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Fernando Bessone, María Valeria Razori, Marcelo G Roma
Nonalcoholic fatty liver disease (NAFLD) is a main hepatic manifestation of metabolic syndrome. It represents a wide spectrum of histopathological abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with or without fibrosis and, eventually, cirrhosis and hepatocellular carcinoma. While hepatic simple steatosis seems to be a rather benign manifestation of hepatic triglyceride accumulation, the buildup of highly toxic free fatty acids associated with insulin resistance-induced massive free fatty acid mobilization from adipose tissue and the increased de novo hepatic fatty acid synthesis from glucose acts as the "first hit" for NAFLD development...
October 20, 2018: Cellular and Molecular Life Sciences: CMLS
Nadia Panera, Barbara Barbaro, Claudia Della Corte, Antonella Mosca, Valerio Nobili, Anna Alisi
Nonalcoholic fatty liver disease (NAFLD) is a multifaceted disorder that ranges from simple fatty liver to nonalcoholic steatohepatitis (NASH) with or without fibrosis, which may evolve toward cirrhosis and hepatocellular carcinoma. It is currently considered a "global" and "epidemic" disease, whose prevalence is progressively increasing even in pediatric age. The incidence of NAFLD is very high in overweight/obese children, and a greater risk of disease progression is associated with severe obesity, highlighting the role of nutrition...
October 2018: Nutrition Research
Zobair M Younossi, Giulio Marchesini, Helena Pinto-Cortez, Salvatore Petta
Nonalcoholic fatty liver disease (NAFLD) affects 25% of the global adult population with a range of 13.5% in Africa and 31.8% in the Middle East. NAFLD is closely associated with a constellation of metabolic comorbidities which include: obesity, type 2 diabetes mellitus (T2DM), hypertension, and hypercholesteremia. In fact, the increasing number of metabolic comorbidities not only increase the prevalence of NAFLD but also places patients at higher risk for progressive liver disease. As such, NAFLD is presently among the top etiologies for hepatocellular carcinoma (HCC) and an indication for liver transplantation...
October 17, 2018: Transplantation
Giacomo Germani, Marie Laryea, Laura Rubbia-Brandt, Hiroto Egawa, Patrizia Burra, John O'Grady, Kymberly D Watt
Nonalcoholic steatohepatitis (NASH) is a growing indication for liver transplant whether the primary or secondary cause of liver disease, and it is expected to be the leading indication in the years to come. NASH recurs after transplant but the impact of the recurrence on allograft and patient outcomes is unclear. A group of multidisciplinary transplant practice providers convened at the International Liver Transplant Society NASH consensus conference with the purpose of determining the current knowledge and future directions for understanding the recurrence rates, risk and management of NASH in the transplant allograft...
October 17, 2018: Transplantation
Jesus M Banales, Mercedes Iñarrairaegui, Ander Arbelaiz, Piotr Milkiewicz, Jordi Muntane, Luis Muñoz-Bellvis, Adelaida La Casta, Luis M Gonzalez, Enara Arretxe, Cristina Alonso, Ibon Martínez-Arranz, Ainhoa Lapitz, Alvaro Santos-Laso, Matias A Avila, Maria L Martínez-Chantar, Luis Bujanda, Jose J G Marin, Bruno Sangro, Rocio I R Macias
Early and differential diagnosis of intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC) by non-invasive methods represents a current clinical challenge. The analysis of low-molecular weight metabolites by new high-throughput techniques is a novel strategy for identifying biomarkers. Here, we have investigated whether serum metabolome can provide useful biomarkers in the diagnosis of iCCA and HCC and could discriminate iCCA from HCC. Since primary sclerosing cholangitis (PSC) is a risk factor for CCA, serum metabolomic profiles of PSC and CCA have also been compared...
October 16, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Nicholas O Davidson
There is increasing interest in the role of angiogenesis in fibrogenic signaling, via generation of proangiogenic mediators that perpetuate injury and promote fibrosis [reviewed in (1)]. This is a timely development in understanding the underlying mechanisms and pathways that promote progression of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH) with fibrosis and hepatocellular cancer (HCC), given the global impact of these diseases (2). This article is protected by copyright. All rights reserved...
