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Non alcoholic steatohepatitis

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https://www.readbyqxmd.com/read/28533225/multi-functional-effects-of-a-small-molecule-stat3-inhibitor-on-nash-and-hcc-in-mice
#1
Kwang Hwa Jung, Wonbeak Yoo, Heather L Stevenson, Dipti Deshpande, Hong Shen, Mihai Gagea, Suk-Young Yoo, Jing Wang, Thomas Kris Eckols, Uddalak Bharadwaj, David J Tweardy, Laura Beretta
The incidence of hepatocellular carcinoma (HCC) is increasing in the United States and liver cancer is the second leading cause of cancer-related mortality worldwide. Non-alcoholic steatohepatitis (NASH) is becoming an important risk for HCC and most patients with HCC have underlying liver cirrhosis and compromised liver function, which limit treatment options. Thus, novel therapeutic strategies to prevent or treat HCC in the context of NASH and cirrhosis are urgently needed. <br /><br />Experimental Design: Constitutive activation of signal transducer and activator of transcription 3 (STAT3) is frequently detected in HCC tumors...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28526488/-targeting-the-gut-liver-axis-in-liver-disease
#2
REVIEW
Reiner Wiest, Agustin Albillos, Michael Trauner, Jashmohan Bajaj, Rajiv Jalan
The gut is open to the outer environment, harbours the microbiome containing several fold more genetic material than the human genome and produces a myriad of metabolites as well as hormones/peptides. The liver is at the nexus between this vast source of nutrients, toxins and hormones and the remaining human body. Not surprisingly, this liver-gut-axis has hence, been demonstrated in experimental models and in-vitro systems to contribute to the pathogenesis of most liver diseases such as alcoholic and non-alcoholic fatty liver disease (NAFLD), -steatohepatitis (NASH), cholestatic liver diseases, hepatocellular carcinoma, acute-on-chronic liver failure, progression to fibrosis/cirrhosis and complications of cirrhosis...
May 16, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28525362/fgf21-receptor-agonists-an-emerging-therapeutic-class-for-obesity-related-diseases
#3
Junichiro Sonoda, Mark Z Chen, Amos Baruch
Fibroblast growth factor 21 (FGF21) analogs and FGF21 receptor agonists (FGF21RAs) that mimic FGF21 ligand activity constitute the new "FGF21-class" of anti-obesity and anti-diabetic molecules that improve insulin sensitivity, ameliorate hepatosteatosis and promote weight loss. The metabolic actions of FGF21-class proteins in obese mice are attributed to stimulation of brown fat thermogenesis and increased secretion of adiponectin. The therapeutic utility of this class of molecules is being actively investigated in clinical trials for the treatment of type 2 diabetes and non-alcoholic steatohepatitis (NASH)...
May 19, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28521870/the-use-of-statins-alone-or-in-combination-with-pioglitazone-and-other-drugs-for-the-treatment-of-non-alcoholic-fatty-liver-disease-non-alcoholic-steatohepatitis-and-related-cardiovascular-risk-an-expert-panel-statement
#4
REVIEW
Vasilios G Athyros, Theodore K Alexandrides, Helen Bilianou, Evangelos Cholongitas, Michael Doumas, Emmanuel S Ganotakis, John Goudevenos, Moses S Elisaf, Georgios Germanidis, Olga Giouleme, Asterios Karagiannis, Charalambos Karvounis, Niki Katsiki, Vasilios Kotsis, Jannis Kountouras, Evangelos Liberopoulos, Christos Pitsavos, Stergios Polyzos, Loukianos S Rallidis, Dimitrios Richter, Apostolos G Tsapas, Alexandros D Tselepis, Konstantinos Tsioufis, Konstantinos Tziomalos, Themistoklis Tzotzas, Themistoklis G Vasiliadis, Charalambos Vlachopoulos, Dimitri P Mikhailidis, Christos Mantzoros
Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (>5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28521680/fatty-acids-and-effects-on-in-vitro-and-in-vivo-models-of-liver-steatosis
#5
Laura Vergani
Fatty liver, or steatosis, is a condition of excess accumulation of lipids, mainly under form of triglycerides (TG), in the liver, and it is the hallmark of non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common liver disorder world-wide and it has frequently been associated with obesity, hyperlipidemia and insulin resistance. Free fatty acids (FA) are the major mediators of hepatic steatosis; patients with NAFLD have elevated levels of circulating FA that correlate with disease severity. Steatosis is a reversible condition that can be resolved with changed behaviors, or that can progress towards more severe liver damages such as steatohepatitis (NASH), fibrosis and cirrhosis...
