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https://www.readbyqxmd.com/read/28641031/treatment-options-for-nonalcoholic-steatohepatitis-a-safety-evaluation
#1
Danny Issa, Julia Wattacheril, Arun J Sanyal
Introduction There is an urgent as yet unmet need to develop highly effective and safe therapeutics for nonalcoholic fatty liver disease (NAFLD). The remarkable progress in understanding NAFLD pathogenesis allowed the identification of injury pathways which may be recruited as therapy targets. Areas covered This article reviews the safety and tolerability data of the NAFLD therapies and explains the mechanistic basis for each of the established and investigational drugs. Treatment targets include: weight loss, anti-metabolic agents such as lipid lowering and anti-diabetic drugs, inflammation, fibrosis and others such as targeting gut microbiota, immune modulation and apoptosis...
June 22, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28637104/-treatment-options-in-non-alcoholic-fatty-liver-disease
#2
REVIEW
Won Kim
The prevalence of non-alcoholic fatty liver disease (NAFLD) has sharply increased over the past several decades in Korea. In most cases of NAFLD, metabolic stress and cellular apoptosis are often driven by metabolic abnormality, eventually leading to inflammation and fibrosis . Along with a dramatic surge in the obesity epidemic, 10-20% of NAFLD patients ultimately progress to non-alcoholic steatohepatitis (NASH), a precursor to cirrhosis and hepatocellular carcinoma, as well as multi-organ systemic diseases...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28637102/-the-progression-of-liver-fibrosis-in-non-alcoholic-fatty-liver-disease
#3
REVIEW
Moon Young Kim
Understanding the pathogenesis of non-alcoholic steatohepatitis (NASH) and its fibrosis progression is still evolving. Nonetheless, current evidence suggests that mechanisms involved are very complex parallel processes with multiple metabolic factors. Lipotoxicity related with excess saturated free fatty acids, obesity, and insulin resistance acts as the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence are also contribute to the activation of inflammasome via various intra- and inter-cellular signaling mechanisms that lead to fibrosis...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28637101/-cardiovascular-risk-in-patients-with-non-alcoholic-fatty-liver-disease
#4
REVIEW
Hak Soo Kim, Yong Kyun Cho
Non-alcoholic fatty liver disease (NAFLD) includes a wide spectrum of diseases that range from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. In addition, the burden of NAFLD is rapidly growing. Previously, NAFLD was regarded as a hepatic manifestation of metabolic syndrome, which is a traditional cardiovascular disease (CVD) risk factor. However, there has been an increasing evidence that suggest NAFLD to be an independent risk factor of CVD. Therefore, currently, NAFLD should be reconsidered as not only a simple manifestation of metabolic syndrome, but also a systemic disease that contribute to CVD...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#5
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis and increased cardiovascular mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are indirect glucagon like peptide 1 (GLP-1) agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28635128/development-of-a-classification-model-for-non-alcoholic-steatohepatitis-nash-using-confocal-raman-micro-spectroscopy
#6
Jie Yan, Yang Yu, Jeon Woong Kang, Zhi Yang Tam, Shuoyu Xu, Eliza Li Shan Fong, Surya Pratap Singh, Ziwei Song, Lisa Tucker-Kellogg, Peter T C So, Hanry Yu
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in developed countries [1]. A subset of individuals with NAFLD progress to non-alcoholic steatohepatitis (NASH), an advanced form of NAFLD which predisposes individuals to cirrhosis, liver failure and hepatocellular carcinoma. The current gold standard for NASH diagnosis and staging is based on histological evaluation, which is largely semi-quantitative and subjective. To address the need for an automated and objective approach to NASH detection, we combined Raman micro-spectroscopy and machine learning techniques to develop a classification model based on a well-established NASH mouse model, using spectrum pre-processing, biochemical component analysis (BCA) and logistic regression...
