAFLD is associated with subclinical atherosclerosis (coronary artery (CAC) and abdominal aortic calcification (AAC)) independent of obesity. MethodsParticipants from the Coronary Artery Risk Development in Young Adults study with CT quantification of liver fat, CAC and AAC were included (n = 2424). NAFLD was defined as liver attenuation ≤40 Hounsfield Units after exclusion of other causes of liver fat. CAC and AAC presence was defined as Agatston score >0. ResultsMean participant age was 50.1 ± 3.6 years, (42.7% men, 50.0% black) and BMI was 30.6 ± 7.2 kg/m2. The prevalence of NAFLD, CAC, and AAC was 9.6%, 27.1%, and 51.4%. NAFLD participants had increased prevalence of CAC (37.9% vs. 26.0%, p < 0.001) and AAC (65.1% vs. 49.9%, p < 0.001). NAFLD remained associated with CAC (OR, 1.33; 95% CI, 1.001–1.82) and AAC (OR, 1.74; 95% CI, 1.29–2.35) after adjustment for demographics and health behaviors. However, these associations were attenuated after additional adjustment for visceral adipose tissue (CAC OR, 1.05; 95% CI, 0.74–1.48, AAC OR = 1.20; 95% CI, 0.86–1.67). There was no interaction by race or sex. ConclusionIn contrast to prior research, these findings suggest that obesity attenuates the relationship between NAFLD and subclinical atherosclerosis. Further studies evaluating the role of NAFLD duration on atherosclerotic progression and cardiovascular events are needed.

Section 1. Image evaluation of fatty liver in living donor liver transplantation.

Preoperative evaluation of donors for living-donor liver transplantation aims to select a suitable donor with optimal graft quality and to ensure donor safety. Hepatic steatosis, a common finding in living liver donors, not only influences the outcome of liver transplantation for the recipient but also affects the recovery of the living donor after partial hepatectomy. Histopathologic analysis is the reference standard to detect and quantify fat in the liver, but it is invasive, and results are vulnerable to sampling error. Imaging can be repeated regularly and allows assessment of the entire liver, thus avoiding sampling error. Selection of appropriate imaging methods demands understanding of their advantages and limitations and the suitable clinical setting. This article describes potential clinical applications for liver fat quantification of imaging methods for fat detection and quantification, with an emphasis on the advantages and limitations of ultrasonography, computed tomography, and magnetic resonance imaging for quantifying liver fat.

Abstract 52: Associations of Nonalcoholic Fatty Liver Disease with Subclinical Myocardial Dysfunction: The CARDIA Study

Background: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related condition with high cardiovascular morbidity. NAFLD patients often have echocardiographic features of left ventricular (LV) diastolic dysfunction. In a large population-based cross-sectional sample of black and white adults free from prevalent liver or heart disease, we tested the hypothesis that NAFLD is associated with subclinical myocardial dysfunction independent of BMI or visceral adipose tissue (VAT). Methods: Participants from the Coronary Artery Risk Development in Young Adults study (Y25 exam; age 43-55 years) with concurrent CT quantification of liver fat and tissue Doppler echocardiography with myocardial strain measured by speckle tracking were included (n=2,572). NAFLD was defined as liver attenuation ≤ 40 Hounsfield units after exclusion of other causes of liver fat (medication/alcohol use). Linear regression models were used to test associations. Results: NAFLD prevalence was 9.9%. NAFLD participants were more likely to be male (57.1% vs. 41.5%), white (57.5% vs. 50.6%), and had higher BMI (36.3 vs. 29.8 kg/m2) and VAT (222.4 vs. 120.5 cm3) than non-NAFLD. Those with NAFLD also had lower e’ tissue velocity (10.8 vs. 11.9 cm/s), lower E/A ratio (1.2 vs. 1.3), and higher E/e’ ratio (8.4 vs. 7.7). Increased LV mass, left atrial area, LV relative wall thickness, and cardiac output (CO) were present in NAFLD. Global longitudinal strain was also worse in NAFLD (-14.2% vs. -15.2%, all p&lt;0.05). In multivariable analyses adjusted for demographics, health behaviors and BMI, the associations of NAFLD with markers of subclinical myocardial dysfunction were attenuated but remained significant (Table 1). Only e’ velocity, LV mass and CO remained significant after adjustment for VAT. Effect modification by race and sex was not statistically significant. Conclusion: NAFLD is associated with subclinical myocardial dysfunction independent of BMI. Attenuation of the relationship by VAT supports the hypothesis that VAT may be a marker of NAFLD.

