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Non alcoholic steatohepatitis

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https://www.readbyqxmd.com/read/29928018/polymorphisms-in-the-receptor-for-advanced-glycation-end-products-rage-gene-and-circulating-rage-levels-as-a-susceptibility-factor-for-non-alcoholic-steatohepatitis-nash
#1
Rohini Mehta, Gladys Shaw, Peter Masschelin, Sean Felix, Munkzhul Otgonsuren, Ancha Baranova, Zachary Goodman, Zobair Younossi
Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and major cause of chronic liver disease in developed countries. Its prevalence is increasing in parallel with the prevalence of obesity and other components of the metabolic syndrome. As the liver is central to the clearance and catabolism of circulating advanced glycosylation end-products (AGEs), AGEs and their cognate receptors-RAGE (receptor for AGEs) system might be involved in NAFLD in obese patients. To examine this, we investigated four common polymorphisms of RAGE gene: 1704G/T (rs184003), G82S (rs2070600), -374T/A (rs1800624) and -429T/C (rs1800625) in 340 obese patients with metabolic syndrome...
2018: PloS One
https://www.readbyqxmd.com/read/29926478/medi0382-a-glp-1-glucagon-receptor-dual-agonist-meets-safety-and-tolerability-endpoints-in-a-single-dose-healthy-subject-randomised-phase-1-study
#2
Philip D Ambery, Sebastian Klammt, Maximillian G Posch, Marcella Petrone, Wenji Pu, Cristina Rondinone, Lutz Jermutus, Boaz Hirshberg
AIMS: MEDI0382 is a balanced glucagon-like peptide-1/glucagon receptor dual agonist under development for the treatment of type 2 diabetes mellitus and non-alcoholic steatohepatitis. The primary objective was to assess the safety of MEDI0382 in healthy subjects. METHODS: In this placebo-controlled, double-blind, phase 1 study, healthy subjects (aged 18-45 years) were randomised (3:1) to receive a single subcutaneous dose of MEDI0382 or placebo after ≥8 hours of fasting...
June 21, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29924722/interaction-of-volatile-organic-compounds-and-underlying-liver-disease-a-new-paradigm-for-risk
#3
Anna L Lang, Juliane I Beier
Occupational and environmental exposures to industrial chemicals are known to cause hepatotoxicity and liver injury, in humans and in animal models. Historically, research has focused on severe acute liver injury (e.g., fulminant liver failure) or endstage diseases (e.g., cirrhosis and HCC). However, it has become recently recognized that toxicants can cause more subtle changes to the liver. For example, toxicant-associated steatohepatitis (TASH), characterized by hepatic steatosis, and inflammation, was recently recognized in an occupational cohort exposed to vinyl chloride...
June 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29915639/a-case-of-concomitant-obstructive-sleep-apnea-and-non-alcoholic-steatohepatitis-treated-with-cpap-therapy
#4
Bharat Bajantri, Dmitry Lvovsky
Obstructive sleep apnea syndrome is a disorder of sleep breathing that is a result of recurrent and intermittent hypoxia during sleep induced by the repeated partial or complete collapse of the upper airway, eventually causing chronic intermittent hypoxia. Non-alcoholic fatty liver disease is divided into non-alcoholic fatty liver and non-alcoholic steatohepatitis. Animal and human studies showed that obesity is associated with chronic liver hypoxia, even in the presence of systemic normoxia causing inflammation and release of cytokines...
June 2018: Gastroenterology Research
https://www.readbyqxmd.com/read/29915227/microrna-214-promotes-hepatic-stellate-cell-activation-and-liver-fibrosis-by-suppressing-sufu-expression
#5
Liping Ma, Xiaoxue Yang, Rong Wei, Tinghong Ye, Jian-Kang Zhou, Maoyao Wen, Ruoting Men, Ping Li, Biao Dong, Lunxu Liu, Xianghui Fu, Heng Xu, Rami I Aqeilan, Yu-Quan Wei, Li Yang, Yong Peng
MicroRNAs (miRNAs) have been demonstrated to modulate cellular processes in the liver. However, the role of miRNAs in liver fibrosis is poorly understood. Because the activation of hepatic stellate cells (HSCs) is a pivotal event in the initiation and progression of hepatic fibrosis, we investigate the differential expression of miRNAs in activated and quiescent rat HSCs by microarray analysis and find that miR-214 (miR-214-3p) is significantly upregulated during HSC activation. Moreover, the robust induction of miR-214 is correlated with liver fibrogenesis in carbon tetrachloride (CCl4 )-treated rats and mice, high-fat diet-induced non-alcoholic steatohepatitis in mice, and cirrhosis in humans...
