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Alcoholic Steatohepatitis

Xilin Li, Zemin Wang, James E Klaunig
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the western countries. The histological spectrum of NAFLD includes simple steatosis, steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Nuclear receptors are a large group of ligand-dependent transcription factors that sense the environmental and endogenous changes and regulate numerous physiological and pathological processes. Accumulating evidence has suggested that a dysregulation of nuclear receptors in NAFLD may effect on the metabolism of endogenous and exogenous chemicals in the liver...
August 15, 2018: Toxicology
Grace Hatton, Tommaso Alterio, Valerio Nobili, Jake P Mann
Paediatric non-alcoholic fatty liver disease (NAFLD) is common disorder that has complex pathophysiology and unquantified clinical significance. Though there have been major advances in the field there is much yet to be understood. Areas covered: PubMed/MEDLINE and Embase were searched for articles related to paediatric NAFLD and non-alcoholic steatohepatitis between January 1998 and January 2018. The areas considered to be "unmet needs" were: The relationship between the intestinal microbiome and perinatal events; clinical event risk stratification; and mechanisms underlying portal inflammation...
August 17, 2018: Expert Review of Gastroenterology & Hepatology
Helmut K Seitz, Ramon Bataller, Helena Cortez-Pinto, Bin Gao, Antoni Gual, Carolin Lackner, Philippe Mathurin, Sebastian Mueller, Gyongyi Szabo, Hidekazu Tsukamoto
Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease worldwide. ALD can progress from alcoholic fatty liver (AFL) to alcoholic steatohepatitis (ASH), which is characterized by hepatic inflammation. Chronic ASH can eventually lead to fibrosis and cirrhosis and in some cases hepatocellular cancer (HCC). In addition, severe ASH (with or without cirrhosis) can lead to alcoholic hepatitis, which is an acute clinical presentation of ALD that is associated with liver failure and high mortality...
August 16, 2018: Nature Reviews. Disease Primers
Cho-Rong Bae, Jun Hino, Hiroshi Hosoda, Mikiya Miyazato, Kenji Kangawa
AIMS: Our previous study revealed that mice transgenic for endothelial-cell-specific overexpression of CNP (E-CNP Tg mice) are protected against the increased fat weight, inflammation, and insulin resistance associated with high-fat diet (HFD)-induced obesity. In addition, E-CNP overexpression prevented abnormal lipid profiles and metabolism and blocked inflammation in the livers of HFD-fed mice. Because obesity, dyslipidemia, and insulin resistance increase the risk of various liver diseases, including non-alcoholic steatohepatitis (NASH), we here studied the role of E-CNP overexpression in the livers of mice in which NASH was induced through feeding of either HFD or a choline-deficient defined l‑amino-acid diet (CDAA)...
August 13, 2018: Life Sciences
Keisuke Danno, Takuto Nakamura, Natsumi Okoso, Naohiko Nakamura, Kohta Iguchi, Yoshiaki Iwadate, Takahiro Kenmotsu, Masaya Ikegawa, Shinji Uemoto, Kenichi Yoshikawa
Although biopsy is one of the most important methods for diagnosis in diseases, there is ambiguity based on the information obtained from the visual inspection of tissue slices. Here, we studied the effect of external extension on tissue slices from mouse liver with different stages of disease: Healthy normal state, Simple steatosis, Non-alcoholic steatohepatitis and Hepatocellular carcinoma. We found that the cracking pattern of a tissue slice caused by extension can provide useful information for distinguishing among the disease states...
August 15, 2018: Scientific Reports
Yuki Inada, Eishiro Mizukoshi, Takuya Seike, Toshikatsu Tamai, Noriho Iida, Masaaki Kitahara, Tatsuya Yamashita, Kuniaki Arai, Takeshi Terashima, Kazumi Fushimi, Taro Yamashita, Masao Honda, Shuichi Kaneko
Host antitumor immune responses may be different between hepatocellular carcinoma (HCC) caused by metabolic disorders and HCC associated with hepatitis virus infection. In this study, we examined the immune response of tumor-associated antigen (TAA)-specific T cells and immune cell profile in HCC patients separated by cause. Thirty two patients with HBV-related HCC, 42 patients with HCV-related HCC, and 18 patients with non-alcoholic steatohepatitis (NASH)-related HCC were analyzed. The frequencies of TAA-specific T cells, the expression levels of surface markers on each immune cell and the expression of each TAA in HCC tissue were measured...
August 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Xiaojing Wang, Marcelle Ribeiro, Arvin Iracheta-Vellve, Patrick Lowe, Aditya Ambade, Abhishek Satishchandran, Terence Bukong, Donna Catalano, Karen Kodys, Gyongyi Szabo
Inflammatory cell activation drives diverse cellular programming during hepatic diseases. Hypoxia-inducible factors (HIFs) have recently been identified as important regulators of immunity and inflammation. In non-alcoholic steatohepatitis (NASH), HIF-1α is upregulated in hepatocytes where it induces steatosis; however, the role of HIF-1α in macrophages under metabolic stress has not been explored. In this study, we found increased HIF-1α levels in hepatic macrophages in methionine-choline-deficient (MCD) diet-fed mice and in macrophages of NASH patients compared to controls...
