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non-alcoholic steatohepatitis AND (treatment or therapy)

Eleonora Scorletti, Christopher D Byrne
For many years it has been known that high doses of long chain omega-3 fatty acids are beneficial in the treatment of hypertriglyceridaemia. Over the last three decades, there has also been a wealth of in vitro and in vivo data that has accumulated to suggest that long chain omega-3 fatty acid treatment might be beneficial to decrease liver triacylglycerol. Several biological mechanisms have been identified that support this hypothesis; notably, it has been shown that long chain omega-3 fatty acids have a beneficial effect: a) on bioactive metabolites involved in inflammatory pathways, and b) on alteration of nuclear transcription factor activities such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), involved in inflammatory pathways and liver lipid metabolism...
March 12, 2018: Molecular Aspects of Medicine
Karen Louise Thomsen, Francesco De Chiara, Krista Rombouts, Hendrik Vilstrup, Fausto Andreola, Rajeshwar P Mookerjee, Rajiv Jalan
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases ranging from steatosis, through non-alcoholic steatohepatitis (NASH) to cirrhosis. The development of fibrosis is the most important factor contributing to NASH-associated morbidity and mortality. Hepatic stellate cells (HSCs) are responsible for extracellular matrix deposition in conditions of frank hepatocellular injury and are key cells involved in the development of fibrosis. In experimental models and patients with NASH, urea cycle enzyme gene and protein expression is reduced resulting in functional reduction in the in vivo capacity for ureagenesis and subsequent hyperammonemia at a pre-cirrhotic stage...
April 2018: Medical Hypotheses
Claus Uhrenholt Christensen, Emilie Glavind, Karen Louise Thomsen, Yong Ook Kim, Sara Heebøll, Detlef Schuppan, Stephen Hamilton-Dutoit, Christian Würtz Heegaard, Henning Grønbæk
BACKGROUND AND AIMS: Hepatic cholesterol deposition drives inflammation and fibrosis in non-alcoholic steatohepatitis (NASH). The Niemann-Pick type C2 (NPC2) protein plays an important role in regulating intracellular cholesterol trafficking and homeostasis. We hypothesized that intravenous NPC2 supplementation reduces cholesterol accumulation, hepatic inflammation and fibrogenesis in a nutritional NASH rat model. METHODS: Rats were fed a high-fat, high-cholesterol (HFHC) diet for four weeks resulting in moderately severe NASH...
2018: PloS One
Stephen A Harrison, Mary E Rinella, Manal F Abdelmalek, James F Trotter, Angelo H Paredes, Hays L Arnold, Marcelo Kugelmas, Mustafa R Bashir, Mark J Jaros, Lei Ling, Stephen J Rossi, Alex M DePaoli, Rohit Loomba
BACKGROUND: Non-alcoholic steatohepatitis is a chronic liver disease characterised by the presence of hepatic steatosis, inflammation, and hepatocellular injury, for which no Food and Drug Administration (FDA)-approved treatment exists. FGF19 is a hormone that regulates bile acid synthesis and glucose homoeostasis. We aimed to assess the safety and efficacy of NGM282, an engineered FGF19 analogue, for the treatment of non-alcoholic steatohepatitis. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 study, we recruited patients aged 18-75 years with biopsy-confirmed non-alcoholic steatohepatitis as defined by the non-alcoholic steatohepatitis clinical research network histological scoring system, from hospitals and gastroenterology and liver clinics in Australia and the USA...
March 5, 2018: Lancet
J W M Greve, N D Bouvy
The EndoBarrier (duodenal-jejunal bypass liner) became available in 2009 as an endoscopic treatment method for obesity and type 2 diabetes mellitus (T2D). The treatment results in significant weight loss and improvement of the obesity-related morbidities such as T2D, non-alcoholic steatohepatitis, hypertension and other cardiovascular diseases. However, unexpected complications such as liver abscesses can occur, in addition to expected adverse events such as bleeding, obstruction, and migration. The incidence of these complications is low however, and to date no treatment-related mortality has occurred with the use of EndoBarrier...
2018: Nederlands Tijdschrift Voor Geneeskunde
Shoji Yamada, Yoko Takashina, Mitsuhiro Watanabe, Ryogo Nagamine, Yoshimasa Saito, Nobuhiko Kamada, Hidetsugu Saito
Gut microbiota plays a significant role in the development of hepatocellular carcinoma (HCC) in non-alcoholic steatohepatitis (NASH). However, understanding of the precise mechanism of this process remains incomplete. A new class steatohepatitis-inducing high-fat diet (HFD), namely STHD-01, can promote the development of HCC without the administration of chemical carcinogens. Using this diet, we comprehensively analyzed changes in the gut microbiota and its metabolic functions during the development of HCC in NASH...