June 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29913280/emricasan-improves-liver-function-in-patients-with-cirrhosis-and-high-model-for-end-stage-liver-disease-scores-compared-with-placebo
#6
Catherine T Frenette, Giuseppe Morelli, Mitchell L Shiffman, R Todd Frederick, Raymond A Rubin, Michael B Fallon, Jason T Cheng, Matt Cave, Saira A Khaderi, Omar Massoud, Nikolaos Pyrsopoulos, James S Park, James M Robinson, Mason Yamashita, Alfred P Spada, Jean L Chan, David T Hagerty
BACKGROUND & AIMS: Caspase-mediated apoptosis and inflammation contribute to progression of liver disease. Emricasan is a pan-caspase inhibitor that reduced serum markers of apoptosis and liver inflammation in patients with hepatitis C and non-alcoholic steatohepatitis (NASH). METHODS: We performed a multicenter study of 86 patients with cirrhosis (Child-Pugh class A or B; mean score, 6.9; 38% with alcohol-associated cirrhosis, 29% with HCV-associated cirrhosis, and 23% with NASH) and model for end-stage liver disease (MELD) scores of 11-18 (mean, 12...
June 15, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29913275/rates-and-factors-associated-with-placebo-response-in-trials-of-pharmacotherapies-for-nonalcoholic-steatohepatitis-systematic-review-and-meta-analysis
#7
REVIEW
Ma Ai Thanda Han, Osama Altayar, Shadi Hamdeh, Varun Takyar, Yaron Rotman, Ohad Etzion, Eric Lefebvre, Rifaat Safadi, Vlad Ratziu, Larry J Prokop, Mohammad Hassan Murad, Mazen Noureddin
BACKGROUND & AIMS: Understanding the extent of the placebo effect in randomized controlled trials of studying nonalcoholic steatohepatitis (NASH) is important for optimal trial design, including sample size calculations and treatment endpoint definition. METHODS: We performed a systematic review and meta-analysis of the placebo groups from randomized controlled trials of adults with NASH that provided histological and/or magnetic resonance image-based measurements of intrahepatic triglyceride...
June 15, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29912756/hyperlipidemia-and-nonalcoholic-steatohepatitis-predispose-to-hepatocellular-carcinoma-development-without-cirrhosis
#8
Jennifer Phan, Vivian Ng, Alan Sheinbaum, Sam French, Gina Choi, Mohamed El Kabany, Francisco Durazo, Sammy Saab, Myron Tong, Ronald Busuttil, Steven-Huy Han
BACKGROUND: Hepatocellular carcinoma (HCC) accounts for 90% of primary hepatic malignancies. With the exception of chronic hepatitis B (CHB), other etiologies of chronic liver disease require progression to cirrhosis before HCC development. Case reports have described HCC in noncirrhotic patients with hepatitis C (HCV) and nonalcoholic fatty liver disease. GOAL: The aim of this study was to determine the prevalence of patients without cirrhosis and CHB who developed HCC among a large cohort of HCC patients and to identify independent variables that are associated with no cirrhosis among patients with HCC...
June 16, 2018: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/29908364/non-alcoholic-steatohepatitis-is-the-fastest-growing-cause-of-hepatocellular-carcinoma-in-liver-transplant-candidates
#9
Zobair Younossi, Maria Stepanova, Janus P Ong, Ira M Jacobson, Elisabetta Bugianesi, Ajay Duseja, Yuichiro Eguchi, Vincent W Wong, Francesco Negro, Yusuf Yilmaz, Manuel Romero-Gomez, Jacob George, Aijaz Ahmed, Robert Wong, Issah Younossi, Mariam Ziayee, Arian Afendy
BACKGROUND: While hepatitis B and C have been the main drivers of hepatocellular carcinoma (HCC), non-alcoholic steatohepatitis (NASH) has recently become an important cause of HCC. The aim of this study was to assess the causes of HCC among liver transplant (LT) candidates in the U.S. METHODS: The Scientific Registry of Transplant Recipients (2002-2016) was used to estimate the trends in prevalence of HCC in LT candidates with the most common types of chronic liver disease: alcoholic liver disease (ALD), chronic hepatitis B (CHB), chronic hepatitis C, and NASH...