May 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28517024/treatment-of-severe-alcoholic-hepatitis-past-present-and-future
#6
REVIEW
Nicolas Lanthier, Peter Stärkel
Alcoholic hepatitis manifests as a clinical syndrome characterized by recent jaundice and liver function deterioration in an actively drinking patient. The principal cause of alcoholic hepatitis is alcoholic steatohepatitis defined histologically by the coexistence of steatosis, hepatocyte ballooning and satellitosis. While non-severe alcoholic hepatitis usually responds to alcohol abstinence, severe alcoholic hepatitis, identified by Maddrey scoring ≥ 32, has a bad prognosis and is traditionally treated by a 28-day course of prednisone therapy...
May 18, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28512251/inhibition-of-the-cell-death-pathway-in-non-alcoholic-steatohepatitis-nash-related-hepatocarcinogenesis-is-associated-with-histone-h4-lysine-16-deacetylation
#7
Aline de Conti, Kostiantyn Dreval, Volodymyr Tryndyak, Orish Ebere Orisakwe, Sharon Ross, Frederick Beland, Igor P Pogribny
Hepatocellular carcinoma (HCC) is one of the most aggressive human cancers and its incidence is steadily increasing worldwide. Recent epidemiological findings have suggested that the increased incidence of HCC is associated with obesity, type 2 diabetes mellitus, and nonalcoholic steatohepatitis (NASH); however, the mechanisms and the molecular pathogenesis of NASH-related HCC are not fully understood. In order to elucidate the underlying mechanisms of the development of NASH-related HCC, we investigated the hepatic transcriptomic and histone modification profiles in Stelic Animal Model (STAM) mice, the first animal model of NASH-related HCC to resemble the disease pathogenesis in humans...
May 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28511575/liver-transplantation-for-non-alcoholic-steatohepatitis-related-cirrhosis
#8
R C Siriwardana, Madunil A Niriella, A S Dassnayake, B Gunathillake, H J de Silva
No abstract text is available yet for this article.
March 2017: Progress in Transplantation
https://www.readbyqxmd.com/read/28511161/-the-diagnostics-and-clinical-pattern-of-nonalcoholic-fatty-liver-disease-in-patients-with-pre-diabetes-and-type-2-diabetes-and-obesity
#9
Ксенія І Чубірко
INTRODUCTION: The data of epidemiological researches confirm the tendency in increasing of non alcoholic fatty liver disease (NAFLD) in patients with insulin resistance which occurs because of obesity, diabetes type 2 and metabolic syndrome. AIM: Optimization of diagnostic and treatment efficacy in patients with non alcoholic steatosis and steatohepatitis on the background of obesity. MATERIALS AND METHODS: General clinical examination of patients, laboratory and instrumental methods ( fatty liver index, non invasive assessment of liver, morphology, electrocardiography, treadmillergometry, ultrasound examination of abdominal organs, liver elastography,CT,MRI, methods of statistical analysis...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28511023/efficacy-of-docosahexaenoic-acid-choline-vitamin-e-dha-cho-ve-in-paediatric-nash-a-randomized-controlled-clinical-trial
#10
Evelyn Zöhrer, Alisi Anna, Jörg Jahnel, Antonella Moscla, Claudia Della Corte, Annalisa Crudele, Günter Fauler, Valerio Nobili
Non-alcoholic steatohepatitis (NASH), a progressive form of non-alcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in children. We conducted a randomized controlled clinical trial on children with biopsy-proven NASH based on a combinatorial nutritional approach compared to placebo. Participants were assigned to lifestyle modification plus placebo, or lifestyle modification plus a mix containing docosahexaenoic acid, choline and vitamin E (DHA-CHO-VE). Forty children and adolescents concluded the trial...
