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Marlies Bekaert, D Margriet Ouwens, Tina Hörbelt, Frederique Van de Velde, Pia Fahlbusch, Daniella Herzfeld de Wiza, Yves Van Nieuwenhove, Patrick Calders, Marleen Praet, Anne Hoorens, Anja Geerts, Xavier Verhelst, Jean-Marc Kaufman, Bruno Lapauw
OBJECTIVE: This study aimed to evaluate whether circulating levels and/or visceral adipose tissue (VAT) expression of recently described adipokines associate with histopathological severity of nonalcoholic fatty liver disease (NAFLD), independent of obesity and insulin resistance. METHODS: Serum levels of adiponectin, omentin, chemerin, monocyte chemoattractant protein-1, and secreted frizzled-related protein 4 were measured using enzyme-linked immunosorbent assay in 81 patients with obesity and NAFLD and 18 lean control subjects...
October 21, 2016: Obesity
Ryan D Sheldon, Kayla M Kanosky, Kevin D Wells, Lili Miles, James W Perfield, Stavra Xanthakos, Thomas H Inge, R Scott Rector
BACKGROUND: Mechanisms responsible for progression of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH) remain poorly defined. METHODS: To examine the potential contribution of adipose tissue to NAFLD progression, we performed a complete transcriptomic analysis using RNA-sequencing (RNA-seq) on intra-abdominal adipose tissue (IAT) from severely obese adolescents (Mage 16.9±0.4 yrs; BMI z-score 2.7±0.1) undergoing bariatric surgery and liver biopsy categorized into 3 groups; No steatosis (Normal, n=8), steatosis only (n=13), or NASH (n=10) by liver histology...
October 7, 2016: Physiological Genomics
Thomas Gilliland, Sylvie Dufour, Gerald I Shulman, Kitt Falk Petersen, Sukru H Emre
NAFLD is a common condition linked to obesity, type 2 diabetes, and metabolic syndrome. Simple hepatic steatosis is a risk factor for inflammatory reactions in the liver (NASH), which may lead to cirrhosis. While the mechanism is unclear, NAFLD and NASH are associated with panhypopituitarism, which in the pediatric population often results from craniopharyngioma or pituitary adenoma and the sequelae of treatment, causing hypothyroidism, adrenal insufficiency, hypogonadotropic hypogonadism, and GH deficiency...
October 20, 2016: Pediatric Transplantation
Ajit Dash, Robert A Figler, Arun J Sanyal, B R Wamhoff
Drug induced steatohepatitis (DISH), a form of drug induced liver injury (DILI) is characterized by intracellular accumulation of lipids in hepatocytes and subsequent inflammatory events, in some ways similar to the pathology seen with other metabolic, viral and genetic causes of non alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH). Areas covered: This paper provides a comprehensive review of the main underlying mechanisms by which various drugs cause DISH, and outlines existing preclinical tools to predict it and study underlying pathways involved...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
Jennie Ka Ching Lau, Xiang Zhang, Jun Yu
Non-alcoholic fatty liver disease (NAFLD) is a continuous spectrum of diseases characterized by excessive lipid accumulation in hepatocytes. NAFLD progresses from simple liver steatosis to non-alcoholic steatohepatitis (NASH) and in more severe cases to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Due to its growing worldwide prevalence, various animal models that mirror both the histopathology and pathophysiology of each stage of human NAFLD have been developed. The selection of appropriate animal models continues to be one of the key questions faced in this field...
October 18, 2016: Journal of Pathology
Ran Ao, Ying Wang, Jing Tong, Bai-Fang Wang
BACKGROUND MicroRNA-9 (miR-9) was detected in nonalcoholic fatty liver disease (NAFLD) patients to understand the role of miR-9 in NAFLD development. MATERIAL AND METHODS Between February 2014 and February 2015, 105 cases of NAFLD were recruited and confirmed by liver biopsy pathology, including patients with mild NAFLD (n=58) and moderate-severe NAFLD (n=47); nonalcoholic steatohepatitis (NASH) (n=53) and non-NASH (n=52); and 50 healthy participants were regarded as the healthy control group. MiR-9 expression was measured by qRT-PCR...
