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https://www.readbyqxmd.com/read/30508523/mitochondria-targeting-to-oppose-the-progression-of-nonalcoholic-fatty-liver-disease
#1
REVIEW
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
https://www.readbyqxmd.com/read/30506586/vitamin-e-improves-transplant-free-survival-and-hepatic-decompensation-among-patients-with-nash-and-advanced-fibrosis
#2
Eduardo Vilar-Gomez, Raj Vuppalanchi, Samer Gawrieh, Marwan Ghabril, Romil Saxena, Oscar W Cummings, Naga Chalasani
Vitamin E improves liver histology in non-diabetic adults with nonalcoholic steatohepatitis (NASH), but its impact on long-term patient outcomes is unknown. We evaluated whether vitamin E treatment improves clinical outcomes of NASH patients with bridging fibrosis or cirrhosis. Two hundred and thirty-six patients with biopsy-proven NASH and bridging fibrosis or cirrhosis seen at Indiana University Medical Center between October 2004, and January 2016 were included. Ninety of them took 800 IU/day of vitamin E for ≥ 2 years (vitamin E users) and were propensity matched to 90 adults who did not take vitamin E (controls) after adjusting for fibrosis severity, age, gender, body mass index, comorbidities and their treatment, LDL cholesterol, liver biochemistries and length of follow-up on vitamin E...
December 1, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30502373/obesity-and-nonalcoholic-fatty-liver-disease-from-pathophysiology-to-therapeutics
#3
REVIEW
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
https://www.readbyqxmd.com/read/30502056/liver-iron-load-influences-hepatic-fat-fraction-in-end-stage-renal-disease-patients-on-dialysis-a-proof-of-concept-study
#4
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
https://www.readbyqxmd.com/read/30500848/portal-lymphadenopathy-predicts-non-alcoholic-steatohepatitis-and-advanced-fibrosis-in-non-alcoholic-fatty-liver-disease
#5
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
https://www.readbyqxmd.com/read/30498712/new-insights-into-genetic-predisposition-and-novel-therapeutic-targets-for-nonalcoholic-fatty-liver-disease
#6
REVIEW
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
https://www.readbyqxmd.com/read/30498706/comorbidities-as-an-indication-for-metabolic-surgery
#7
REVIEW
Anne-Catherine Schwarz, Adrian T Billeter, Katharina M Scheurlen, Matthias Blüher, Beat P Müller-Stich
Metabolic diseases, comprising type 2 diabetes mellitus (T2DM), dyslipidemia, and non-alcoholic steatohepatitis (NASH), are rapidly increasing worldwide. Conservative medical therapy, including the newly available drugs, has only limited effects and does neither influence survival or the development of micro- or macrovascular complications, nor the progression of NASH to liver cirrhosis, nor the development of hepatocellular carcinomas in the NASH liver. In contrast, metabolic surgery is very effective independent of the preoperative body mass index (BMI) in reducing overall and cardiovascular mortality in patients with T2DM...
October 2018: Visceral Medicine
https://www.readbyqxmd.com/read/30487694/promoting-genetics-in-non-alcoholic-fatty-liver-disease-combined-risk-score-through-polymorphisms-and-clinical-variables
#8
EDITORIAL
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
https://www.readbyqxmd.com/read/30487332/-secondary-osteoporosis-bone-disease-in-liver-cirrhosis
#9
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
https://www.readbyqxmd.com/read/30479664/advances-and-challenges-in-the-management-of-advanced-fibrosis-in-nonalcoholic-steatohepatitis
#10
REVIEW
Mehmet Sayiner, Brian Lam, Pegah Golabi, Zobair M Younossi
Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common type of chronic liver disease worldwide. From the spectrum of NAFLD, it is nonalcoholic steatohepatitis (NASH) that predominantly predisposes patients to higher risk for development of cirrhosis and hepatocellular carcinoma. There is growing evidence that the risk of progression to cirrhosis and hepatocellular carcinoma is not uniform among all patients with NASH. In fact, NASH patients with increasing numbers of metabolic diseases such as diabetes, hypertension, visceral obesity and dyslipidemia are at a higher risk of mortality...