August 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Chunwei Cheng, Jun Tan, Wei Qian, Lei Zhang, Xiaohua Hou
AIMS: Gut inflammation has been put forward to be associated with hepatic injury in the clinical practice. The dismantled intestinal barrier was highly concerned, however, largely unknown about the role of gut-vascular barrier (GVB) in this process. This study aimed to investigate if inflamed gut directly contributes to the progression of non-alcoholic steatohepatitis (NASH), especially attention to the GVB dysfunction. MAIN METHODS: Male C57bl/6 mice were fed with a high-fat diet (HFD) and 1% DSS for 12 weeks...
August 7, 2018: Life Sciences
Arlin B Rogers
Inbred mice are the most popular animals used for in vivo liver research. These mice are genetically defined, readily available, less expensive to maintain than larger animals, and enjoy a broad array of commercial reagents for scientific characterization. C57BL/6 mice are the most commonly used strain. However, other strains discussed including BALB/c, C3H, A/J, and FVB/N may be better suited to a particular disease model or line of investigation. Understanding the phenotypes of different inbred mouse strains facilitates informed decision-making during experimental design...
August 9, 2018: Gene Expression
Joselyn Allen, Jingtao Zhang, Michael D Quickel, Mary Kennett, Andrew D Patterson, Pamela A Hankey-Giblin
Liver fibrosis is commonly observed in the terminal stages of non-alcoholic steatohepatitis (NASH) and with no specific and effective anti-fibrotic therapies available, this disease is a major global health burden. The MSP/Ron receptor axis has been shown to have anti-inflammatory properties in a number of mouse models, due at least in part, to its ability to limit pro-inflammatory responses in tissue-resident macrophages and hepatocytes. In this study, we established the role of the Ron receptor in steatohepatitis-induced hepatic fibrosis using Ron ligand domain knockout mice on an apolipoprotein E knockout background (DKO)...
August 9, 2018: Journal of Proteome Research
James E Klaunig, Xilin Li, Zemin Wang
Non-alcoholic fatty liver disease is a major cause of chronic liver pathology in humans. Fatty liver disease involves the accumulation of hepatocellular fat in hepatocytes that can progress to hepatitis. Steatohepatitis is categorized into alcoholic (ASH) or non-alcoholic (NASH) steatohepatitis based on the etiology of the insult. Both pathologies involve an initial steatosis followed by a progressive inflammation of the liver and eventual hepatic fibrosis (steatohepatitis) and cirrhosis. The involvement of pharmaceuticals and other chemicals in the initiation and progression of fatty liver disease has received increased study...
July 1, 2018: Toxicology Research
Xiao-Jun Li, Yun-Mei Mu, Qiu-Fang Qin, Zi-Xuan Zeng, Yu-Sang Li, Wei Kevin Zhang, He-Bin Tang, Gui-Hua Tian, Hong-Cai Shang
In the present study, intestinal tight junctions (TJs) and Kupffer cell polarization were investigated in an alcoholic steatohepatitis (ASH) mouse model to uncover the potential side effects of overexposure to fish oil or omega-3 fatty acids. The mice were fed ad libitum with a liquid diet containing ethanol and fish oil. In the meantime, ethanol was given every 5-7 days by gavage to simulate binge drinking. After the 7th binge, steatosis, necrosis, inflammatory infiltration, and bridging fibrosis were observed in the liver by histological staining...
September 1, 2017: Toxicology Research
Fabiola Rabelo, Jose Tadeu Stefano, Ana Mercedes Cavaleiro, Rodrigo Vieira Costa Lima, Daniel Ferraz de Campos Mazo, Flair Jose Carrilho, Maria Lúcia Correa-Giannella, Claudia P Oliveira
BACKGROUND: Oxidative stress has been implicated in the progression of severe forms of non-alcoholic fatty liver disease (NAFLD). NADPH oxidase produces reactive oxygen species. In the present study, we investigated for the first time two single nucleotide polymorphisms (SNPs) in the regulatory region of genes encoding NADPH oxidase 4 (NOX4) and p22phox (CYBA) in NAFLD. METHODS: A total of 207 biopsy-proven NAFLD patients [simple steatosis (n = 27); nonalcoholic steatohepatitis (NASH) (n = 180)] were evaluated...