October 16, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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
Carlos J Pirola, Martin Garaycoechea, Diego Flichman, Marco Arrese, Julio San Martino, Carla Gazzi, Gustavo O Casta Ntildeo, Silvia Sookoian
Hydroxysteroid 17βdehydrogenase 13 (HSD17B13) is a lipid droplet-associated protein; its gene-encoding variants affect the chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD). To estimate the effect of rs72613567, a splice variant with an adenine insertion (A-INS), on NAFLD susceptibility and severity, we performed a case-control study with 609 individuals. We investigated the effect of carrying the A-INS allele in 356 patients with biopsy-proven disease and explored the relationship between rs72613567genotypes and the hepatic transcriptome...
October 15, 2018: Journal of Lipid Research
Mustafa R Bashir, Tanya Wolfson, Anthony C Gamst, Kathryn J Fowler, Michael Ohliger, Shetal N Shah, Adina Alazraki, Andrew T Trout, Cynthia Behling, Daniela S Allende, Rohit Loomba, Arun Sanyal, Jeffrey Schwimmer, Joel E Lavine, Wei Shen, James Tonascia, Mark L Van Natta, Adrija Mamidipalli, Jonathan Hooker, Kris V Kowdley, Michael S Middleton, Claude B Sirlin
BACKGROUND: The liver R2* value is widely used as a measure of liver iron but may be confounded by the presence of hepatic steatosis and other covariates. PURPOSE: To identify the most influential covariates for liver R2* values in patients with nonalcoholic fatty liver disease (NAFLD). STUDY TYPE: Retrospective analysis of prospectively acquired data. POPULATION: Baseline data from 204 subjects enrolled in NAFLD/NASH (nonalcoholic steatohepatitis) treatment trials...
October 14, 2018: Journal of Magnetic Resonance Imaging: JMRI
Ludovico Abenavoli, Tetyana Falalyeyeva, Luigi Boccuto, Olena Tsyryuk, Nazarii Kobyliak
The main treatments for patients with nonalcoholic fatty liver disease (NAFLD) are currently based on lifestyle changes, including ponderal decrease and dietary management. However, a subgroup of patients with nonalcoholic steatohepatitis (NASH), who are unable to modify their lifestyle successfully, may benefit from pharmaceutical support. Several drugs targeting pathogenic mechanisms of NAFLD have been evaluated in clinical trials for the treatment of NASH. Farnesoid X receptor (FXR) is a nuclear key regulator controlling several processes of the hepatic metabolism...
October 11, 2018: Pharmaceuticals
Lisa K Koch, Matthew M Yeh
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and strongly associated with obesity, diabetes and the metabolic syndrome, not only in the Western societies, but also in most regions of the world in the 21st century. The spectrum of its histopathology ranges from steatosis to nonalcoholic steatohepatitis (NASH), with risk for progressive fibrosis that may lead to cirrhosis and hepatocellular carcinoma (HCC). Benign and malignant liver tumors have also been more frequently reported with the increasing prevalence of obesity and diabetes...
September 27, 2018: Annals of Diagnostic Pathology
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
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
Irene Pierantonelli, Gianluca Svegliati-Baroni
Nonalcoholic fatty liver disease (NAFLD) represents a growing cause of chronic liver injury, especially in Western Countries, where it is becoming the most frequent indication for liver transplantation (OLTx). NAFLD encompasses a spectrum of diseases that from simple steatosis (pure NAFLD) can progress to Nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of NAFLD and the mechanisms behind its progression to NASH have been extensively studied. However, while the processes that determine fat accumulation are mostly clear, the mechanisms associated with the progression of the disease are not fully characterized...
