Transient elastography with controlled attenuation parameter (CAP) for diagnosis of moderate or severe steatosis in people with suspected non-alcoholic fatty liver disease

Objectives: This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To determine the diagnostic accuracy of transient elastography with CAP for diagnosis of moderate and severe hepatic steatosis in people with suspected NAFLD when compared with liver biopsy as reference standard. To achieve this, we will compare none/mild hepatic steatosis (S0 to S1) versus moderate/severe hepatic steatosis (S2 to S3); and none/mild/moderate hepatic steatosis (S0 to S2) versus severe hepatic steatosis (S3). Secondary objectives: We aim to also identify the pooled sensitivity and specificity for the most common cut‐off values of CAP for diagnosis of none/mild hepatic steatosis (S0 to S1) and moderate/severe hepatic steatosis (S2 to S3); or none/mild/moderate hepatic steatosis (S0 to S2) and severe hepatic steatosis (S3) in people with suspected NAFLD, and to explore potential sources of heterogeneity influencing the diagnostic test accuracy of CAP (see: Investigations of heterogeneity)

MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice

Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL/6 wild-type (WT) and miR-155−/− mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL/LDL cholesterol and alanine transaminase (ALT) levels, as well as increased hepatic expression of genes involved in glucose regulation (Pck1, Cebpa), fatty acid uptake (Cd36) and lipid metabolism (Fasn, Fabp4, Lpl, Abcd2, Pla2g7). Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155−/− livers, we identified and validated that Nr1h3 (LXRα) as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155−/− mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes

Gender Differences in Bile Acids and Microbiota in Relationship with Gender Dissimilarity in Steatosis Induced by Diet and FXR Inactivation.

This study aims to uncover how specific bacteria and bile acids (BAs) contribute to steatosis induced by diet and farnesoid X receptor (FXR) deficiency in both genders. A control diet (CD) and Western diet (WD), which contains high fat and carbohydrate, were used to feed wild type (WT) and FXR knockout (KO) mice followed by phenotyping characterization as well as BA and microbiota profiling. Our data revealed that male WD-fed FXR KO mice had the most severe steatosis and highest hepatic and serum lipids as well as insulin resistance among the eight studied groups. Gender differences in WD-induced steatosis, insulin sensitivity, and predicted microbiota functions were all FXR-dependent. FXR deficiency enriched Desulfovibrionaceae, Deferribacteraceae, and Helicobacteraceae, which were accompanied by increased hepatic taurine-conjugated cholic acid and β-muricholic acid as well as hepatic and serum lipids. Additionally, distinct microbiota profiles were found in WD-fed WT mice harboring simple steatosis and CD-fed FXR KO mice, in which the steatosis had a potential to develop into liver cancer. Together, the presented data revealed FXR-dependent concomitant relationships between gut microbiota, BAs, and metabolic diseases in both genders. Gender differences in BAs and microbiota may account for gender dissimilarity in metabolism and metabolic diseases

Transient elastography with controlled attenuation parameter (CAP) for diagnosis of moderate or severe steatosis in people with suspected non-alcoholic fatty liver disease

© 2020 The Cochrane Collaboration. This article [Turankova T, Blyuss O, Brazhnikov A, Svistunov A, Gurusamy KS, Pavlov CS. Transient elastography with controlled attenuation parameter (CAP) for diagnosis of moderate or severe steatosis in people with suspected non-alcoholic fatty liver disease (Protocol). Cochrane Database of Systematic Reviews 2020, Issue 7. Art. No.: CD013670. DOI: 10.1002/14651858.CD013670.], has been published in final form at https://doi.org/10.1002/14651858.CD013670.Objectives: This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows:. To determine the diagnostic accuracy of transient elastography with CAP for diagnosis of moderate and severe hepatic steatosis in people with suspected NAFLD when compared with liver biopsy as reference standard. To achieve this, we will compare none/mild hepatic steatosis (S0 to S1) versus moderate/severe hepatic steatosis (S2 to S3); and none/mild/moderate hepatic steatosis (S0 to S2) versus severe hepatic steatosis (S3). Secondary objectives We aim to also identify the pooled sensitivity and specificity for the most common cut-off values of CAP for diagnosis of none/mild hepatic steatosis (S0 to S1) and moderate/severe hepatic steatosis (S2 to S3); or none/mild/moderate hepatic steatosis (S0 to S2) and severe hepatic steatosis (S3) in people with suspected NAFLD, and to explore potential sources of heterogeneity influencing the diagnostic test accuracy of CAP (see: Investigations of heterogeneity).Peer reviewe

