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Junjiang Pan, Zhibing Ou, Can Cai, Peizhi Li, Jianping Gong, Xiong Z Ruan, Kun He
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in many developed and developing countries worldwide. It has been well established that the chronic sterile inflammation caused by the NLRP3 inflammasome is closely related to NAFLD development. Kupffer cells (KCs) are involved in the pathogenesis of various liver diseases. We used methionine choline-deficient diets to establish a mouse nonalcoholic steatohepatitis (NASH) model. The expression and formation of the NLRP3 inflammasome in the KCs from the mouse and cell models were determined by Western blotting and co-immunoprecipitation...
August 10, 2018: Cellular Immunology
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
Ahmed Abdel-Razik, Nasser Mousa, Walaa Shabana, Mohamed Refaey, Rasha Elzehery, Rania Elhelaly, Khaled Zalata, Mostafa Abdelsalam, Ahmed A Eldeeb, Mahmoud Awad, Ayman Elgamal, Ahmed Attia, Niveen El-Wakeel, Waleed Eldars
BACKGROUND/AIMS: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) may include increased insulin resistance, upregulation of proinflammatory cytokines, lipopolysaccharide, and BMI. Rifaximin is a minimally absorbable antibiotic that might act against a broad spectrum of gut bacteria. This study aimed to investigate the effects of rifaximin on NAFLD. PATIENTS AND METHODS: Fifty participants with biopsy-proven nonalcoholic steatohepatitis (NASH) were registered in this multicentric, double-blind, randomized, placebo-controlled study...
August 9, 2018: European Journal of Gastroenterology & Hepatology
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
Uchenna Agbim, Yu Jiang, Satish K Kedia, Ashwani Singal, Aijaz Ahmed, Kalyan Ram Bhamidimarri, David Bernstein, Stephen A Harrison, Zobair M Younossi, Sanjaya K Satapathy
Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition and its more severe progressive state, nonalcoholic steatohepatitis (NASH), is currently the second most common indication for waitlisted adults in the United States. The association of portal vein thrombosis (PVT) prior to or at transplant and poor graft and patient outcomes is not well established, particularly among NASH patients who inherently have an increased hypercoagulable profile. Using the United Network for Organ Sharing dataset, we analyzed graft and patient outcomes of patients transplanted for the indication of NASH with and without PVT...
August 9, 2018: Liver Transplantation
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
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
Jeong-Ju Yoo, Won Kim, Moon Young Kim, Dae Won Jun, Sang Gyune Kim, Jong-Eun Yeon, Jin Woo Lee, Yong Kyun Cho, Sang Hoon Park, Joo Hyun Sohn
Nonalcoholic fatty liver disease (NAFLD), together with metabolic syndrome and obesity, has shown a rapid increase in prevalence worldwide and is emerging as a major cause of chronic liver disease and liver transplantation. Among the various phenotypes of NAFLD, nonalcoholic steatohepatitis (NASH) is highly likely to progress to development of end-stage liver disease and cardiometabolic disease, resulting in liver-related and non-liver-related mortality. Nonetheless, there is no standardized pharmacotherapy against NASH and many drugs are under development in ongoing clinical trials...
August 8, 2018: Clinical and Molecular Hepatology
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
Sherin E Mathews, Rekha B Kumar, Alpana P Shukla
PURPOSE OF REVIEW: Obesity and nonalcoholic steatohepatitis (NASH) are epidemiologically and pathophysiologically linked disorders. Here, we summarize the effect of obesity on NASH and how it has a cascading effect on cardiovascular dysfunction. We also review the current and emerging treatment options for NASH. RECENT FINDINGS: The link between NASH and cardiac dysfunction has been further delineated in recent studies demonstrating endothelial dysfunction, diastolic dysfunction, and increased coronary artery calcification in patients with known NASH...
August 1, 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
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
Ping Ye, Mei Xiang, Hua Liao, Jijun Liu, Hongbo Luo, Yayun Wang, Ling Huang, Manhua Chen, Jiahong Xia
Non-alcoholic fatty liver disease (NAFLD), ranging from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), is the leading cause of chronic liver diseases. Until now, no medications for NAFLD have been approved by relevant governmental agencies. Dual-specificity phosphatase 9 (Dusp9) is a member of the DUSP protein family. Dusp9 is expressed in insulin-sensitive tissues, and its expression may be modified with the development of insulin resistance (IR). However, the molecular targets and mechanisms of Dusp9 action on NAFLD and NASH remain poorly understood...