July 9, 2018: Hepatobiliary & Pancreatic Diseases International: HBPD INT
Susanne Schuster, Casey D Johnson, Marie Hennebelle, Theresa Holtmann, Ameer Y Taha, Irina A Kirpich, Akiko Eguchi, Christopher E Ramsden, Bettina G Papouchado, Craig J McClain, Ariel E Feldstein
Circulating oxidized linoleic acid (LA) metabolites (OXLAMs) are increased in patients with non-alcoholic steatohepatitis (NASH) and their levels correlate with disease severity. However, the mechanisms by which OXLAMs contribute to NASH development are incompletely understood. We tested the hypothesis that LA or OXLAMs provided directly through the diet are involved in the development of hepatic injury. C57BL/6 mice were fed an isocaloric high-fat diet containing low LA, high LA or OXLAMs for 8 weeks. Livers of OXLAM fed mice showed lower triglyceride concentrations but higher fatty acid oxidation and lipid peroxidation in association with increased oxidative stress...
July 3, 2018: Journal of Lipid Research
Yoon Mee Yang, Masato Fukui, Zhijun Wang, Fiona Miao, Margo J Karriker, Ekihiro Seki
Background and Aims: Hepatocyte growth factor (HGF) is a multifunctional pleiotropic protein involved in tissue regeneration, protection, angiogenesis, anti-inflammatory and anti-fibrotic responses, and tumorigenesis, through binding to its receptor MET. Recombinant HGF protein has been shown to mitigate various liver disease models, such as alcohol-induced liver injury, hepatic ischemia-reperfusion injury, and fibrosis. This study aimed to investigate the anti-inflammatory, anti-fibrotic, and anti-lipogenic effects of exogenous administration of feline HGF on a non-alcoholic steatohepatitis (NASH) mouse model...
2018: Frontiers in Endocrinology
Tayyab S Diwan, Teresa C Rice, Julie K Heimbach, Daniel P Schauer
Non-alcoholic steatohepatitis (NASH) is projected to become the leading indication for liver transplantation (LT) in the next decade in the United States. Strategies to treat the underlying etiology of NASH, which is almost always obesity, are being pursued. One such strategy is the utilization of bariatric surgery in the peri-transplant period. The use of bariatric surgery prior to LT could prevent the progression of NASH, and abrogate the need for LT. Bariatric surgery at the time of LT or post-operatively has the potential to not only improve obesity associated conditions such as diabetes, but also the potential to influence the incidence of NASH in the post LT setting...
August 6, 2018: Liver Transplantation
Fabio Baganate, Eliza W Beal, Dmitry Tumin, Daniel Azoulay, Khalid Mumtaz, Sylvester M Black, Kenneth Washburn, Timothy M Pawlik
BACKGROUND: The objective of the current study was to define the incidence, as well as time course of mortality within the first year after liver transplantation. METHODS: Data on adult, first-time liver transplant recipients transplanted between February 2002 and June 2016 were obtained from the United Network for Organ Sharing. RESULTS: Among 64,977 who underwent liver transplantation, the incidence of 90-day and 1-year mortality was 5% and 10%, respectively...
July 30, 2018: Surgery
Marina Kawaguchi-Suzuki, Kenneth Cusi, Fernando Bril, Yan Gong, Taimour Langaee, Reginald F Frye
Pioglitazone is used effectively to treat non-alcoholic steatohepatitis (NASH), but there is marked variability in response. This study examined whether genetic variation contributes to pioglitazone response variability in patients with NASH. This genetic substudy includes 55 participants of a randomized controlled trial designed to determine the efficacy of long-term pioglitazone treatment in patients with NASH. The primary outcome of the clinical trial was defined as ≥2-point reduction in the non-alcoholic fatty liver disease activity score (NAS)...
2018: Frontiers in Pharmacology
George Boon-Bee Goh, Philip R Schauer, Arthur J McCullough
With the ever increasing global obesity pandemic, clinical burden from obesity related complications are anticipated in parallel. Bariatric surgery, a treatment approved for weight loss in morbidly obese patients, has reported to be associated with good outcomes, such as reversal of type two diabetes mellitus and reducing all-cause mortality on a long term basis. However, complications from bariatric surgery have similarly been reported. In particular, with the onslaught of non-alcoholic fatty liver disease (NAFLD) epidemic, in associated with obesity and metabolic syndrome, there is increasing prevalence of NAFLD related liver cirrhosis, which potentially connotes more risk of specific complications for surgery...
July 28, 2018: World Journal of Gastroenterology: WJG
Sara Heebøll, Henrik Vilstrup, Henning Grønbæk
Non-alcoholic fatty liver disease and especially non-alcoholic steatohepatitis (NASH) and fibrosis are associated with severe liver disease and increased cardiovascular risk. It is therefore important to identify patients with NASH fibrosis. Therapeutical options include life style intervention and pharmacological treatment with vitamin E and pioglitazone; however, evidence of effect is scarce for all options. New treatments are under investigation and include glucagon-like peptide-1, farnesoid receptor as well as peroxisome proliferator-activated receptor-α/δ agonists...
July 30, 2018: Ugeskrift for Laeger
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