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https://www.readbyqxmd.com/read/28088462/activation-of-the-hypoxia-inducible-factor-1-alpha-subunit-pathway-in-steatotic-liver-contributes-to-formation-of-cholesterol-gallstones
#1
Yoichiro Asai, Tetsuya Yamada, Sohei Tsukita, Kei Takahashi, Masamitsu Maekawa, Midori Honma, Masanori Ikeda, Keigo Murakami, Yuichiro Munakata, Yuta Shirai, Shinjiro Kodama, Takashi Sugisawa, Yumiko Chiba, Yasuteru Kondo, Keizo Kaneko, Kenji Uno, Shojiro Sawada, Junta Imai, Yasuhiro Nakamura, Hiroaki Yamaguchi, Kozo Tanaka, Hironobu Sasano, Nariyasu Mano, Yoshiyuki Ueno, Tooru Shimosegawa, Hideki Katagiri
BACKGROUND AND AIMS: Hypoxia inducible factor 1 alpha subunit (HIF1A) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with non-alcoholic fatty liver disease (NAFLD). NAFLD increases risk for cholesterol gallstone disease by unclear mechanisms. We studied the relationship between HIF1A and gallstone formation associated with liver steatosis. METHODS: We performed studies with mice with inducible disruption of Hif1a in hepatocytes, via a Cre adenoviral vector (iH-HIFKO mice), and mice without disruption of Hif1a (control mice)...
January 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28087885/absence-of-intestinal-microbiota-increases-%C3%A3-cyclodextrin-stimulated-reverse-cholesterol-transport
#2
Rima H Mistry, Henkjan J Verkade, Uwe J F Tietge
SCOPE: Non-digestible oligosaccharides are used as prebiotics for perceived health benefits, among these modulating lipid metabolism. However, the mechanisms of action are incompletely understood. The present study characterized the impact of dietary ß-cyclodextrin (ßCD, 10%, w/w), a cyclic oligosaccharide, on sterol metabolism and reverse cholesterol transport (RCT) in conventional and also germ-free mice to establish dependency on metabolism by intestinal bacteria. METHODS AND RESULTS: In conventional ßCD-fed C57BL/6J wild-type mice plasma cholesterol decreased significantly (-40%, p<0...
January 14, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28070198/clinical-course-and-genetic-susceptibility-of-primary-biliary-cirrhosis-analysis-of-a-prospective-cohort
#3
Piero Luigi Almasio, Anna Licata, Marcello Maida, Fabio Salvatore Macaluso, Andrea Costantino, Nicola Alessi, Stefania Grimaudo, Giulia Accardi, Calogero Caruso, Antonio Craxi
BACKGROUND: Natural history of primary biliary cirrhosis (PBC) is partially characterized in patients from the Mediterranean area whose genetic background differs from that of Northern Europeans. OBJECTIVES: We aimed to describe genetic susceptibility and clinical course of PBC in patients from Southern Italy. METHODS: Socio-demographic, clinical, biochemical and histological data at diagnosis as well as disease progression of 81 PBC consecutive patients were collected...
November 2016: Hepatitis Monthly
https://www.readbyqxmd.com/read/28067818/the-diagnostic-usefulness-of-serum-total-bile-acid-concentrations-in-the-early-phase-of-acute-pancreatitis-of-varied-etiologies
#4
Aleksandra Maleszka, Paulina Dumnicka, Aleksandra Matuszyk, Michał Pędziwiatr, Małgorzata Mazur-Laskowska, Mateusz Sporek, Piotr Ceranowicz, Rafał Olszanecki, Marek Kuźniewski, Beata Kuśnierz-Cabala
The most common causes of acute pancreatitis (AP) are biliary tract diseases with cholestasis and alcohol consumption. In 10%-15% of patients, etiology determination is difficult. Identification of the etiology allows for the implementation of adequate treatment. The aim of this study was to assess the utility of the serum concentrations of total bile acids (TBA) to diagnose AP etiology in the early phase of the disease. We included 66 patients with AP, admitted within the first 24 h from the onset of symptoms...
January 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28067465/cholestyramine-alters%C3%A2-bile-acid%C3%A2-amounts-and-the-expression-of-cholesterol-related-genes-in-rabbit-intestinal-and-hepatic-tissues
#5
Dong Ni Qiu, Quan Shang, Da Yu Sun, Wei Qun Ding, Zhong Guang Luo, Jian Chen, Wei Ru Jiang, Jian Ping Huang, Xiao Yun Jiang
OBJECTIVE: Cholestyramine, as a bile acid sequestering exchange resin, has been wildly used to treat hypercholesterolemia. The aim of this study was to explore how cholestyramine regulated serum cholesterol amounts and bile acid levels in animal models. METHODS: The New Zealand White rabbits were randomly assigned to the control (given distilled water) and cholestyramine (CHO)-treated (given cholestyramine 1 g/kg/day for 2 weeks) groups. To assess bile acid pool size, bile fistulas were generated in five rabbits in each group...
