Metabolic syndrome and nonalcoholic fatty liver disease: Is insulin resistance the link?

Metabolic syndrome (MetS) is a disease composed of different risk factors such as obesity, type 2 diabetes or dyslipidemia. The prevalence of this syndrome is increasing worldwide in parallel with the rise in obesity. Nonalcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease in western countries, affecting more than 30% of the general population. NAFLD encompasses a spectrum of liver manifestations ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis, which may ultimately progress to hepatocellular carcinoma. There is accumulating evidence supporting an association between NAFLD and MetS. Indeed, NAFLD is recognized as the liver manifestation of MetS. Insulin resistance is increasingly recognized as a key factor linking MetS and NAFLD. Insulin resistance is associated with excessive fat accumulation in ectopic tissues, such as the liver, and increased circulating free fatty acids, which can further promote inflammation and endoplasmic reticulum stress. This in turn aggravates and maintains the insulin resistant state, constituting a vicious cycle. Importantly, evidence shows that most of the patients developing NAFLD present at least one of the MetS traits. This review will define MetS and NAFLD, provide an overview of the common pathophysiological mechanisms linking MetS and NAFLD, and give a perspective regarding treatment of these ever growing metabolic diseases.

Prevalence of simple liver cysts and hemangiomas in cirrhotic and non-cirrhotic patients submitted to magnetic resonance imaging

Objective To determine the prevalence of liver cysts and hemangiomas in the general population and in cirrhotic patients. Materials and Methods Retrospective, observational, and cross-sectional study selecting consecutive magnetic resonance imaging studies performed in the period from February to July 2011. A total of 303 patients (187 women and 116 men) with mean age of 53.3 years were included in the present study. Patients with previously known liver lesions were excluded. The images were consensually analyzed by two observers in the search for simple liver cysts and typical liver hemangiomas, according to universally accepted imaging criteria. Lesions prevalence, diameters and location were determined in both cirrhotic and non-cirrhotic individuals. Results The authors observed prevalence of 8.6% for hemangiomas and 14.5% for simple cysts. No statistically significant difference was observed in relation to prevalence of hemangiomas and cysts among cirrhotic and non-cirrhotic patients (p = 0.954; p = 0.472). Conclusion In the present study, the prevalence of cysts and hemangiomas was higher than the prevalence reported by autopsy series. No influence of cirrhosis was observed on the prevalence and appearance of such incidental lesions.

Comparative dosimetry in intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT for brain tumors

Objective Comparative analysis of dosimetry in intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT for treatment of brain tumors. Materials and Methods Simulations of intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT were performed with the MCNP5 code, modeling the treatment of a brain tumor on a voxel computational phantom representing a human head. Absorbed dose rates were converted into biologically weighted dose rates. Results Intracavitary balloon catheter brachytherapy with I-125 produced biologically weighted mean dose rates of 3.2E-11, 1.3E-10, 1.9E-11 and 6.9E-13 RBE.Gy.h-1.p-1.s, respectively, on the healthy tissue, on the balloon periphery and on the I 1 and I 2 tumor infiltration zones. On the other hand, Cf-252 brachytherapy combined with BNCT produced a biologically weighted mean dose rate of 5.2E-09, 2.3E-07, 8.7E-09 and 2.4E-09 RBE.Gy.h-1.p-1.s, respectively on the healthy tissue, on the target tumor and on the I 1 and I 2 infiltration zones. Conclusion Cf-252 brachytherapy combined with BNCT delivered a selective irradiation to the target tumor and to infiltration zones, while intracavitary balloon catheter brachytherapy with I-125 delivered negligible doses on the tumor infiltration zones.