October 8, 2018: Transplantation
Takaomi Kessoku, Kento Imajo, Takashi Kobayashi, Yasushi Honda, Yuji Ogawa, Masato Yoneda, Satoru Saito, Atsushi Nakajima
Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), is a disease that may lead to liver cirrhosis or hepatocellular carcinoma. The number of patients is increasing steadily and the pathology is diverse. Effective treatment is still mainly focused on diet and exercise therapy. With the advent of the next-generation sequencer, the intestinal flora in NAFLD/NASH is being elucidated. We believe that elevation of endotoxin in the blood caused by intestinal bacterial dysbiosis caused by intestinal permeability enhancement is important for NASH pathology and control of intestinal permeability enhancement has a new possibility for treatment of NAFLD/NASH...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
Donghee Kim, Won Kim, Sae Kyung Joo, Jung Ho Kim, Stephen A Harrison, Zobair M Younossi, Aijaz Ahmed
AIMS: We compared (1) demographic and clinical characteristics, and (2) determinants of nonalcoholic steatohepatitis (NASH) and significant fibrosis in non-obese and obese NAFLD. METHODS: A cross-sectional study of 664 Asian subjects (mean age 53.1 years; men 50.3%) with biopsy-proven NAFLD and controls was conducted. Subjects were divided by their body mass index (BMI) into obese (BMI ≥25 kg/m2 ) and non-obese (BMI <25 kg/m2 ). RESULTS: Observations in subjects with non-obese NAFLD were in between non-obese controls and obese NAFLD subjects for BMI, sagittal abdominal diameter (SAD), aminotransferase levels, insulin resistance, and abdominal visceral adipose tissue (VAT) area...
October 8, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Hirofumi Okubo, Akifumi Kushiyama, Yusuke Nakatsu, Takeshi Yamamotoya, Yasuka Matsunaga, Midori Fujishiro, Hideyuki Sakoda, Haruya Ohno, Masayasu Yoneda, Tomoichiro Asano
The rising prevalence of non-alcoholic fatty liver disease (NAFLD) parallels the global increase in the number of people diagnosed with obesity and metabolic syndrome. The gut-liver axis (GLA) plays an important role in the pathogenesis of NAFLD/non-alcoholic steatohepatitis (NASH). In this review, we discuss the clinical significance and underlying mechanisms of action of gut-derived secretory factors in NAFLD/NASH, focusing on recent human studies. Several studies have identified potential causal associations between gut-derived secretory factors and NAFLD/NASH, as well as the underlying mechanisms...
October 8, 2018: International Journal of Molecular Sciences
Jose Cordoba-Chacon, Andre Sarmento-Cabral, Mercedes Del Rio-Moreno, Alberto Diaz-Ruiz, Papasani V Subbaiah, Rhonda D Kineman
Nonalcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH), is associated with reduced growth hormone (GH) input/signaling and GH therapy is effective in the reduction/resolution of NAFLD/NASH in select patient populations. Our laboratory has focused on isolating the direct vs. indirect effects of GH in preventing NAFLD/NASH. We reported that chow-fed, adult-onset hepatocyte-specific GH receptor knockdown (aHepGHRkd) mice rapidly (within 7d) develop steatosis associated with increased hepatic de novo lipogenesis (DNL), independent of changes in systemic metabolic function...
October 5, 2018: Endocrinology
Saumya Jayakumar, Michael S Middleton, Eric J Lawitz, Parvez S Mantry, Stephen H Caldwell, Hays Arnold, Anna Mae Diehl, Reem Ghalib, Magdy Elkhashab, Manal F Abdelmalek, Kris V Kowdley, C Stephen Djedjos, Ren Xu, Ling Han, G Mani Subramanian, Robert P Myers, Zachary D Goodman, Nezam H Afdhal, Michael R Charlton, Claude B Sirlin, Rohit Loomba
BACKGROUND & AIMS: Non-invasive tools for monitoring treatment response and disease progression in non-alcoholic steatohepatitis (NASH) are needed. Our objective was to evaluate the utility of magnetic resonance (MR)-based hepatic imaging measures for the assessment of liver histology in patients with NASH. METHODS: We analyzed data from patients with NASH and stage 2 or 3 fibrosis enrolled in a phase II study of selonsertib. Pre- and post-treatment assessments included centrally read MR elastography (MRE)-estimated liver stiffness, MR imaging-estimated proton density fat fraction (MRI-PDFF), and liver biopsies evaluated according to the NASH Clinical Research Network classification and the non-alcoholic fatty liver disease activity score (NAS)...
October 4, 2018: Journal of Hepatology
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