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Nonalcoholic steatohepatitis

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https://www.readbyqxmd.com/read/28079667/stage-of-fibrosis-and-portal-pressure-correlation-in-nonalcoholic-steatohepatitis
#1
Achuthan Sourianarayanane, Jyothsna Talluri, Abinav Humar, Arthur J McCullough
BACKGROUND: Hepatic venous pressure gradient (HVPG) measurement correlates with staging of liver fibrosis. Patients with nonalcoholic steatohepatitis (NASH) have a different pattern of fibrosis compared with hepatitis C virus (HCV) with possible alterations in pressures. AIM: The aim of this study was to compare portal pressures with the stage of fibrosis in NASH in comparison with other liver diseases. PATIENTS AND METHODS: Records of all patients who had undergone transjugular liver biopsy with pressure measurements between January 2001 and June 2013 were reviewed...
January 10, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28077381/metabolic-syndrome-increases-dietary-%C3%AE-tocopherol-requirements-as-assessed-using-urinary-and-plasma-vitamin-e-catabolites-a-double-blind-crossover-clinical-trial
#2
Maret G Traber, Eunice Mah, Scott W Leonard, Gerd Bobe, Richard S Bruno
BACKGROUND: Vitamin E supplementation improves liver histology in patients with nonalcoholic steatohepatitis, which is a manifestation of the metabolic syndrome (MetS). We reported previously that α-tocopherol bioavailability in healthy adults is higher than in those with MetS, thereby suggesting that the latter group has increased requirements. OBJECTIVE: We hypothesized that α-tocopherol catabolites α-carboxyethyl hydroxychromanol (α-CEHC) and α-carboxymethylbutyl hydroxychromanol (α-CMBHC) are useful biomarkers of α-tocopherol status...
January 11, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28075092/diabetes-mellitus-management-of-gastrointestinal-complications
#3
Beth Careyva, Brian Stello
Gastrointestinal disorders are common complications of diabetes mellitus and include gastroparesis, nonalcoholic fatty liver disease, gastroesophageal reflux disease, and chronic diarrhea. Symptoms of gastroparesis include early satiety, postprandial fullness, nausea, vomiting of undigested food, bloating, and abdominal pain. Gastroparesis is diagnosed based on clinical symptoms and a delay in gastric emptying in the absence of mechanical obstruction. Gastric emptying scintigraphy is the preferred diagnostic test...
December 15, 2016: American Family Physician
https://www.readbyqxmd.com/read/28073164/protective-role-of-endogenous-plasmalogens-against-hepatic-steatosis-and-steatohepatitis
#4
Jung Eun Jang, Han-Sol Park, Hyun Ju Yoo, In-Jeoung Baek, Ji Eun Yoon, Myoung Seok Ko, Ah-Ram Kim, Hyoun Sik Kim, Hye-Sun Park, Seung Eun Lee, Seung-Whan Kim, Su Jung Kim, Jaechan Leem, Yu Mi Kang, Min Kyo Jung, Chan-Gi Pack, Chong Jai Kim, Chang Ohk Sung, In-Kyu Lee, Joong-Yeol Park, José C Fernández-Checa, Eun Hee Koh, Ki-Up Lee
: Free cholesterol (FC) accumulation in the liver is an important pathogenic mechanism of nonalcoholic steatohepatitis (NASH). Plasmalogens, key structural components of the cell membrane, act as endogenous antioxidants and are primarily synthesized in the liver. However, the role of hepatic plasmalogens in metabolic liver disease is unclear. In this study, we found that hepatic levels of docosahexaenoic acid (DHA)-containing plasmalogens, expression of glyceronephosphate O-acyltransferase (Gnpat, the rate-limiting enzyme in plasmalogen biosynthesis), and expression of Pparα were lower in mice with NASH caused by accumulation of free cholesterol (FC) in the liver...
January 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28073147/treating-nonalcoholic-steatohepatitis-nash-in-children-not-a-cinch-task
#5
Naim Alkhouri, Ariel E Feldstein
BACKGROUND & AIMS: No treatment for nonalcoholic fatty liver disease (NAFLD) has been approved by regulatory agencies. We performed a randomized controlled trial to determine whether 52 weeks of cysteamine bitartrate delayed release (CBDR) reduces the severity of liver disease in children with NAFLD. METHODS: We performed a double-masked trial of 169 children with NAFLD Activity Scores ≥ 4 at 10 centers. From June 2012 to January 2014, the patients were randomly assigned to receive CBDR or placebo twice daily (300 mg for ≤65 kg, 375 mg for >65-80 kg, 450 mg for >80 kg) for 52 weeks...