Assessment of hepatic fatty infiltration using dual-energy computed tomography: a phantom study

The purpose of this study was to examine the performance of dual-energy computed tomography (DECT) for the quantification of liver fat content (LFC). We prepared two phantoms: homogenized mixtures of porcine liver and fat and homogeneous mixtures of liver- and fat-equivalent solutions. Tubes containing mixtures with known fat concentrations were scanned on a dual-source CT scanner using two DE scanning protocols (80 kV/Sn140 kV and 100 kV/Sn140 kV). Attenuation curves obtained from DECT were used to describe attenuations of various degrees of LFC at different energies. LFC was calculated from DECT data and compared with the known LFC. The phantom made of liver/fat mixtures was not used for liver fat quantification because the increase of fat content did not show a decline of CT numbers. This may be due to inhomogeneity as observed in CT images. Attenuation curves obtained from two DE scanning protocols had the ability to discriminate small differences in fat concentrations. Our results also showed a strong correlation between DECT measurements and known LFC (R2 > 0.99, P < 0.005). DECT will be a reliable tool for liver fat quantification. Furthermore, attenuation curves obtained from DECT data can be used for discriminating various degrees of LFC.

Detection of hepatic steatosis using the controlled attenuation parameter: a comparative study with liver biopsy

Objective. Measurements of controlled attenuation parameter (CAP) with transient elastography (FibroScan®; EcoSens SA, Paris, France) may provide an accurate noninvasive assessment of hepatic steatosis. Herein, we prospectively determined the accuracy of liver fat quantification with CAP values in patients with chronic liver diseases and compare the results with those of histological assessment of steatosis as reference standard. Materials and methods. We enrolled 50 Turkish patients with various forms of chronic liver diseases. All patients underwent both CAP assessment and ultrasonography-guided liver biopsy. Results. On liver biopsy, 16 (32%) patients had S0, 12 (24%) had S1, 9 (18%) had S2, and 13 (26%) had S3. The CAP values increased significantly (p < 0.001) for each steatosis stage on liver biopsy: S0, 222 dB/m; S1, 250 dB/m; S2, 270 dB/m; and S3, 318 dB/m. A cutoff value of 257 dB/m could distinguish significant steatosis (S2–S3) from S0 (Sn 89%, Sp 83%, positive likelihood ratio 5.33, negative likelihood ratio 0.13, AUROC = 0.93). Multivariable analysis indicated that neither liver fibrosis (p = 0.58) nor disease etiology (p = 0.96) had a significant impact on the association between CAP and the stage of steatosis. Conclusion. The determination of CAP using transient elastography can represent an important step forward toward the goal of an “imaging liver biopsy”.

Assessment of liver fat in an obese patient population using noncontrast CT fat percent index

ObjectiveTo develop a simplified method to quantify liver fat using computed tomography (CT) fat % index (CTFPI) compared to liver spleen method (CTL/S, CTL−S). MethodsNoncontrast CT of the liver was performed in 89 patients (overweight, obese, severely obese) to quantify fat, using the following: CTFPI=[(65−patient HU)/65]×100, normal live r=65 HU. ResultsThere was a strong linear correlation between CTFPI and the standard method of assessing liver fat using CTL/S (r=−0.901), CTL−S (r=−0.911). Hepatic HU and CTFPI were significantly different in the severely obese group compared to other two groups (P<.05). ConclusionSignificant correlation indicates equal diagnostic accuracy of the two methods in appropriately calibrated scanners.