October 19, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
S Di Mauro, M Ragusa, F Urbano, A Filippello, A Di Pino, A Scamporrino, A Pulvirenti, A Ferro, A M Rabuazzo, M Purrello, F Purrello, S Piro
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD has the potential to progress through the inflammatory phase of nonalcoholic steatohepatitis (NASH) to fibrosis, cirrhosis, and hepatocellular carcinoma. Identifying patients at risk for this transition is a relevant clinical challenge. The complexity of these phenotypes in vivo made necessary the development of in vitro models in order to dissect the molecular signalling affected in NAFLD and NASH, but also to identify potential circulating biomarkers...
August 20, 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Kojiro Seki, Toshihide Shima, Hirohisa Oya, Yasuhide Mitsumoto, Masayuki Mizuno, Takeshi Okanoue
AIM: Transient elastography (TE) is a noninvasive method for predicting liver fibrosis. However, there is limited data regarding the performance of TE in Japanese patients with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the association between liver stiffness measurement (LSM) by TE and liver fibrosis stage, and define a cut-off value for predicting liver fibrosis. METHODS: A total of 171 Japanese patients with biopsy-proven NAFLD underwent LSM using TE with FibroScan®...
October 18, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Zheng-Jie Xu, Jun-Ping Shi, De-Rong Yu, Li-Juan Zhu, Ji-Dong Jia, Jian-Gao Fan
INTRODUCTION: Non-alcoholic steatohepatitis (NASH) is a serious form of non-alcoholic fatty liver disease (NAFLD) that can progress to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Differentiating between non-alcoholic fatty liver (NAFL) and NASH/advanced fibrosis is an important step in the management of NAFLD. Metabolic syndrome (MS) and its components are important risk factors for NAFLD, and NASH is thought to be the hepatic injury of MS. The prevalence of NASH among NAFLD patients with MS is thought to be high...
October 14, 2016: Advances in Therapy
Terry D Hinds, Katherine A Burns, Peter A Hosick, Lucien McBeth, Andrea Nestor-Kalinoski, Heather A Drummond, Adbulhadi A AlAmodi, Michael W Hankins, John P Vanden Heuvel, David E Stec
Non-alcoholic fatty liver disease (NAFLD) is the most rapidly growing form of liver disease, and if left untreated can result in non-alcoholic steatohepatitis (NASH) ultimately resulting in liver cirrhosis and failure. Biliverdin reductase-A (BVRA) is a multi-functioning protein primarily responsible for the reduction of biliverdin to bilirubin. Also, BVRA can function as a kinase and transcription factor, regulating several cellular functions. We report here that liver BVRA protects against hepatic steatosis by inhibiting glycogen synthase kinase-3β (GSK3β) by enhancing serine 9 phosphorylation, which inhibits its activity...
October 10, 2016: Journal of Biological Chemistry
J E Nelson, P Handa, B Aouizerat, L Wilson, L A Vemulakonda, M M Yeh, K V Kowdley
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in non-alcoholic steatohepatitis (NASH). AIM: To investigate the relationship between IL1B and IL6 gene polymorphisms and histological features of NAFLD in the NASH CRN cohort. METHODS: A total of 604 adult (≥18 years) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563...
October 11, 2016: Alimentary Pharmacology & Therapeutics
Herbert Tilg, Alexander R Moschen, Michael Roden
The liver constitutes a key organ in systemic metabolism, contributing substantially to the development of insulin resistance and type 2 diabetes mellitus (T2DM). The mechanisms underlying these processes are not entirely understood, but involve hepatic fat accumulation, alterations of energy metabolism and inflammatory signals derived from various cell types including immune cells. Lipotoxins, mitochondrial function, cytokines and adipocytokines have been proposed to play a major part in both NAFLD and T2DM...
October 12, 2016: Nature Reviews. Gastroenterology & Hepatology
Tsuyoshi Chiba, Sachina Suzuki, Yoko Sato, Tatsuki Itoh, Keizo Umegaki
AIM: Non-alcoholic steatohepatitis (NASH) is a globally recognized liver disease. A methionine- and choline-deficient diet is used to induce NASH in mice; however, this diet also causes severe body weight loss. To resolve this issue, we examined the effects of methionine content in a high-fat and choline-deficient (HFCD) diet on body weight and the development of NASH in mice. METHODS: C57BL/6J mice (male, 10 weeks of age) were fed an L-amino acid rodent (control) diet, high-fat (HF) diet, or HFCD diet containing various amounts of methionine (0...