January 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28068223/hepatocyte-taz-wwtr1-promotes-inflammation-and-fibrosis-in-nonalcoholic-steatohepatitis
#6
Xiaobo Wang, Ze Zheng, Jorge Matias Caviglia, Kathleen E Corey, Tina M Herfel, Bishuang Cai, Ricard Masia, Raymond T Chung, Jay H Lefkowitch, Robert F Schwabe, Ira Tabas
Nonalcoholic steatohepatitis (NASH) is a leading cause of liver disease worldwide. However, the molecular basis of how benign steatosis progresses to NASH is incompletely understood, which has limited the identification of therapeutic targets. Here we show that the transcription regulator TAZ (WWTR1) is markedly higher in hepatocytes in human and murine NASH liver than in normal or steatotic liver. Most importantly, silencing of hepatocyte TAZ in murine models of NASH prevented or reversed hepatic inflammation, hepatocyte death, and fibrosis, but not steatosis...
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28068221/devilish-effects-of-taz-in-nonalcoholic-steatohepatitis
#7
Scott L Friedman, Youngmin A Lee
Nonalcoholic steatohepatitis leads to cirrhosis and cancer in a rising number of patients with metabolic syndrome. In this issue of Cell Metabolism, Wang et al. (2016) identify the transcriptional co-activator Taz as a driver of inflammation and fibrosis through the induction of Indian hedgehog in hepatocytes, which stimulates fibrogenesis by hepatic stellate cells.
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28067690/iron-overload-in-the-liver-of-2-children-nonalcoholic-steatohepatitis-and-juvenile-hemochromatosis
#8
Aysel Ünlüsoy Aksu, Angela Caleffi, Antonello Pietrangelo, Sinan Sari, Ödül Eğritaş Gürkan, Zeliha Demirtaş, Güldal Yilmaz, Buket Dalgiç
BACKGROUND: Iron overload disorders are hereditary hemochromatosis and secondary etiologies other than hereditary hemochromatosis. We describe 2 boys presenting with iron overload. Juvenile hemochromatosis and nonalcoholic steatohepatitis (NASH) related iron overload are the genetic and secondary causes, respectively. OBSERVATIONS: Both patients benefited from phlebotomy even if they had different etiologies. CONCLUSIONS: In childhood, the diagnosis of iron overload syndromes is crucial because they do not confront us with obvious symptoms and findings...
January 6, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28063505/alternative-treatment-methods-attenuate-the-development-of-nafld-a-review-of-resveratrol-molecular-mechanisms-and-clinical-trials
#9
REVIEW
Tomasz Charytoniuk, Krzysztof Drygalski, Karolina Konstantynowicz-Nowicka, Klaudia Berk, Adrian Chabowski
Nonalcoholic fatty liver disease (NAFLD) is considered to be one of the most common liver pathologies that occur widely among societies with a predominance of the Western dietary pattern. NAFLD may progress from hepatic steatosis to nonalcoholic steatohepatitis (NASH), subsequently leading to cirrhosis and becoming a major cause of hepatocellular carcinoma. Thus its prevention and therapy play an important role in hepatology. To our knowledge, there is no effective treatment for patients with NAFLD. The aim of this review was to summarize the results of recent alternative treatment studies conducted both on cell cultures and in vivo that concern molecular effects of resveratrol (3,5,4'-trihydroxystilbene) in the treatment of NAFLD...
February 2017: Nutrition
https://www.readbyqxmd.com/read/28056321/-the-significance-of-8-hydroxy-deoxyguanosine-acid-in-the-diagnosis-of-nonalcoholic-steatohepatitis
#10
Y Jiang, T Han, Z G Zhang, S Q Lu, Y Q Mi, L Xu, F X Qi, Y Zhang, G D Song
Objective: To evaluate the significance of serum 8-hydroxy-deoxyguanosine acid(8-OHdG) in the diagnosis of nonalcoholic steatohepatitis (NASH). Methods: Patients or healthy subjects were enrolled at the Second Hospital of Tianjin Medical University and the Second People's Hospital of Tianjin from May 2013 to December 2015. A total of 41 patients with nonalcoholic fatty liver disease were enrolled in the study, including 20 nonalcoholic simple fatty liver (NAFL) patients and 21 NASH patients whose diagnosis were proven by liver biopsy...