February 9, 2018: Oncotarget
Shinji Takai, Denan Jin
Non-alcoholic steatohepatitis (NASH) is characterized by inflammation and fibrosis, in addition to steatosis, of the liver, but no therapeutic agents have yet been established. The mast cell protease chymase can generate angiotensin II, matrix metalloproteinase-9 and transforming growth factor-β, all of which are associated with liver inflammation or fibrosis. In animal models of NASH, augmented chymase has been observed in the liver. In histological analysis, chymase inhibitor prevented hepatic steatosis, inflammation, and fibrosis...
2018: Frontiers in Pharmacology
Kyosuke Yamanishi, Keiichiro Mukai, Takuya Hashimoto, Kaoru Ikubo, Keiji Nakasho, Yosif El-Darawish, Wen Li, Daisuke Okuzaki, Yuko Watanabe, Tetsu Hayakawa, Hiroshi Nojima, Hiromichi Yamanishi, Haruki Okamura, Hisato Matsunaga
BACKGROUND: The cytokine interleukin-18 was originally identified as an interferon-γ-inducing proinflammatory factor; however, there is increasing evidence to suggest that it has non-immunological effects on physiological functions. We previously investigated the potential pathophysiological relationship between interleukin-18 and dyslipidemia, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis, and suggested interleukin-18 as a possible novel treatment for not only these diseases but also for cancer immunotherapy...
March 7, 2018: Journal of Translational Medicine
Kyoko Hara, Seiji Yoshitomi, Hisashi Tsuji
A 66-years-old woman was referred to our hospital with the chief complaint of a huge exposed left breast mass, associated massive exudates, bleedingand foul-smelling discharge. Invasive ductal carcinoma was diagnosed by core needle biopsy. The computed tomography showed left axillary lymph node metastases and no distant metastasis. Her performance status(PS) was Grade 3. She had serious comorbidities such as non-alcoholic steatohepatitis and liver cirrhosis, renal dysfunction. DMpC therapy and Mohs paste therapy were started since her overall status was improved...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Islam N Mohamed, Nahla Reda Sarhan, Mohamed Ahmed Eladl, Azza B El-Remessy, Mohamed El-Sherbiny
Endemic prevalence of obesity is associated with alarming increases in non-alcoholic steatohepatitis (NASH) with limited available therapeutics. Toll-like receptor2 (TLR2) and Nod-like receptor protein 3 (NLRP3) Inflammasome are implicated in hepatic steatosis, inflammation and fibrosis; the histological landmark stages of NASH. TXNIP, a member of α-arrestin family activates NLRP3 in response to various danger stimuli. The aim of current work was to investigate the effect of TXNIP genetic deletion on histological manifestations of high fat diet-induced steatohepatitis and activation of TLR2-NLRP3-inflammasome axis...
February 23, 2018: Acta Histochemica
Cynthia Lebeaupin, Déborah Vallée, Déborah Rousseau, Stéphanie Patouraux, Stéphanie Bonnafous, Gilbert Adam, Frederic Luciano, Carmelo Luci, Rodolphe Anty, Antonio Iannelli, Sandrine Marchetti, Guido Kroemer, Sandra Lacas-Gervais, Albert Tran, Philippe Gual, Béatrice Bailly-Maitre
Endoplasmic reticulum (ER) stress is activated in non-alcoholic fatty liver disease (NAFLD), raising the possibility that ER stress-dependent metabolic dysfunction, inflammation and cell death underlie the transition from steatosis to steatohepatitis (NASH). Bax inhibitor-1 (BI-1), a negative regulator of the ER stress sensor IRE1α, has yet to be explored in NAFLD as a hepatoprotective agent. We hypothesized that the genetic ablation of BI-1 would render the liver vulnerable to NASH due to unrestrained IRE1α signaling...
February 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Frank Tacke
Nonalcoholic fatty liver disease (NAFLD) has an increasing prevalence worldwide. At present, no specific pharmacotherapy is approved for NAFLD. Simple steatosis and nonalcoholic steatohepatitis (NASH) can progress to liver fibrosis that is associated with mortality in NAFLD. The recruitment of inflammatory monocytes and macrophages via chemokine receptor CCR2 as well as of lymphocytes and hepatic stellate cells via CCR5 promote the progression of NASH to fibrosis. Areas covered: I summarize preclinical and clinical data on the efficacy and safety of the dual CCR2/CCR5 inhibitor cenicriviroc (CVC, also TBR-652 or TAK-652) for the treatment of NASH and fibrosis...
February 16, 2018: Expert Opinion on Investigational Drugs
Yuichiro Amano, Shuntarou Tsuchiya, Mayumi Imai, Kimio Tohyama, Jun Matsukawa, Osamu Isono, Hironobu Yasuno, Kazuaki Enya, Emiko Koumura, Hiroshi Nagabukuro
This study aimed to evaluate the effects of combination therapy with a dipeptidyl peptidase-4 inhibitor, alogliptin, and a peroxisome proliferator-activated receptor-γ agonist, pioglitazone, in a preclinical model of nonalcoholic steatohepatitis using low-density lipoprotein receptor-knockout mice fed a modified choline-deficient l-amino acid-defined diet. Monotherapy with either alogliptin (10-200 mg/kg) or pioglitazone (6-20 mg/kg) significantly decreased hepatic triglyceride content and fibrosis. The concomitant treatment of alogliptin (30 mg/kg), pioglitazone (20 mg/kg) also decreased hepatic triglyceride and hepatic collagen-I mRNA at greater extent compared to monotherapy...
