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https://www.readbyqxmd.com/read/29235014/increased-bile-acid-signals-after-duodenal-jejunal-bypass-improve-non-alcoholic-steatohepatitis-nash-in-a-rodent-model-of-diet-induced-nash
#1
Takahiro Tsuchiya, Takeshi Naitoh, Munenori Nagao, Naoki Tanaka, Kazuhiro Watanabe, Hirofumi Imoto, Tomohiro Miyachi, Fuyuhiko Motoi, Michiaki Unno
BACKGROUND: The increasing incidence of non-alcoholic steatohepatitis (NASH) has resulted in it becoming a common cause of liver-related mortality; however, no efficient treatment has been established. It has been reported that bariatric surgery improves metabolic comorbidities, such as diabetes mellitus and NASH. Although the mechanism is unclear, it is thought that the changes in bile acid (BA) signaling via its nuclear receptor, farnesoid X receptor (FXR), produce various metabolic effects...
December 12, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/29234397/artemisia-iwayomogi-plus-curcuma-longa-synergistically-ameliorates-nonalcoholic-steatohepatitis-in-hepg2-cells
#2
Hyeong-Geug Kim, Sung-Bae Lee, Jin-Seok Lee, Won-Young Kim, Seung-Hoon Choi, Chang-Gue Son
The combination of Artemisia iwayomogi and Curcuma longa radix is frequently prescribed for liver diseases in TKM. However, the synergic effects of the two herbs on nonalcoholic steatohepatitis (NASH) have not yet been studied. Therefore, we investigated the anti-NASH effects of the water extract of A. iwayomogi (AI), C. longa radix (CL), and combination of the two herbs (ACE). Hepatic steatosis and NASH were induced in HepG2 cells by treatment with palmitic acid (PA, for 6 h) with/without pretreatment of ACE (25 or 50 μg/mL), AI (50 or 100 μg/mL), CL (50 or 100 μg/mL), curcumin (5 μg/mL), or scopoletin (5 μg/mL)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29234193/results-of-portosystemic-shunt-embolization-in-selected-patients-with-cirrhosis-and-recurrent-hepatic-encephalopathy
#3
Narendra S Choudhary, Sanjay Saran Baijal, Sanjiv Saigal, Amit Agarwal, Neeraj Saraf, Rohit Khandelwal, Vaibhav Jain, Anubhav Harish Khandelwal, Abhay Kapoor, Deepak Jain, Smurti R Misra, Rajesh Puri, Randhir Sud, Arvinder S Soin
Background: Large portosystemic shunts (PSSs) may lead to recurrent encephalopathy in patients with cirrhosis and embolization of these shunts may improve encephalopathy. Material and methods: Five patients underwent balloon-occluded retrograde transvenous obliteration (BRTO) or plug-assisted retrograde transvenous obliteration (PARTO) of a large PSS at our center in last 2 years for recurrent hepatic encephalopathy (HE) at a tertiary care center at north India...
December 2017: Journal of Clinical and Experimental Hepatology
https://www.readbyqxmd.com/read/29231919/-non-alcoholic-liver-disease-diagnosis-and-treatment
#4
REVIEW
Anna Sarosiekjeznach-Steinhagen, Joanna Ostrowska, Aneta Czerwonogrodzka-Senczyna, Iwona Boniecka
Non-alcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease in the developed world (15% to 40% of the adult population). Introduction of lifestyle changes including dietary intervention and increased physical activity is most often the first-line treatment and is intended to support not only the treatment of liver disease, but also for diseases associated with obesity, insulin resistance, diabetes and dyslipidemia. In addition to well-known metformin, there are new classes of antidiabetic drugs, including GLP-1analog, SGLT-2 antagonist, pioglitazon...
November 23, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29229391/hepatocyte-specific-clusterin-overexpression-attenuates-diet-induced-nonalcoholic-steatohepatitis
#5
Jin-Sung Park, Young-Jun Shim, Byeong-Ho Kang, Woon-Kyu Lee, Bon-Hong Min
Clusterin is a multifunctional glycoprotein that plays important roles and is up-regulated in liver diseases such as hepatitis and hepatocellular carcinoma. However, little is known about the significance of clusterin in the pathogenesis of non-alcoholic steatohepatitis (NASH). The aim of this study is to examine the role of clusterin in progression of steatohepatitis in mice fed a methionine and choline deficient (MCD) diet. We generated hepatocyte-specific clusterin overexpression (hCLU-tg) mice, and hCLU-tg mice showed lower levels of hepatic triglycerides, less infiltration of macrophages and reduction of TNF-α, activation of Nrf-2 than wild-type littermates fed the MCD diet...