January 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28051796/%C3%A2-differences-in-hepatic-expression-of-iron-inflammation-and-stress-related-genes-in-patients-with-nonalcoholic-steatohepatitis
#11
Priya Handa, Akhila L Vemulakonda, Bryan D Maliken, Vicki Morgan-Stevenson, James E Nelson, Barjinder K Dhillon, Kelly A Hennessey, Rohit Gupta, Matthew M Yeh, Kris V Kowdley
 Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. We have previously shown that hepatic reticuloendothelial system (RES) iron deposition is associated with an advanced degree of nonalcoholic steatohepatitis (NASH) in humans. In this study, we aimed to determine differentially expressed genes related to iron overload, inflammation and oxidative stress pathways, with the goal of identifying factors associated with NASH progression. Seventy five patients with NAFLD were evaluated for their biochemical parameters and their liver tissue analyzed for NASH histological characteristics...
January 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28051792/-u-u-%C3%A2-management-strategies-for-liver-fibrosis
#12
Alejandra Altamirano-Barrera, Beatriz Barranco-Fragoso, Nahum Méndez-Sánchez
 Liver fibrosis resulting from chronic liver injury are major causes of morbidity and mortality worldwide. Among causes of hepatic fibrosis, viral infection is most common (hepatitis B and C). In addition, obesity rates worldwide have accelerated the risk of liver injury due to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Also liver fibrosis is associated with the consumption of alcohol, or autoimmune hepatitis and chronic cholangiophaties. The response of hepatocytes to inflammation plays a decisive role in the physiopathology of hepatic fibrosis, which involves the recruitment of both pro- and anti-inflammatory cells such as monocytes and macrophages...
January 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28051263/psychological-factors-associated-with-nafld-nash-a-systematic-review
#13
B Macavei, A Baban, D L Dumitrascu
OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) represents one of the most common chronic liver diseases worldwide. So far, the pathogenesis of NAFLD and its more severe variant nonalcoholic steatohepatitis (NASH) is yet unclear, with many mechanisms being proposed as possible causes. This article aims to review the psychological factors associated with NAFLD/NASH. MATERIALS AND METHODS: Three main categories of factors have been investigated: emotional, cognitive and behavioral...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28044208/hepatic-vagus-nerve-regulates-kupffer-cell-activation-via-%C3%AE-7-nicotinic-acetylcholine-receptor-in-nonalcoholic-steatohepatitis
#14
Takahiro Nishio, Kojiro Taura, Keiko Iwaisako, Yukinori Koyama, Kazutaka Tanabe, Gen Yamamoto, Yukihiro Okuda, Yoshinobu Ikeno, Kenji Yoshino, Yosuke Kasai, Masayuki Okuno, Satoru Seo, Takaki Sakurai, Masataka Asagiri, Etsuro Hatano, Shinji Uemoto
BACKGROUND: Nonalcoholic fatty liver disease ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Kupffer cells play a central role in promoting hepatic inflammation, which leads to the development of NASH. We investigated the anti-inflammatory effect of hepatic vagus-mediated stimulation of the α7 nicotinic acetylcholine receptor (α7nAChR) on Kupffer cells in NASH pathogenesis. METHODS: Wild-type (WT) mice undergoing hepatic vagotomy (HV) were fed a methionine- and choline-deficient (MCD) diet for 1 week...
January 2, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28039158/inhibition-of-sphingosine-1-phosphate-signaling-ameliorates-murine-nonalcoholic-steatohepatitis
#15
Amy S Mauer, Petra Hirsova, Jessica L Maiers, Vijay H Shah, Harmeet Malhi
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a lipotoxic disorder, wherein proinflammatory lipids, such as ceramide and its derivative sphingosine 1-phosphate (S1P), contribute to macrophage-associated liver inflammation. For example, we have previously demonstrated a role for S1P in steatotic hepatocyte-derived S1P enriched extracellular vesicles in macrophage chemotaxis in vitro. Therefore, we hypothesized that FTY720, an S1P antagonist, would ameliorate NASH by inhibiting proinflammatory monocyte chemotaxis...
December 30, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28038359/green-tea-extract-treatment-reduces-nf%C3%AE%C2%BAb-activation-in-mice-with-diet-induced-nonalcoholic-steatohepatitis-by-lowering-tnfr1-and-tlr4-expression-and-ligand-availability
#16
Jinhui Li, Teryn N Sapper, Eunice Mah, Meredith V Moller, Joshua B Kim, Chureeporn Chitchumroonchokchai, Joshua D McDonald, Richard S Bruno
NFκB-mediated inflammation contributes to liver injury during nonalcoholic steatohepatitis (NASH). We hypothesized that antiinflammatory activities of green tea extract (GTE) during NASH would lower tumor necrosis factor receptor-1 (TNFR1)- and Toll-like receptor-4 (TLR4)-mediated NFκB activation. Male C57BL6/J mice (6 weeks old) were fed a low-fat (LF) or high-fat (HF) diet for 12 weeks to induce NASH. They were then randomized to continue on these diets supplemented with 0 or 2% GTE (n=10/group) for an additional 8 weeks prior to evaluating NASH, NFκB inflammation and TNFR1 and TLR4 receptor complexes and their respective ligands, TNFα and endotoxin...
