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https://www.readbyqxmd.com/read/29473277/the-formation-of-p62-positive-inclusion-body-is-associated-with-macrophage-polarization-in-non-alcoholic-fatty-liver-disease
#1
Hirofumi Fukushima, Shunhei Yamashina, Atsushi Arakawa, Gentaro Taniguchi, Tomonori Aoyama, Akira Uchiyama, Kazuyoshi Kon, Kenichi Ikejima, Sumio Watanabe
BACKGROUND: Hepatic inclusion composed of autophagy-specific substrate p62 is one of the histological features of non-alcoholic fatty liver disease (NAFLD) and can be a precursor to hepatic carcinogenesis. The expression of p62 was enhanced by not only autophagic dysfunction but also oxidative stress and inflammation. M1/M2 phenotypic balance of macrophages plays a pivotal role in the progression of NAFLD. We evaluated the correlation between macrophage-polarization and the formation of p62 aggregation in NAFLD...
February 23, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29471595/circulating-piiinp-levels-identify-adipose-tissue-associated-inflammation-in-individuals-with-type-2-diabetes-mellitus-with-and-without-non-alcoholic-fatty-liver-disease
#2
I Barchetta, F A Cimini, R De Gioannis, G Ciccarelli, L Bertoccini, A Lenzi, M G Baroni, M G Cavallo
AIMS: Procollagen-III peptide (PIIINP) is a marker of fibrosis associated with increased cardio-metabolic risk and progression of chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH); its association with type 2 diabetes mellitus has not been elucidated yet. Aim of this study was to investigate the relationship between circulating PIIINP levels, metabolic traits and body fat distribution in subjects with T2DM with or without NAFLD. MATERIALS AND METHODS: Data from sixty-two T2DM subjects recruited in our Diabetes outpatient clinics at Sapienza University of Rome, Italy, were analysed...
February 22, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29471562/can-elastography-differentiate-isolated-fatty-liver-from-nonalcoholic-steatohepatitis
#3
Veeral Ajmera, Rohit Loomba
Ultrasound and magnetic resonance (MR)-based elastography have demonstrated excellent performance for noninvasive staging of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD); however, their ability to differentiate isolated fatty liver from nonalcoholic steatohepatitis (NASH) is unclear. In this review, the authors provide background on elastography and review the ability of elastography to discriminate between isolated steatosis and NASH. Studies with available data on the diagnosis of NASH histology are limited to vibration-controlled transient elastography and MR elastography...
February 2018: Seminars in Liver Disease
https://www.readbyqxmd.com/read/29470286/genetic-variants-associated-with-obesity-and-insulin-resistance-in-hispanic-boys-with-nonalcoholic-fatty-liver-disease
#4
John C Rausch, Joel E Lavine, Naga Chalasani, Xiuqing Guo, Soonil Kwon, Jeffrey B Schwimmer, Jean P Molleston, Rohit Loomba, Elizabeth M Brunt, Yii-Der Ida Chen, Mark O Goodarzi, Kent D Taylor, Katherine P Yates, Jerome I Rotter
BACKGROUND AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) disproportionately affects Hispanic boys. Further, obesity and insulin resistance are major risk factors for NAFLD. No gene localization studies had been performed on children with biopsy-proven NAFLD. This study aims to identify genomic variants associated with increased adiposity and insulin resistance in a population of children with varying histologic severity of NAFLD. METHODS: We conducted a genome-wide association scan (GWAS) including 624,297 single-nucleotide polymorphisms (SNPs) distributed among all 22 autosomal chromosomes in 234 Hispanic boys (up to 18 years of age) who were consecutively recruited in a prospective cohort study in the Nonalcoholic Steatohepatitis Clinical Research Network Studies...
February 21, 2018: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/29469051/nonalcoholic-fatty-liver-disease-progresses-into-severe-nash-when-physiological-mechanisms-of-tissue-homeostasis-collapse
#5
Silvia Sookoian, Carlos J Pirola
Phenotypic modulation of NAFLD-severity by molecules derived from white (adipokines) and brown (batokines) adipose tissue may be important in inducing or protecting against the progression of the disease. Adipose tissue-derived factors can promote the progression of NAFLD towards severe histological stages (NASH-fibrosis and NASHcirrhosis). This effect can be modulated by the release of adipokines or batokines that directly trigger an inflammatory response in the liver tissue or indirectly modulate related phenotypes, such as insulin resistance...
