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Nonalcoholic steatohepatitis

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https://www.readbyqxmd.com/read/29471562/can-elastography-differentiate-isolated-fatty-liver-from-nonalcoholic-steatohepatitis
#1
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/29471561/nonalcoholic-fatty-liver-disease-in-children
#2
Jake P Mann, Luca Valenti, Eleonora Scorletti, Christopher D Byrne, Valerio Nobili
Nonalcoholic steatohepatitis, a progressive form of nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in children who present with particular risk factors including obesity, sedentary lifestyle, and/or a predisposing genetic background. The worldwide prevalence of NAFLD in children is a worrying phenomenon because this disease is closely associated with the development of both cirrhosis and cardiometabolic syndrome in adulthood. To date, the etiopathogenesis of primary NAFLD in children is unknown...
February 2018: Seminars in Liver Disease
https://www.readbyqxmd.com/read/29470354/poor-survival-after-retransplantation-in-nash-cirrhosis
#3
Avesh J Thuluvath, Po-Hung Chen, Paul J Thuluvath, Sergey Kantsevoy, Yulia Savva
BACKGROUND: Nonalcoholic steatohepatitis (NASH) cirrhosis is a common indication for liver transplantation (LT) in the U.S. There is a paucity of data on retransplantation (re-LT) in those who were initially transplanted for NASH. METHODS: We queried the UNOS data sets from 2002-2016 to analyze the outcomes of adults with NASH (n=128) and compared them to groups that received re-LT for cryptogenic cirrhosis (CC, n=189), alcoholic cirrhosis (AC, n=300) or autoimmune hepatitis cirrhosis (AIH-C, n=118) after excluding multiple-organ re-LT and individuals with HCC...
February 20, 2018: Transplantation
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/29463024/overexpression-of-the-vitronectin-v10-subunit-in-patients-with-nonalcoholic-steatohepatitis-implications-for-noninvasive-diagnosis-of-nash
#5
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/29452403/mechanisms-controlling-nucleic-acid-sensing-toll-like-receptors
#6
Kensuke Miyake, Takuma Shibata, Umeharu Ohto, Toshiyuki Shimizu, Shin-Ichiroh Saitoh, Ryutaro Fukui, Yusuke Murakami
Nucleic acid (NA)-sensing Toll-like receptors (TLRs) respond to DNA/RNA derived from pathogens and dead cells. Structural studies have revealed a variety of molecular mechanisms by which TLRs sense NAs. Double-stranded RNA and single-stranded DNA directly bind to TLR3 and TLR9, respectively, whereas TLR7 and 8 bind to nucleosides and oligoribonucleotides derived from RNAs. Activation of ligand-bound TLRs is influenced by the functional status of TLRs. Proteolytic cleavage of NA-sensing TLRs enables ligand-dependent TLR dimerization...
February 14, 2018: International Immunology
https://www.readbyqxmd.com/read/29450137/liver-and-metformin-lessons-of-a-fructose-diet-in-mice
#7
Iara Karise, Fernanda Ornellas, Sandra Barbosa-da-Silva, Cristiane Matsuura, Mariano Del Sol, Marcia Barbosa Aguila, Carlos A Mandarim-de-Lacerda
Studies show that the continuous consumption of fructose can lead to nonalcoholic fatty liver disease (NAFLD) and steatohepatitis. We aimed to investigate the role of Metformin in an animal model of liver injury caused by fructose intake, focusing on the molecular markers of lipogenesis, beta-oxidation, and antioxidant defenses. Male three months old C57BL/6 mice were divided into control group (C) and fructose group (F, 47% fructose), maintained for ten weeks. After, the groups received Metformin or vehicle for a further eight weeks: control (C), control + Metformin (CM), fructose (F), and fructose + Metformin (FM)...
