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https://www.readbyqxmd.com/read/28721532/-chronic-cholestatic-liver-diseases-differential-diagnosis-pathogenesis-and-current-treatment-in-adults
#1
S Hohenester, U Beuers
In the long-term course chronic cholestasis regularly leads to fibrotic restructuring and ultimately to functional failure of the liver, independent of the cause. Cholestatic diseases are often clinically asymptomatic. In order to avoid progression, early diagnosis of the underlying disease and a targeted therapy are therefore decisive. The differential diagnoses of chronic cholestasis are broad; therefore, algorithms are of assistance in the diagnostic work-up. A better understanding of the pathogenesis is now leading to the development of new therapeutic agents in addition to ursodeoxycholic acid, which has long been known for its anticholestatic effects...
July 18, 2017: Der Internist
https://www.readbyqxmd.com/read/28669591/primary-biliary-cholangitis-old-and-novel-therapy
#2
Annarosa Floreani, Chiara Mangini
Primary biliary cholangitis (PBC), formerly called primary biliary cirrhosis, is a chronic cholestatic liver disease that progresses slowly to end-stage liver disease. The first Food and Drug Administration (FDA)-approved treatment for PBC was ursodeoxycholic acid (UDCA). This treatment slows the progress of the disease, but approximatively 30-40% of patients fail to respond to UDCA. A number of options are under investigation as second line treatment. Obeticholic acid (OCA), a Farnesoid X Receptor agonist, has been approved in May 2017 by FDA for patients non responders or intolerant to UDCA...
June 29, 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28641031/treatment-options-for-nonalcoholic-steatohepatitis-a-safety-evaluation
#3
Danny Issa, Julia Wattacheril, Arun J Sanyal
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...
July 6, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28637104/-treatment-options-in-non-alcoholic-fatty-liver-disease
#4
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/28624576/agreement-between-magnetic-resonance-imaging-proton-density-fat-fraction-measurements-and-pathologist-assigned-steatosis-grades-of-liver-biopsies-from-adults-with-nonalcoholic-steatohepatitis
#5
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 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28560290/farnesoid-x-receptor-agonist-treatment-alters-bile-acid-metabolism-but%C3%A2-exacerbates-liver-damage-in-a-piglet-model-of-short-bowel%C3%A2-syndrome
#6
Prue M Pereira-Fantini, Susan Lapthorne, Cormac G M Gahan, Susan A Joyce, Jenny Charles, Peter J Fuller, Julie E Bines
BACKGROUND & AIMS: Options for the prevention of short-bowel syndrome-associated liver disease (SBS-ALDs) are limited and often ineffective. The farnesoid X receptor (FXR) is a newly emerging pharmaceutical target and FXR agonists have been shown to ameliorate cholestasis and metabolic disorders. The aim of this study was to assess the efficacy of obeticholic acid (OCA) treatment in preventing SBS-ALDs. METHODS: Piglets underwent 75% small-bowel resection (SBS) or sham surgery (sham) and were assigned to either a daily dose of OCA (2...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28546061/primary-biliary-cholangitis-advances-in-management-and-treatment-of-the-disease
#7
Pietro Invernizzi, Annarosa Floreani, Marco Carbone, Marco Marzioni, Antonio Craxi, Luigi Muratori, Umberto Vespasiani Gentilucci, Ivan Gardini, Antonio Gasbarrini, Paola Kruger, Francesco Saverio Mennini, Virginia Ronco, Elena Lanati, Pier Luigi Canonico, Domenico Alvaro
Primary Biliary Cholangitis, previously known as Primary Biliary Cirrhosis, is a rare disease, which mainly affects women in their fifth to seventh decades of life. It is a chronic autoimmune disease characterized by a progressive damage of interlobular bile ducts leading to ductopenia, chronic cholestasis and bile acids retention. Even if the disease usually presents a long asymptomatic phase and a slow progression, in many patients it may progress faster toward cirrhosis and its complications. The 10year mortality is greater than in diseases such as human immunodeficiency virus/Hepatitis C Virus coinfection and breast cancer...