February 8, 2018: Biochemical and Biophysical Research Communications
Pierre Bedossa
The pattern of non-alcoholic fatty liver disease is complex with an association of several lesions, each of them related to different pathophysiological mechanisms. Despite the progress in non-invasive tools, liver biopsy remains the only diagnostic procedure that can reliably assess these various patterns, their related severity and associations. The most important difficulties of liver biopsy can be avoided if this procedure is performed by an experienced hepatologist and read by a liver pathologist. However, for obvious reasons, biopsy should be restricted to selected patients, especially in the context of clinical trials...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Danny Issa, Vaishali Patel, Arun J Sanyal
Non-alcoholic fatty liver disease is a leading cause of chronic liver disease and can lead to cirrhosis, hepatocellular cancer and end stage liver disease. It is also associated with increased cardiovascular and cancer related morbidity and mortality. The pathogenesis of non-alcoholic fatty liver disease includes metabolic stress to the liver associated with insulin resistance with downstream cell stress from reactive oxygen species and unfolded protein response with activation of inflammatory and fibrotic pathways...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Lawrence Serfaty
Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is a prevalent condition that is associated with the development of cirrhosis and hepatocellular carcinoma and with no approved treatment options except for lifestyle changes. Guidelines have been drafted for the management of NAFLD patients in this setting. Because of the lack of real-life cohort data, we will focus on practice surveys on the management of patients with NAFLD/NASH, which included primary care practitioners, gastroenterologists/hepatologists and other specialists from various countries...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Xinshou Ouyang, Sheng-Na Han, Ji-Yuan Zhang, Balazs Tamas Nemeth, Pal Pacher, Dechun Feng, Ramon Bataller, Joaquin Cabezas, Peter Stärkel, Joan Caballeria, Rebecca LePine Pongratz, Shi-Ying Cai, Bernd Schnabl, Rafaz Hoque, Yonglin Chen, Wei-Hong Yang, Irma Garcia Martinez, Fu-Sheng Wang, Bin Gao, Natalie Julia Torok, Richard Glenn Kibbey, Wajahat Zafar Mehal
Sterile inflammation after tissue damage is a ubiquitous response, yet it has the highest amplitude in the liver. This has major clinical consequences, for alcoholic and non-alcoholic steatohepatitis (ASH and NASH) account for the majority of liver disease in industrialized countries and both lack therapy. Requirements for sustained sterile inflammation include increased oxidative stress and activation of the HIF-1α signaling pathway. We demonstrate the ability of digoxin, a cardiac glycoside, to protect from liver inflammation and damage in ASH and NASH...
February 6, 2018: Cell Metabolism
Antonella Borrelli, Patrizia Bonelli, Franca Maria Tuccillo, Ira D Goldfine, Joseph L Evans, Franco Maria Buonaguro, Aldo Mancini
Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD progresses through the inflammatory phase of non-alcoholic steatohepatitis (NASH) to fibrosis and cirrhosis, with some cases developing liver failure or hepatocellular carcinoma (HCC). Liver biopsy remains the gold standard approach to a definitive diagnosis of NAFLD and the distinction between simple steatosis and NASH. The pathogenesis of NASH is still not clear. Several theories have been proposed ranging from the "Two Hit Theory" to the "Multiple Hit Theory"...
January 27, 2018: Redox Biology
Adil Mardinoglu, Mathias Uhlen, Jan Borén
Multi-omics multi-tissue data are used to interpret genome-wide association study results from mice to identify key driver genes of non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease (NAFLD) is the accumulation of fat (steatosis) in the liver due to causes other than excessive alcohol consumption. The disease may progress to more severe forms of liver diseases, including non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. In this issue of Cell Systems, Krishnan et al. (2018) reveal mechanisms underlying NAFLD by generating multi-omics data using liver and adipose tissues obtained from the Hybrid Mouse Diversity Panel, consisting of 113 mouse strains with various degrees of NAFLD...
January 24, 2018: Cell Systems
Qiaozhu Su, Virender Kumar, Neetu Sud, Ram I Mahato
Non-alcoholic fatty liver disease (NAFLD) increases the risk of various liver injuries, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis, and ultimately hepatocellular carcinoma (HCC). Ample evidence has suggested that aberrant expression of microRNAs (miRNAs) is functionally involved in the activation of cellular stress, inflammation and fibrogenesis in hepatic cells, including hepatocytes, Kupffer and hepatic stellate cells (HSCs), at different pathological stages of NAFLD and liver fibrosis...
January 31, 2018: Advanced Drug Delivery Reviews
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