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Alcoholic Steatohepatitis

Kannan Sridharan, Gowri Sivaramakrishnan, Reginald Paul Sequeira, Abdelaziz Elamin
AIM: Several drugs have been used for treating non-alcoholic fatty liver disease (NAFLD). The present study is a network meta-analysis of such drugs. DESIGN, SETTING AND PATIENTS: Randomised clinical trials comparing drug interventions in patients with NAFLD were analysed. OR and weighted mean difference (95 % CI) were the effect estimates for categorical and numerical outcomes, respectively. Random-effects model was used to generate pooled estimates. Surface under the cumulative ranking curve was used to rank the treatments...
October 19, 2018: Postgraduate Medical Journal
Yohei Shirakami, Takahiro Kochi, Masaya Kubota, Hiroyasu Sakai, Takashi Ibuka, Kazuto Yoshimi, Takashi Kuramoto, Takuji Tanaka, Masahito Shimizu, Mitsuru Seishima
Chronic inflammation in the colorectum increases the risk of colorectal cancer development. Pentoxifylline, a medicine used for improving the circulation, has been reported to inhibit TNF-α production and to ameliorate inflammatory bowel disease and non-alcoholic steatohepatitis. In this study, we investigated the effects of pentoxifylline on inflammation-related colon tumorigenesis in a rodent model using Kyoto APC delta rats, which have APC mutation and are susceptible to colon carcinogenesis. Male Kyoto APC delta rats were treated with azoxymethane and dextran sodium sulfate, and were subsequently administered water, with or without pentoxifylline...
September 21, 2018: Oncotarget
Natalie Chaves Cayuela, Gabrielly Pascoa Negreti, Roberto Rasslan, Marcia Kiyomi Koike, Edna Frasson de Souza Montero
PURPOSE: To evaluate the oxidative stress, resulting from ischemia and hepatic reperfusion, in mice with non-alcoholic hepatic steatosis and steatohepatitis. METHODS: C57BL/6 male mice were used. Part of them were ob/ob mice, and the other part was fed with standard or MCD diets - this last used to develop steatohepatitis. The animals - MCD-I/R, ob/ob-I/R and I/R groups - were submitted to 30 minutes of partial hepatic ischemia, followed by reperfusion for 24 hours...
September 2018: Acta Cirúrgica Brasileira
Uday Sanglodkar, Mayank Jain, Dinesh Jothimoni, Subhashree Parida, Balajee G, Jayanthi Venkataraman
Introduction: Cirrhosis of the liver predisposes patients to serious bacterial infections including cellulitis. The aim of the study was to determine the clinical and bacteriological profile of cellulitis in patients with liver cirrhosis. Material and methods: In this prospective study, consecutive cirrhotic patients hospitalized between February and September 2017 were enrolled. Data retrieved included demographics, aetiology, co-morbidity, cirrhosis-related complications, site of cellulitis, baseline investigations, and wound and blood culture...
September 2018: Clinical and Experimental Hepatology
Christiana Lucas, Georgia Lucas, Nicholas Lucas, Joanna Krzowska-Firych, Krzysztof Tomasiewicz
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world. Ongoing research has furthered our understanding of NAFLD, the nature of progression of this disease, and its impact on morbidity and mortality. An active form of NAFLD is non-alcoholic steatohepatitis (NASH); it is the most severe subtype, without any current recommended therapies, according to the European Medicines Agency. The development of new therapies presents challenges, notably due to the slow progression of NASH and the clinically relevant endpoints...
September 2018: Clinical and Experimental Hepatology
Guozhen Cui, Robert C Martin, Xingkai Liu, Qianqian Zheng, Harshul Pandit, Ping Zhang, Wei Li, Yan Li
Background: Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of lesions ranging from steatosis to a complex pattern, nonalcoholic steatohepatitis (NASH). Ultrasonography provides important information on hepatic architecture for steatosis. NASH patients have an increased risk of hepatocellular carcinoma (HCC). Early detection of NASH is critical for clinicians to advise on necessary treatments to prevent the onset of HCC. Methods: We established a NASH-HCC mouse model using diethylnitrosamine as a carcinogen to induce HCC and a high-fat diet to induce metabolic disorders...
2018: Nutrition & Metabolism
Mitchell Bijnen, Nicky Beelen, Suzan Wetzels, José van de Gaar, Maria Vroomen, Erwin Wijnands, Jean L Scheijen, Marjo P H van de Waarenburg, Marion J Gijbels, Jack P Cleutjens, Erik A L Biessen, Coen D A Stehouwer, Casper G Schalkwijk, Kristiaan Wouters
Non-alcoholic fatty liver disease is a spectrum of liver diseases ranging from steatosis only to non-alcoholic steatohepatitis (NASH). The latter is characterized by hepatic inflammation, which increases the risk of cardiovascular disease. It is poorly understood which factors contribute to the onset of hepatic inflammation characterizing the progression from steatosis to NASH. Previously, we demonstrated increased advanced glycation endproducts (AGEs) in the livers of NASH patients. We hypothesise that AGEs play a key role in NASH development by activating their proinflammatory receptor, RAGE...