2018: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/30469530/mtor-activation-in-liver-tumors-is-associated-with-metabolic-syndrome-and-non-alcoholic-steatohepatitis-in-both-mouse-models-and-humans
#11
Takahiro Okuno, Anna Kakehashi, Naomi Ishii, Masaki Fujioka, Min Gi, Hideki Wanibuchi
Non-alcoholic steatohepatitis (NASH) can cause liver fibrosis and cirrhosis, with final progression to hepatocellular carcinoma (HCC) in some cases. Various factors have been suggested to be involved in the development of NASH. Considering the many possible contributing factors, we postulated that mechanisms of progression from NASH to HCC could differ depending on the risk factors. In the present study, we applied two mouse models of NASH⁻HCC and performed histopathological and proteome analyses of mouse liver tumors...
November 22, 2018: Cancers
https://www.readbyqxmd.com/read/30467325/bet-inhibition-improves-nash-and-liver-fibrosis
#12
Sarah A Middleton, Neetu Rajpal, Leanne Cutler, Palwinder Mander, Inmaculada Rioja, Rab K Prinjha, Deepak Rajpal, Pankaj Agarwal, Vinod Kumar
Non-alcoholic fatty liver disease (NAFLD) is a leading form of chronic liver disease with large unmet need. Non-alcoholic steatohepatitis (NASH), a progressive variant of NAFLD, can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. To identify potential new therapeutics for NASH, we used a computational approach based on Connectivity Map (CMAP) analysis, which pointed us to bromodomain and extra-terminal motif (BET) inhibitors for treating NASH. To experimentally validate this hypothesis, we tested a small-molecule inhibitor of the BET family of proteins, GSK1210151A (I-BET151), in the STAM mouse NASH model at two different dosing timepoints (onset of NASH and progression to fibrosis)...
November 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30459251/targeting-metabolism-insulin-resistance-and-diabetes-to-treat-nonalcoholic-steatohepatitis
#13
Brian N Finck
Obesity, insulin resistance, and diabetes are strongly linked to the accumulation of excessive lipids in the liver parenchyma, a condition known as nonalcoholic fatty liver disease (NAFLD). Given its association with obesity and related metabolic diseases, it is not surprising that the prevalence of NAFLD has dramatically increased in the past few decades. NAFLD has become the most common liver disease in many areas of the world. The term, NAFLD, encompasses a spectrum of disorders that ranges from simple steatosis to steatosis with inflammatory lesions (nonalcoholic steatohepatitis [NASH])...
December 2018: Diabetes
https://www.readbyqxmd.com/read/30454647/obesity-drives-stat-1-dependent-nash-and-stat-3-dependent-hcc
#14
Marcus Grohmann, Florian Wiede, Garron T Dodd, Esteban N Gurzov, Geraldine J Ooi, Tariq Butt, Aliki A Rasmiena, Supreet Kaur, Twishi Gulati, Pei K Goh, Aislinn E Treloar, Stuart Archer, Wendy A Brown, Mathias Muller, Matthew J Watt, Osamu Ohara, Catriona A McLean, Tony Tiganis
Obesity is a major driver of cancer, especially hepatocellular carcinoma (HCC). The prevailing view is that non-alcoholic steatohepatitis (NASH) and fibrosis or cirrhosis are required for HCC in obesity. Here, we report that NASH and fibrosis and HCC in obesity can be dissociated. We show that the oxidative hepatic environment in obesity inactivates the STAT-1 and STAT-3 phosphatase T cell protein tyrosine phosphatase (TCPTP) and increases STAT-1 and STAT-3 signaling. TCPTP deletion in hepatocytes promoted T cell recruitment and ensuing NASH and fibrosis as well as HCC in obese C57BL/6 mice that normally do not develop NASH and fibrosis or HCC...
November 15, 2018: Cell
https://www.readbyqxmd.com/read/30446221/alleviation-of-fatty-liver-in-a-rat-model-by-enhancing-n-1-methylnicotinamide-bioavailability-through-aldehyde-oxidase-inhibition
#15
Kenji Takeuchi, Chie Yokouchi, Hirohiko Goto, Ken Umehara, Hideyuki Yamada, Yuji Ishii
Nonalcoholic fatty liver disease (NAFLD) has increased worldwide in recent years. NAFLD is classified into two types, nonalcoholic fatty liver (NAFL), with few complications, and nonalcoholic steatohepatitis (NASH), which leads to liver cirrhosis or cancer. This study was based on previous reports that N1 -methylnicotinamide (MNA) can stabilise sirtuin 1 protein, leading to decreased lipid levels in the liver. We hypothesised that fatty liver improvement by MNA would be further enhanced by suppressing its rapid metabolism by aldehyde oxidase in the liver...