The role of gadoxetic acid as a paramagnetic contrast medium in the characterization and detection of focal liver lesions: a review

Recent studies have demonstrated that the use of paramagnetic hepatobiliary contrast agents in the acquisition of magnetic resonance images remarkably improves the detection and differentiation of focal liver lesions, as compared with extracellular contrast agents. Paramagnetic hepatobiliary contrast agents initially show the perfusion of the lesions, as do extracellular agents, but delayed contrast-enhanced images can demonstrate contrast uptake by functional hepatocytes, providing further information for a better characterization of the lesions. Additionally, this intrinsic characteristic increases the accuracy in the detection of hepatocellular carcinomas and metastases, particularly the small-sized ones. Recently, a hepatobiliary contrast agent called gadolinium ethoxybenzyl dimeglumine, that is simply known as gadoxetic acid, was approved by the National Health Surveillance Agency for use in humans. The authors present a literature review and a practical approach of magnetic resonance imaging utilizing gadoxetic acid as contrast agent, based on patients' images acquired during their initial experiment.

Ultrasonographic study and Doppler flow velocimetry of maternal kidneys and liver in low-risk pregnancy

AbstractObjective:Longitudinal study with B-mode ultrasonography and Doppler ultrasonography of maternal kidneys and liver in low-risk pregnancy, to establish and quantify normality parameters, correlating them with physiological changes.Materials and Methods:Twenty-five pregnant women were assessed and selected to participate in the study, each of them undergoing four examinations at the first, second, third trimesters and postpartum.Results:Findings during pregnancy were the following: increased renal volume, pyelocaliceal dilatation with incidence of 45.4% in the right kidney, and 9% in the left kidney; nephrolithiasis, 18.1% in the right kidney, 13.6% in the left kidney. With pyelocaliceal dilatation, mean values for resistivity index were: 0.68 for renal arteries; 0.66 for segmental arteries; 0.64 for interlobar arteries; 0.64 for arcuate arteries. Without pyelocaliceal dilatation, 0.67 for renal arteries; 0.64 for segmental arteries; 0.63 for interlobar arteries; and 0.61 for arcuate arteries. Portal vein flow velocities presented higher values in pregnancy, with mean value for maximum velocity of 28.9 cm/s, and 22.6 cm/s postpartum. The waveform pattern of the right hepatic vein presented changes persisting in the postpartum period in 31.8% of the patients. Cholelithiasis was observed in 18.1% of the patients.Conclusion:Alterations in renal volume, pyelocaliceal dilatation, nephrolithiasis, cholelithiasis, changes in portal vein flow velocity, alterations in waveform pattern of the right hepatic vein, proved to be significant.

The importance of PET/CT in the evaluation of patients with Ewing tumors

AbstractThe effective evaluation for the treatment of patients with Ewing tumors depends on the accuracy in the determination of the primary tumor extent and the presence of metastatic disease. Currently, no universally accepted staging system is available to assess Ewing tumors. The present study aimed at discussing the use of PET/CT as a tool for staging, restaging and assessment of therapeutic response in patients with Ewing tumors. In spite of some limitations of PET/CT as compared with anatomical imaging methods, its relevance in the assessment of these patients is related to the capacity of the method to provide further physiological information, which often generates important clinical implications. Currently, the assessment of patients with Ewing tumor should comprise a study with PET/CT combined with other anatomical imaging modalities, such as radiography, computed tomography and magnetic resonance imaging.

Accuracy of computer-aided ultrasound as compared with magnetic resonance imaging in the evaluation of nonalcoholic fatty liver disease in obese and eutrophic adolescents