October 15, 2018: Scientific Reports
Barbara Kern, Benedikt Feurstein, Josef Fritz, Cornelia Fabritius, Robert Sucher, Ivo Graziadei, Reto Bale, Herbert Tilg, Heinz Zoller, Philip Newsome, Stephan Eschertzhuber, Raimund Margreiter, Dietmar Öfner, Stefan Schneeberger
BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is an increasingly prevalent indication for liver transplantation (LT) across the world. The relative outcomes following transplantation are poorly described in this cohort. We aimed to analyze the incidence and outcome of LT for NASH as compared with other indications. PATIENTS AND METHODS: This is a retrospective analysis of 513 patients who underwent deceased-donor, adult LT between 2002 and 2012 as recorded at the Medical University of Innsbruck, Austria...
October 12, 2018: European Journal of Gastroenterology & Hepatology
Jingyun Luan, Dianwen Ju
Inflammasomes have emerged as critical innate sensors of host immune that defense against pathogen infection, metabolism syndrome, cellular stress and cancer metastasis in the liver. The assembly of inflammasome activates caspase-1, which promotes the maturation of interleukin-1β (IL-1β) and interleukin-18 (IL-18), and initiates pyroptotic cell death (pyroptosis). IL-18 exerts pleiotropic effects on hepatic NK cells, priming FasL-mediated cytotoxicity, and interferon-γ (IFN-γ)-dependent responses to prevent the development of liver diseases...
2018: Frontiers in Immunology
X X Mi, J Yan, X D Zeng, J P Shi
Objective: To establish overfed zebrafish model for non-alcoholic steatohepatitis. Methods: The wild-type zebrafish was fed 3 times a day with normal diet. Body length, weight, and triglyceride levels were measured after 20 days of feeding. The changes in expression of genes associated with cholesterol metabolism, lipid metabolism, endoplasmic reticulum stress, and inflammation were detected by quantitative PCR. Liver tissue sections were stained with H&E. Statistical analyses between groups were compared using t-test...
July 20, 2018: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Ning Ji, Yuqi Yang, Chao-Yun Cai, Zi-Ning Lei, Jing-Quan Wang, Pranav Gupta, Suneet Shukla, Suresh V Ambudkar, Dexin Kong, Zhe-Sheng Chen
Overexpression of ATP-binding cassette (ABC) transporters is one of the most important mechanisms responsible for the development of multidrug resistance (MDR). Selonsertib, a serine/threonine kinase inhibitor, targets apoptosis signal-regulating kinase 1 (ASK1) and is now in phase III clinical trial for the treatment of non-alcoholic steatohepatitis (NASH). In this study, we investigated whether selonsertib could reverse MDR-mediated by ABC transporters, including ABCB1, ABCG2, ABCC1 and ABCC10. The results showed that selonsertib significantly reversed ABCB1- and ABCG2-mediated MDR, but not MDR-mediated by ABCC1 or ABCC10...
October 10, 2018: Cancer Letters
Andrea Kristina Horst, Sonia M Najjar, Christoph Wagener, Gisa Tiegs
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a transmembrane glycoprotein that is expressed on epithelial, endothelial and immune cells. CEACAM1 is a differentiation antigen involved in the maintenance of epithelial polarity that is induced during hepatocyte differentiation and liver regeneration. CEACAM1 regulates insulin sensitivity by promoting hepatic insulin clearance, and controls liver tolerance and mucosal immunity. Obese insulin-resistant humans with non-alcoholic fatty liver disease manifest loss of hepatic CEACAM1...
October 11, 2018: International Journal of Molecular Sciences
Fernando Bril, Michael J McPhaul, Michael P Caulfield, Jean-Marie Castille, Thierry Poynard, Consuelo Soldevila-Pico, Virginia C Clark, Roberto J Firpi-Morell, Jinping Lai, Kenneth Cusi
Fibromax is a diagnostic tool composed of the combination of 4 non-invasive biomarker panels for the diagnosis of steatosis (SteatoTest), necrosis and inflammation (ActiTest and NashTest-2) and fibrosis (FibroTest). The purpose of this study was to assess the performance of these biomarker panels in patients with type 2 diabetes mellitus (T2DM). All patients underwent routine labs, a 75 g oral glucose tolerance test, a liver proton magnetic resonance spectroscopy (1 H-MRS) to measure intrahepatic triglyceride content, and a percutaneous liver biopsy to establish the diagnosis of non-alcoholic steatohepatitis (NASH) and to grade and stage the disease in those patients with non-alcoholic fatty liver disease (NAFLD) by 1 H-MRS...