March 1, 2018: Annals of Hepatology
https://www.readbyqxmd.com/read/29463024/overexpression-of-the-vitronectin-v10-subunit-in-patients-with-nonalcoholic-steatohepatitis-implications-for-noninvasive-diagnosis-of-nash
#6
Maria Del Ben, Diletta Overi, Licia Polimeni, Guido Carpino, Giancarlo Labbadia, Francesco Baratta, Daniele Pastori, Valeria Noce, Eugenio Gaudio, Francesco Angelico, Carmine Mancone
Nonalcoholic steatohepatitis (NASH) is the critical stage of nonalcoholic fatty liver disease (NAFLD). The persistence of necroinflammatory lesions and fibrogenesis in NASH is the leading cause of liver cirrhosis and, ultimately, hepatocellular carcinoma. To date, the histological examination of liver biopsies, albeit invasive, remains the means to distinguish NASH from simple steatosis (NAFL). Therefore, a noninvasive diagnosis by serum biomarkers is eagerly needed. Here, by a proteomic approach, we analysed the soluble low-molecular-weight protein fragments flushed out from the liver tissue of NAFL and NASH patients...
February 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29462566/non-alcoholic-fatty-liver-disease-and-gastric-bypass-surgery-regulate-serum-and-hepatic-levels-of-pyruvate-kinase-isoenzyme-m2
#7
Luca Meoli, Nitin K Gupta, Nima Saeidi, Courtney Panciotti, Sudha B Biddinger, Kathleen E Corey, Nicholas Stylopoulos
Treatment of non-alcoholic fatty liver disease (NAFLD) focuses on the underlying metabolic syndrome, and Roux-en-Y gastric bypass surgery (RYGB) remains one of the most effective options. In rodents and human patients, RYGB induces an increase in the gene and protein expression levels of the M2 isoenzyme of Pyruvate Kinase (PKM2) in the jejunum. Since PKM2 can be secreted in the circulation, our hypothesis was that the circulating levels of PKM2 increase after RYGB. Our data, however, revealed an unexpected finding and a potential new role of PKM2 for the natural history of metabolic syndrome and NAFLD...
February 20, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29457838/bax-inhibitor-1-protects-from-non-alcoholic-steatohepatitis-by-limiting-ire1%C3%AE-signaling
#8
Cynthia Lebeaupin, Déborah Vallée, Déborah Rousseau, Stéphanie Patouraux, Stéphanie Bonnafous, Gilbert Adam, Frederic Luciano, Carmelo Luci, Rodolphe Anty, Antonio Iannelli, Sandrine Marchetti, Guido Kroemer, Sandra Lacas-Gervais, Albert Tran, Philippe Gual, Béatrice Bailly-Maitre
Endoplasmic reticulum (ER) stress is activated in non-alcoholic fatty liver disease (NAFLD), raising the possibility that ER stress-dependent metabolic dysfunction, inflammation and cell death underlie the transition from steatosis to steatohepatitis (NASH). Bax inhibitor-1 (BI-1), a negative regulator of the ER stress sensor IRE1α, has yet to be explored in NAFLD as a hepatoprotective agent. We hypothesized that the genetic ablation of BI-1 would render the liver vulnerable to NASH due to unrestrained IRE1α signaling...
February 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29452601/reactive-hyperemia-index-rhi-and-cognitive-performance-indexes-are-associated-with-histologic-markers-of-liver-disease-in-subjects-with-non-alcoholic-fatty-liver-disease-nafld-a-case-control-study
#9
Antonino Tuttolomondo, Salvatore Petta, Alessandra Casuccio, Carlo Maida, Vittoriano Della Corte, Mario Daidone, Domenico Di Raimondo, Rosaria Pecoraro, Roberto Fonte, Anna Cirrincione, Rita Zafonte, Daniela Cabibi, Calogero Cammà, Vito Di Marco, Anna Licata, Franco Magliozzo, Giulio Marchesini, Giovanni Merlino, Antonio Craxì, Antonio Pinto
BACKGROUND: No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes. AIM OF THE STUDY: We aimed to assess whether NAFLD and its histological severity are associated with impairment of arterial stiffness and RH-PAT indexes in a mixed cohort of patients with biopsy-proven NAFLD. MATERIALS AND METHODS: The Kleiner classification was used to grade NAFLD grade...
February 16, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29448843/cenicriviroc-for-the-treatment-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#10
Frank Tacke
Nonalcoholic fatty liver disease (NAFLD) has an increasing prevalence worldwide. At present, no specific pharmacotherapy is approved for NAFLD. Simple steatosis and nonalcoholic steatohepatitis (NASH) can progress to liver fibrosis that is associated with mortality in NAFLD. The recruitment of inflammatory monocytes and macrophages via chemokine receptor CCR2 as well as of lymphocytes and hepatic stellate cells via CCR5 promote the progression of NASH to fibrosis. Areas covered: I summarize preclinical and clinical data on the efficacy and safety of the dual CCR2/CCR5 inhibitor cenicriviroc (CVC, also TBR-652 or TAK-652) for the treatment of NASH and fibrosis...
