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NASH cirrhosis

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
Mala Dharmalingam, P Ganavi Yamasandhi
Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) commonly exist together. It has been regarded as a manifestation of the metabolic syndrome. The presentations of NAFLD range from simple steatosis (NAFL), nonalcoholic steatohepatitis (NASH), and cirrhosis. NAFLD has a prevalence of 70% among T2DM patients. Overweight/obesity and insulin resistance (IR) have been strongly linked with NAFLD. Noninvasive assessment and staging of disease are based on clinical parameters such as age, sex, liver function test, platelet count, lipid profile, BMI, and imaging modalities such as USG, transient elastography (TE), and magnetic resonance imaging mass spectroscopy...
May 2018: Indian Journal of Endocrinology and Metabolism
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
Maria Reig, Martina Gambato, Nancy Kwan Man, John P Roberts, David Victor, Lorenzo A Orci, Christian Toso
BACKGROUND: Patients with nonalcoholic fatty liver disease (NAFLD) are at risk of developing hepatocellular carcinoma (HCC), but the magnitude of the association still needs to be determined in order to define the need for a specific surveillance strategy. METHODS: We based our assessment on a previously published review by White et al (1992-2011) and on a systematic review (2012-2017). RESULTS: The new search identified 328 abstracts. Combining both eras (1992-2011 and 2012-2017), 25 studies were included in the analysis...
August 4, 2018: Transplantation
Pegah Golabi, Haley Bush, Maria Stepanova, Cameron T Locklear, Ira M Jacobson, Alita Mishra, Gregory Trimble, Madeline Erario, Chapy Venkatesan, Issah Younossi, Zachary Goodman, Zobair M Younossi
Nonalcoholic steatohepatitis (NASH)-related cirrhosis and cryptogenic cirrhosis (CC) have become leading indications for liver transplantation (LT) in the US. Our aim was to compare the trends, clinical presentation, and outcomes for transplant candidates with NASH and CC.The Scientific Registry of Transplant Recipients (1994-2016) was used to select adult LT candidates and recipients with primary diagnoses of NASH and CC without hepatocellular carcinoma.Two lakh twenty-three thousand three hundred ninety-one LT candidates were listed between 1994 and 2016...
August 2018: Medicine (Baltimore)
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
Guadalupe Garcia-Tsao, Michael Fuchs, Mitchell Shiffman, Brian B Borg, Nikolaos Pyrsopoulos, Kirti Shetty, Juan F Gallegos-Orozco, K Rajender Reddy, Eyob Feyssa, Jean L Chan, Mason Yamashita, James M Robinson, Alfred P Spada, David T Hagerty, Jaime Bosch
BACKGROUND AND RATIONALE: Caspases play a central role in apoptosis, inflammation and fibrosis. They produce hemodynamically-active, pro-inflammatory microparticles that cause intrahepatic inflammation, vasoconstriction and extrahepatic splanchnic vasodilation. Emricasan is a pan-caspase inhibitor that lowers portal hypertension (PH) and improves survival in murine models of cirrhosis. This exploratory study assessed whether emricasan lowers PH in patients with compensated cirrhosis. This multicenter, open-label study enrolled 23 subjects with compensated cirrhosis and PH (HVPG >5 mmHg)...
July 31, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Yanrong Guo, Haoming Lin, Changfeng Dong, Xinyu Zhang, Huiying Wen, Yuanyuan Shen, Tianfu Wang, Siping Chen, Yingxia Liu, Xin Chen
Acoustic radiation force impulse (ARFI) elastography is a non-invasive method for performing liver assessment via liver shear wave velocity (SWV) measurements. The aim of this study was to evaluate the performance of the ARFI technique in the diagnosis of nonalcoholic steatohepatitis (NASH) and fibrosis and to investigate the effect of steatosis and inflammation on liver fibrosis SWV measurements in a rat model of nonalcoholic fatty liver disease (NAFLD). The ex vivo right liver lobes from 110 rats were processed and embedded in a fabricated gelatin phantom, and the other lobes were used for histologic assessment...