AbstractObjective:To compare the accuracy of computer-aided ultrasound (US) and magnetic resonance imaging (MRI) by means of hepatorenal gradient analysis in the evaluation of nonalcoholic fatty liver disease (NAFLD) in adolescents.Materials and Methods:This prospective, cross-sectional study evaluated 50 adolescents (aged 11–17 years), including 24 obese and 26 eutrophic individuals. All adolescents underwent computer-aided US, MRI, laboratory tests, and anthropometric evaluation. Sensitivity, specificity, positive and negative predictive values and accuracy were evaluated for both imaging methods, with subsequent generation of the receiver operating characteristic (ROC) curve and calculation of the area under the ROC curve to determine the most appropriate cutoff point for the hepatorenal gradient in order to predict the degree of steatosis, utilizing MRI results as the gold-standard.Results:The obese group included 29.2% girls and 70.8% boys, and the eutrophic group, 69.2% girls and 30.8% boys. The prevalence of NAFLD corresponded to 19.2% for the eutrophic group and 83% for the obese group. The ROC curve generated for the hepatorenal gradient with a cutoff point of 13 presented 100% sensitivity and 100% specificity. As the same cutoff point was considered for the eutrophic group, false-positive results were observed in 9.5% of cases (90.5% specificity) and false-negative results in 0% (100% sensitivity).Conclusion:Computer-aided US with hepatorenal gradient calculation is a simple and noninvasive technique for semiquantitative evaluation of hepatic echogenicity and could be useful in the follow-up of adolescents with NAFLD, population screening for this disease as well as for clinical studies.

Prevalence and sonographic changes compatible with fatty liver disease in patients referred for abdominal ultrasound examination in Aracaju, SE

Abstract Objective: To estimate the prevalence and evaluate sonographic findings compatible with changes consistent with hepatic steatosis in patients referred for abdominal ultrasonography at four reference centers in Aracaju, SE, Brazil. Materials and Methods: Prospective, descriptive survey, with analytical and quantitative approach, comprising abdominal ultrasonography scans performed with a convex, dynamic 3.75 MHz transducer. Liver dimensions and parenchymal echotexture were evaluated, classifying hepatic steatosis into grades (1, 2 or 3). The SPSS® 22.0 software was used for statistical analysis, adopting p < 0.05 as significance level. Results: A total of 800 individuals (561 women and 239 men) were evaluated. The prevalence of steatosis was 29.1%, and the male patients were most affected, presenting with more advanced grades of disease (p = 0.021), as follows: 119 grade 1 (51.0%); 94 grade 2 (40.4%); and 20 grade 3 (8.6%). The median age patients' was 46 years. Conclusion: In the present study sample, the prevalence of hepatic steatosis was high, particularly in the male patients. Ultrasonography is suggested as a first choice for the diagnosis of this condition, considering its wide availability, low cost and absence of side effects or risks to the patient.

Analyzing the temporal regulation of translation efficiency in mouse liver.

Mammalian physiology and behavior follow daily rhythms that are orchestrated by endogenous timekeepers known as circadian clocks. Rhythms in transcription are considered the main mechanism to engender rhythmic gene expression, but important roles for posttranscriptional mechanisms have recently emerged as well (reviewed in Lim and Allada (2013) [1]). We have recently reported on the use of ribosome profiling (RPF-seq), a method based on the high-throughput sequencing of ribosome protected mRNA fragments, to explore the temporal regulation of translation efficiency (Janich et al., 2015 [2]). Through the comparison of around-the-clock RPF-seq and matching RNA-seq data we were able to identify 150 genes, involved in ribosome biogenesis, iron metabolism and other pathways, whose rhythmicity is generated entirely at the level of protein synthesis. The temporal transcriptome and translatome data sets from this study have been deposited in NCBI's Gene Expression Omnibus under the accession number GSE67305. Here we provide additional information on the experimental setup and on important optimization steps pertaining to the ribosome profiling technique in mouse liver and to data analysis.

Using transient elastography to detect chronic liver diseases in a primary care nurse consultancy

Background: Chronic liver diseases (CLDs) are significant causes of death in adults in many countries and are usually diagnosed at late stages. Early detection may allow time for treatment to prevent disease progression. Objectives: The aim of this study was to assess the feasibility of screening for unrecognized CLDs in a primary care nurse consultancy and report findings from screening. Methods: Two experienced nurses in a primary care nurse consultancy were trained to perform transient elastography (TE). Subjects aged from 18 to 70 years were identified randomly from the health registry and invited to participate in a feasibility pilot study. Exclusion criteria were past or current history of liver diseases. Nurses collected demographic and clinical data and performed TE tests using Fibroscan tomeasure liver stiffness; a cutoff score of 6.8 kPa or greater was used as an indicator of the presence of CLD with fibrosis. Results: Accurate measurements were obtained in 495 of 502 participants (98.6%). Prevalence of elevated liver stiffness was observed in 28 of 495 subjects (5.7%). Compared to patients with normal liver stiffness, patients with increased liver stiffness were older, were more frequently male, and had higher frequency of metabolic syndrome. Nonalcoholic fatty liver was the most common cause of CLD. Discussion: Following training in procedures for conducting TE, nurses in a primary care clinic were able to detect unrecognized CLDs in presumably healthy subjects. Early detection of CLDs is feasible in primary care clinics and may facilitate identification of undiagnosed CLD in adults.

