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https://www.readbyqxmd.com/read/27913155/early-molecular-stratification-of-high-risk-primary-biliary-cholangitis
#1
Claire Hardie, Kile Green, Laura Jopson, Ben Millar, Barbara Innes, Sarah Pagan, Dina Tiniakos, Jessica Dyson, Muzlifah Haniffa, Venetia Bigley, David E Jones, John Brain, Lucy J Walker
High-risk primary biliary cholangitis (PBC), defined by inadequate response at one year to Ursodeoxycholic acid (UDCA), is associated with disease progression and liver transplantation. Stratifying high-risk patients early would facilitate improved approaches to care. Using long-term follow-up data to define risk at presentation, 6 high-risk PBC patients and 8 low-risk patients were identified from biopsy, transplant and biochemical archival records. Formalin-fixed paraffin-embedded (FFPE) liver biopsies taken at presentation were graded (Scheuer and Nakanuma scoring) and gene expression analysed using the NanoString® nCounter PanCancer Immunity 770-gene panel...
November 21, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27906472/long-term-clinical-impact-and-cost-effectiveness-of-obeticholic-acid-for-the-treatment-of-primary-biliary-cholangitis
#2
Sumeyye Samur, Matthew Klebanoff, Reiner Banken, Daniel S Pratt, Rick Chapman, Daniel A Ollendorf, Anne M Loos, Kathleen Corey, Chin Hur, Jagpreet Chhatwal
: Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease that mainly affects middle-aged women. Obeticholic acid (OCA), which was recently approved by the Food and Drug Administration for PBC treatment, has demonstrated positive effects on biochemical markers of liver function. Our objective was to evaluate the long-term clinical impact and cost-effectiveness of OCA as a second-line treatment for PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA...
November 7, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27898169/cross-sectional-analysis-of-progressive-familial-intrahepatic-cholestasis-in-puerto-rican-children
#3
Dellys M Soler, Antonio I Del Valle, David Fernandez-Lube, Benjamin L Shneider
OBJECTIVE: Specific inherited disorders may be more common in island communities. Prior case reports suggest that cholestatic liver diseases may constitute a group of these inherited disorders in Puerto Rico. A cross-sectional survey of liver diseases in children was conducted to assess this hypothesis. METHODS: A cross-sectional analysis was performed in patients with chronic cholestasis at "Hospital Pediátrico Universitario" in San Juan, Puerto Rico. Ten potential participants with high gamma-glutamyl transpeptidase (GGTP) cholestasis were identified...
December 2016: Puerto Rico Health Sciences Journal
https://www.readbyqxmd.com/read/27895309/hepatocyte-specific-expression-of-an-oncogenic-variant-of-%C3%AE-catenin-results-in-cholestatic-liver-disease
#4
Ursula J Lemberger, Claudia Fuchs, Matthias Karer, Stefanie Haas, Tatjana Stojakovic, Christian Schöfer, Hanns-Ulrich Marschall, Fritz Wrba, Makoto M Taketo, Gerda Egger, Michael Trauner, Christoph H Österreicher
BACKGROUND: The Wnt/β-catenin signaling pathway plays a crucial role in embryonic development, tissue homeostasis, wound healing and malignant transformation in different organs including the liver. The consequences of continuous β-catenin signaling in hepatocytes remain elusive. RESULTS: Livers of Ctnnb1CA hep mice were characterized by disturbed liver architecture, proliferating cholangiocytes and biliary type of fibrosis. Serum ALT and bile acid levels were significantly increased in Ctnnb1CA hep mice...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893675/a-multicenter-randomized-double-blind-trial-comparing-the-efficacy-and-safety-of-tudca-and-udca-in-chinese-patients-with-primary-biliary-cholangitis
#5
Hong Ma, Minde Zeng, Ying Han, Huiping Yan, Hong Tang, Jifang Sheng, Heping Hu, Liufang Cheng, Qing Xie, Youfu Zhu, Guofeng Chen, Zhiliang Gao, Wen Xie, Jiyao Wang, Shanming Wu, Guiqiang Wang, Xiaohui Miao, Xiaoqing Fu, Liping Duan, Jie Xu, Lai Wei, Guangfeng Shi, Chengwei Chen, Minhu Chen, Qin Ning, Chen Yao, Jidong Jia
AIM: Tauroursodeoxycholic acid (TUDCA) is a taurine conjugated form of ursodeoxycholic acid (UDCA) with higher hydrophility. To further evaluate the efficacy and safety of TUDCA for primary biliary cholangitis (PBC), we performed this study on Chinese patients. METHODS: 199 PBC patients were randomly assigned to either 250 mg TUDCA plus UDCA placebo or 250 mg UDCA plus TUDCA placebo, 3 times per day for 24 weeks. The primary endpoint was defined as percentage of patients achieving serum alkaline phosphatase (ALP) reduction of more than 25% from baseline...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27882682/prevalence-of-equine-hepacivirus-infections-in-france-and-evidence-for-two-viral-subtypes-circulating-worldwide
#6
S Pronost, E Hue, C Fortier, M Foursin, G Fortier, F Desbrosse, F A Rey, P-H Pitel, E Richard, B Saunier
Like hepatitis C virus (HCV) in humans, the newly identified equine hepacivirus (NPHV) displays a predominating liver tropism that may evolve into chronic infections. The genomes of the two viruses share several organizational and functional features and are phylogenetically closest amongst the Hepacivirus genus. A limited amount of data is available regarding the spread of hepacivirus infections in horses. In this study, we asked whether in a more representative sample the prevalence and distribution of NPHV infections in France would resemble that reported so far in other countries...