July 2, 2018: Medical Engineering & Physics
David A Brenner
Mouse models of non-alcoholic fatty liver disease (NAFLD) are required to both elucidate the pathogenesis of the disease and also to assess therapeutic interventions. The first criterion for a useful model is that it reproduces the histopathology of the disease. NAFLD is characterized by centrilobular and macrovesicular steatosis. In non-alcoholic steatohepatitis (NASH), the steatosis is accompanied by intralobular inflammation and hepatocellular ballooning. Mallory's hyaline (eosinophilic, amorphous structures in the cytoplasm) may be present...
July 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Juan P Arab, Marco Arrese
The hepatic inflammatory response is one of the main driving forces of disease progression in chronic liver diseases mainly by promoting a sustained hepatic fibrogenesis, which can lead to cirrhosis (1). Thus, reducing persistent inflammatory activity over time is an important goal of therapy as it may abrogate disease progression. Important advances have been made over the past decade in the understanding of the molecular pathways and cellular players involved in liver inflammation. In particular, a more detailed knowledge of the underlying mechanisms of initiation and perpetuation of sterile inflammation have shed light on the pathophysiology of both alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) (2), which are by far the most common causes of liver disease in industrialized countries, and are major causes of morbidity and mortality worldwide This article is protected by copyright...
July 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Daiane Gonçalves de Oliveira, Fabiana de Faria Ghetti, Ana Paula Boroni Moreira, Helen Hermana Miranda Hermsdorff, Juliano Machado de Oliveira, Lincoln Eduardo Villela Vieira de Castro Ferreira
PURPOSE: Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, ballooning, and in some cases, fibrosis, which can progress to cirrhosis and carcinoma. The progression of NASH is closely related to oxidative stress. Dietary intake of antioxidants has been suggested in protection against oxidative damage and related clinical complications. Thus, we evaluated the potential association of dietary total antioxidant capacity (TAC) with disease severity in NASH patients, as well as with anthropometric and body composition markers and biochemical parameters...
July 17, 2018: European Journal of Nutrition
Tiziano Balzano, Jerónimo Forteza, Irene Borreda, Pilar Molina, Juan Giner, Paola Leone, Amparo Urios, Carmina Montoliu, Vicente Felipo
Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) affect 29 million people in the European Union. Patients with ASH and NASH may exhibit cognitive impairment, reducing their quality of life. Steatohepatitis induces cerebral alterations. It is not known if histological analysis could allow distinguishing ASH, NASH, and/or cirrhosis neuropathology and other entities. The aim of this work was to analyze a set of histopathological features characterizing the brain lesions due to ASH, NASH, and cirrhosis...
July 16, 2018: Journal of Neuropathology and Experimental Neurology
Nahum Mendez-Sanchez, Vania Cesar Cruz-Ramon, Oscar Lenin Ramirez-Perez, Jessica P Hwang, Beatriz Barranco-Fragoso, Jaqueline Cordova-Gallardo
NASH is becoming increasingly common worldwide because of the growing global prevalence of obesity and consequently NAFLD. Unfortunately, the mechanism of progression of NAFLD to NASH and then cirrhosis is not completely understood. Several factors, including insulin resistance, inflammation, oxidative stress, lipotoxicity, and bile acid (BA) toxicity, have been reported to be associated with NASH progression. The release of fatty acids from dysfunctional and insulin-resistant adipocytes results in lipotoxicity, which is caused by the ectopic accumulation of triglyceride-derived toxic metabolites and the subsequent activation of inflammatory pathways, cellular dysfunction, and lipoapoptosis...
July 13, 2018: International Journal of Molecular Sciences
Yue Jia, Barbara French, Brittany Tillman, Samuel French
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer related deaths worldwide. Among others, non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the two major risk factors as both of them may develop cirrhosis and hepatocellular carcinoma (HCC) if left untreated. However, patients with NASH progress to HCC at a rate around 0.5% annually, while 3-10% ASH patients may progress to HCC annually. The present study is to demonstrate the molecular differences in oncogenesis pathway between NASH and ASH...
August 2018: Experimental and Molecular Pathology
Ariel D Quiroga, Richard Lehner
Excessive triacylglycerol (TG) accumulation is the distinctive feature of obesity. In the liver, sustained TG accretion leads to nonalcoholic fatty liver disease (NAFLD), eventually progressing to non-alcoholic steatohepatitis (NASH) and cirrhosis, which is associated with complications including hepatic failure, hepatocellular carcinoma and death. Pharmacological interventions are actively pursued to prevent lipid accumulation in hepatocytes and, therefore, to ameliorate the associated pathophysiological conditions...