Performance of 18F-FET versus 18F-FDG-PET for the diagnosis and grading of brain tumors: systematic review and meta-analysis.

BACKGROUND: For the past decade (18)F-fluoro-ethyl-l-tyrosine (FET) and (18)F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) have been used for the assessment of patients with brain tumor. However, direct comparison studies reported only limited numbers of patients. Our purpose was to compare the diagnostic performance of FET and FDG-PET. METHODS: We examined studies published between January 1995 and January 2015 in the PubMed database. To be included the study should: (i) use FET and FDG-PET for the assessment of patients with isolated brain lesion and (ii) use histology as the gold standard. Analysis was performed on a per patient basis. Study quality was assessed with STARD and QUADAS criteria. RESULTS: Five studies (119 patients) were included. For the diagnosis of brain tumor, FET-PET demonstrated a pooled sensitivity of 0.94 (95% CI: 0.79-0.98) and pooled specificity of 0.88 (95% CI: 0.37-0.99), with an area under the curve of 0.96 (95% CI: 0.94-0.97), a positive likelihood ratio (LR+) of 8.1 (95% CI: 0.8-80.6), and a negative likelihood ratio (LR-) of 0.07 (95% CI: 0.02-0.30), while FDG-PET demonstrated a sensitivity of 0.38 (95% CI: 0.27-0.50) and specificity of 0.86 (95% CI: 0.31-0.99), with an area under the curve of 0.40 (95% CI: 0.36-0.44), an LR+ of 2.7 (95% CI: 0.3-27.8), and an LR- of 0.72 (95% CI: 0.47-1.11). Target-to-background ratios of either FDG or FET, however, allow distinction between low- and high-grade gliomas (P > .11). CONCLUSIONS: For brain tumor diagnosis, FET-PET performed much better than FDG and should be preferred when assessing a new isolated brain tumor. For glioma grading, however, both tracers showed similar performances.

Effect of diet composition and ration size on key enzyme activities of glycolysis-gluconeogenesis, pentose phosphate pathway and amino acid metabolism in liver of Sparus aurata

The effects of diet composition and ration size on the activities of key enzymes involved in intermediary metabolism were studied in the liver of gilthead sea bream (Sparus aurata). Highcarbohydrate, low-protein diets stimulated 6-phosphofructo 1-kinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40), glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (EC 1.1.1.44) enzyme activities, while they decreased alanine aminotransferase (EC 2.6.1.2) activity. A high degree of correlation was found between food ration size and the activity of the enzymes 6-phosphofructo 1-kinase, pyruvate kinase, glucose-6-phosphate dehydrogenase (positive correlations) and fructose-1,6-bisphosphatase (EC 3.1.3.11) (negative correlation). These correlations matched well with the high correlation also found between ration size and growth rate in starved fish refed for 22 d. Limited feeding (5 g/kg body weight) for 22 d decreased the activities of the key enzymes for glycolysis and lipogenesis, and alanine aminotransferase activity. The findings presented here indicate a high level of metabolic adaptation to both diet type and ration size. In particular, adaptation of enzyme activities to the consumption of a diet with a high carbohydrate level suggests that a carnivorous fish like Sparus aurata can tolerate partial replacement of protein by carbohydrate in the commercial diets supplied in culture. The relationship between enzyme activities, ration size and fish growth indicates that the enzymes quickly respond to dietary manipulations of cultured fish.