November 24, 2016: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/27881673/sortilin-1-modulates-hepatic-cholesterol-lipotoxicity-in-mice-via-functional-interaction-with-liver-carboxylesterase-1
#7
Jibiao Li, Yifeng Wang, David Matye, Hemantkumar Chavan, Partha Krishnamurthy, Feng Li, Tiangang Li
Liver plays a key role in cholesterol metabolism. Impaired hepatic cholesterol homeostasis causes intracellular free cholesterol accumulation and hepatocyte injury. Sortilin 1 (Sort1) is an intracellular lysosomal trafficking receptor that was recently identified by GWAS as a novel regulator of cholesterol metabolism in humans. Here we report that Sort1 deficiency protected against cholesterol accumulation-induced liver injury and inflammation in mice. Using LC-MS/MS based proteomics approach, we identified liver carboxyesterase 1 (CES1) as a novel Sort1 interacting protein...
November 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27875503/influence-of-partial-external-biliary-diversion-on-the-lipid-profile-in-children-with-progressive-familial-intrahepatic-cholestasis
#8
Irena Jankowska, Piotr Czubkowski, Aldona Wierzbicka, Joanna Pawłowska, Piotr Kaliciński, Piotr Socha
OBJECTIVES: The concentration of bile acids is highly increased in progressive familial intrahepatic cholestasis (PFIC). Bile acids are the end products of cholesterol metabolism, and aid in the absorption of fat-soluble vitamins and dietary fat. The aim of our study was to investigate lipid metabolism in patients with PFIC with focus on the effect of partial external biliary diversion (PEBD). METHODS: In 26 patients with PFIC, who underwent PEBD surgery at the median age of 2...
December 2016: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/27860118/association-between-serum-soluble-cd14-and-il-8-levels-and-clinical-outcome-in-primary-biliary-cholangitis
#9
Takeji Umemura, Tomohiro Sekiguchi, Satoru Joshita, Tomoo Yamazaki, Naoyuki Fujimori, Soichiro Shibata, Yuki Ichikawa, Michiharu Komatsu, Akihiro Matsumoto, Zakera Shums, Gary L Norman, Eiji Tanaka, Masao Ota
BACKGROUND & AIMS: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by portal inflammation and immune-mediated destruction of intrahepatic bile ducts that often leads to liver decompensation, and liver failure. Although the biochemical response to ursodeoxycholic acid (UDCA) can predict disease outcome in PBC, few biomarkers have been identified as prognostic tools applicable prior to UDCA treatment. We therefore sought to identify such indicators of long-term outcome in PBC in the Japanese population...
