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Lee-Lee Lai, Wan Nur Illyana Wan Yusoff, Shireene Ratna Vethakkan, Nik Raihan Nik Mustapha, Sanjiv Mahadeva, Wah-Kheong Chan
BACKGROUND: The recommendation in regards to screening for non-alcoholic fatty liver disease (NAFLD) among type 2 diabetes mellitus (T2DM) patients differs in major guidelines. AIM: To study the prevalence of NALFD and advanced fibrosis among T2DM patients. METHODS: Cross-sectional study of consecutive adult T2DM patients attending the Diabetes Clinic of a university hospital. Significant hepatic steatosis and advanced fibrosis was diagnosed based on transient elastography if the controlled attenuation parameter was ≥263dB/m and the liver stiffness measurement (LSM) was ≥9...
December 14, 2018: Journal of Gastroenterology and Hepatology
Elizabeth M Brunt, David E Kleiner, Laura A Wilson, Arun J Sanyal, Brent A Neuschwander-Tetri
Hepatocellular injury and inflammation are believed to be the primary drivers of fibrogenesis that ultimately lead to cirrhosis in patients with NASH. AIM: This study sought associations between observed improvements in fibrosis with improvement in specific histologic features, NAFLD Activity Score (NAS) ≥ 2, diagnostic category, and primary histologically based outcomes of two adult NASH treatment trials. The primary outcome for the study was fibrosis improvement from baseline to end of treatment, defined as a 1 point or more improvement in fibrosis stage...
December 14, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Xiaoying Liu, Richard M Green
Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of abnormal liver chemistry tests in the United States and western world. The mechanisms underlying hepatic steatosis and the progression to nonalcoholic steatohepatitis (NASH) remain incompletely understood. Multiple cellular stress pathways are believed to contribute to the pathogenesis of fatty liver, including endoplasmic reticulum (ER) stress and its adaptive unfolded protein response (UPR). Numerous studies have demonstrated the important role of ER stress and UPR activation in a host of liver diseases including viral hepatitis, alcohol and drug hepatotoxicity, cholestatic liver disorders and genetic liver diseases...
December 14, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Paola Dongiovanni, Marica Meroni, Miriam Longo, Silvia Fargion, Anna Ludovica Fracanzani
Nonalcoholic fatty liver disease (NAFLD) defines a wide pathological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which may predispose to liver cirrhosis and hepatocellular carcinoma. It represents the leading cause of hepatic damage worldwide. Diagnosis of NASH still requires liver biopsy but due to the high prevalence of NAFLD, this procedure, which is invasive, is not practicable for mass screening. Thus, it is crucial to non-invasively identify NAFLD patients at higher risk of progression to NASH and fibrosis...
December 10, 2018: International Journal of Molecular Sciences
Daisuke Uehara, Yosuke Seki, Satoru Kakizaki, Norio Horiguchi, Hiroki Tojima, Yuichi Yamazaki, Ken Sato, Masanobu Yamada, Toshio Uraoka, Kazunori Kasama
BACKGROUND: Patients with morbid obesity are complicated with metabolic diseases and have a high incidence of non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH). METHODS: We report on a follow-up study of a cohort included 102 obese patients (55 males and 47 females, mean age 42.9 ± 10.6 years) undergoing bariatric surgery for the management of morbid obesity. Abdominal computed tomography was performed before and 1 year after surgery...
December 12, 2018: Obesity Surgery
Aline Gottlieb, Wesal Mosthael, Jan-Peter Sowa, Ali Canbay
BACKGROUND: Nonalcoholic-fatty-liver-disease/nonalcoholic steatohepatitis (NAFLD/NASH) is expected to become the leading liver disease worldwide. Typical liver-related complications are fibrosis, cirrhosis, and the development of hepatocellular cancer (HCC) with the need for liver transplantation. Up to now there is no approved pharmacotherapy. Indeed, this might be due to the complexity of this disease. While the cheapest therapeutic approach is still a lifestyle change leading to weight loss, the proportion of people achieving sufficient weight reduction without additional support is low...
December 7, 2018: Digestion
David J Orlicky, Andrew E Libby, Elise S Bales, Rachel H McMahan, Jenifer Monks, Francisco G La Rosa, James L McManaman
KEY POINTS: Wild type mice as well as mice with hepatocyte-specific or whole-body deletions of perilipin-2 (Plin2) were used to define hepatocyte and extra-hepatocyte effects of altered cellular lipid storage on obesity and non-alcoholic fatty liver disease (NAFLD) pathophysiology in a western-diet (WD) model of these disorders. Extra-hepatocyte actions of Plin2 are responsible for obesity, adipose inflammation, and glucose clearance abnormalities in WD-fed mice. Hepatocyte and extra-hepatic actions of Plin2 mediate fatty liver formation in WD-fed mice through distinct mechanisms...