Liver fat quantification using a multi‐step adaptive fitting approach with multi‐echo GRE imaging

The purpose of this study was to develop a multi-step adaptive fitting approach for liver proton density fat fraction (PDFF) and R(2)* quantification, and to perform an initial validation on a broadly available hardware platform. The proposed method uses a multi-echo three-dimensional gradient echo acquisition, with initial guesses for the fat and water signal fractions based on a Dixon decomposition of two selected echoes. Based on magnitude signal equations with a multi-peak fat spectral model, a multi-step nonlinear fitting procedure is then performed to adaptively update the fat and water signal fractions and R(2)* values. The proposed method was validated using numeric phantoms as ground truth, followed by preliminary clinical validation of PDFF calculations against spectroscopy in 30 patients. The results of the proposed method agreed well with the ground truth of numerical phantoms, and were relatively insensitive to changes in field strength, field homogeneity, monopolar/bipolar readout, signal to noise ratio, and echo time selections. The in vivo patient study showed excellent consistency between the PDFF values measured with the proposed approach compared with spectroscopy. This multi-step adaptive fitting approach performed well in both simulated and initial clinical evaluation, and shows potential in the quantification of hepatic steatosis.

Exercise Training in Polycystic Ovarian Syndrome Enhances Flow-Mediated Dilation in the Absence of Changes in Fatness

Polycystic ovarian syndrome (PCOS) is associated with an adverse cardiovascular disease (CVD) profile. A surrogate marker for CVD risk is endothelial dysfunction. Limited studies exist examining the cardiovascular and metabolic effects of exercise in PCOS and specifically its impact on endothelial function. Therefore, the aim of the current study was to investigate the impact of exercise on endothelial function, in parallel with body composition, insulin resistance, and cardiopulmonary fitness in PCOS. Ten women with PCOS (27 yr, 95% confidence interval [CI] = 23-32; 31 kg·m⁻², 95% CI = 28-34) completed a 16-wk exercise (EX) program, and seven women with PCOS (29 yr, 95% CI = 24-35; 35 kg·m⁻², 95% CI = 31-40) undertook conventional care (CC) following lifestyle advice. Brachial artery endothelial function was assessed pre- and postintervention using flow-mediated dilation adjusted for variability in baseline diameter. Visceral and abdominal subcutaneous adipose tissue was assessed using whole-body magnetic resonance imaging and ¹H magnetic resonance spectroscopy quantified liver fat. Cardiorespiratory fitness, glycemic control, hormone, and lipid profiles were also assessed. Data were analyzed using covariate-controlled generalized estimating equations. At follow-up, EX improved flow-mediated dilation by 3.6% (95% CI = 0.5-6.7, P = 0.03) more than CC. There was a parallel improvement in cardiorespiratory fitness of 4.7 mL·kg⁻¹·min⁻¹ (95% CI = 1.4-7.9, P < 0.001) with EX versus CC. These changes were not explained by changes in visceral adipose tissue, subcutaneous adipose tissue, liver fat or insulin resistance. Supervised exercise in women with PCOS improves endothelial function, an adaptation associated with reduced CVD risk. This change occurs independent of changes in body weight or composition. The success of public health interventions in this patient group should not be solely judged by weight loss.

Quantitative chemical shift-encoded MRI is an accurate method to quantify hepatic steatosis

To compare the accuracy of liver fat quantification using a three-echo chemical shift-encoded magnetic resonance imaging (MRI) technique without and with correction for confounders with spectroscopy (MRS) as the reference standard. Fifty patients (23 women, mean age 56.6 ± 13.2 years) with fatty liver disease were enrolled. Patients underwent T2-corrected single-voxel MRS and a three-echo chemical shift-encoded gradient echo (GRE) sequence at 3.0T. MRI fat fraction (FF) was calculated without and with T2* and T1 correction and multispectral modeling of fat and compared with MRS-FF using linear regression. The spectroscopic range of liver fat was 0.11%-38.7%. Excellent correlation between MRS-FF and MRI-FF was observed when using T2* correction (R(2) = 0.96). With use of T2* correction alone, the slope was significantly different from 1 (1.16 ± 0.03, P < 0.001) and the intercept was different from 0 (1.14% ± 0.50%, P < 0.023). This slope was significantly different than 1.0 when no T1 correction was used (P = 0.001). When T2*, T1, and spectral complexity of fat were addressed, the results showed equivalence between fat quantification using MRI and MRS (slope: 1.02 ± 0.03, P = 0.528; intercept: 0.26% ± 0.46%, P = 0.572). Complex three-echo chemical shift-encoded MRI is equivalent to MRS for quantifying liver fat, but only with correction for T2* decay and T1 recovery and use of spectral modeling of fat. This is necessary because T2* decay, T1 recovery, and multispectral complexity of fat are processes which may otherwise bias the measurements.