June 21, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28632778/over-expressing-the-soluble-gp130-fc-does-not-ameliorate-methionine-and-choline-deficient-diet-induced-non-alcoholic-steatohepatitis-in-mice
#7
Helene L Kammoun, Tamara Louise Allen, Darren Colin Henstridge, Michael James Kraakman, Lone Peijs, Stefan Rose-John, Mark Anthony Febbraio
Non-alcoholic steatohepatitis (NASH) is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6) has been implicated in the pathogenesis of NASH, with the so-called IL-6 'trans-signaling' cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 'trans-signaling', using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice) fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet) and hypothesized that markers of NASH would be ameliorated in such mice...
2017: PloS One
https://www.readbyqxmd.com/read/28632732/fructo-oligosaccharides-and-intestinal-barrier-function-in-a-methionine-choline-deficient-mouse-model-of-nonalcoholic-steatohepatitis
#8
Kotaro Matsumoto, Mayuko Ichimura, Koichi Tsuneyama, Yuki Moritoki, Hiromichi Tsunashima, Katsuhisa Omagari, Masumi Hara, Ichiro Yasuda, Hiroshi Miyakawa, Kentaro Kikuchi
Impairments in intestinal barrier function, epithelial mucins, and tight junction proteins have been reported to be associated with nonalcoholic steatohepatitis. Prebiotic fructo-oligosaccharides restore balance in the gastrointestinal microbiome. This study was conducted to determine the effects of dietary fructo-oligosaccharides on intestinal barrier function and steatohepatitis in methionine-choline-deficient mice. Three groups of 12-week-old male C57BL/6J mice were studied for 3 weeks; specifically, mice were fed a methionine-choline-deficient diet, a methionine-choline-deficient diet plus 5% fructo-oligosaccharides in water, or a normal control diet...
2017: PloS One
https://www.readbyqxmd.com/read/28630652/verification-of-b-lymphocyte-activating-factor-s-involvement-in-the-exacerbation-of-insulin-resistance-as-well-as-an-autoimmune-response-in-patients-with-nonalcoholic-steatohepatitis-and-patients-with-hcv-related-chronic-liver-disease
#9
Takashi Himoto, Koji Fujita, Takako Nomura, Joji Tani, Asahiro Morishita, Hirohito Yoneyama, Reiji Haba, Tsutomu Masaki
BACKGROUND: Ten to forty percent of nonalcoholic steatohepatitis (NASH) and HCV-related chronic liver disease (CLD-C) patients have antinuclear antibodies (ANAs). However, the relationship between autoimmune response and insulin resistance remains uncertain among those patients. The primary purpose of this study was to investigate whether or not ANA status was associated with the development of insulin resistance and obesity in NASH and CLD-C patients. METHODS: Degrees of hepatic fibrosis and steatosis were evaluated by the classification proposed by Brunt et al...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28628263/insulin-resistance-increases-the-risk-of-incident-type-2-diabetes-mellitus-in-patients-with-nonalcoholic-fatty-liver-disease
#10
Yuya Seko, Yoshio Sumida, Saiyu Tanaka, Kojiroh Mori, Hiroyoshi Taketani, Hiroshi Ishiba, Tasuku Hara, Akira Okajima, Atsushi Umemura, Taichiro Nishikawa, Kanji Yamaguchi, Michihisa Moriguchi, Kazuyuki Kanemasa, Kohichiroh Yasui, Shunsuke Imai, Keiji Shimada, Yoshito Itoh
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major complication of patients with nonalcoholic fatty liver disease (NAFLD). The aim of this retrospective study is to determine the risk factor for development of T2DM in patients with biopsy proven NAFLD. METHODS: Consecutive 162 patients with biopsy-proven NAFLD patients who received 75g oral glucose tolerance test (OGTT) were enrolled as the total cohort. Among them, we analyzed 89 patients without T2DM diagnosed by OGTT to estimate the cumulative rate for development of T2DM as the follow-up cohort...