October 10, 2018: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Sabine Mihm
Inflammatory liver diseases in the absence of pathogens such as intoxication by xenobiotics, cholestatic liver injury, hepatic ischemia-reperfusion injury (I/R), non-alcoholic steatohepatitis (NASH), or alcoholic liver disease (ALD) remain threatening conditions demanding specific therapeutic options. Caused by various different noxae, all these conditions have been recognized to be triggered by danger- or death-associated molecular patterns (DAMPs), discompartmentalized self-structures released by dying cells...
October 10, 2018: International Journal of Molecular Sciences
Koji Nishikawa, Yosuke Osawa, Kiminori Kimura
Cirrhosis is a form of liver fibrosis resulting from chronic hepatitis and caused by various liver diseases, including viral hepatitis, alcoholic liver damage, nonalcoholic steatohepatitis, and autoimmune liver disease. Cirrhosis leads to various complications, resulting in poor prognoses; therefore, it is important to develop novel antifibrotic therapies to counter liver cirrhosis. Wnt/β-catenin signaling is associated with the development of tissue fibrosis, making it a major therapeutic target for treating liver fibrosis...
October 10, 2018: International Journal of Molecular Sciences
Omar Yaxmehen Bello-Chavolla, Anuar Kuri-García, Monserratte Ríos-Ríos, Arsenio Vargas-Vázquez, Jorge Eduardo Cortés-Arroyo, Gabriela Tapia-González, Ivette Cruz-Bautista, Carlos Alberto Aguilar-Salinas
Familial combined hyperlipidemia (FCHL) is the most prevalent primary dyslipidemia; however, it frequently remains undiagnosed and its precise definition is a subject of controversy. FCHL is characterized by fluctuations in serum lipid concentrations and may present as mixed hyperlipidemia, isolated hypercholesterolemia, hypertriglyceridemia, or as a normal serum lipid profile in combination with abnormally elevated levels of apolipoprotein B. FCHL is an oligogenic primary lipid disorder, which can occur due to the interaction of several contributing variants and mutations along with environmental triggers...
2018: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
Andrea Mosqueda-Solís, Juana Sánchez, Bárbara Reynés, Mariona Palou, María P Portillo, Andreu Palou, Catalina Picó
We aimed to assess the potential effects of hesperidin and capsaicin, independently and in combination, to prevent the development of obesity and its related metabolic alterations in rats fed an obesogenic diet. Three-month-old male Wistar rats were divided into 5 groups: Control (animals fed a standard diet), WD (animals fed a high fat/sucrose (western) diet), HESP (animals fed a western diet + hesperidin (100 mg/kg/day)), CAP (animals fed a western diet + capsaicin (4 mg/kg/day)), and HESP + CAP (animals fed a western diet + hesperidin (100 mg/kg/day) + capsaicin (4 mg/kg/day))...
October 10, 2018: Scientific Reports
Natalia Presa, Robin D Clugston, Susanne Lingrell, Samuel E Kelly, Alfred H Merrill, Sayantan Jana, Zamaneh Kassiri, Antonio Gómez-Muñoz, Dennis E Vance, Rene L Jacobs, Jelske N van der Veen
Phosphatidylethanolamine N-methyltransferase (PEMT) converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC), mainly in the liver. Pemt-/- mice are protected from high-fat diet (HFD)-induced obesity and insulin resistance, but develop severe non-alcoholic fatty liver disease (NAFLD) when fed a HFD, mostly due to impaired VLDL secretion. Oxidative stress is thought to be an essential factor in the progression from simple steatosis to steatohepatitis. Vitamin E is an antioxidant that has been clinically used to improve NAFLD pathology...
October 6, 2018: Biochimica et biophysica acta. Molecular basis of disease
Vlad Ratziu, Marwan Ghabril, Manuel Romero-Gomez, Gianluca Svegliati-Baroni
The prevalence of nonalcoholic liver disease (NAFLD) is increasing worldwide in conjunction with the epidemic increase in obesity and metabolic risk factors. Consequently, NAFLD has become a leading indication for liver transplantation. While genetic factors play an important role in the pathogenesis of NAFLD, detrimental lifestyle trends favoring a calorically unrestricted diet rich in carbohydrates and unsaturated fat, prolonged sedentary periods or limited physical activity have major metabolic implications...
October 8, 2018: Transplantation
Misaki Matsumoto
Reactive oxygen species (ROS) are known to play a critical role in the development of non-alcoholic steatohepatitis (NASH). To clarify the source of ROS, we examined the expression of superoxide-generating NADPH oxidase isoforms in the liver of high-fat and high-cholesterol (HFC) diet-fed mice. The mRNA expression of NOX1 was significantly elevated in mice on HFC diet for 8 weeks. Increased levels of serum alanine aminotransferase and hepatic cleaved caspase-3 in HFC diet-fed wild-type mice (WT) were significantly ameliorated in mice deficient in Nox1 (Nox1-KO)...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
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