August 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28542140/mir-21-ablation-and-obeticholic-acid-ameliorate-nonalcoholic-steatohepatitis-in-mice
#8
Pedro M Rodrigues, Marta B Afonso, André L Simão, Catarina C Carvalho, Alexandre Trindade, António Duarte, Pedro M Borralho, Mariana V Machado, Helena Cortez-Pinto, Cecília Mp Rodrigues, Rui E Castro
This corrects the article DOI: 10.1038/cddis.2017.172.
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28536529/activation-of-sirt1-fxr-signaling-pathway-attenuates-triptolide-induced-hepatotoxicity-in-rats
#9
Jing Yang, Lixin Sun, Lu Wang, Hozeifa M Hassan, Xuan Wang, Phillip B Hylemon, Tao Wang, Huiping Zhou, Luyong Zhang, Zhenzhou Jiang
Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28517369/treatment-of-primary-biliary-cholangitis-non-responders-a-systematic-review
#10
Duminda Suraweera, Harman Rahal, Melissa Jimenez, Matthew Viramontes, Gina Choi, Sammy Saab
BACKGROUND: Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a chronic cholestatic liver disease characterized by an immune mediated destruction of intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) has been the primary medication for the treatment of PBC, resulting in improved liver tests, resolution of symptoms and increased transplant free survival. However, not all patients respond to UDCA. The aim of this systematic review is to provide an evidence based assessment of the medications that have been studied in patients who are refractory to UDCA...
May 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28506401/plecanatide-nusinersen-and-obeticholic-acid
#11
Daniel A Hussar, Deborah K Douglas
No abstract text is available yet for this article.
May 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28468009/what-comes-after-ursodeoxycholic-acid-in-primary-biliary-cholangitis
#12
Lin Lee Wong, Vinod S Hegade, David E J Jones
Primary biliary cholangitis (PBC) is a rare autoimmune liver disease characterized by chronic cholestasis. Treatment with the accepted primary therapy ursodeoxycholic acid (UDCA) has been shown to be associated with delayed disease progression probably through reduced impact of cholestatic injury on the target biliary epithelial cells. Patients with inadequate response to UDCA (which can be identified through validated biochemical criteria) are at increased risk of disease progression, need for liver transplantation, and death...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28427765/easl-clinical-practice-guidelines-the-diagnosis-and-management-of-patients-with-primary-biliary-cholangitis
#13
(no author information available yet)
Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune cholestatic liver disease, which when untreated will culminate in end-stage biliary cirrhosis. Diagnosis is usually based on the presence of serum liver tests indicative of a cholestatic hepatitis in association with circulating antimitochondrial antibodies. Patient presentation and course can be diverse and risk stratification is important to ensure all patients receive a personalised approach to their care. The goals of treatment and management are the prevention of end-stage liver disease, and the amelioration of associated symptoms...
April 18, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28411380/metabolic-profile-of-obeticholic-acid-and-endogenous-bile-acids-in-rats-with-decompensated-liver-cirrhosis
#14
A Roda, R Aldini, C Camborata, S Spinozzi, P Franco, M Cont, A D'Errico, F Vasuri, A Degiovanni, L Maroni, L Adorini
Obeticholic acid (OCA) is a semisynthetic bile acid (BA) analog and potent farnesoid X receptor agonist approved to treat cholestasis. We evaluated the biodistribution and metabolism of OCA administered to carbon tetrachloride-induced cirrhotic rats. This was to ascertain if plasma and hepatic concentrations of OCA are potentially more harmful than those of endogenous BAs. After administration of OCA (30 mg/kg), we used liquid chromatography-mass spectrometry to measure OCA, its metabolites, and BAs at different timepoints in various organs and fluids...
July 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28406477/mir-21-ablation-and-obeticholic-acid-ameliorate-nonalcoholic-steatohepatitis-in-mice
#15
Pedro M Rodrigues, Marta B Afonso, André L Simão, Catarina C Carvalho, Alexandre Trindade, António Duarte, Pedro M Borralho, Mariana V Machado, Helena Cortez-Pinto, Cecília Mp Rodrigues, Rui E Castro
microRNAs were recently suggested to contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a disease lacking specific pharmacological treatments. In that regard, nuclear receptors are arising as key molecular targets for the treatment of nonalcoholic steatohepatitis (NASH). Here we show that, in a typical model of NASH-associated liver damage, microRNA-21 (miR-21) ablation results in a progressive decrease in steatosis, inflammation and lipoapoptosis, with impairment of fibrosis. In a complementary fast food (FF) diet NASH model, mimicking features of the metabolic syndrome, miR-21 levels increase in both liver and muscle, concomitantly with decreased expression of peroxisome proliferator-activated receptor α (PPARα), a key miR-21 target...