December 21, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28035202/nonalcoholic-steatohepatitis-and-endpoints-in-clinical-trials
#17
William N Hannah, Dawn M Torres, Stephen A Harrison
Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in developed countries, and the rates of NAFLD continue to rise in conjunction with the obesity pandemic. While the majority of patients with isolated steatosis generally have a benign course, a diagnosis of nonalcoholic steatohepatitis (NASH) carries a significantly higher risk for progression of disease, cirrhosis, and death. Pharmacologic therapeutic interventions in NASH have largely proven to be ineffective or unappealing due to long-term side-effect profiles, and the majority of patients cannot achieve or sustain targeted weight loss goals, necessitating an urgent need for therapeutic trials and drug development...
December 2016: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28032901/structure-of-proof-of-concept-studies-that-precede-a-nonalcoholic-steatohepatitis-development-program
#18
R N Williams, C Filozof, B J Goldstein, K Cusi
Surrogate endpoints for clinical proof of concept (POC) trials in nonalcoholic steatohepatitis (NASH) are based upon expert pathological review of liver biopsies. During early development, these long-term POC studies (≥48 weeks) add cost and time to the "Go/No Go" decision process. However, it is possible to conduct short-term noninvasive POC studies utilizing biomarkers and magnetic resonance imaging. Here, we discuss the use of shorter noninvasive POC studies relative to biopsy-driven studies for drug development in NASH...
November 7, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28030556/hepatocyte-hypoxia-inducible-factor-1-mediates-the-development-of-liver-fibrosis-in-a-mouse-model-of-nonalcoholic-fatty-liver-disease
#19
Omar A Mesarwi, Mi-Kyung Shin, Shannon Bevans-Fonti, Christina Schlesinger, Janet Shaw, Vsevolod Y Polotsky
BACKGROUND: Obstructive sleep apnea (OSA) is associated with the progression of non-alcoholic fatty liver disease (NAFLD) to steatohepatitis and fibrosis. This progression correlates with the severity of OSA-associated hypoxia. In mice with diet induced obesity, hepatic steatosis leads to liver tissue hypoxia, which worsens with exposure to intermittent hypoxia. Emerging data has implicated hepatocyte cell signaling as an important factor in hepatic fibrogenesis. We hypothesized that hepatocyte specific knockout of the oxygen sensing α subunit of hypoxia inducible factor-1 (HIF-1), a master regulator of the global response to hypoxia, may be protective against the development of liver fibrosis...
2016: PloS One
https://www.readbyqxmd.com/read/28029729/combination-treatment-of-dipeptidyl-peptidase-iv-inhibitor-sitagliptin-and-angiotensin-ii-type-1-receptor-blocker-losartan-suppresses-progression-in-a-nondiabetic-rat-model-of-steatohepatitis
#20
Yasushi Okura, Tadashi Namisaki, Kei Moriya, Mitsuteru Kitade, Kosuke Takeda, Kosuke Kaji, Ryuichi Noguchi, Norihisa Nishimura, Kenichiro Seki, Hideto Kawaratani, Hiroaki Takaya, Shinya Sato, Yasuhiko Sawada, Naotaka Shimozato, Masanori Furukawa, Keisuke Nakanishi, Saikawa Soichiro, Takuya Kubo, Kiyoshi Asada, Hitoshi Yoshiji
AIM: Dipeptidyl peptidase-4 (DPP4) inhibitors (DPP4-I) are oral glucose-lowering drugs for type 2 diabetes mellitus. Previously, we demonstrated that DPP4-I (sitagliptin) exerted suppressive effects on experimental liver fibrosis in rats. Blockade of the renin-angiotensin system by angiotensin-II type 1 receptor blocker (ARB: losartan), commonly used in the management of hypertension, has been shown to significantly alleviate hepatic fibrogenesis and carcinogenesis. We aimed to elucidate the effects and possible mechanisms of a sitagliptin + losartan combination on the progression of nondiabetic nonalcoholic steatohepatitis (NASH) in a rat model...
December 28, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
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