July 11, 2018: Biochemical Pharmacology
Tilman Kühn, Tobias Nonnenmacher, Disorn Sookthai, Ruth Schübel, Daniel Antonio Quintana Pacheco, Oyunbileg von Stackelberg, Mirja E Graf, Theron Johnson, Christopher L Schlett, Romy Kirsten, Cornelia M Ulrich, Rudolf Kaaks, Hans-Ulrich Kauczor, Johanna Nattenmüller
BACKROUND: Non-alcoholic fatty liver disease (NAFLD) comprises non-progressive steatosis and non-alcoholic steatohepatitis (NASH), the latter of which may cause cirrhosis and hepatocellular carcinoma (HCC). As NAFLD detection is imperative for the prevention of its complications, we evaluated whether a combination of blood-based biomarkers and anthropometric parameters can be used to predict NAFLD among overweight and obese adults. METHODS: 143 overweight or obese non-smokers free of diabetes (50% women, age: 35-65 years) were recruited...
July 13, 2018: BMC Gastroenterology
Tatsuo Kanda, Shunichi Matsuoka, Motomi Yamazaki, Toshikatsu Shibata, Kazushige Nirei, Hiroshi Takahashi, Tomohiro Kaneko, Mariko Fujisawa, Teruhisa Higuchi, Hitomi Nakamura, Naoki Matsumoto, Hiroaki Yamagami, Masahiro Ogawa, Hiroo Imazu, Kazumichi Kuroda, Mitsuhiko Moriyama
The number of patients with nonalcoholic fatty liver diseases (NAFLD) including nonalcoholic steatohepatitis (NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma (HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines...
July 7, 2018: World Journal of Gastroenterology: WJG
Daniel Jahn, Stefan Kircher, Heike M Hermanns, Andreas Geier
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder closely linked to obesity, hyperlipidemia and type 2 diabetes and is increasingly recognized as a major health problem in many parts of the world. While early stages of NAFLD are characterized by a bland accumulation of fat (steatosis) in hepatocytes, the disease can progress to non-alcoholic steatohepatitis (NASH) which involves chronic liver inflammation, tissue damage and fibrosis and can ultimately lead to end-stage liver disease including cirrhosis and cancer...
July 7, 2018: Biochimica et Biophysica Acta
Stephen A Harrison, Manal F Abdelmalek, Stephen Caldwell, Mitchell L Shiffman, Anna Mae Diehl, Reem Ghalib, Eric J Lawitz, Don C Rockey, Raul Aguilar Schall, Catherine Jia, Bryan J McColgan, John G McHutchison, G Mani Subramanian, Robert P Myers, Zobair Younossi, Vlad Ratziu, Andrew J Muir, Nezam H Afdhal, Zachary Goodman, Jaime Bosch, Arun J Sanyal
BACKGROUND & AIMS: Lysyl oxidase like 2 (LOXL2) contributes to fibrogenesis by catalyzing cross linkage of collagen. We evaluated the safety and efficacy of simtuzumab, a monoclonal antibody against LOXL2, in a phase 2b trial of patients with advanced fibrosis caused by nonalcoholic steatohepatitis (NASH). METHODS: We performed a double-blind study of 219 patients with bridging fibrosis, caused by NASH, randomly assigned (1:1:1) to groups given weekly subcutaneous injections of simtuzumab (75 or 125 mg) or placebo for a planned duration of 240 weeks...
July 7, 2018: Gastroenterology
Paul J Thuluvath, Steven Hanish, Yulia Savva
BACKGROUND: Patients with NASH cirrhosis have excellent post liver transplant (LT) survival despite having many co-morbidities. We hypothesized that this could be due to a selection bias. METHODS: We analyzed the UNOS data from 2002 to 2016 and compared post-LT survival of NASH (n=7,935) patients with cryptogenic (CC, n= 6,087), alcoholic AC, n=16,810) and autoimmune hepatitis (AIH, n= 2,734) cirrhosis. RESULTS: By 3 years of listing, the cumulative incidence (CI) of death or deterioration was 29% for NASH, 28% for CC and AC, and 24% for AIH, but when adjusted for risk factors, the CI was similar for NASH and AIH...
July 5, 2018: Transplantation
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