January 9, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28062491/reverse-cholesterol-transport-is-increased-in-germ-free-mice
#6
Rima H Mistry, Henkjan J Verkade, Uwe J F Tietge
OBJECTIVE: The intestinal microbiota is emerging as a clinically relevant modulator of atherosclerotic risk. Reverse cholesterol transport (RCT) is an atheroprotective metabolic pathway. How the microbiota impacts RCT has not been investigated. Therefore, the aim of this study was to characterize cholesterol metabolism and RCT in germ-free mice compared with conventional mice. APPROACH AND RESULTS: In chow-fed germ-free mice, plasma cholesterol was unchanged, whereas liver cholesterol content was higher (1...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28052628/management-of-cholestatic-disease-in-2017
#7
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/28052132/association-between-promoter-hypomethylation-and-overexpression-of-autotaxin-with-outcome-parameters-in-biliary-atresia
#8
Wanvisa Udomsinprasert, Nakarin Kitkumthorn, Apiwat Mutirangura, Voranush Chongsrisawat, Yong Poovorawan, Sittisak Honsawek
OBJECTIVE: Biliary atresia (BA) is a progressive fibroinflammatory liver disease. Autotaxin (ATX) has a profibrotic effect resulting from lysophosphatidic acid activity. The purpose of this study was to examine ATX expression and ATX promoter methylation in peripheral blood leukocytes and liver tissues from BA patients and controls and investigate their associations with outcome parameters in BA patients. METHODS: A total of 130 subjects (65 BA patients and 65 age-matched controls) were enrolled...
2017: PloS One
https://www.readbyqxmd.com/read/28051047/evaluation-of-the-use-of-laparoscopic-guided-cholecystocholangiography-and-liver-biopsy-in-definitive-diagnosis-of-neonatal-cholestatic-jaundice
#9
Khalid Shreef, Abdullah Alhelal
BACKGROUND: Once it is established that a jaundiced infant has direct hyperbilirubinemia, the principal diagnostic concern is to differentiate hepatocellular from obstructive cholestasis. Traditional tests such as ultrasonography, percutaneous liver biopsy and technetium 99 m hepatobiliary iminodiacetic acid (HIDA) scan are often not sufficiently discriminating. Definitive exclusion of biliary atresia (BA) in the infant with cholestatic jaundice usually requires mini-laparotomy and intra-operative cholangiography...
October 2016: African Journal of Paediatric Surgery: AJPS
https://www.readbyqxmd.com/read/28049946/ursodeoxycholic-acid-ameliorates-intrahepatic-cholestasis-independent-of-biliary-bicarbonate-secretion-in-vil2-kd-kd-mice
#10
Ryo Hatano, Kotoku Kawaguchi, Fumitaka Togashi, Masato Sugata, Shizuka Masuda, Shinji Asano
Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid that possesses many pharmacological effects, including increasing bile flow, changing the hydrophobicity of the bile acid pool, and modulation of the immune response. UDCA has been approved for treating cholestatic liver disease, such as primary biliary cholangitis. However, several unanticipated severe side effects of UDCA are observed in cholestatic patients, and its pharmacological benefits remain controversial. We reported that ezrin-knockdown (Vil2(kd/kd)) mice exhibited severe hepatic injury because of a functional disorder in bile duct fluidity and alkalinity regulation, resembling human intrahepatic cholestatic disease...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28034761/bile-acid-receptor-tgr5-overexpression-is-associated-with-decreased-intestinal-mucosal-injury-and-epithelial-cell-proliferation-in-obstructive-jaundice
#11
Chen-Guang Ji, Xiao-Li Xie, Jie Yin, Wei Qi, Lei Chen, Yun Bai, Na Wang, Dong-Qiang Zhao, Xiao-Yu Jiang, Hui-Qing Jiang
Bile acids stimulate intestinal epithelial proliferation in vitro. We sought to investigate the role of the bile acid receptor TGR5 in the protection of intestinal epithelial proliferation in obstructive jaundice. Intestinal tissues and serum samples were obtained from patients with malignant obstructive jaundice and from bile duct ligation (BDL) rats. Intestinal permeability and morphological changes in the intestinal mucosa were observed. The functions of TGR5 in cell proliferation in intestinal epithelial injury were determined by overexpression or knockdown studies in Caco-2 and FHs 74 Int cells pretreated with lipopolysaccharide (LPS)...
