Wisteria floribundaagglutinin-positive Mac-2-binding protein and type 4 collagen 7S: useful markers for the diagnosis of significant fibrosis in patients with non-alcoholic fatty liver disease

2018 ◽  
Vol 33 (10) ◽  
pp. 1795-1803 ◽  
Author(s):  
Yuji Ogawa ◽  
Yasushi Honda ◽  
Takaomi Kessoku ◽  
Wataru Tomeno ◽  
Kento Imajo ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Binding Protein ◽  
Alcoholic Fatty Liver ◽  
Significant Fibrosis ◽  
Alcoholic Fatty Liver Disease

Non-invasive Stratification of Non-Alcoholic Fatty Liver Disease by Whole-transcriptome Cell-free mRNA Characterization

2021 ◽  
Author(s):  
Naga Chalasani ◽  
Shusuke Toden ◽  
John J Sninsky ◽  
Richard P Rava ◽  
Jerome V Braun ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Healthy Subjects ◽  
Rna Seq ◽  
Alcoholic Fatty Liver ◽  
Significant Fibrosis ◽  
Non Invasive ◽  
Clinically Significant ◽  
Alcoholic Fatty Liver Disease

Hepatic fibrosis stage is the most important determinant of outcomes in patients with non-alcoholic fatty liver disease (NAFLD). There is an urgent need for non-invasive tests that can accurately stage fibrosis and determine efficacy of interventions. Here we describe a novel cf-mRNA-Sequencing approach that can accurately and reproducibly profile low levels of circulating mRNAs and evaluate the feasibility of developing a cf-mRNA-based NAFLD fibrosis classifier. Using separate discovery and validation cohorts with biopsy-confirmed NAFLD (n=176 and 59, respectively) and healthy subjects (n=23), we performed serum cf-mRNA RNA-Seq profiling. Differential expression analysis identified 2498 dysregulated genes between NAFLD and healthy subjects and 134 fibrosis-associated genes in NAFLD patients. Comparison between cf-mRNA and liver tissues transcripts revealed significant overlap of fibrosis associated genes and pathways indicating that the circulating cf-mRNA transcriptome reflects molecular changes in the livers of NAFLD patients. In particular, metabolic and immune pathways reflective of known underlying steatosis and inflammation were highly dysregulated in the cf-mRNA profile of patients with advanced fibrosis. Finally, we used an elastic net ordinal logistic model to develop a classifier that predicts clinically significant fibrosis (F2-4). In an independent cohort, the cf-mRNA classifier was able to identify 50% of patients with at least 90% probability of clinically significant fibrosis. We demonstrate a novel and robust cf-mRNA-based RNA-Seq platform for non-invasive identification of diverse hepatic molecular disruptions and for fibrosis staging with promising potential for clinical trials and clinical practice.

scholarly journals A Diet-Induced Pediatric Model of Non Alcoholic Fatty Liver Disease Using Neonatal Iberian Pigs (OR26-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Gabriella Hernandez ◽  
Victoria Smith ◽  
Mieko Temple ◽  
Darin Bennet ◽  
Daniel Columbus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Liver Disease ◽  
Liver Injury ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Binding Protein ◽  
Alcoholic Fatty Liver ◽  
Element Binding Protein ◽  
Alcoholic Fatty Liver Disease

Abstract Objectives The prevalence of non-alcoholic fatty liver disease (NAFLD) in children has increased over the past decades, creating a need for animal models that recapitulate the features of the pediatric disease. Iberian pigs have a leptin-resistant phenotype characterized by hyperleptinemia, hyperphagia, and extreme adipogenesis. We hypothesized that neonatal Iberian pigs fed a high-fat high-fructose (HFF) diet will develop a pattern of liver injury resembling pediatric NAFLD. In addition, we sought to determine if a mixture of probiotics would prevent the disease. Methods Animals were fed 1 of 4 diets containing (g/kg body weight × d) 0 g fructose, 11 g fat and 199 kcal (CON-N; n = 8), 22 g fructose, 16 g fat and 300 kcal (HFF-N; n = 6), CON + probiotic (CON-P; n = 6), or HFF + probiotic (HFF-P; n = 6) every 6 h for 70 d. The probiotic mixture (6.2 × 104cfu/mL) contained Pediococcus, Lactobacillus and Bacillus. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 65 at 2 h post feeding. Fasting leptin, insulin, glucose and homeostatic model assessment (HOMA) values were assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and gene expression of tumor necrosis factor (TNF) α, tumor growth factor (TGF) β, interleukin (IL) 1α, peroxisome proliferator-activated receptor (PPAR) γ, carbohydrate-responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein (SREBP) 1c. Results Body weight was higher in CON-P, and insulin and HOMA values in HFF-P and CON-P (P ≤ 0.05). Leptin, alanine and aspartate aminotransferases, alkaline phosphatase, lactate dehydrogenase and total bilirubin were increased (P ≤ 0.001), and high and low density lipoproteins decreased (P ≤ 0.05) in HFF-N and HFF-P. Livers in HFF-P and HFF-N had higher relative weight and TG (P ≤ 0.001), micro and macrovesicular steatosis, ballooning degeneration, Mallory-denk bodies, inflammation and necrosis, increased gene expression of TNFα, TGFβ, IL1α and PPARγ (P ≤ 0.001), and decreased ChREBP (P ≤ 0.001). Conclusions Iberian pigs fed a HFF diet recapitulate many pediatric NAFLD-associated features, in the absence of obesity and independently of probiotic supplementation, suggesting a potentially suitable model for pediatric NAFLD research. Funding Sources ARI, AcornSeekers.

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