July 31, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Hannes Hagström, Olof Elfwén, Rolf Hultcrantz, Per Stål
Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease globally. The majority of NAFLD patients have fatty liver without inflammation (nonalcoholic fatty liver, NAFL), whereas a minority develop steatohepatitis (nonalcoholic steatohepatitis, NASH). Only NASH and not NAFL has been considered to increase the risk for fibrosis progression. The present study investigates risk factors for fibrosis progression in patients with NAFLD, and if fibrosis progression associates with subsequent mortality...
2018: Gastroenterology Research and Practice
Marta A Kowalik, Amedeo Columbano, Andrea Perra
The signaling pathways activated by thyroid hormone receptors (THR) are of fundamental importance for organogenesis, growth and differentiation, and significantly influence energy metabolism, lipid utilization and glucose homeostasis. Pharmacological control of these pathways would likely impact the treatment of several human diseases characterized by altered metabolism, growth or differentiation. Not surprisingly, biomedical research has been trying for the past decades to pharmacologically target the 3,5,3'-triiodothyronine (T3)/THR axis...
2018: Frontiers in Endocrinology
Kang-Yu Peng, Matthew J Watt, Sander Rensen, Jan-Willem Greve, Kevin Huynh, Kaushala S Jayawardana, Peter J Meikle, Ruth C R Meex
To gain insight into the relationship between lipid metabolism and disease progression through the different stages of non-alcoholic fatty liver disease (NAFLD), we performed lipidomic analysis of plasma and liver from obese subjects with non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH), and obese subjects without NAFLD. We found that lipid species that differed with NAFLD severity are related to mitochondrial dysfunction, a process that has been suggested to play an important role in the development and progression of NAFLD...
July 24, 2018: Journal of Lipid Research
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
Ángela Vinué, Andrea Herrero-Cervera, Herminia González-Navarro
The development of certain chronic metabolic diseases has been attributed to elevated levels of dietary cholesterol. However, decades of research in animal models and humans have demonstrated a high complexity with respect to the impact of dietary cholesterol on the progression of these diseases. Thus, recent investigations in non-alcoholic fatty liver disease (NAFLD) point to dietary cholesterol as a key factor for the activation of inflammatory pathways underlying the transition from NAFLD to non-alcoholic steatohepatitis (NASH) and to hepatic carcinoma...
July 21, 2018: Nutrients
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
Benjamin Wildman-Tobriner, Michael M Middleton, Cynthia A Moylan, Stephen Rossi, Omar Flores, Zac Anchi Chang, Manal F Abdelmalek, Claude B Sirlin, Mustafa R Bashir
BACKGROUND & AIMS: Patients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic; steatohepatitis (NASH) often require histologic assessment via liver biopsy. Magnetic; resonance imaging (MRI)-based methods for measuring liver triglycerides based on proton density fat fraction (PDFF) are increasingly as a non-invasive tool to identify patients with hepatic steatosis and to assess for change in liver fat over time. We aimed to determine whether MRI-PDFF accurately reflects a variety of liver histology features in patients with NAFLD or NASH...
July 19, 2018: Gastroenterology
Rebeca Mayo, Javier Crespo, Ibon Martínez-Arranz, Jesus M Banales, Mayte Arias, Itziar Mincholé, Rocío Aller de la Fuente, Raúl Jimenez-Agüero, Cristina Alonso, Daniel A de Luis, Libor Vitek, Jan Stritesky, Joan Caballería, Manuel Romero-Gómez, Antonio Martín-Duce, Jose Maria Mugüerza Huguet, José Ignacio Busteros-Moraza, Michael O Idowu, Azucena Castro, M Luz Martínez-Chantar, Pablo Ortiz, Radan Bruha, Shelly C Lu, Pierre Bedossa, Mazen Noureddin, Arun J Sanyal, José M Mato
Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease worldwide and includes a broad spectrum of histologic phenotypes, ranging from simple hepatic steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). While liver biopsy is the reference gold standard for NAFLD diagnosis and staging, it has limitations due to its sampling variability, invasive nature, and high cost. Thus, there is a need for noninvasive biomarkers that are robust, reliable, and cost effective...
July 2018: Hepatology communications
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