June 19, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28628040/lipogenic-transcription-factor-chrebp-mediates-fructose-induced-metabolic-adaptations-to-prevent-hepatotoxicity
#11
Deqiang Q Zhang, Xin Tong, Kyle VanDommelen, Neil Gupta, Kenneth Stamper, Graham F Brady, Zhuoxian Meng, Jiandie D Lin, Liangyou Y Rui, M Bishr Omary, Lei Yin
Epidemiologic and animal studies implicate overconsumption of fructose in the development of nonalcoholic fatty liver disease, but the molecular mechanisms underlying fructose-induced chronic liver diseases remain largely unknown. Here, we have presented evidence supporting the essential function of the lipogenic transcription factor carbohydrate response element-binding protein (ChREBP) in mediating adaptive responses to fructose and protecting against fructose-induced hepatotoxicity. In WT mice, a high-fructose diet (HFrD) activated hepatic lipogenesis in a ChREBP-dependent manner; however, in Chrebp-KO mice, a HFrD induced steatohepatitis...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28627213/nonalcoholic-fatty-liver-disease-nafld-pathophysiology-in-obese-children-and-adolescents-update
#12
Silvana Neves Ferraz de Assunção, Ney Christian Boa Sorte, Crésio Dantas Alves, Patricia S Almeida Mendes, Carlos Roberto Brites Alves, Luciana Rodrigues Silva
OBJECTIVE: Although the nonalcoholic fatty liver disease was first identified in 1980, it presents multifactorial and unclear pathophysiology. In this review, we intend to update the pathophysiological mechanisms of a high morbidity and mortality associated disease that is affecting obese children worldwide. DATA SOURCES: The PubMed and the Cochrane Library databases were used in the search strategy for articles related to nonalcoholic fatty liver disease and published in the last three decades...
June 5, 2017: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
https://www.readbyqxmd.com/read/28626169/new-discriminant-method-for-identifying-the-aggressive-disease-phenotype-of-non-alcoholic-fatty-liver-disease
#13
Yusuke Kawamura, Kenji Ikeda, Yasuji Arase, Shunichiro Fujiyama, Tetsuya Hosaka, Masahiro Kobayashi, Satoshi Saitoh, Hitomi Sezaki, Norio Akuta, Fumitaka Suzuki, Yoshiyuki Suzuki, Hiromitsu Kumada
Objective To detect the aggressive phenotype (AP) of non-alcoholic fatty liver disease (NAFLD) based on the initial laboratory data and clinical characteristics. Methods We enrolled 144 patients with histologically proven NAFLD. For the first analysis, 24 NAFLD patients underwent repeat biopsy to establish a discriminant formula for predicting the AP of NAFLD (D-APN). The AP was defined by NAFLD that had been maintained or progressed to a fibrotic stage beyond stage 2. In the second analysis, we analyzed the distribution of the AP in each stage of disease and the incidence of the PNPLA3 rs738409 GG genotype in AP in 120 other patients...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28625068/hepatic-glycogenosis-a-diagnostic-challenge
#14
Diana Horta, Maria-Rosa Escoda, Luigi Melcarne
Recently, several cases of hepatic glycogenosis (HG) have been reported. García-Suárez et al. described a young female patient with poorly controlled type 1 diabetes, right upper quadrant pain and elevated serum transaminases and GGT. After other causes of liver disease were excluded and a liver biopsy was performed, the patient was diagnosed with HG. HG is rare and can be misdiagnosed as steatohepatitis. To date, less than 20 cases have been reported in adults.
June 19, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28624576/agreement-between-magnetic-resonance-imaging-proton-density-fat-fraction-measurements-and-pathologist-assigned-steatosis-grades-of-liver-biopsies-from-adults-with-nonalcoholic-steatohepatitis
#15
Michael S Middleton, Elhamy R Heba, Catherine A Hooker, Mustafa R Bashir, Kathryn J Fowler, Kumar Sandrasegaran, Elizabeth M Brunt, David E Kleiner, Edward Doo, Mark L Van Natta, James Tonascia, Joel E Lavine, Brent A Neuschwander-Tetri, Arun Sanyal, Rohit Loomba, Claude B Sirlin
BACKGROUND & AIMS: We assessed the diagnostic performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in grading hepatic steatosis and change in hepatic steatosis in adults with nonalcoholic steatohepatitis (NASH) in a multi-center study, using central histology as reference. METHODS: We collected data from 113 adults with NASH participating in a multi-center, randomized, double-masked, placebo-controlled, phase 2b trial to compare the efficacy cross-sectionally and longitudinally of obeticholic acid vs placebo...