November 17, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27859498/the-srl-peptide-of-rhesus-rotavirus-vp4-protein-governs-cholangiocyte-infection-and-the-murine-model-of-biliary-atresia
#10
Sujit K Mohanty, Bryan Donnelly, Inna Lobeck, Ashley Walther, Phylicia Dupree, Abigail Coots, Jaroslaw Meller, Monica McNeal, Karol Sestak, Greg Tiao
: Biliary atresia (BA) is a neonatal obstructive cholangiopathy which progresses to end stage liver disease, often requiring transplantation. The murine model of BA, employing rhesus rotavirus (RRV), parallels human disease and has been used to elucidate mechanistic aspects of a virus induced biliary cholangiopathy. We previously reported that RRV VP4 gene plays an integral role in activating the immune system and induction of BA. Utilizing rotavirus binding and blocking assays, this study elucidated how RRV VP4 protein governs cholangiocyte susceptibility to infection both in vitro and in vivo in the murine model of BA...
November 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27855457/-cholestatic-liver-disease
#11
Christine Pichler, Tobias Boettler, Robert Thimme
Common cholestatic liver diseases are primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Both diseases are considered autoimmune disorders; however, the precise pathogenesis remains elusive. Patients usually show no symptoms or present with pruritus and fatigue. High alkaline phosphatase and the presence of antimitochondrial antibodies are sufficient to diagnose PBC. Ursodeoxycholic acid is approved and recommended for the treatment of PBC. The diagnosis of PSC is established by elevated alkaline phosphatase-levels and typical cholangiographic findings...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27832649/bile-acids-and-the-potential-role-in-primary-biliary-cirrhosis
#12
Hang Yang, Zhijun Duan
BACKGROUND: Bile acids (BAs) play a potential role in regulating the whole-body metabolic homeostasis via the interaction with gut microbiome and the signal transduction as messengers, which establish a link between the primary biliary cirrhosis (PBC) and gut microbiome in many aspects, particularly with regard to the immune system of the body. PBC, as a chronic cholestatic liver disease characterised by the destruction of small intrahepatic bile ducts, causes fibrosis and potential cirrhosis without efficient therapies...
November 11, 2016: Digestion
https://www.readbyqxmd.com/read/27825634/obeticholic-acid-in-primary-biliary-cholangitis
#13
Serge Erlinger
In a double-blind, randomized, placebo-controlled study including 217 patients with primary biliary cholangitis, the authors show that obeticholic acid (a potent farnesoid X agonist) administered with ursodeoxycholic acid or as monotherapy significantly decreases serum alkaline phosphatase and bilirubin when compared to placebo. Pruritus (and serious adverse effects) was observed more frequently in obeticholic acid-treated patients than in controls, in spite of a decrease in serum bile acid concentration. These results are encouraging, but more studies are needed on clinical efficacy and safety before obeticholic acid can be widely recommended...
November 4, 2016: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/27812789/serum-plant-sterols-associate-with-gallstone-disease-independent-of-weight-loss-and-non-alcoholic-fatty-liver-disease
#14
Pirjo Käkelä, Ville Männistö, Imre Ilves, Maija Vaittinen, Milla-Maria Tauriainen, Matti Eskelinen, Helena Gylling, Hannu Paajanen, Jussi Pihlajamäki
BACKGROUND: Gallstone disease (GD) has been associated with low serum levels of plant sterols. We evaluated the impact of laparoscopic Roux-en-Y gastric bypass (LRYGB) and non-alcoholic fatty liver disease (NAFLD) on the association of GD with low levels of serum plant sterols. METHODS: Two hundred forty-two consecutive morbidly obese patients were recruited to this prospective study. Histological analysis of liver biopsy to diagnose NAFLD was performed. Bile sample was taken during the LRYGB...
November 3, 2016: Obesity Surgery
https://www.readbyqxmd.com/read/27806795/-infantile-cholestasis-caused-by-cftr-mutation-case-report-and-literature-review
#15
L Li, N L Wang, J Y Gong, J S Wang
Objective: To study the clinical presentation, biochemical features and genetic analysis of an infant with cholestasis related to the CFTR mutations. Method: The clinical presentation, laboratory investigations and management of a case with infantile cholestasis caused by CFTR mutations were summarized and the relevant literature was reviewed. Result: (1) The patient was a 5 months old boy with cholestasis which developed in neonatal period with delayed meconium exclusion.The laparoscopic exploration was performed to exclude biliary atresia because of acholic stool when he was two months old...