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28371104/old-and-new-treatments-for-primary-biliary-cholangitis
#16
David Chascsa, Elizabeth J Carey, Keith D Lindor
Primary biliary cholangitis (formerly primary biliary cirrhosis) is a rare progressive cholestatic liver disease, whose hallmark features include a persistently elevated alkaline phosphatase level, presence of anti-mitochondrial antibodies and characteristic histology. Since 1998, ursodeoxycholic acid (UDCA), a bile acid, has been the only available therapeutic agent. Primary biliary cholangitis is associated with the development of end-stage liver disease, increased morbidity and mortality. UDCA has been shown to improve serum biochemistries, histology and delay the need for liver transplantation...
April 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28371102/treatment-of-pbc-a-step-forward
#17
Marco Carbone, Pietro Invernizzi
Recent years have seen a growing interest in PBC within the scientific community, healthcare providers and industries, coupled with great advances in the understanding of the molecular and genetic basis and the natural history of the disease. Several disease-modifying agents targeting the immune-mediated response and bile-acid therapies are at different stages of development, some with promising results. A new drug, obeticholic acid, has been recently registered in the US and Europe as a second-line treatment in refractory PBC...
April 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28371099/finding-the-cure-for-primary-biliary-cholangitis-still-waiting
#18
Atsushi Tanaka, M Eric Gershwin
The introduction of ursodeoxycholic acid (UDCA)may well have contributed to some of the improvements in morbidity and mortality of primary biliary cholangitis (PBC). Yet nearly 40% of PBC patients are unresponsive to UDCA. Further the data on UDCA is confounded by the changes in the goepidemiology and particularly the earlier diagnosis of PBC. In this regard we welcome the addition of obeticholic acid (OCA) as an alternative therapeutic option forthe treatment of PBC in those patients refractory to UDCA. However, OCA is intellectually disappointing...
April 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28365879/geoepidemiology-and-changing-mortality-in-primary-biliary-cholangitis
#19
REVIEW
Annarosa Floreani, Atsushi Tanaka, Christopher Bowlus, Merrill Eric Gershwin
Primary biliary cholangitis (PBC), formerly called primary biliary cirrhosis, is a chronic cholestatic disease characterized by an autoimmune-mediated destruction of small and medium-sized intrahepatic bile ducts. Originally PBC was considered to be rare and almost invariably fatal, mainly because the diagnosis was made in patients presenting with advanced symptomatic disease (jaundice and decompensated cirrhosis). However, the development of a reproducible indirect immunofluorescence assay for antimitochondrial antibody made it possible to diagnose the disease at an earlier stage, and introduction of ursodeoxycholic acid therapy as the first-line therapy for PBC drastically changed PBC-related mortality...
June 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28350426/pharmacological-interventions-for-primary-biliary-cholangitis-an-attempted-network-meta-analysis
#20
REVIEW
Francesca Saffioti, Kurinchi Selvan Gurusamy, Leonardo Henry Eusebi, Emmanuel Tsochatzis, Brian R Davidson, Douglas Thorburn
BACKGROUND: Primary biliary cholangitis (previously primary biliary cirrhosis) is a chronic liver disease caused by the destruction of small intra-hepatic bile ducts resulting in stasis of bile (cholestasis), liver fibrosis, and liver cirrhosis. The optimal pharmacological treatment of primary biliary cholangitis remains uncertain. OBJECTIVES: To assess the comparative benefits and harms of different pharmacological interventions in the treatment of primary biliary cholangitis through a network meta-analysis and to generate rankings of the available pharmacological interventions according to their safety and efficacy...
March 28, 2017: Cochrane Database of Systematic Reviews
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