A Flexible Method for Multi-Material Decomposition of Dual-Energy CT Images

The ability of dual-energy computed-tomographic (CT) systems to determine the concentration of constituent materials in a mixture, known as material decomposition, is the basis for many of dual-energy CT's clinical applications. However, the complex composition of tissues and organs in the human body poses a challenge for many material decomposition methods, which assume the presence of only two, or at most three, materials in the mixture. We developed a flexible, model-based method that extends dual-energy CT's core material decomposition capability to handle more complex situations, in which it is necessary to disambiguate among and quantify the concentration of a larger number of materials. The proposed method, named multi-material decomposition (MMD), was used to develop two image analysis algorithms. The first was virtual unenhancement (VUE), which digitally removes the effect of contrast agents from contrast-enhanced dual-energy CT exams. VUE has the ability to reduce patient dose and improve clinical workflow, and can be used in a number of clinical applications such as CT urography and CT angiography. The second algorithm developed was liver-fat quantification (LFQ), which accurately quantifies the fat concentration in the liver from dual-energy CT exams. LFQ can form the basis of a clinical application targeting the diagnosis and treatment of fatty liver disease. Using image data collected from a cohort consisting of 50 patients and from phantoms, the application of MMD to VUE and LFQ yielded quantitatively accurate results when compared against gold standards. Furthermore, consistent results were obtained across all phases of imaging (contrast-free and contrast-enhanced). This is of particular importance since most clinical protocols for abdominal imaging with CT call for multi-phase imaging. We conclude that MMD can successfully form the basis of a number of dual-energy CT image analysis algorithms, and has the potential to improve the clinical utility of dual-energy CT in disease management.

MR Fat Fraction Mapping: A Simple Biomarker for Liver Steatosis Quantification in Nonalcoholic Fatty Liver Disease Patients

To assess the performance, postprocessing time, and intra- and interobserver agreement of a simple magnetic resonance-based mapping technique to quantify liver fat.This prospective, single-center study included 26 patients who were overweight with type 2 diabetes and at risk for nonalcoholic fatty liver disease. Mapping of the liver was based on a triple echo gradient-echo sequence, and (1)H magnetic resonance spectroscopy was used as the reference standard. The nonparametric Spearman correlation coefficient and the Wilcoxon test were used for comparisons between mapping and spectroscopy. The mapping was assessed for its predictive performance using the area under the curve of a receiver operating characteristic curve. Intraclass correlation coefficients were used to calculate intra- and interobserver's agreement for mapping measurements.Patients had a mean fat percentage of 11.7% (range, 2-35.4%). A strong correlation was seen between mapping and spectroscopy (r = 0.89, P < .0001). A cutoff of 6.9% for fat fraction mapping was found to diagnose steatosis with 93% sensitivity and 100% specificity with an area under the curve of 0.99. Mapping of the liver had shorter acquisition and post-processing times than spectroscopy (5 min vs. 38 min; P < .0001). Mapping measurements had an intra- and interobserver agreement of 0.98 and 0.99, respectively.The magnetic resonance-based liver mapping can accurately quantify liver fat with a cutoff value of 6.9% and excellent intra- and interobserver agreement. This mapping technique, with its simple methodology and short postprocessing time, has the potential to be included in routine abdominal protocols.

Genetic Variation in NR1H4 Encoding the Bile Acid Receptor FXR Determines Fasting Glucose and Free Fatty Acid Levels in Humans