May 16, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28507930/non-alcoholic-fatty-liver-disease-in-south-asians-a-review-of-the-literature
#11
REVIEW
Sital Singh, Gabriela N Kuftinec, Souvik Sarkar
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are national and global epidemics. The disease is characterized by a spectrum of liver steatosis (fat deposition), inflammation (in NASH) and fibrosis. NAFLD and specifically NASH can lead to cirrhosis, which carry risks of progression to portal hypertension and hepatocellular carcinoma (HCC). NASH is also associated with higher mortality from cardiovascular causes. Most of the data for NAFLD has been obtained from the perspective of developed nations, although the disease is increasing and threatening to reach epidemic proportions across the world...
March 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28499273/inhibition-of-nlrp3-inflammasome-by-thioredoxin-interacting-protein-in-mouse-kupffer-cells-as-a-regulatory-mechanism-for-non-alcoholic-fatty-liver-disease-development
#12
Kun He, Xiwen Zhu, Yan Liu, Chunmu Miao, Tao Wang, Peizhi Li, Lei Zhao, Yaxi Chen, Junhua Gong, Can Cai, Jinzheng Li, Shengwei Li, Xiong Z Ruan, Jianping Gong
NOD-like receptor (NLR) NLRP3 inflammasome activation has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It has been also shown that palmitic acid (PA) activates NLRP3 inflammasome and promotes interleukin-1β (IL-1β) secretion in Kupffer cells (KCs). However, the specific mechanism of the NLRP3 inflammasome activation is unclear. We studies the molecular mechanisms by investigating the roles of Thioredoxin-interacting protein (TXNIP) and NLRP3 on NAFLD development in patients, high-fat diet (HFD)-induced NAFL and methionine choline deficient (MCD) diet-induced NASH in wild type (WT), TXNIP-/- (thioredoxin-interacting protein) and NLRP3-/- mice, and isolated KCs...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498022/thyroid-hormone-analogs-for-the-treatment-of-dyslipidemia-past-present-and-future
#13
Alessandro P Delitala, Giuseppe Delitala, Paolo Sioni, Giuseppe Fanciulli
OBJECTIVE: Treatment of dyslipidemia is a major burden for public health. Thyroid hormone regulates lipid metabolism by binding the thyroid hormone receptor (TR), but the use of thyroid hormone to treat dyslipidemia is not indicated due to its deleterious effects on heart, bone, and muscle. Thyroid hormone analogs have been conceived to selectively activate TR in the liver, thus reducing potential side effects. METHODS: We searched the PubMed database to review TR and the action of thyromimetics in vitro and in animal models...
May 12, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28497760/the-intestinal-microbiome-and-paediatric-liver-disease
#14
REVIEW
Daniel H Leung, Dean Yimlamai
The intestinal microbiome has been the intense focus of recent study, but how the microbiota affects connected organs, such as the liver, has not been fully elucidated. The microbiome regulates intestinal permeability and helps to metabolise the human diet into small molecules, thus directly affecting liver health. Several studies have linked intestinal dysbiosis to the severity and progression of liver diseases, such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, primary sclerosing cholangitis, total parenteral nutrition-associated liver disease, and cystic fibrosis-associated liver disease...
June 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28494529/nash-therapy-omega-3-supplementation-vitamin-e-insulin-sensitizers-and-statin-drugs
#15
Stephen Caldwell
Non-alcoholic steatohepatitis (NASH) is the more aggressive form of non-alcoholic fatty liver disease (NAFLD). NASH can progress to hepatic fibrosis, cirrhosis, portal hypertension and primary liver cancer. Therapy is evolving with a substantial number of trials of promising new agents now in progress. In this article however, we will examine data for several older forms of therapy which have been fairly extensively studied over the years: Polyunsaturated Fatty Acid (PUFA) supplements, vitamin E, insulin sensitizing agents with a focus on pioglitazone and statin agents...