December 8, 2018: Journal of Physiology
Fabian Lanuza, Jorge Sapunar, Edmundo Hofmann
Non-alcoholic fatty liver disease (NAFDL) includes fatty liver or simple steatosis, characterized by lipid deposits in hepatocytes and more advanced stages such as steatohepatitis (NASH) and non-alcoholic cirrhosis. Physical inactivity, hypercaloric and unbalanced diet together with aging play a key role in the pathogenesis of NAFLD and are strongly associated with metabolic and physical activity continue to be major components in prevention and first-line treatment to attenuate or reverse NAFLD. Dietary patterns, their composition and weight reduction would be the most relevant nutritional aspects in NAFDL treatment...
August 2018: Revista Médica de Chile
Maria Kalogirou, Emmanouil Sinakos
Nonalcoholic fatty liver disease (NAFLD) is highly associated with insulin resistance (IR), type 2 diabetes mellitus and metabolic syndrome, being characterized as the hepatic component of metabolic syndrome. Despite its high prevalence, no pharmacological treatment has been established, as of yet. A growing body of evidence, however, shows that reducing IR can result in improvement of the biochemical and histological features of nonalcoholic steatohepatitis (NASH)-the aggressive form of NAFLD that can lead to cirrhosis and hepatocellular carcinoma...
November 27, 2018: World Journal of Hepatology
Kan Chen, Jianbo Ma, Xiaoyuan Jia, Wen Ai, Zhongren Ma, Qiuwei Pan
Nonalcoholic fatty liver disease (NAFLD) has recently been recognized as an important etiology contributing to the increased incidence of hepatocellular carcinoma (HCC). NAFLD, characterized by fat accumulation in the liver, is affecting at least one-third of the global population. The more aggressive form, nonalcoholic steatohepatitis (NASH), is characterized by hepatocyte necrosis and inflammation. The development of effective approaches for disease prevention and/or treatment heavily relies on deep understanding of the mechanisms underlying NAFLD to HCC development...
December 5, 2018: Biochimica et biophysica acta. Reviews on cancer
Brett McGettigan, Rachel McMahan, David Orlicky, Matthew Burchill, Thomas Danhorn, Prashanth Francis, Lin Ling Cheng, Lucy Golden-Mason, Claudia Jakubzick, Hugo Rosen
A crucial component of non-alcoholic fatty liver disease (NAFLD) pathogenesis is lipid stress, which may contribute to hepatic inflammation and activation of innate immunity in the liver. However, little is known regarding how dietary lipids, including fat and cholesterol, may facilitate innate immune activation in vivo. We hypothesized that dietary fat and cholesterol drive NAFLD progression to steatohepatitis and hepatic fibrosis by altering the transcription and phenotype of hepatic macrophages METHODS: This hypothesis was tested by using RNA-seq methods to characterize and analyze sort-purified hepatic macrophage populations that were isolated from mice fed diets with varying amounts of fat and cholesterol RESULTS: The addition of cholesterol to a high fat diet triggered hepatic pathology reminiscent of advanced non-alcoholic steatohepatitis (NASH) in humans characterized by signs of cholesterol dysregulation, generation of oxidized LDL, increased recruitment of hepatic macrophages, and significant fibrosis...
December 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Da Zhou, Yuan-Wen Chen, Ze-Hua Zhao, Rui-Xu Yang, Feng-Zhi Xin, Xiao-Lin Liu, Qin Pan, Huiping Zhou, Jian-Gao Fan
Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients...
December 3, 2018: Experimental & Molecular Medicine
Ignazio Grattagliano, Liliana P Montezinho, Paulo J Oliveira, Gema Frühbeck, Javier Gómez-Ambrosi, Fabrizio Montecucco, Federico Carbone, Mariusz R Wieckowski, David Q-H Wang, Piero Portincasa
Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by the excessive accumulation of triglycerides in hepatocytes. NAFLD is the most frequent chronic liver disease in developed countries, and is often associated with metabolic disorders such as obesity and type 2 diabetes. NAFLD definition encompasses a spectrum of chronic liver abnormalities, ranging from simple steatosis (NAFL), to steatohepatitis (NASH), significant liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD, therefore, represents a global public health issue...