December 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30444584/guideline-of-prevention-and-treatment-of-nonalcoholic-fatty-liver-disease-2018-china
#16
Jian Gao Fan, Lai Wei, Hui Zhuang
Non-alcoholic fatty liver disease (NAFLD) is an acquired metabolic stress-induced liver disease associated closely with genetic susceptibility and insulin resistance (IR), the spectrum of the disease includes non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH) and related liver cirrhosis, and hepatocellular carcinoma (HCC).1,2 This article is protected by copyright. All rights reserved.
November 16, 2018: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/30441981/future-of-pharmacological-treatment-of-non-alcoholic-steatohepatitis-in-terms-of-key-pathophysiological-mechanisms
#17
Marek Rác, Ľubomír Skladaný
Obesity reaches the dimensions of the global epidemic. It directly contributes to an increase in the prevalence of systemic diseases associated with obesity. Obesity and overweight globally cause 3.5 million deaths annually [1]. Non-alcoholic fatty liver disease has become the most common chronic liver disease in developed countries and is considered to be a liver manifestation of metabolic syndrome. The extent and burden of the disease are increasing and reaching epidemic proportions because of its close association with the epidemic of obesity and diabetes mellitus type [2]...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/30418431/steatosis-in-liver-transplantation-current-limitations-and-future-strategies
#18
Ivan Linares, Matyas Hamar, Nazia Selzner, Markus Selzner
In parallel with the pandemic of obesity and diabetes, the prevalence of nonalcoholic fatty liver disease (NAFLD) has progressively increased. Non-alcoholic steatohepatitis (NASH), a subtype of NAFLD has also augmented considerably being currently cirrhosis due to NASH the second indication for liver transplantation in USA. Innovative treatments for NASH have shown promising results in phase-2 studies and are being presently evaluated in phase-3 trials.On the other hand, the high mortality on the liver transplant wait list and the organ shortage has obligated the transplant centres to consider suboptimal grafts, such as steatotic livers for transplantation...
November 9, 2018: Transplantation
https://www.readbyqxmd.com/read/30415572/-non-alcoholic-fatty-liver-disease-a-summary-and-update-based-on-the-easl-easd-easo-clinical-practice-guidelines-of-2016
#19
Ákos Nádasdi, Anikó Somogyi, Péter Igaz, Gábor Firneisz
The non-alcoholic fatty liver disease (NAFLD) as a common metabolic disease affects nearly one third of the population in the developed countries. The significance of the NAFLD is due to its spectrum disease (simple steatosis → NASH [non-alcoholic steatohepatitis] ± fibrosis → cirrhosis → HCC [hepatocellular carcinome]) character; its association with obesity, type 2 diabetes mellitus (T2DM), dyslipidaemia, metabolic syndrome, insulin resistance; and its complications both as a consequence of the direct progression of the liver disease and also related to the additional target organ damage due to the progression of the metabolic disease (cardiovascular, renal)...
November 2018: Orvosi Hetilap
https://www.readbyqxmd.com/read/30400243/stable-isotope-labeled-lipidomics-to-unravel-the-heterogeneous-development-lipotoxicity
#20
Lu-Min Shih, Hsiang-Yu Tang, Ke-Shiuan Lynn, Cheng-Yu Huang, Hung-Yao Ho, Mei-Ling Cheng
Non-alcoholic fatty liver disease (NAFLD) as a global health problem has clinical manifestations ranging from simple non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), cirrhosis, and cancer. The role of different types of fatty acids in driving the early progression of NAFL to NASH is not understood. Lipid overload causing lipotoxicity and inflammation has been considered as an essential pathogenic factor. To correlate the lipid profiles with cellular lipotoxicity, we utilized palmitic acid (C16:0)- and especially unprecedented palmitoleic acid (C16:1)-induced lipid overload HepG2 cell models coupled with lipidomic technology involving labeling with stable isotopes...
November 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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