June 13, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29906416/bioactive-lipid-species-and-metabolic-pathways-in-progression-and-resolution-of-non-alcoholic-steatohepatitis
#10
REVIEW
Giovanni Musso, Maurizio Cassader, Elena Paschetta, Roberto Gambino
The prevalence of non-alcoholic steatohepatitis (NASH) is increasing worldwide, yet there are no effective treatments. A decade has passed since initial lipidomic analyses of liver tissues from patients with non-alcoholic fatty liver disease. We have learned that liver cells from patients with NASH have an abnormal lipid composition, and the accumulation of lipids leads to organelle dysfunction, cell injury and death, and chronic inflammation, called liptoxicity. We review the lipid species and metabolic pathways that contribute to pathogenesis of NASH, as well as potential therapeutic targets, including enzymes involved in fatty acid and triglyceride synthesis, bioactive sphingolipids and polyunsaturated-derived eicosanoids and specialized proresolving lipid mediators...
June 12, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29902522/role-of-camp-and-phosphodiesterase-signaling-in-liver-health-and-disease
#11
Banrida Wahlang, Craig McClain, Shirish Barve, Leila Gobejishvili
Liver disease is a significant health problem worldwide with mortality reaching around 2 million deaths a year. Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the major causes of chronic liver disease. Pathologically, NAFLD and ALD share similar patterns of hepatic disorders ranging from simple steatosis to steatohepatitis, fibrosis and cirrhosis. It is becoming increasingly important to identify new pharmacological targets, given that there is no FDA-approved therapy yet for either NAFLD or ALD...
June 11, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29900399/the-effect-of-synbiotics-bifidobacterium-infantis-and-milk-oligosaccharides-on-shaping-gut-microbiota-community-structure-and-nash-treatment
#12
Prasant Kumar Jena, Lili Sheng, Nidhi Nagar, Chao Wu, Daniela Barile, David A Mills, Yui-Jui Yvonne Wan
Probiotic Bifidobacterium longum subspecies infantis ( Bifidobacterium infantis ) consumes human milk oligosaccharides (MO) and protects intestinal permeability thereby having anti-inflammatory effects (Underwood et al., 2015; Bode, 2006; Asakuma et al., 2011) [1-3]. Via the gut-liver axis, gut barrier disruption and dysbiosis lead to hepatic inflammation (Sheng et al., 2017; Jena et al., 2017) [4,5,6]. Our published data revealed that butyrate, as well as synbiotics of B. infantis in combination with MO, had protective effects against cancer-prone non-alcoholic steatohepatitis (NASH) mouse models, i...
August 2018: Data in Brief
https://www.readbyqxmd.com/read/29899851/association-of-mrna-expression-of-iron-metabolism-associated-genes-and-progression-of-non-alcoholic-steatohepatitis-in-rats
#13
Teruhisa Higuchi, Mitsuhiko Moriyama, Akiko Fukushima, Hiroshi Matsumura, Shunichi Matsuoka, Tatsuo Kanda, Masahiko Sugitani, Akiko Tsunemi, Takahiro Ueno, Noboru Fukuda
Background: Excess iron is associated with non-alcoholic steatohepatitis (NASH). Results: mRNA expression of duodenal cytochrome b, divalent metal transporter 1, ferroportin 1, hepcidin, hephaestin and transferrin receptor 1 in liver were higher in high fat, high cholesterol-containing diet (HFCD) group than in normal diet (ND) group. mRNA levels of divalent metal transporter 1 and transferrin receptor 1, which stimulate iron absorption and excretion, were enhanced in small intestine...
May 25, 2018: Oncotarget
https://www.readbyqxmd.com/read/29893699/impact-of-diabetes-mellitus-and-insulin-on-nonalcoholic-fatty-liver-disease-in-the-morbidly-obese
#14
Cláudia B M Strey, Luiz A de Carli, Marciane Fantinelli, Sabrina S Gobbato, Guilherme F Bassols, Alexandre Losekann, Gabriela P Coral
INTRODUCTION AND AIM: The prevalence of obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease are increasing. Type 2 diabetes mellitus may aggravate non-alcoholic fatty liver disease, increasing the risk of developing cirrhosis and hepatocellular carcinoma. This study aims to determine the effect of type 2 diabetes mellitus and insulin therapy on non-alcoholic fatty liver disease in the patients with morbid obesity. MATERIAL AND METHODS: Clinical, anthropometric and laboratory data were analyzed together with intraoperative liver biopsies from morbidly obese patients undergoing bariatric surgery...