Bile acid signaling via farnesoid X receptor (FXR) regulates glucose and lipid levels, fat mass, and hepatic steatosis in animal models. To understand the role of FXR in human metabolism, we investigated associations of common single-nucleotide polymorphisms (SNPs) in the FXR-encoding gene NR1H4 with glucose and lipid metabolism, body fat mass, and liver fat content. We genotyped 2166 healthy German subjects for 7 tagging SNPs within NR1H4 (rs35735, rs1030454, rs11110415, rs11610264, rs17030285, rs4764980, and rs11110390) covering 100% of common genetic variation (minor allele frequency > 10%). Subjects were metabolically characterized by an oral glucose tolerance test. In subgroups, hyperinsulinemic-euglycemic clamp and liver fat quantification by (1)H-magnetic resonance spectroscopy were performed. SNP rs4764980 was significantly associated with fasting glycemia (P = .0043) and nominally associated with fasting and postglucose load free fatty acid (FFA) levels (P = .01). Upon interrogation of publicly available Meta-Analyses of Glucose and Insulin-related traits Consortium data, the association of rs4764980 with fasting glycemia was replicated (Meta-Analyses of Glucose and Insulin-related traits Consortium, P = .005). Additionally, SNP rs11110390 showed significant associations with fasting (P = .0054) and postload (P = .0051) FFA levels. For none of the investigated SNPs, associations with insulin secretion or sensitivity, body fat mass, or liver fat content were detected. We conclude that FXR contributes to fasting glucose and FFA levels in humans independent of unhealthy body fat accumulation. The receptor represents an interesting target to influence lipid and glucose metabolism.

Investigation of 1H MRS for quantification of hepatic triglyceride in lean and obese cats

1H magnetic resonance spectroscopy (1H MRS) is the preferred technique for noninvasive quantification of hepatic triglyceride in humans. Domestic cats are subject to liver lipid accumulation, but MRS has not been investigated for quantification of liver fat in cats. The purpose of this project was to explore a technique for 1H MRS measurement of hepatic triglyceride in lean and obese cats. Hepatic 1H MRS was performed, using a 3T imaging unit and a single-voxel spin-echo spectroscopy sequence, on 6 lean (3.3–4.6kg) and 12 obese cats (5.2–9.8kg). Median liver fat percentages in lean and obese cats were 1.3% and 6.8%, respectively. Results are biologically plausible, based on chemical assay in a separate group of cats; however, full validation of the method is necessary before other conclusions can be drawn. This report should provide a foundation for the further development of spectroscopic techniques for studying hepatic lipid accumulation in cats.

Abstract 007: Nonalcoholic Fatty Liver Disease and Subclinical Atherosclerosis: Analyses from the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Nonalcoholic Fatty Liver Disease (NAFLD) and excess visceral adipose tissue (VAT) are associated with cardiovascular disease (CVD). Recent studies suggest that NAFLD and coronary artery calcification (CAC) are related independent of VAT. In a population-based cross-sectional sample of black and white adults free from prevalent liver or heart disease, we tested the hypothesis that NAFLD is associated with the presence of CAC and abdominal aortoiliac calcification (AAC) independent of VAT and other CVD risk factors. Methods: Participants from the Coronary Artery Risk Development in Young Adults study (Y25 exam) with concurrent computed tomography quantification of liver fat, CAC and AAC were included (n=2,163). NAFLD was defined as liver attenuation ≤ 40 Hounsfield Units after exclusion of other causes of liver fat (medication/alcohol use). Using the Agatston method, CAC/AAC presence was defined as a score &gt; 0. Logistic regression models were used to calculate odds ratios and 95% confidence intervals. Results: Participant age was 49.9 (3.7) years and the sample was equally distributed by sex (55.6% female) and race (50.1% black). Mean BMI was 30.6 (7.1). The CAC and AAC prevalence was 26.5% and 49.6%. NAFLD prevalence was 9.6%. NAFLD participants were 50.1 (3.7) years old and more likely to be male (59.8% vs. 51.7%, p&lt;0.0001), white (56.5% vs. 49.3%, p&lt;0.05) and have the metabolic syndrome (70.1% vs. 22.6%, p&lt;0.0001) than those with no NAFLD. They were also more likely to have CAC (37.2%) and AAC (60.9%) than those with no NAFLD (25.4% and 49.4%, respectively). In multivariable analyses adjusted for demographics and health behaviors, NAFLD was associated with the presence of CAC and AAC (Table 1). This association was attenuated after adjustment for CVD risk factors and VAT. Effect modification by race and sex was not statistically significant. Conclusion: In contrast to prior studies, our results suggest that the relationship between NAFLD and subclinical CVD is mediated by the presence of other CVD risk factors.