February 16, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29446106/impact-of-controlled-attenuation-parameter-on-detecting-fibrosis-using-liver-stiffness-measurement
#11
T Karlas, D Petroff, M Sasso, J-G Fan, Y-Q Mi, V de Lédinghen, M Kumar, M Lupsor-Platon, K-H Han, A C Cardoso, G Ferraioli, W-K Chan, V W-S Wong, R P Myers, K Chayama, M Friedrich-Rust, M Beaugrand, F Shen, J-B Hiriart, S K Sarin, R Badea, H W Lee, P Marcellin, C Filice, S Mahadeva, G L-H Wong, P Crotty, K Masaki, J Bojunga, P Bedossa, V Keim, J Wiegand
BACKGROUND: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis...
February 15, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29427488/global-epidemiology-of-non-alcoholic-fatty-liver-disease-non-alcoholic-steatohepatitis-what-we-need-in-the-future
#12
REVIEW
Ana Ruth Araújo, Natalia Rosso, Giorgio Bedogni, Claudio Tiribelli, Stefano Bellentani
The estimated prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide is approximately 25%. However, the real prevalence of NAFLD and the associated disorders is unknown mainly because reliable and applicable diagnostic tests are lacking. This is further complicated by the lack of consensus on the terminology of different entities such as NAFLD or nonalcoholic steatohepatitis (NASH). Although assessing fatty infiltration in the liver is simple by ultrasound, the gold standard for the assessment of fibrosis, the only marker of progression towards more severe liver disease is still liver biopsy...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29427486/management-of-patients-with-non-alcoholic-steatohepatitis-nash-in-real-life
#13
REVIEW
Lawrence Serfaty
Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is a prevalent condition that is associated with the development of cirrhosis and hepatocellular carcinoma and with no approved treatment options except for lifestyle changes. Guidelines have been drafted for the management of NAFLD patients in this setting. Because of the lack of real-life cohort data, we will focus on practice surveys on the management of patients with NAFLD/NASH, which included primary care practitioners, gastroenterologists/hepatologists and other specialists from various countries...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29420066/cc-chemokine-receptor-2-promotes-recruitment-of-myeloid-cells-associated-with-insulin-resistance-in-non-alcoholic-fatty-liver-disease
#14
Richard Parker, Christopher J Weston, Zhenhua Miao, Christopher Corbett, Matthew Armstrong, Linda Ertl, Karen Ebsworth, Matthew Walters, Trageen Baumart, Dale Newland, Jeff McMahon, Penglie Zhang, Rajinder Singh, James Campbell, Philip N Newsome, Israel Charo, Thomas Schall, David H Adams
Non-alcoholic fatty liver disease (NAFLD) is a common disease, closely associated with obesity and insulin resistance. We investigated the presence of a subset of myeloid cells associated with metabolic disturbance in the liver of patients with NAFLD and a murine model of obesity-induced liver disease. Gene and protein expression in liver and serum was investigated with rt-PCR or ELISA and correlated to clinical disease. Liver-infiltrating immune cells were isolated from normal or diseased human liver for flow cytometric analysis...
February 8, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29414249/recent-insights-into-the-pathogenesis-of-nonalcoholic-fatty-liver-disease
#15
Juan Pablo Arab, Marco Arrese, Michael Trauner
Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide and an important risk factor for both hepatic and cardiometabolic mortality. The rapidly increasing prevalence of this disease and of its aggressive form nonalcoholic steatohepatitis (NASH) will require novel therapeutic approaches based on a profound understanding of its pathogenesis to halt disease progression to advanced fibrosis or cirrhosis and cancer. The pathogenesis of NAFLD involves a complex interaction among environmental factors (i...
January 24, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/29413959/role-of-gut-microbiota-and-oxidative-stress-in-the-progression-of-non-alcoholic-fatty-liver-disease-to-hepatocarcinoma-current-and-innovative-therapeutic-approaches
#16
REVIEW
Antonella Borrelli, Patrizia Bonelli, Franca Maria Tuccillo, Ira D Goldfine, Joseph L Evans, Franco Maria Buonaguro, Aldo Mancini
Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD progresses through the inflammatory phase of non-alcoholic steatohepatitis (NASH) to fibrosis and cirrhosis, with some cases developing liver failure or hepatocellular carcinoma (HCC). Liver biopsy remains the gold standard approach to a definitive diagnosis of NAFLD and the distinction between simple steatosis and NASH. The pathogenesis of NASH is still not clear. Several theories have been proposed ranging from the "Two Hit Theory" to the "Multiple Hit Theory"...