July 2018: Annals of Hepatology
https://www.readbyqxmd.com/read/29892294/the-interleukin-20-cytokine-family-in-liver-disease
#15
REVIEW
Esther Caparrós, Rubén Francés
The three main causes of inflammation and chronic injury in the liver are viral hepatitis, alcohol consumption, and non-alcoholic steatohepatitis, all of which can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma, which in turn may prompt the need for liver transplant. The interleukin (IL)-20 is a subfamily part of the IL-10 family of cytokines that helps the liver respond to damage and disease, they participate in the control of tissue homeostasis, and in the immunological responses developed in this organ...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29892281/distinct-housing-conditions-reveal-a-major-impact-of-adaptive-immunity-on-the-course-of-obesity-induced-type-2-diabetes
#16
Julia Sbierski-Kind, Jonas Kath, Sebastian Brachs, Mathias Streitz, Matthias G von Herrath, Anja A Kühl, Katharina Schmidt-Bleek, Knut Mai, Joachim Spranger, Hans-Dieter Volk
Obesity is associated with adipose tissue inflammation, insulin resistance, and the development of type 2 diabetes (T2D). However, our knowledge is mostly based on conventional murine models and promising preclinical studies rarely translated into successful therapies. There is a growing awareness of the limitations of studies in laboratory mice, housed in abnormally hygienic specific pathogen-free (SPF) conditions, as relevant aspects of the human immune system remain unappreciated. Here, we assessed the impact of housing conditions on adaptive immunity and metabolic disease processes during high-fat diet (HFD)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29890136/hepatocyte-specific-deletion-of-brg1-alleviates-methionine-and-choline-deficient-diet-mcd-induced-non-alcoholic-steatohepatitis-in-mice
#17
Ming Kong, Xuyang Chen, Huihui Xu, Wenping, Mingming Fang, Yong Xu
Uncontrolled inflammatory response and augmented lipid accumulation represent two key pathophysiological events in the pathogenesis of non-alcoholic steatohepatitis (NASH). NF-κB and SREBP1c program transcriptional regulation of cellular inflammatory response and lipid metabolism, respectively. The epigenetic mechanism underlying NF-κB-dependent pro-inflammatory transcription and SREBP1c-dependent pro-lipogenic transcription remains incompletely understood. In the present study we investigated the investigated the involvement of Brg1, a chromatin remodeling protein, in NASH pathogenesis in methionine-and-choline diet (MCD) induced mouse model...
June 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29883718/genetically-modified-mouse-models-to-study-hepatic-neutral-lipid-mobilization
#18
REVIEW
Guenter Haemmerle, Achim Lass
Excessive accumulation of triacylglycerol is the common denominator of a wide range of clinical pathologies of liver diseases, termed non-alcoholic fatty liver disease. Such excessive triacylglycerol deposition in the liver is also referred to as hepatic steatosis. Although liver steatosis often resolves over time, it eventually progresses to steatohepatitis, liver fibrosis and cirrhosis, with associated complications, including liver failure, hepatocellular carcinoma and ultimately death of affected individuals...
June 5, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29883530/fat-and-liver-transplantation-clinical-implications
#19
REVIEW
Carmen Vinaixa, Nazia Selzner, Marina Berenguer
Non-alcoholic steatohepatitis (NASH), with or without hepatocellular carcinoma (HCC) is a growing indication for liver transplantation (LT) worldwide, particularly in the western world. Patients with NASH typically combine features of metabolic syndrome with cardiovascular comorbidities, which challenge pre-LT evaluation, surgical approaches, post-LT management and outcomes. Post-LT survival in NASH patients is excellent, similar to that achieved with other indications, particularly in the absence of cardiovascular comorbidities...
June 8, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/29883377/circulating-phospholipid-patterns-in-nafld-patients-associated-with-a-combination-of-metabolic-risk-factors
#20
Shilpa Tiwari-Heckler, Hongying Gan-Schreier, Wolfgang Stremmel, Walee Chamulitrat, Anita Pathil
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with inefficient macro- and micronutrient metabolism, and alteration of circulating phospholipid compositions defines the signature of NAFLD. This current study aimed to assess the pattern of serum phospholipids in the spectrum of NAFLD, and its related comorbidities and genetic modifications. METHODS: 97 patients with diagnosed NAFLD were recruited at a single center during 2013⁻2016. Based on histological and transient elastography assessment, 69 patients were divided into non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver (NAFL) subgroups...
May 21, 2018: Nutrients
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