June 2017: Biochimie Open
https://www.readbyqxmd.com/read/29448843/cenicriviroc-for-the-treatment-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#8
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/29446942/design-synthesis-and-evaluation-of-a-novel-series-of-indole-sulfonamide-peroxisome-proliferator-activated-receptors-ppar-%C3%AE-%C3%AE-%C3%AE-triple-activators-discovery-of-lanifibranor-a-new-anti-fibrotic-clinical-candidate
#9
Benaissa Boubia, Olivia Poupardin, Martine Barth, Jean Binet, Philippe Peralba, Laurent Mounier, Elise Jacquier, Emilie Gauthier, Valerie Lepais, Maryline Chatar, Stephanie Ferry, Anne Thourigny, Fabrice Guillier, Jonathan Llacer, Jerome Amaudrut, Pierre Dodey, Olivier Lacombe, Philippe Masson, Christian Montalbetti, Guillaume Wettstein, Jean Michel Luccarini, Christiane Legendre, Jean Louis Junien, Pierre Broqua
Here we describe the identification and synthesis of novel indole sulfonamide derivatives that activate the three peroxisome proliferator activated receptor (PPAR) isoforms. Starting with a PPARα activator, compound 4, identified during a high throughput screening (HTS) of our proprietary screening library, a systematic optimization led to the discovery of lanifibranor (IVA337) 5, a moderately potent and well balanced pan PPAR agonist with an excellent safety profile. In vitro and in vivo, compound 5 demonstrated strong activity in models that are relevant to NonAlcoholic SteatoHepatitis (NASH) pathophysiology suggesting therapeutical potential for NASH patients...
February 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29438418/bile-acid-detoxifying-enzymes-limit-susceptibility-to-liver-fibrosis-in-female-shrsp5-dmcr-rats-fed-with-a-high-fat-cholesterol-diet
#10
Husna Yetti, Hisao Naito, Yuan Yuan, Xiaofang Jia, Yumi Hayashi, Hazuki Tamada, Kazuya Kitamori, Katsumi Ikeda, Yukio Yamori, Tamie Nakajima
During middle age, women are less susceptible to nonalcoholic steatohepatitis (NASH) than men. Thus, we investigated the underlying molecular mechanisms behind these sexual differences using an established rat model of NASH. Mature female and male stroke-prone spontaneously hypertensive 5/Dmcr rats were fed control or high-fat-cholesterol (HFC) diets for 2, 8, and 14 weeks. Although HFC-induced hepatic fibrosis was markedly less severe in females than in males, only minor gender differences were observed in expression levels of cytochrome P450 enzymes (CYP)7A1, CYP8B1 CYP27A1, and CYP7B1, and multidrug resistance-associated protein 3, and bile salt export pump, which are involved in fibrosis-related bile acid (BA) kinetics...
2018: PloS One
https://www.readbyqxmd.com/read/29428719/combination-effects-of-alogliptin-and-pioglitazone-on-steatosis-and-hepatic-fibrosis-formation-in-a-mouse-model-of-non-alcoholic-steatohepatitis
#11
Yuichiro Amano, Shuntarou Tsuchiya, Mayumi Imai, Kimio Tohyama, Jun Matsukawa, Osamu Isono, Hironobu Yasuno, Kazuaki Enya, Emiko Koumura, Hiroshi Nagabukuro
This study aimed to evaluate the effects of combination therapy with a dipeptidyl peptidase-4 inhibitor, alogliptin, and a peroxisome proliferator-activated receptor-γ agonist, pioglitazone, in a preclinical model of nonalcoholic steatohepatitis using low-density lipoprotein receptor-knockout mice fed a modified choline-deficient l-amino acid-defined diet. Monotherapy with either alogliptin (10-200 mg/kg) or pioglitazone (6-20 mg/kg) significantly decreased hepatic triglyceride content and fibrosis. The concomitant treatment of alogliptin (30 mg/kg), pioglitazone (20 mg/kg) also decreased hepatic triglyceride and hepatic collagen-I mRNA at greater extent compared to monotherapy...