May 10, 2017: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/28487615/urinary-metabolomics-analysis-identifies-key-biomarkers-of-different-stages-of-nonalcoholic-fatty-liver-disease
#16
Shu Dong, Zong-Ying Zhan, Hong-Yan Cao, Chao Wu, Yan-Qin Bian, Jian-Yuan Li, Gen-Hong Cheng, Ping Liu, Ming-Yu Sun
AIM: To identify a panel of biomarkers that can distinguish between non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and explore molecular mechanism involved in the process of developing NASH from NAFLD. METHODS: Biomarkers may differ during stages of NAFLD. Urine and blood were obtained from non-diabetic subjects with NAFLD and steatosis, with normal liver function (n = 33), from patients with NASH, with abnormal liver function (n = 45), and from healthy age and sex-matched controls (n = 30)...
April 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28487605/changes-in-human-hepatic-metabolism-in-steatosis-and-cirrhosis
#17
Zoe Schofield, Michelle Ac Reed, Philip N Newsome, David H Adams, Ulrich L Günther, Patricia F Lalor
AIM: To understand the underlying metabolic changes in human liver disease we have applied nuclear magnetic resonance (NMR) metabolomics analysis to human liver tissue. METHODS: We have carried out pilot study using (1)H-NMR to derive metabolomic signatures from human liver from patients with steatosis, nonalcoholic steatohepatitis (NASH) or alcohol-related liver damage (ARLD) to identify species that can predict outcome and discriminate between alcohol and metabolic-induced liver injuries...
April 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28484247/total-fecal-microbiota-transplantation-alleviates-high-fat-diet-induced-steatohepatitis-in-mice-via-beneficial-regulation-of-gut-microbiota
#18
Da Zhou, Qin Pan, Feng Shen, Hai-Xia Cao, Wen-Jin Ding, Yuan-Wen Chen, Jian-Gao Fan
Non-alcoholic steatohepatitis (NASH) is an epidemic metabolic disease with limited therapeutic strategies. Cumulative data support the pivotal role of gut microbiota in NASH. Here, we investigated the hypothesis regarding whether fecal microbiota transplantation (FMT) is effective in attenuating high-fat diet (HFD)-induced steatohepatitis in mice. Mice were randomized into control, HFD and HFD + FMT groups. After an 8-week HFD, FMT treatment was initiated and carried out for 8 weeks. The gut microbiota structure, butyrate concentrations of the cecal content, liver pathology and intrahepatic lipid and cytokines were examined...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28481357/tmbim1-is-a-multivesicular-body-regulator-that-protects-against-non-alcoholic-fatty-liver-disease-in-mice-and-monkeys-by-targeting-the-lysosomal-degradation-of-tlr4
#19
Guang-Nian Zhao, Peng Zhang, Jun Gong, Xiao-Jing Zhang, Pi-Xiao Wang, Miao Yin, Zhou Jiang, Li-Jun Shen, Yan-Xiao Ji, Jingjing Tong, Yutao Wang, Qiao-Fang Wei, Yong Wang, Xue-Yong Zhu, Xin Zhang, Jing Fang, Qingguo Xie, Zhi-Gang She, Zhihua Wang, Zan Huang, Hongliang Li
Non-alcoholic steatohepatitis (NASH) is an increasingly prevalent liver pathology that can progress from non-alcoholic fatty liver disease (NAFLD), and it is a leading cause of cirrhosis and hepatocellular carcinoma. There is currently no pharmacological therapy for NASH. Defective lysosome-mediated protein degradation is a key process that underlies steatohepatitis and a well-recognized drug target in a variety of diseases; however, whether it can serve as a therapeutic target for NAFLD and NASH remains unknown...
May 8, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28479500/histologic-scores-for-fat-and-fibrosis-associate-with-development-of-type-2-diabetes-in-patients-with-non-alcoholic-fatty-liver-disease
#20
Karl Björkström, Per Stål, Rolf Hultcrantz, Hannes Hagström
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a strong risk factor for development of type 2 diabetes, but little is known about how long-term NAFLD or its histologic features affect risk. We aimed to investigate the cumulative incidence of type 2 diabetes in patients with NAFLD, and to identify histologic factors that affect risk of diabetes. METHODS: We performed a retrospective study of 396 patients in Sweden diagnosed with NAFLD by biopsy analysis from 1971 through 2009 who did not have type 2 diabetes at baseline...
May 4, 2017: Clinical Gastroenterology and Hepatology
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