Immune and Inflammatory Pathways in Non-Alcoholic Steatohepatitis (NASH). An update

Non-alcoholic steatohepatitis (NASH), also known as fatty liver disease (FLD), is a major public health problem. It is considered to be the hepatic manifestation of the metabolic syndrome. Chronic inflammation of the liver is an essential key in the progression from simple hepatic steatosis to steatohepatitis, the evolutionary stage of fatty liver disease. Moreover, the innate immune system plays a crucial role in the progression of hepatic inflammation. For this reason, it is of utmost importance to elucidate the connections between immune mechanisms, Toll-like receptor cytokine signalling, in order to find new effective treatments. Further studies are necessary to test theories presented in this paper. The elucidation of mechanisms underlying the progression of hepatic steatosis towards steatohepatitis is essential for the development of useful diagnosis and treatment for medical practice

Esteatose hepática em crianças e adolescentes obesos

Objective: To assess the frequency of hepatic steatosis and metabolic syndrome among obese children and adolescents.Method: A descriptive case series was conducted with 77 patients, aged 2 to 13 years and 11 months, who were followed up from February to July 2007. Obesity was defined as body mass index >= P-95 adjusted for age and sex. Liver ultrasound was performed to diagnose hepatic steatosis. Metabolic syndrome was defined according to the modified criteria suggested by Cook et al.Results: Hepatic steatosis was diagnosed in 33/77 patients (42.9%), 25/33 (75.8%) with mild steatosis and 8/33 (24.2%) with moderate steatosis. Those aged less than 10 years showed only mild steatosis, and the moderate degree of the disease was restricted to adolescents. Aminotransferase alterations were found in 9.1% (3/33) of patients with hepatic steatosis and in 4.9% (2/41) of those without the disorder. Mean waist circumference was 84.74 +/- 2.84 cm for patients with hepatic steatosis and 78.24 +/- 1.60 cm for those without the disease (p = 0.04). Metabolic syndrome was diagnosed in 27.3% (21/77) of obese patients, 47.6% (10/21) of them having steatosis, 60% had mild steatosis and 40% had a moderate degree of the disorder.Conclusions: the frequency of hepatic steatosis and metabolic syndrome was high. the association of larger waist circumference with hepatic steatosis highlights the importance of taking this parameter into consideration when investigating obese patients.Fundacao de Amparo a Ciencia e Tecnologia do estado de Pernambuco (FACEPE)Univ Fed Pernambuco, Dept Materno Infantil, Ctr Ciencias Saude, Recife, PE, BrazilHosp Barao Lucena, Serv Endocrinol Pediat, Recife, PE, BrazilUniversidade Federal de São Paulo, EPM, São Paulo, BrazilUniversidade Federal de São Paulo, EPM, São Paulo, BrazilWeb of Scienc

Prevalence of hepatic steatosis as diagnosed on unenhanced abdominal computed tomography

Background/Objectives: The prevalence of non-alcoholic fatty liver disease (NAFLD) has been found to be lower in the African American population when compared to European American or Hispanics, even after controlling for obesity and insulin resistance. The prevalence of hepatic steatosis in the local population is unknown. No studies looking at the association between metabolic syndrome and non-alcoholic fatty liver disease have been done in the local population. The aim of this study is to determine the prevalence of hepatic steatosis in patients undergoing unenhanced abdominal Computed Tomography (CT) at Aga Khan University Hospital, NairobiSubjects/Methods: A cross-sectional analytical study of resident indigenous African patients undergoing an unenhanced CT abdomen at Aga Khan University Hospital, Nairobi’s (AKUHN) Radiology department. Data from 246 patients who meet the inclusion and exclusion criteria was collected. Metabolic syndrome was diagnosed using the WHO definition.Results: Of the 246 patients, 39.3% were female and 60.7% were male. Only 77 patients consented to undergo testing for fasting lipid profile. This limited the number of patients who could be diagnosed with metabolic syndrome. Out of the 246 patients, 33 had hepatic steatosis giving a prevalence of 13.4%, at a P value of 0.05 and a confidence interval of 9.0 to 17.8.Although a large number of people reported occasional/social alcohol intake, only 10 patients had alcohol uptake threshold meeting the criteria used. The causes of hepatic steatosis were mainly attributable to non-alcoholic fatty liver disease; only 2.5% had hepatic steatosis due to alcohol consumption. Obesity was found to be a strong risk factor for hepatic steatosis and patients with elevated BMI were up to 4 times more likely to have hepatic steatosis. Diabetes was also found to be a strong risk factor for hepatic steatosis, diabetics were 3 times more likely to have steatosis when compared to non-diabetics.Conclusions: The prevalence of hepatic steatosis was 13.4%. There was a strong association of hepatic steatosis and diabetes, with diabetics 3 times more likely to have hepatic steatosis. An association was found between the components of metabolic syndrome and hepatic steatosis