December 18, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28008998/impaired-hepatic-adaptation-to-chronic-cholestasis-induced-by-primary-sclerosing-cholangitis
#12
Malgorzata Milkiewicz, Marta Klak, Agnieszka Kempinska-Podhorodecka, Anna Wiechowska-Kozlowska, Elzbieta Urasinska, Malgorzata Blatkiewicz, Ewa Wunsch, Elwyn Elias, Piotr Milkiewicz
Pathogenesis of primary sclerosing cholangitis (PSC) may involve impaired bile acid (BA) homeostasis. We analyzed expressions of factors mediating enterohepatic circulation of BA using ileal and colonic (ascending and sigmoid) biopsies obtained from patients with PSC with and without ulcerative colitis (UC) and explanted PSC livers. Two-fold increase of BA-activated farnesoid X receptor (FXR) protein levels were seen in ascending and sigmoid colon of PSC patients with correspondingly decreased apical sodium-dependent BA transporter (ASBT) gene expression...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28007481/looking-into-the-crystal-ball-predicting-non-response-to-ursodeoxycholic-acid-in-primary-biliary-cholangitis
#13
Vincent Zimmer, Frank Lammert
No abstract text is available yet for this article.
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28003721/primary-biliary-cholangitis-disease-pathogenesis-and-implications-for-established-and-novel-therapeutics
#14
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/27989148/chemical-reactivity-of-emodin-and-its-oxidative-metabolites-to-thiols
#15
Boyang Qin, Yang Xu, Jiaming Chen, Wenlin Huang, Ying Peng, Jiang Zheng
Polygonum multiflorum is an herbal medicine widely employed in China. Hepatotoxicity of the herbal medicine has been well documented, but the mechanisms of the toxicity remain unknown. Emodin (EM) is a major constituent of the herb and has been reported to be hepatotoxic. The main purpose of this study was to define the metabolic pathways of EM in order to characterize the potential reactive intermediates. EM was incubated with rat liver microsomes or human liver microsomes, followed by LC-MS/MS analysis to investigate the in vitro and in vivo metabolism of EM...
December 19, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27986173/liver-function-assessment-by-magnetic-resonance-imaging
#16
Emre Ünal, Deniz Akata, Musturay Karcaaltincaba
Liver function assessment by hepatocyte-specific contrast-enhanced magnetic resonance imaging is becoming a new biomarker. Liver function can be assessed by T1 mapping (reduction rate) and signal intensity measurement (relative enhancement ratio) before and after GD-EOB-DTPA (gadoxetic acid) administration, as alternative to Tc-99m galactosyl serum albumin scintigraphy, 99m Tc-labeled mebrofenin scintigraphy, and indocyanine green clearance test. Magnetic resonance imaging assessment of liver function can enable diagnosis of cirrhosis, nonalcoholic fatty liver disease associated fibrosis and steatohepatitis, primary sclerosing cholangitis, toxic hepatitis, and chemotherapy and radiotherapy-related changes, which may be only visible on hepatobiliary phase images...
December 2016: Seminars in Ultrasound, CT, and MR
https://www.readbyqxmd.com/read/27981308/primary-biliary-cirrhosis-and-primary-sclerosing-cholangitis-an-update-on-mr-imaging-findings-with-recent-developments
#17
REVIEW
Jelena Djokić Kovač, Marc-André Weber
Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are the most common immune-mediated chronic cholestatic liver diseases leading to cirrhosis and liver failure. Although magnetic resonance imaging (MRI) is not a necessary procedure for the diagnosis of PBC, MRI is recommended for monitoring disease progression and early detection of complications. Even though liver cirrhosis subtypes have similar MR imaging features, there are some findings which could indicate PBC, such as the periportal halo sign...
December 2016: Journal of Gastrointestinal and Liver Diseases: JGLD
https://www.readbyqxmd.com/read/27959606/obeticholic-acid-in-primary-biliary-cholangitis
#18
LETTER
Ankur Jindal, Aditi Gupta, Shiv Sarin
No abstract text is available yet for this article.
17, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27959605/obeticholic-acid-in-primary-biliary-cholangitis
#19
LETTER
(no author information available yet)
No abstract text is available yet for this article.
17, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27957759/systematic-review-recurrent-autoimmune-liver-diseases-after-liver-transplantation
#20
REVIEW
A J Montano-Loza, R A Bhanji, S Wasilenko, A L Mason
BACKGROUND: Autoimmune liver diseases (AILD) constitute the third most common indication for liver transplantation (LT) worldwide. Outcomes post LT are generally good but recurrent disease is frequently observed. AIMS: To describe the frequency and risk factors associated with recurrent AILD post-LT and provide recommendations to reduce the incidence of recurrence based on levels of evidence. METHODS: A systematic review was performed for full-text papers published in English-language journals, using the keywords 'autoimmune hepatitis (AIH)', 'primary biliary cholangitis and/or cirrhosis (PBC)', 'primary sclerosing cholangitis (PSC)', 'liver transplantation' and 'recurrent disease'...
December 12, 2016: Alimentary Pharmacology & Therapeutics
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