December 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29227477/the-deubiquitinating-enzyme-tnfaip3-mediates-inactivation-of-hepatic-ask1-and-ameliorates-nonalcoholic-steatohepatitis
#6
Peng Zhang, Pi-Xiao Wang, Ling-Ping Zhao, Xin Zhang, Yan-Xiao Ji, Xiao-Jing Zhang, Chun Fang, Yue-Xin Lu, Xia Yang, Mao-Mao Gao, Yan Zhang, Song Tian, Xue-Yong Zhu, Jun Gong, Xin-Liang Ma, Feng Li, Zhihua Wang, Zan Huang, Zhi-Gang She, Hongliang Li
Activation of apoptosis signal-regulating kinase 1 (ASK1) in hepatocytes is a key process in the progression of nonalcoholic steatohepatitis (NASH) and a promising target for treatment of the condition. However, the mechanism underlying ASK1 activation is still unclear, and thus the endogenous regulators of this kinase remain open to be exploited as potential therapeutic targets. In screening for proteins that interact with ASK1 in the context of NASH, we identified the deubiquitinase tumor necrosis factor alpha-induced protein 3 (TNFAIP3) as a key endogenous suppressor of ASK1 activation, and we found that TNFAIP3 directly interacts with and deubiquitinates ASK1 in hepatocytes...
December 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29225775/fibromax-based-nonalcoholic-fatty-liver-disease-in-chronic-obstructive-pulmonary-disease-patients-with-obstructive-sleep-apnea-methodological-considerations
#7
Denis Monneret
The relationship between nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) has been well demonstrated, but remains to be evidenced in chronic obstructive pulmonary disease (COPD). Recently, Viglino et al. (Eur Respir J, 2017) attempted to determine the prevalence of liver fibrosis, steatosis and nonalcoholic steatohepatitis (NASH) in COPD patients, some of whom had OSA, basing the NAFLD diagnostic on three circulating biomarker-based liver scores: the FibroTest, SteatoTest and NashTest, from the Fibromax® panel...
2017: F1000Research
https://www.readbyqxmd.com/read/29224910/regulation-of-sirt3-foxo1-signaling-pathway-in-rats-with-non-alcoholic-steatohepatitis-by-salvianolic-acid-b
#8
Yingchun Wang, Juan Chen, Weizong Kong, Ruiping Zhu, Kai Liang, Quanxiang Kan, Yanhong Lou, Xiangyu Liu
AIMS: To explore the effect of salvianolic acid B (Sal B) on regulation of SIRT3/FOXO1 signaling pathway in rats with non-alcoholic steatohepatitis (NASH). METHODS: Sixty Sprague Dawley (SD) rats were randomly divided into control, model and treatment groups. After 12 weeks of successful model establishment with high fat diet, treatment group was given Sal B by intragastric administration. After 12 weeks of treatment, rats were sacrificed and livers were taken to test indicators such as liver index, TG, TC, ALT, AST, reactive oxygen species (ROS) by DCFH-DA probe, SOD2 activity by WST-8 test...
December 7, 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/29224471/clinical-relevance-of-liver-histopathology-and-different-histological-classifications-of-nash-in-adults
#9
Fabio Nascimbeni, Stefano Ballestri, Mariana Verdehlho Machado, Alessandro Mantovani, Helena Cortez-Pinto, Giovanni Targher, Amedeo Lonardo
Nonalcoholic fatty liver disease (NAFLD) encompasses simple steatosis and steatohepatitis (NASH) with or without fibrosis/cirrhosis and hepatocellular carcinoma. NAFLD occurs epidemically in most areas of the world, contributes to cardiovascular events and liver-related mortality and therefore exacts a major economic toll. Areas covered: Here we summarize what clinicians should know about NAFLD histopathology in adults. We report on the individual histological features and scoring systems of NAFLD: the NAFLD activity score (NAS) introduced by the NASH-Clinical Research Network, the "Fatty Liver Inhibition of Progression" algorithm and Steatosis, Activity, and Fibrosis (SAF) score...
December 11, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29223443/response-to-pioglitazone-in-patients-with-nonalcoholic-steatohepatitis-with-vs-without-type-2-diabetes
#10
Fernando Bril, Srilaxmi Kalavalapalli, Virginia C Clark, Romina Lomonaco, Consuelo Soldevila-Pico, I-Chia Liu, Beverly Orsak, Fermin Tio, Kenneth Cusi
BACKGROUND & AIMS: Pioglitazone is effective for long-term treatment of patients with nonalcoholic steatohepatitis (NASH) with prediabetes or type-2 diabetes. However, it is not clear how the presence of type-2 diabetes affects the drug's efficacy. We compared metabolic and histologic responses to pioglitazone in patients with NASH and prediabetes vs type-2 diabetes. METHODS: We performed a prospective study of adults with biopsy-proven NASH (52 with type-2 diabetes and 49 with prediabetes), enrolled from the general population of San Antonio, Texas from 2008 through 2014...
