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https://www.readbyqxmd.com/read/28427765/easl-clinical-practice-guidelines-the-diagnosis-and-management-of-patients-with-primary-biliary-cholangitis
#1
Gideon M Hirschfield, Ulrich Beuers, Christophe Corpechot, Pietro Invernizzi, David Jones, Marco Marzioni, Christoph Schramm
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 17, 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
#2
Aldo Roda, Rita Aldini, Cecilia Camborata, Silvia Spinozzi, Placido Franco, Massimiliano Cont, Antonia D'Errico, Francesco Vasuri, Alessio Degiovanni, Lorenzo Maroni, Luciano Adorini
Obeticholic acid (OCA) is a semisynthetic bile acid (BA) analogue and potent farnesoid X receptor agonist approved to treat cholestasis. We evaluated the biodistribution and metabolism of OCA administered to CCl4 -induced cirrhotic rats. This was to ascertain if plasma and hepatic concentrations of OCA are potentially more harmful than those of endogenous BA. After administration of OCA (30 mg/kg), we used liquid chromatography-mass spectrometry to measure OCA, its metabolites, and BA at different time-points in various organs and fluids...
April 14, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28406477/mir-21-ablation-and-obeticholic-acid-ameliorate-nonalcoholic-steatohepatitis-in-mice
#3
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
#4
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
#5
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
#6
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
#7
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...
April 1, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28350426/pharmacological-interventions-for-primary-biliary-cholangitis-an-attempted-network-meta-analysis
#8
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
https://www.readbyqxmd.com/read/28323811/obeticholic-acid-ocaliva-for-primary-biliary-cholangitis
#9
(no author information available yet)
No abstract text is available yet for this article.
March 27, 2017: Medical Letter on Drugs and Therapeutics
https://www.readbyqxmd.com/read/28297794/-research-advances-in-autoimmune-liver-diseases-in-2016
#10
B Li, Q X Wang, X Ma
Autoimmune liver diseases are a group of abnormal autoimmune-mediated inflammatory hepatobiliary injuries, mainly including autoimmune hepatitis(AIH), primary biliary cholangitis(PBC), and primary sclerosing cholangitis (PSC). The diagnosis and treatment of autoimmune liver diseases, an important type of non-viral liver disease, have become a prominent issue in hepatology. In 2016, many new advances have been achieved in the clinical and basic research on autoimmune liver diseases, including the phase 3 clinical trial of obeticholic acid, the proposal of UK-PBC risk score, and the research on gut microbiota associated with PSC...
February 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28201850/novel-treatment-strategies-for-primary-biliary-cholangitis
#11
Albert Parés
Despite the presumed immunological pathogenesis of primary biliary cholangitis, no clear or even harmful consequences have resulted from treatments designed to modify the immunological condition. Ursodeoxycholic acid (13-16 mg/kg/d) has, however, clear favorable effects that not only improve biochemical cholestasis, but also delay histological progression. Long-term treatment with ursodeoxycholic acid is associated with excellent transplant-free survival in cases showing a biochemical response at 1 year. Data on the effects of obeticholic acid and fibrates are encouraging...
February 2017: Seminars in Liver Disease
https://www.readbyqxmd.com/read/28195307/effect-of-obeticholic-acid-on-liver-regeneration-following-portal-vein-embolization-in-an-experimental-model
#12
P B Olthof, F Huisman, F G Schaap, K P van Lienden, R J Bennink, R F van Golen, M Heger, J Verheij, P L Jansen, S W Olde Damink, T M van Gulik
BACKGROUND: The bile salt-activated transcription factor farnesoid X receptor (FXR) is a key mediator of proliferative bile salt signalling, which is assumed to play a role in the early phase of compensatory liver growth. The aim of this study was to evaluate the effect of a potent FXR agonist (obeticholic acid, OCA) on liver growth following portal vein embolization (PVE). METHODS: Rabbits were allocated to receive daily oral gavage with OCA (10 mg/kg) or vehicle (control group) starting 7 days before PVE (n = 18 per group), and continued until 7 days after PVE...
April 2017: British Journal of Surgery
https://www.readbyqxmd.com/read/28130067/farnesoid-x-receptor-activation-promotes-hepatic-amino-acid-catabolism-and-ammonium-clearance-in-mice
#13
Vittoria Massafra, Alexandra Milona, Harmjan R Vos, Rúben J J Ramos, Johan Gerrits, Ellen C L Willemsen, José M Ramos Pittol, Noortje Ijssennagger, Martin Houweling, Hubertus C M T Prinsen, Nanda M Verhoeven-Duif, Boudewijn M Burgering, Saskia W C van Mil
BACKGROUND & AIMS: The nuclear receptor subfamily 1 group H member 4 (NR1H4 or farnesoid X receptor [FXR]) regulates bile acid synthesis, transport, and catabolism. FXR also regulates postprandial lipid and glucose metabolism. We performed quantitative proteomic analyses of liver tissues from mice to evaluate these functions and investigate whether FXR regulates amino acid metabolism. METHODS: To study the role of FXR in mouse liver, we used mice with a disruption of Nr1h4 (FXR-knockout mice) and compared them with floxed control mice...
January 25, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28116470/-obeticholic-acid-in-primary-biliary-cholangitis-pbc-oca-international-study-of-efficacy-poise
#14
G Gerken, S Nitschmann
No abstract text is available yet for this article.