January 27, 2018: Redox Biology
https://www.readbyqxmd.com/read/29411334/regulation-and-bioactivity-of-the-ccn-family-of-genes-and-proteins-in-obesity-and-diabetes
#17
REVIEW
Stephen M Twigg
Across the years the CCNs have been increasingly implicated in the development of obesity, diabetes and its complications. Evidence for this is currently derived from their dysregulation in key metabolic pathological states in humans, animal and in vitro models, and also pre-clinical effects of their bioactivities. CCN2 is the best studied in this disease process and the other CCNs are yet to be better defined. Key steps where CCNs may play a pathogenic metabolic role include: (i) obesity and insulin resistance, where CCN2 inhibits fat cell differentiation in vitro and CCN3 may induce obesity and insulin resistance; (ii) elevated blood glucose levels to diabetes mellitus onset, where CCN2 may contribute to pancreatic beta cell and islet function; and (iii) in diabetes complications, such as nephropathy, retinopathy, liver disease (NAFLD/NASH), CVD and diabetes with heart failure...
February 6, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29411270/haptoglobin-genotype-and-vitamin%C3%A2-e-versus-placebo-for-the-treatment-of-nondiabetic-patients-with-nonalcoholic-steatohepatitis-in-china-a-multicenter-randomized-placebo-controlled-trial-design
#18
Shufei Zang, Jin Chen, Yu Song, Lang Bai, Jinjun Chen, Xiaoling Chi, Fangping He, Huiping Sheng, Jing Wang, Shilong Xie, Wen Xie, Yongfeng Yang, Jing Zhang, Minghua Zheng, Zhengsheng Zou, Bingyuan Wang, Junping Shi
INTRODUCTION: Vitamin E is one of the most promising agents for nonalcoholic steatohepatitis (NASH) treatment, and its drug responsiveness may be closely associated with haptoglobin (Hp) genotype. However, its efficacy and safety remain unknown in China. This clinical trial of vitamin E versus placebo for the treatment of nondiabetic patients with nonalcoholic steatohepatitis (VENS) is conducted to evaluate (a) the efficacy and safety of treatment with vitamin E softgel (300 mg/day) determined from standardized histologic scoring of liver biopsies, (b) whether treatment with vitamin E improves biochemical parameters, cytokines, anthropometric parameters, controlled attenuation parameter (CAP), and transient elastography (TE) values determined by Fibroscan and health-related quality of life (SF-36), (c) whether the efficacy of vitamin E treatment is associated with the Hp genotype in nondiabetic adults with NASH...
February 6, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/29410708/dietary-fat-stimulates-development-of-nafld-more-potently-than-dietary-fructose-in-sprague-dawley-rats
#19
Victoria Svop Jensen, Henning Hvid, Jesper Damgaard, Helle Nygaard, Camilla Ingvorsen, Erik Max Wulff, Jens Lykkesfeldt, Christian Fledelius
Background: In humans and animal models, excessive intake of dietary fat, fructose and cholesterol has been linked to the development of non-alcoholic fatty liver disease (NAFLD). However, the individual roles of the dietary components remain unclear. To investigate this further, we compared the effects of a high-fat diet, a high-fructose diet and a combination diet with added cholesterol on the development of NAFLD in rats. Methods: Forty male Sprague-Dawley rats were randomized into four groups receiving either a control-diet (Control: 10% fat); a high-fat diet (HFD: 60% fat, 20% carbohydrate), a high-fructose diet [HFr: 10% fat, 70% carbohydrate (mainly fructose)] or a high-fat/high-fructose/high-cholesterol-diet (NASH: 40% fat, 40% carbohydrate (mainly fructose), 2% cholesterol) for 16 weeks...
2018: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/29408694/fructose-and-sugar-a-major-mediator-of-nonalcoholic-fatty-liver-disease
#20
REVIEW
Thomas Jensen, Manal F Abdelmalek, Shelby Sullivan, Kristen J Nadeau, Melanie Green, Carlos Roncal, Takahiko Nakagawa, Masanari Kuwabara, Yuka Sato, Duk-Hee Kang, Dean R Tolan, Laura G Sanchez-Lozada, Hugo R Rosen, Miguel A Lanaspa, Anna Mae Diehl, Richard J Johnson
Nonalcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high fructose corn syrup (HFCS)) not only increases the risk for NAFLD, but also, nonalcoholic steatohepatitis (NASH). Here we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation...
January 31, 2018: Journal of Hepatology
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