December 6, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29223369/a-critical-review-of-endpoints-for-non-cirrhotic-nash-therapeutic-trials
#11
REVIEW
Vlad Ratziu
Non-alcoholic steatohepatitis is a disease without a single, specific, diagnostic marker, hence multiple indicators are required to measure therapeutic efficacy. Moreover, drug candidates for non-alcoholic steatohepatitis target many distinct mechanisms that are believed to promote hepatic injury. Therefore, a wide range of endpoints must be reached, sequentially, as required by the drug development process. Some of these endpoints validate the mechanism of action, others are used to anticipate histological efficacy...
December 6, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29222917/diagnostic-modalities-for-non-alcoholic-fatty-liver-disease-nafld-non-alcoholic-steatohepatitis-nash-and-associated-fibrosis
#12
REVIEW
Zobair M Younossi, Rohit Loomba, Quentin M Anstee, Mary E Rinella, Elisabetta Bugianesi, Giulio Marchesini, Brent A Neuschwander-Tetri, Lawrence Serfaty, Francesco Negro, Stephen H Caldwell, Vlad Ratziu, Kathleen E Corey, Scott L Friedman, Manal F Abdelmalek, Stephen A Harrison, Arun J Sanyal, Joel E Lavine, Philippe Mathurin, Michael R Charlton, Zachary D Goodman, Naga P Chalasani, Kris V Kowdley, Jacob George, Keith Lindor
NAFLD is a spectrum comprised of isolated steatosis, NASH, advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not have NASH and don't carry a significant risk for adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high prevalence rates to low rates are noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition as an important liver disease, the diagnosis of NASH still requires a liver biopsy which is suboptimal...
December 9, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29222911/current-and-future-therapeutic-regimens-for-non-alcoholic-fatty-liver-disease-nafld-and-non-alcoholic-steatohepatitis-nash
#13
REVIEW
Zobair M Younossi, Rohit Loomba, Mary E Rinella, Elisabetta Bugianesi, Giulio Marchesini, Brent A Neuschwander-Tetri, Lawrence Serfaty, Francesco Negro, Stephen H Caldwell, Vlad Ratziu, Kathleen E Corey, Scott L Friedman, Manal F Abdelmalek, Stephen A Harrison, Arun J Sanyal, Joel E Lavine, Philippe Mathurin, Michael R Charlton, Naga P Chalasani, Quentin M Anstee, Kris V Kowdley, Jacob George, Zachary D Goodman, Keith Lindor
NASH/NAFLD is rapidly becoming one of top causes of cirrhosis, hepatocellular carcinoma and indication for liver transplantation. Except for life style modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is hard to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD and has been shown to improve liver histology. In order to have approved regimens for treatment of NASH/NAFLD, a number of issues that must be addressed...
December 9, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29222421/the-transcriptomic-signature-of-disease-development-and-progression-of-nonalcoholic-fatty-liver-disease
#14
Sophie Cazanave, Alexei Podtelezhnikov, Kristian Jensen, Mulugeta Seneshaw, Divya P Kumar, Hae-Ki Min, Prasanna K Santhekadur, Bubu Banini, Adolfo Gabriele Mauro, Abdul M Oseini, Robert Vincent, Keith Q Tanis, Andrea L Webber, Liangsu Wang, Pierre Bedossa, Faridoddin Mirshahi, Arun J Sanyal
A longitudinal molecular model of the development and progression of nonalcoholic fatty liver disease (NAFLD) over time is lacking. We have recently validated a high fat/sugar water-induced animal (an isogenic strain of C57BL/6 J:129S1/SvImJ mice) model of NAFLD that closely mimics most aspects of human disease. The hepatic transcriptome of such mice with fatty liver (8 weeks), steatohepatitis with early fibrosis (16-24 weeks) and advanced fibrosis (52 weeks) after initiation of the diet was evaluated and compared to mice on chow diet...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29221950/dha-supplementation-prevent-the-progression-of-nash-via-gpr120-signaling
#15
Kazuo Nakamoto, Koki Shimada, Shinichi Harada, Yasuko Morimoto, Akira Hirasawa, Shogo Tokuyama
Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases involving chronic accumulation of fat and inflammation, often leading to advanced fibrosis, cirrhosis and carcinoma. However, the pathological mechanism for this is unknown. GPR120/FFAR4 has been recognized as a functional fatty acid receptor and an attractive therapeutic target for metabolic diseases. In this study, we investigated the involvement of GPR120/FFAR4 in the pathogenesis of NASH. Mice fed with a 0.1% methionine and choline deficient high-fat (CDAHF) diet showed a significant increase in plasma aspartate transaminase and alanine transaminase levels, fatty deposition, inflammatory cell infiltration, and mild fibrosis...