November 30, 2018: Biochemical Pharmacology
Stergios A Polyzos, Jannis Kountouras, Christos S Mantzoros
The obesity epidemic is closely associated with the rising prevalence and severity of nonalcoholic fatty liver disease (NAFLD): obesity has been linked not only with simple steatosis (SS), but also with advanced disease, i.e., nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma (HCC). As a consequence, apart from increasing all-cause mortality, obesity seems to increase liver-specific mortality in NAFLD patients. Given the lack of approved pharmacological interventions for NAFLD, targeting obesity is a rational option for its management...
November 28, 2018: Metabolism: Clinical and Experimental
Guy Rostoker, Christelle Loridon, Mireille Griuncelli, Clémentine Rabaté, Fanny Lepeytre, Pablo Ureña-Torres, Belkacem Issad, Nasredine Ghali, Yves Cohen
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a spectrum of diseases including steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis, and end-stage liver failure. Hepatic iron accumulation has been linked to hepatic fibrosis severity in NASH and NAFLD. Iron overload induced by parenteral (IV) iron therapy is a potential clinical problem in dialysis patients. We analyzed the hypothetical triggering and aggravating role of iron on NAFLD in patients on dialysis. METHODS: Liver iron concentration (LIC) and hepatic proton density fat fraction (PDFF) were analyzed prospectively in 68 dialysis patients by magnetic resonance imaging (MRI)...
November 27, 2018: EBioMedicine
Justin McNair Canada, Antonio Abbate, Rebecca Collen, Hayley Billingsley, Leo Francis Buckley, Salvatore Carbone, Cory Ross Trankle, Michael Ola Idowu, Dinesh Kadariya, Benjamin Van Tassell, Arun Jayant Sanyal, Mohammad Shadab Siddiqui
The purpose of this study was to determine the relation between liver histology, exercise tolerance, and diastolic function in patients with nonalcoholic fatty liver disease (NAFLD). Myocardial remodeling and diastolic dysfunction have been associated with NAFLD. However, its physiological impact and relationship to the histological severity of NAFLD is not known. Cardiopulmonary exercise testing and stress echocardiography was performed in subjects with biopsy-confirmed NAFLD. Maximal aerobic exercise capacity (peak oxygen consumption [VO2 ]) was related to diastolic function (mitral annulus Doppler velocity e' and ratio of early diastolic filling pressure [E] to e' [E/e']) at rest and peak exercise...
November 6, 2018: American Journal of Cardiology
Saleh Daher, Namma Lev Cohen, Muhammad Massarwa, Mahmud Mahamid, Mira Nasser, Wadi Hazou, Rani Oren, Rifaat Safadi, Tawfik Khoury
BACKGROUND AND AIM: The progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) is believed to be the driver for future development of fibrosis and cirrhosis. Nevertheless, there remains a clear deficit in non-invasive methods for the diagnosis of NASH. The aim of the present study was to evaluate the prevalence of portal lymphadenopathy (PL) in biopsy- proven NAFLD patients and to determine whether PL correlates with NAFLD stage and severity. METHODS: A retrospective study included biopsy-proven NAFLD patients with up to date (within one year) abdominal imaging by computed tomography (CT) and/or magnetic resonance imaging (MRI)...
2018: PloS One
Mary Barbara, Andrea Scott, Naim Alkhouri
Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the United States affecting 80-100 million Americans. NAFLD encompasses a spectrum of diseases ranging from excess liver fat (nonalcoholic fatty liver or NAFL), to necro-inflammation (nonalcoholic steatohepatitis or NASH), to fibrosis/ cirrhosis, and malignant transformation (hepatocellular carcinoma). Susceptibility to NAFLD is highly variable and it remains unclear why some patients with NAFLD exhibit NASH, whereas patients with known risk factors have NAFL only...
October 2018: Hepatobiliary Surgery and Nutrition
Umberto Vespasiani-Gentilucci, Paolo Gallo, Chiara Dell'Unto, Mara Volpentesta, Raffaele Antonelli-Incalzi, Antonio Picardi
Non-alcoholic fatty liver disease (NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma (HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis...
November 21, 2018: World Journal of Gastroenterology: WJG
Susumu Shiomi
Because of improved treatment of cirrhosis, patients are living longer and bone disesae such as osteoporosis is found in an increasing proportion of patients with cirrhosis. As the causes for bone diseases in cirrhosis, inhibition of vitamin D hydration and inhibition of vitamin D absorption due to decreased secretion of cholic acid have been reported, and various other causes are concerned. These bone diseases have been treated with bisphosphonates, but no definite opinion has been obtained in relation to therapeutic effects...
2018: Clinical Calcium
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