February 2017: Der Internist
https://www.readbyqxmd.com/read/28115235/anti-fibrotic-effects-of-chronic-treatment-with-the-selective-fxr-agonist-obeticholic-acid-in-the-bleomycin-induced-rat-model-of-pulmonary-fibrosis
#15
Paolo Comeglio, Sandra Filippi, Erica Sarchielli, Annamaria Morelli, Ilaria Cellai, Francesca Corcetto, Chiara Corno, Elena Maneschi, Alessandro Pini, Luciano Adorini, Gabriella Barbara Vannelli, Mario Maggi, Linda Vignozzi
Farnesoid X receptor (FXR) activation by obeticholic acid (OCA) has been demonstrated to inhibit inflammation and fibrosis development in liver, kidney and intestine in multiple disease models. FXR activation has also been demonstrated to suppress the inflammatory response and to promote lung repair after lung injury. This study investigated the protective effects of OCA treatment (3 or 10mg/kg/day) on inflammation, tissue remodeling and fibrosis in the bleomycin-induced pulmonary fibrosis rat model. Effects of OCA treatment on morphological and molecular alterations of the lung, as well as remodeling of the alveoli and the right ventricle were also evaluated...
January 20, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28060943/farnesoid-x-receptor-activation-attenuates-intestinal-ischemia-reperfusion-injury-in-rats
#16
Laurens J Ceulemans, Len Verbeke, Jean-Paul Decuypere, Ricard Farré, Gert De Hertogh, Kaatje Lenaerts, Ina Jochmans, Diethard Monbaliu, Frederik Nevens, Jan Tack, Wim Laleman, Jacques Pirenne
INTRODUCTION: The farnesoid X receptor (FXR) is abundantly expressed in the ileum, where it exerts an enteroprotective role as a key regulator of intestinal innate immunity and homeostasis, as shown in pre-clinical models of inflammatory bowel disease. Since intestinal ischemia reperfusion injury (IRI) is characterized by hyperpermeability, bacterial translocation and inflammation, we aimed to investigate, for the first time, if the FXR-agonist obeticholic acid (OCA) could attenuate intestinal ischemia reperfusion injury...
2017: PloS One
https://www.readbyqxmd.com/read/28052628/management-of-cholestatic-disease-in-2017
#17
REVIEW
Elsemieke de Vries, Ulrich Beuers
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the most frequent chronic cholestatic liver diseases and serve as model diseases to discuss the management of cholestasis in 2017 in the lecture that is summarized in this report. PBC and PSC are characterized by inflammation and fibrosis of small intrahepatic (PBC) or larger intra- and/or extrahepatic (PSC) bile ducts. Bile duct damage leads to cholestasis and can progress to liver fibrosis and even cirrhosis. Various genetic, environmental and endogenous factors may contribute to the development of chronic cholestatic liver diseases, but the exact pathogenesis of PBC and PSC has not been clarified...
January 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28003721/primary-biliary-cholangitis-disease-pathogenesis-and-implications-for-established-and-novel-therapeutics
#18
REVIEW
Amitkumar Patel, Anil Seetharam
Primary Biliary Cholangitis is a progressive, autoimmune cholestatic liver disorder. Cholestasis with disease progression may lead to dyslipidemia, osteodystrophy and fat-soluble vitamin deficiency. Portal hypertension may develop prior to advanced stages of fibrosis. Untreated disease may lead to cirrhosis, hepatocellular cancer and need for orthotopic liver transplantation. Classically, diagnosis is made with elevation of alkaline phosphatase, demonstration of circulating antimitochondrial antibody, and if performed: asymmetric destruction/nonsupperative cholangitis of intralobular bile ducts on biopsy...
December 2016: Journal of Clinical and Experimental Hepatology
https://www.readbyqxmd.com/read/27993716/the-fxr-agonist-px20606-ameliorates-portal-hypertension-by-targeting-vascular-remodelling-and-sinusoidal-dysfunction
#19
Philipp Schwabl, Eva Hambruch, Berit A Seeland, Hubert Hayden, Michael Wagner, Lukas Garnys, Bastian Strobel, Tim-Lukas Schubert, Florian Riedl, Dieter Mitteregger, Michael Burnet, Patrick Starlinger, Georg Oberhuber, Ulrich Deuschle, Nataliya Rohr-Udilova, Bruno K Podesser, Markus Peck-Radosavljevic, Thomas Reiberger, Claus Kremoser, Michael Trauner
BACKGROUND & AIMS: Steroidal farnesoid X receptor (FXR) agonists demonstrated potent anti-fibrotic activities and lowered portal hypertension in experimental models. The impact of the novel non-steroidal and selective FXR agonist PX20606 on portal hypertension and fibrosis was explored in this study. METHODS: In experimental models of non-cirrhotic (partial portal vein ligation, PPVL, 7days) and cirrhotic (carbon tetrachloride, CCl4, 14weeks) portal hypertension, PX20606 (PX,10mg/kg) or the steroidal FXR agonist obeticholic acid (OCA,10mg/kg) were gavaged...
December 18, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27959606/obeticholic-acid-in-primary-biliary-cholangitis
#20
LETTER
Ankur Jindal, Aditi Gupta, Shiv Sarin
No abstract text is available yet for this article.
November 17, 2016: New England Journal of Medicine
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