December 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29220698/synergistic-interaction-of-fatty-acids-and-oxysterols-impairs-mitochondrial-function-and-limits-liver-adaptation-during-nafld-progression
#16
Francesco Bellanti, Rosanna Villani, Rosanna Tamborra, Maria Blonda, Giuseppina Iannelli, Giorgia di Bello, Antonio Facciorusso, Giuseppe Poli, Luigi Iuliano, Carlo Avolio, Gianluigi Vendemiale, Gaetano Serviddio
The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression...
December 5, 2017: Redox Biology
https://www.readbyqxmd.com/read/29216638/microrna-122-inhibits-lipid-droplet-formation-and-hepatic-triglyceride-accumulation-via-yin-yang-1
#17
Guo-Yi Wu, Chen Rui, Ji-Qiao Chen, Eiketsu Sho, Shan-Shan Zhan, Xian-Wen Yuan, Yi-Tao Ding
BACKGROUND/AIMS: An increase in intracellular lipid droplet formation and hepatic triglyceride (TG) content usually results in nonalcoholic fatty liver disease. However, the mechanisms underlying the regulation of hepatic TG homeostasis remain unclear. METHODS: Oil red O staining and TG measurement were performed to determine the lipid content. miRNA expression was evaluated by quantitative PCR. A luciferase assay was performed to validate the regulation of Yin Yang 1 (YY1) by microRNA (miR)-122...
December 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29216341/use-and-importance-of-nonhuman-primates-in-metabolic-disease-research-current-state-of-the-field
#18
Peter J Havel, Paul Kievit, Anthony G Comuzzie, Andrew A Bremer
Obesity and its multiple metabolic sequelae, including type 2 diabetes, cardiovascular disease, and fatty liver disease, are becoming increasingly widespread in both the developed and developing world. There is an urgent need to identify new approaches for the prevention and treatment of these costly and prevalent metabolic conditions. Accomplishing this will require the use of appropriate animal models for preclinical and translational investigations in metabolic disease research. Although studies in rodent models are often useful for target/pathway identification and testing hypotheses, there are important differences in metabolic physiology between rodents and primates, and experimental findings in rodent models have often failed to be successfully translated into new, clinically useful therapeutic modalities in humans...
December 5, 2017: ILAR Journal
https://www.readbyqxmd.com/read/29216278/systematic-integrative-analysis-of-gene-expression-identifies-hnf4a-as-the-central-gene-in-pathogenesis-of-non-alcoholic-steatohepatitis
#19
Cristina Baciu, Elisa Pasini, Marc Angeli, Katherine Schwenger, Jenifar Afrin, Atul Humar, Sandra Fischer, Keyur Patel, Johane Allard, Mamatha Bhat
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and encompasses a spectrum from simple steatosis to steatohepatitis (NASH). There is currently no approved pharmacologic therapy against NASH, partly due to an incomplete understanding of its molecular basis. The goal of this study was to determine the key differentially expressed genes (DEGs), as well as those genes and pathways central to its pathogenesis. We performed an integrative computational analysis of publicly available gene expression data in NASH from GEO (GSE17470, GSE24807, GSE37031, GSE89632)...
2017: PloS One
https://www.readbyqxmd.com/read/29215462/liver-transplantation-in-cryptogenic-cirrhosis-outcome-comparisons-between-nash-alcoholic-and-aih-cirrhosis
#20
Paul Joseph Thuluvath, Steven Hanish, Yulia Savva
BACKGROUND: The outcomes of liver transplantation (LT) in patients with cryptogenic cirrhosis (CC) have not been adequately examined except for small case series. We believe that patients currently listed as CC have truly cryptogenic liver disease and may have different post-LT outcomes compared to nonalcoholic steatohepatitis (NASH). METHODS: We compared the post-LT outcomes of adults with CC (n=3241) and compared them with cirrhosis from NASH (n=4089), alcohol (AC, n=7837) and autoimmune hepatitis (AIH, n=1435) using the UNOS database from 2002-16...
December 5, 2017: Transplantation
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