June 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28624101/reversal-of-liver-fibrosis-from-fiction-to-reality
#16
REVIEW
Miguel Eugenio Zoubek, Christian Trautwein, Pavel Strnad
In chronic liver diseases, an ongoing hepatocellular injury together with inflammatory reaction results in activation of hepatic stellate cells (HSCs) and increased deposition of extracellular matrix (ECM) termed as liver fibrosis. It can progress to cirrhosis that is characterized by parenchymal and vascular architectural changes together with the presence of regenerative nodules. Even at late stage, liver fibrosis is reversible and the underlying mechanisms include a switch in the inflammatory environment, elimination or regression of activated HSCs and degradation of ECM...
April 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28623272/exosomes-derived-from-palmitic-acid-treated-hepatocytes-induce-fibrotic-activation-of-hepatic-stellate-cells
#17
Young-Sun Lee, So Yeon Kim, Eunjung Ko, Jun-Hee Lee, Hyon-Seung Yi, Yang Jae Yoo, Jihye Je, Sang Jun Suh, Young Kul Jung, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Won-Il Jeong, Jong Eun Yeon, Soon Ho Um, Kwan Soo Byun
Non-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains unknown. Here, we investigated the role of exosomes in NAFLD progression. Exosomes were isolated from a human hepatoma cell line treated with palmitic acid (PA) and their miRNA profiles examined by microarray. The human hepatic stellate cell (HSC) line (LX-2) was then treated with exosome isolated from hepatocytes...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622441/cardiovascular-mortality-among-liver-transplant-recipients-with-nonalcoholic-steatohepatitis-nash-in-the-united-states
#18
Sanjaya K Satapathy, Yu Jiang, James D Eason, Satish K Kedia, Emily Wong, Ashwani K Singal, Elizabeth A Tolley, Donna Hathaway, Satheesh Nair, Jason M Vanatta
Nonalcoholic Steatohepatitis (NASH) has become an increasingly important indication for liver transplantation (LT), and there has been a particular concern of excessive cardiovascular-related mortality in this group METHODS: Using the United Network for Organ Sharing-Standard Transplant Analysis and Research (UNOS-STAR) dataset, we reviewed data on 56,995 adult transplants (January 2002 through June 2013). 3,170 NASH liver-only recipients were identified and were matched with 3,012 non-NASH HCV+ and 3,159 non-NASH HCV- controls [matched 1:1 based on gender, age at LT (±3 years), and MELD score (±3)] RESULTS: Cox regression analysis revealed significantly lower hazard of all-cause (HR 0...
June 16, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28621635/clinical-impact-and-risk-factors-of-portal-vein-thrombosis-for-patients-on-wait-list-for-liver-transplant
#19
Martin Montenovo, Amir Rahnemai-Azar, Jorge Reyes, James Perkins
OBJECTIVES: The effect of portal vein thrombosis on the progression of liver disease is controversial, with no consensus on optimal treatment. We aimed to assess how portal vein thrombosis affects wait list outcomes, identify risk factors associated with its development while on a wait list, and assess its effects on patient and graft survival. MATERIALS AND METHODS: This US-based retrospective cohort study analyzed 134 109 adult patients on wait lists for or undergoing primary orthotopic liver transplant between January 2002 and June 2014...
June 16, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28620642/early-intervention-with-live-donor-liver-transplantation-reduces-resource-utilization-in-nash-the-toronto-experience
#20
Andrew S Barbas, Nicolas Goldaracena, Martin J Dib, David P Al-Adra, Aloysious D Aravinthan, Leslie B Lilly, Eberhard L Renner, Nazia Selzner, Mamatha Bhat, Mark S Cattral, Anand Ghanekar, Ian D McGilvray, Gonzalo Sapisochin, Markus Selzner, Paul D Greig, David R Grant
BACKGROUND: In parallel with the obesity epidemic, liver transplantation for nonalcoholic steatohepatitis (NASH) is increasing dramatically in North America. Although survival outcomes are similar to other etiologies, liver transplantation in the NASH population has been associated with significantly increased resource utilization. We sought to compare outcomes between live donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) at a high volume North American transplant center, with a particular focus on resource utilization...
June 2017: Transplantation Direct
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