February 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29427621/brg1-promotes-liver-fibrosis-via-activation-of-hepatic-stellate-cells
#12
Haijie Li, Jingqin Lan, Caishun Han, Kaixuan Guo, Guihua Wang, Junbo Hu, Jianping Gong, Xuelai Luo, Zhixin Cao
Liver fibrosis, an important health concern associated to chronic liver injury that provides a permissive environment for cancer development, is characterized by the persistent deposition of extracellular matrix components mainly derived from activated hepatic stellate cells (HSCs). Brg1, the core subunit of the SWI/SNF chromatin remodeling complex, has been proved to associated with nonalcoholic steatohepatitis which may progress to cirrhosis. Herein, we determined whether Brg1 regulates liver fibrosis and examined its mechanism by focusing on HSCs activation...
February 7, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29427488/global-epidemiology-of-non-alcoholic-fatty-liver-disease-non-alcoholic-steatohepatitis-what-we-need-in-the-future
#13
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/29424123/mouse-models-of-nonalcoholic-steatohepatitis-a-reflection-on-recent-literature
#14
REVIEW
Fahrettin Haczeyni, Matthew M Yeh, George N Ioannou, Isabelle A Leclercq, Robert Goldin, Yock Young Dan, Jun Yu, Narcissus C Teoh, Geoffrey C Farrell
Nonalcoholic steatohepatitis (NASH) is strongly associated with overnutrition, insulin resistance, and predisposition to type 2 diabetes. To critically analyze the translational significance of currently-used animal models of NASH, we reviewed articles published during the last three years that studied NASH pathogenesis using mouse models. Among 146 articles, 34 (23%) used models in which overnutrition was reported, and 36 (25%) demonstrated insulin resistance, with or without glucose intolerance. Half the articles contained no information on whether mice exhibited overnutrition or insulin resistance...
February 9, 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29420067/organic-solute-transporter-ost%C3%AE-%C3%A3-is-over-expressed-in-nonalcoholic-steatohepatitis-and-modulated-by-drugs-associated-with-liver-injury
#15
Melina Miia Malinen, Izna Ali, Jacqueline Bezençon, James John Beaudoin, Kim L R Brouwer
The heteromeric steroid transporter, organic solute transporter alpha/beta (OSTα/β; SLC51), was discovered over a decade ago, but its physiological significance in the liver is still uncertain. A major challenge has been the lack of suitable models expressing OSTα/β. Based on observations first reported herein that hepatic OSTα/β is upregulated in nonalcoholic steatohepatitis (NASH), the aim of this research was to develop an in vitro model to evaluate OSTα/β function and interaction with drugs and bile acids...
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
#16
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/29411291/post-liver-transplantation-diabetes-mellitus-a-review-of-relevance-and-approach-to-treatment
#17
REVIEW
Maria J Peláez-Jaramillo, Allison A Cárdenas-Mojica, Paula V Gaete, Carlos O Mendivil
Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM...
February 6, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
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/29409022/dysregulation-of-kupffer-cells-macrophages-and-natural-killer-t-cells-in-steatohepatitis-in-lxr%C3%AE-knockout-male-mice
#19
Kaori Endo-Umeda, Hiroyuki Nakashima, Naoki Umeda, Shuhji Seki, Makoto Makishima
Liver X receptor (LXR) α expression is mainly localized to metabolic tissues, such as the liver, while LXRβ is ubiquitously expressed. LXRα is activated by oxysterols and plays an important role in the regulation of lipid metabolism in metabolic tissues. In macrophages, LXRs stimulate reverse cholesterol transport and regulate immune responses. Although a high cholesterol diet induces severe steatohepatitis in LXRα-knockout (LXRα-KO) mice, the underlying mechanisms linking lipid metabolism and immune responses remain largely unknown...
February 1, 2018: Endocrinology
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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