November 2, 2016: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/27799961/heterozygous-inactivation-of-the-nuclear-receptor-pxr-nr1i2-in-a-patient-with-anabolic-steroid-induced-intrahepatic-cholestasis
#16
Roman Liebe, Marcin Krawczyk, Joanna Raszeja-Wyszomirska, Beata Kruk, Rebecca Preis, Jocelyn Trottier, Olivier Barbier, Piotr Milkiewicz, Frank Lammert
INTRODUCTION: The incidence of liver damage due to steroid consumption is increasing due to the omnipresence of the idealized body image and the widespread availability of drugs via the Internet. The genetic factors underlying individual susceptibility are not presently known. CASE PRESENTATION: A male patient developed cholestatic liver injury two weeks after a two-month course of anabolic steroids. Next-generation sequencing (NGS) of 24 cholestasis-related genes revealed a heterozygous two-basepair deletion in exon 1 of the pregnane X receptor gene (PXR)...
August 2016: Hepatitis Monthly
https://www.readbyqxmd.com/read/27797067/spontaneous-resolution-of-de-novo-hepatitis-b-after-living-donor-liver-transplantation-with-hepatitis-b-core-antibody-positive-graft-a-case-report
#17
Yasuyuki Hara, Kazuaki Tokodai, Chikashi Nakanishi, Shigehito Miyagi, Naoki Kawagishi
BACKGROUND: Hepatitis B core antibody (HBcAb)-positive graft is reported to cause de novo hepatitis B after liver transplantation with a probability of 38-100 % without prophylaxis. Hepatitis B surface antigen loss is reported to be achieved with a probability of only 3-8 % in the patients treated by antiviral agents. We present an extremely rare case of spontaneous resolution of de novo hepatitis B after living donor liver transplantation (LDLT) with HBcAb-positive graft. CASE PRESENTATION: An 8-year-old female patient underwent LDLT for end-stage biliary atresia using an HBcAb-positive left lobe graft...
December 2016: Surgical Case Reports
https://www.readbyqxmd.com/read/27789682/disrupted-murine-gut-to-human-liver-signaling-alters-bile-acid-homeostasis-in-humanized-mouse-liver-models
#18
Edwin C Y Chow, Holly P Quach, Yueping Zhang, Jason Z Y Wang, David C Evan, Albert P Li, Jose Silva, Rommel G Tirona, Yurong Lai, K Sandy Pang
The humanized liver mouse model is increasingly being exploited for human drug metabolism studies. However, its model stability, inter-communication between human hepatocytes and mouse non-parenchymal cells in liver and murine intestine, and changes in extrahepatic transporter and enzyme expression has not been investigated. We examined these issues in FRGN [Fah(-/-), Rag2(-/-), and IL-2rg(-/-) on NOD background] and chimeric mice: mFRGN, and hFRGN (repopulated with mouse or human hepatocytes, respectively)...
October 27, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27784427/-expression-of-sal-like-4-in-primary-hepatocellular-carcinoma-and-its-association-with-epithelial-mesenchymal-transition
#19
J Xu, J Wang, Y Hu, X X Wang, L L Cheng, H Y Yu
Objective: To investigate the expression of sal-like 4 (SALL4) in tissues of primary hepatocellular carcinoma (HCC) and its association with epithelial-mesenchymal transition (EMT) and clinicopathological characteristics. Methods: Immunohistochemistry and nucleic acid in situ hybridization were used to measure the mRNA expression of SALL4, epithelial cadherin (E-cadherin), vimentin, and Snail in 72 HCC samples, 2 fetal liver samples, and 2 normal adult liver tissue samples. Results: Strong expression of SALL4 was observed in hepatoblasts in fetal liver, but SALL4 expression was not observed in primitive hematopoietic cells and normal adult hepatocytes or biliary epithelial cells...
July 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/27776652/biliary-tract-enhancement-in-gadoxetic-acid-enhanced-mri-correlates-with-liver-function-biomarkers
#20
Yoshifumi Noda, Satoshi Goshima, Kimihiro Kajita, Hiroshi Kawada, Nobuyuki Kawai, Hiromi Koyasu, Masayuki Matsuo, Kyongtae T Bae
PURPOSE: To evaluate the association between gadoxetic-acid-enhanced magnetic resonance (MR) imaging measurements and laboratory and clinical biomarkers of liver function and fibrosis. MATERIALS AND METHODS: One hundred thirty nine consecutive patients with suspected liver disease or liver tumor underwent gadoxetic-acid-enhanced MR imaging. MR imaging measurements during the hepatobiliary phase included biliary tract structure-to-muscle signal intensity ratio (SIR)...
November 2016: European Journal of Radiology
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