2016: PloS One
Ali Canbay, Jan-Peter Sowa, Wing-Kin Syn, Jürgen Treckmann
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a continuously increasing cause of chronic liver disease and a health burden in all populations affected by the obesity and metabolic syndrome pandemic. Cirrhotic alterations or hepatocellular carcinoma developing from NAFLD may require liver transplantation (LTx). METHODS: Current literature was screened for data on LTx in the setting of NAFLD. RESULTS: NAFLD-associated LTx is expected to increase in number and relevance during the next decade...
August 2016: Visc Med
M Maida, F S Macaluso, F Salomone, S Petta
NAFLD (Non-Alcoholic Fatty Liver Disease) is an increasingly significant public health issue, regarded as the most relevant liver disease of the twenty-first century. Approximately 20%-30% of NAFLD subjects develop a NASH (Non-Alcoholic Steato-Hepatitis), a condition which can potentially evolve to liver cirrhosis and hepatocellular carcinoma. For these reasons a proper evaluation of liver damage is a key point for diagnosis and prognosis and liver biopsy still remains the "gold standard" procedure both for discrimination between steatosis and steatohepatitis and assessment of the degree of liver fibrosis...
October 4, 2016: Current Molecular Medicine
Maryam Noori, Bahar Jafari, Azita Hekmatdoost
BACKGROUND: The effects of pomegranate juice (PJ) on the risk factors of Nonalcoholic Fatty Liver Disease (NAFLD)/Nonalcoholic Steatohepatitis (NASH) have been shown previously; however, its effects on NAFLD and its prevention has not yet been elucidated. Our objective was to evaluate the effects of PJ consumption on prevention of NAFLD/NASH development. Sprague-Dawley rats were fed either high-fat, high sugar diet (model group), or high-fat, high sugar diet plus PJ (model+PJ), or chow diet ad libitum for seven weeks...
September 22, 2016: Journal of the Science of Food and Agriculture
Xi-Xi He, Xiao-Li Wu, Ren-Pin Chen, Chao Chen, Xiao-Gang Liu, Bin-Jiao Wu, Zhi-Ming Huang
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome with the main characteristic of diffuse liver cells with fatty changes. The clinical evolution of NAFLD includes simple non-alcoholic fatty liver, non-alcoholic steatohepatitis (NASH), liver fibrosis and cirrhosis, and even hepatocellular carcinoma. METHODS AND FINDINGS: We conducted this review to identify the effectiveness of omega-3 polyunsaturated fatty acids (ω-3 PUFA) in NAFLD. We searched PubMed, Cochrane Library and Embase...
2016: PloS One
Stergios A Polyzos, Jannis Kountouras, Christos S Mantzoros
The association of obesity with nonalcoholic fatty liver disease (NAFLD) has been established. Obesity has been linked not only to initial stages of the disease, i.e., simple steatosis (SS), but also to its severity. Form an epidemiologic point of view, both diseases has an increasing prevalence worldwide. From a pathogenetic point of view, obesity and its associate IR contribute to the initial fat accumulation in the hepatocyte (SS), but also to the progression of SS to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma (HCC)...
October 6, 2016: Minerva Endocrinologica
Nirvair S Kelley
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for type 2 diabetes, cardiovascular disease, and liver failure. Treatment with n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) produced variable success in improving NAFLD. The purpose of this review is to determine if n-3 LCPUFA will decrease markers of NAFLD, compare the efficacies of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and identify factors that contribute to discrepancies in results...
October 6, 2016: Metabolic Syndrome and related Disorders
Yan Zhu, Hongxia Liu, Min Zhang, Grace L Guo
The prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide has increased at an alarming rate, which will likely result in enormous medical and economic burden. NAFLD presents as a spectrum of liver diseases ranging from simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even to hepatocellular carcinoma (HCC). A comprehensive understanding of the mechanism(s) of NAFLD-to-NASH transition remains elusive with various genetic and environmental susceptibility factors possibly involved...
September 2016: Acta Pharmaceutica Sinica. B
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