Targeting a phospho-STAT3-miRNAs pathway improves vesicular hepatic steatosis in an in vitro and in vivo model

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. Although genetic predisposition and epigenetic factors contribute to the development of NAFLD, our understanding of the molecular mechanism involved in the pathogenesis of the disease is still emerging. Here we investigated a possible role of a microRNAs-STAT3 pathway in the induction of hepatic steatosis. Differentiated HepaRG cells treated with the fatty acid sodium oleate (fatty dHepaRG) recapitulated features of liver vesicular steatosis and activated a cell-autonomous inflammatory response, inducing STAT3-Tyrosine-phosphorylation. With a genome-wide approach (Chromatin Immunoprecipitation Sequencing), many phospho-STAT3 binding sites were identified in fatty dHepaRG cells and several STAT3 and/or NAFLD-regulated microRNAs showed increased expression levels, including miR-21. Innovative CARS (Coherent Anti-Stokes Raman Scattering) microscopy revealed that chemical inhibition of STAT3 activity decreased lipid accumulation and deregulated STAT3-responsive microRNAs, including miR-21, in lipid overloaded dHepaRG cells. We were able to show in vivo that reducing phospho-STAT3-miR-21 levels in C57/BL6 mice liver, by long-term treatment with metformin, protected mice from aging-dependent hepatic vesicular steatosis. Our results identified a microRNAs-phosphoSTAT3 pathway involved in the development of hepatic steatosis, which may represent a molecular marker for both diagnosis and therapeutic targeting

MRI overview for fat quantification in non-alcoholic fatty liver disease in the clinical and research settings

The general purpose of this master’s thesis is to describe the MRI techniques used in scanning and post processing for quantifying liver fat percentages for the purpose of diagnosis and research. At the onset we will look at epidemiological data regarding nonalcoholic fatty liver disease, which is often called by the name of hepatic steatosis. Based on the prevalence of this disease it is worthwhile to fully understand non-invasive (MRI) analysis, and its use in the clinical and research setting. Following an introductory section regarding the basis of magnetic resonance imaging, we will take a more in-depth look at current methods utilized for liver fat quantification. Due to the massive population of those of suffer from this disease worldwide it is prudent to analyze current methods, as well as the implications that such research has and will have on the pharmaceutical approach to treating this disease. The purpose of this thesis is to elucidate the MRI techniques utilized for liver fat quantification and provide a comprehensive view of how these techniques are used for diagnosis in the clinical setting, and longitudinal studies in the research setting to measure liver fat levels and how they react to various treatment approaches

Comparison of magnetic resonance spectroscopy, proton density fat fraction and histological analysis in the quantification of liver steatosis in children and adolescents

AIM: To establish a threshold value for liver fat content between healthy children and those with non-alcoholic fatty liver disease (NAFLD) by using magnetic resonance imaging (MRI), with liver biopsy serving as a reference standard. METHODS: The study was approved by the local ethics committee, and written informed consent was obtained from all participants and their legal guardians before the study began. Twenty-seven children with NAFLD underwent liver biopsy to assess the presence of nonalcoholic steatohepatitis. The assessment of liver fat fraction was performed using MRI, with a high field magnet and 2D gradient-echo and multiple-echo T1-weighted sequence with low flip angle and single-voxel point-resolved ¹H MR-Spectroscopy (¹H-MRS), corrected for T1 and T2* decays. Receiver operating characteristic curve analysis was used to determine the best cut-off value. Lin coefficient test was used to evaluate the correlation between histology, MRS and MRI-PDFF. A Mann-Whitney U-test and multivariate analysis were performed to analyze the continuous variables. RESULTS: According to MRS, the threshold value between healthy children and those with NAFLD is 6%; using MRI-PDFF, a cut-off value of 3.5% is suggested. The Lin analysis revealed a good fit between the histology and MRS as well as MRI-PDFF. CONCLUSION: MRS is an accurate and precise method for detecting NAFLD in children